Clinical Study Evaluating Safety and Efficacy of a Nepafenac Punctal Plug Delivery System (N-PPDS) Compared With Placebo Punctal Plug Delivery System (p-PPDS) in Controlling Post-Operative Ocular Pain and Inflammation After Routine Unilateral Cataract Surgery
Phase: PHASE2
Conditions: Pain, Inflammation
Sponsor: Mati Therapeutics Inc.

This document is a confidential communication of Mati Therapeutics Inc. Acceptance of the document 
constitutes agreement by the recipient that the contents will not be disclosed to any unauthorized personnel 
without the prior written authorization of Mati Therapeutics Inc. 
 
Mati Therapeutics Inc. 
4317 Dunning Lane 
Austin TX 78746 
 
CLINICAL STUDY PROTOCOL - NPIF-2018-01 
Nepafenac Punctal Plug Delivery System, 204 µg/L67 
IND 136640 
A CLINICAL STUDY EVALUATING THE SAFETY AND 
EFFICACY OF A PUNCTAL PLUG DELIVERY SYSTEM 
(Evolute®) OF NEPAFENAC (N-PPDS) COMPARED WITH A 
PLACEBO PUNCTAL PLUG DELIVERY SYSTEM (p-PPDS) 
IN CONTROLLING POST-OPERATIVE OCULAR PAIN AND 
INFLAMMATION IN SUBJECTS UNDERGOING ROUTINE 
UNILATERAL CATARACT SURGERY 
Protocol Version 1: December 19, 2017 
Protocol Version 2: January 19, 2018 
Protocol Version 3: February 6, 2018 
Protocol Version 4: April 18, 2018 
Protocol Version 5: April 25, 2018 
Protocol Version 6: June 27, 2018 
Protocol Version 7: August 27, 2018 
 
 
 

IND 136640 
N-PPDS, 204 µg/L67 
Clinical Study Protocol NPIF-2018-01 
PROTOCOL APPROVAL 
Protocol Number: NPIF-2018-01 
Title of Protocol: A Clinical Study Evaluating the Safety and Efficacy of a Punctal Plug 
Delivery System (Evolute®) of Nepafenac  (N-PPDS) compared with a 
Placebo Punctal Plug Delivery System (p-PPDS) in Controlling Post-
Operative Ocular Pain and inflammation in Subjects undergoing Routine 
Unilateral Cataract Surgery 
Prepared by: 
Study Director: 
Approved by: 
Approved by: 
Daniel Schwab, Consultant 
D'Ellis Group Inc. 
Robert Williams, MD 
Clinical Consultant 
Deepank Utkhede 
Chief Scientific Officer, 
Mati Therapeutics Inc. 
Robert Butchofsky 
President, 
Mati Therapeutics Inc. 
Version 7: August 27, 2018 
2 
Zl A4:, 19 
Date 
Date 
Date 
Date 
Mati Therapeutics Inc. -CONFIDENTIAL 

IND 136640 
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Clinical Study Protocol NPIF-2018-01 
 
 
Version 7: August 27, 2018 
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Mati Therapeutics Inc. - CONFIDENTIAL
 
 
PROTOCOL APPROVAL 
 
Protocol Number: NPIF-2018-01   
 
Title  of  Protocol: A  Clinical  Study  Evaluating  the  Safety  and  Efficacy  of  a  Punctal  Plug 
Delivery  System  (Evolute®)  of  Nepafenac  (N-PPDS)  compared  with  a 
Placebo  Punctal  Plug  Delivery  System  (p-PPDS)  in  Controlling  Post-
Operative Ocular Pain and inflammation in Subjects undergoing Routine 
Unilateral Cataract Surgery 
 
Prepared by:   
___________________________________  ____________ 
Daniel Schwob, Consultant  
  
 
Date 
D’Ellis Group Inc. 
 
 
 
Study Director:  ____________________________________  ___________ 
 
Robert Williams, MD    
  
 
Date 
 
Clinical Consultant 
 
 
 
Approved by:  
___________________________________  ____________ 
 
Deepank Utkhede  
  
  
 
Date 
 
Chief Scientific Officer,  
Mati Therapeutics Inc. 
 
 
 
Approved by:  
___________________________________  ____________ 
 
Robert Butchofsky  
  
  
 
Date 
 
President,  
Mati Therapeutics Inc. 
 
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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STATEMENT OF COMPLIANCE 
Mati Therapeutics Inc. Protocol NPIF-2018-01 
A CLINICAL STUDY EVALUATING THE SAFETY AND EFFICACY OF A PUNCTAL PLUG 
DELIVERY SYSTEM (Evolute
®)
 OF NEPAFENAC (N-PPDS) COMPARED WITH A PLACEBO 
PUNCTAL PLUG DELIVERY SYSTEM (
P-PPDS) IN CONTROLLING POST-O
PERATIVE 
OCULAR PAIN AND INFLAMMATION IN SUBJECTS UNDERGOING ROUTINE UNILATERAL 
CATARACT SURGERY 
Protocol Version Date:  June 27 2018 
Sponsor and Medical Monitor Approval: 
Signature:__________________________________________Date:  
_______________ 
 
Dr. Robert Williams, M.D., Medical Monitor 
 
Investigator Agreement: 
I have read this protocol.  I agree to: 
a. Implement and conduct this study in strict compliance with this agreement; the protocol; 
ICH  guidelines  for  Good  Clinical  Practices  and  all  other  applicable  regulatory 
requirements.  No deviation from, or changes to the protocol will take place without prior 
agreement from the sponsor and documented approval from an Institutional Review Board 
(IRB)/Independent  Ethics  Committee  (IEC),  except  where  necessary  to  eliminate  an 
immediate hazard(s) to the study participants. 
b. Obtain written Informed Consent (IC), that is IRB/IEC approved, from each prospective 
study subject at screening and prior to any study specific examination/test. 
c. Maintain  reliable  study  medication  dispensing/dosing  log,  receipt  and  return  shipping 
records, and to store study supplies in a secure, locked facility accessible only to authorized 
study personnel  
d. Maintain  adequate  and  accurate  source  documents  in  accordance  with  Food  and  Drug 
Administration (FDA) regulations (e.g., CRFs, consent forms, AE/SAE forms, IRB/IEC 
documentation,  study  supply  records).    Keep  source  documentation  for  the  maximum 
period of time permitted by the hospital, institution, or private practice.  In addition, will 
notify  
the  Sponsor  
immediately  
if  any  documents  are  
to  be  destroyed,  
transferred  
to  a 
different facility or owner 
e. Maintain all information supplied by Mati Therapeutics Inc. in confidence and, when this 
information  is  submitted  to  an  independent  IRB/IEC  or  any  other  group,  it  will  be 
submitted with a designation that the material is confidential. 
f. Attempt to complete the study within the time designated 
g. By signing this protocol, the Investigator grants permission to personnel from the Sponsor, 
its  representatives,  third  parties  and  appropriate  regulatory  authorities  for  on-site 
monitoring and review of all appropriate study documentation, as well as on-site review of 
the procedures employed in data collection, where clinically appropriate. 

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Clinical Study Protocol NPIF-2018-01 
 
 
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Investigator Signature: ____________________________Date:___________   
 
  
      “TYPE/Print Name of INVESTIGATOR” 
 
Acknowledged By/Sponsor’s Representative Signature:   
  
 
______________________________________________Date:____________   
 
“TYPE/Print Name of Representative” 
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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TABLE OF CONTENTS 
PROTOCOL APPROVAL .....................................................................................................2 
ABBREVIATIONS AND DEFINITIONS 
............................................................................9 
STUDY SYNOPSIS ...............................................................................................................10 
1 
KEY ROLES 
................................
................................
..............................................15 
2 
INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
................................
................................
.............................................17 
2.1 
Background Information 
.............................................................................................17 
2.2 
Rationale 
................................
................................
......................................................18 
2.3 
Potential Risks and Benefits 
................................
........................................................18 
2.3.1 Known Potential Risks 
...............................................................................................18  
2.3.2 Known Potential Benefits 
................................
............................................................19 
3 
OBJECTIVES AND PURPOSE 
..............................................................................19 
4 
STUDY DESIGN AND ENDPOINTS 
.....................................................................19 
4.1 
Description of the Study Design 
................................
..................................................19 
4.2 
Study Endpoints 
................................
................................
...........................................20 
4.2.1 Primary Efficacy Endpoint ..........................................................................................20 
4.2.2 Secondary Efficacy Endpoints 
....................................................................................20 
4.2.3 Safety Endpoints 
................................
................................
..........................................20 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
..................................................20
 
5.1 
Subject Inclusion Criteria ............................................................................................20 
5.2 
Subject Pre-Operative Exclusion Criteria 
...................................................................21 
5.3 
Intra-Operative Exclusion Criteria (Surgical Complications) 
.....................................23
 
5.4 
Strategies for Recruitment and Retention 
................................
....................................24 
5.5 
Study Subject Withdrawal or Termination Criteria 
.....................................................24
 
5.5.1 Reasons for Termination, Discontinuation or Disqualified 
.........................................25 
5.5.2 Handling of Study Subject Termination, Discontinued or Disqualified 
......................25 
5.6 
Premature Termination or Suspension of Study or Study Site 
....................................26 
6 
STUDY AGENT 
.......................................................................................................27 
6.1 
Study Treatments 
................................
................................
.........................................27 
6.1.1 Route of Administration ..............................................................................................27 
6.1.2 Formulation, Appearance, Packaging and Labeling 
....................................................27 
6.1.3 Product Storage and Stability.......................................................................................28 
6.1.4 Starting Dose 
..............................................................................................................28 
6.1.5 Preparation for Insertion of Masked Punctal Plug 
.......................................................28 
6.1.6 Masked Punctal Plug Insertion 
................................
....................................................29 
6.1.7 Unable to Insert/Extruded/Lost Masked Punctal Plug 
.................................................29 
6.1.8 Duration of Therapy 
...................................................................................................30  
6.1.9 Removal of a Masked Punctal Plug 
................................
.............................................30 
6.2 
Study Plug Accountability Procedures 
................................
........................................31 

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Clinical Study Protocol NPIF-2018-01 
 
 
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7 
STUDY PROCEDURES AND SCHEDULE 
...........................................................31
 
7.1 
Protocol Amendments 
................................................................................................32 
7.2 
Study Procedures/Evaluations .....................................................................................32 
7.2.1 Study specific procedures 
................................
............................................................32 
7.2.2 Standard of care Study Procedures 
................................
..............................................33 
7.3 
Laboratory Procedures/Evaluations 
................................
.............................................33 
7.4 
Study Visit Schedule 
..................................................................................................34 
7.4.1 Visit 1:  (Screening/Baseline Visit, Day -30 to -1) 
......................................................34
 
7.4.2 Visit 2: (Masked Punctal Plug Insertion Visit, 1-2 days pre-op) 
.................................34 
7.4.3 Visit 3:  (Surgical Visit, Day 0) 
................................
...................................................35 
7.4.4 Visit 4 through Visit 6: Follow-up visits 
................................
.....................................36 
7.4.5 Visit 7:  (Final Study Visit, Day 14 ± 2 days Post-Op) 
...............................................38
 
7.4.6 Early Exit Visit ............................................................................................................38 
7.4.7 Unscheduled Visit 
......................................................................................................39 
7.5 
Emergency Anaphylactic or Overdose Procedures, Dose Modification .....................41 
7.6 
Concomitant Medications 
................................
............................................................41 
7.6.1 Pre-Study Concomitant Medication Use .....................................................................41 
7.6.2 Concomitant Medication Use ......................................................................................41 
7.7 
Prohibited Medications, Treatments and Procedures 
...................................................42 
7.7.1 Prohibited Medications 
................................
................................
................................42 
7.7.2 Prohibited Procedures 
................................
................................
..................................42 
7.8 
Prophylactic Medications.............................................................................................42
 
7.9 
Rescue Medications 
................................
................................
.....................................42 
7.9.1 Administration of a Rescue Medication ......................................................................43 
8 
ASSESSMENT OF SAFETY 
...................................................................................43 
8.1 
Safety Variables 
................................
................................
...........................................43 
8.2 
Definitions....................................................................................................................43 
8.2.1 Adverse Event 
............................................................................................................43 
8.2.2 Serious Adverse Events 
................................
...............................................................43 
8.3 
Adverse Event Descriptions 
........................................................................................45 
8.3.1 Intensity........................................................................................................................45 
8.3.2 Relationship to Study Treatment .................................................................................45 
8.4 
Follow-up for Adverse Events Definitions 
................................
..................................45 
8.5 
Pregnancy Follow-up 
................................
................................
...................................45 
8.6 
Reporting of Technical Complaints 
................................
.............................................46 
8.6.1 Definitions....................................................................................................................46
 
8.6.2 Reporting of Technical Complaints 
................................
.............................................46 
8.6.3 Punctal Plug Serious Adverse Events and Technical Complaints 
...............................47 
8.6.4 Anticipated Adverse Events 
........................................................................................47 
8.7 
Reporting Procedures 
.................................................................................................48 
8.7.1 Adverse Event Reporting 
............................................................................................48 
8.7.2 Serious Adverse Event Reporting 
...............................................................................48 
8.7.3 Unanticipated Problem Reporting................................................................................49 
8.7.4 Events of Special Interest.............................................................................................49
 
8.7.5 Unmasking Study Treatment 
................................
.......................................................49 

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Clinical Study Protocol NPIF-2018-01 
 
 
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8.8 
Study Halting Rules 
................................
................................
.....................................50 
8.9 
Safety Oversight...........................................................................................................50
 
9 
CLINICAL MONITORING 
................................
.....................................................50 
10 
STATISTICAL CONSIDERATIONS 
................................
.....................................51 
10.1 Statistical and Analytical Plans 
...................................................................................51 
10.2 Statistical Hypotheses 
................................
................................
..................................51 
10.3 Analysis Datasets 
................................
................................
.........................................52 
10.4 Description of Statistical Methods 
..............................................................................52 
10.4.1 General Approach 
................................
................................
........................................52 
10.4.2 Analysis of the Primary Efficacy Endpoint(s) 
.............................................................52 
10.4.3 Analysis of the Secondary Endpoint(s)........................................................................52 
10.4.4 Safety Analyses 
..........................................................................................................53 
10.4.5 Adherence and Retention Analyses 
................................
.............................................53 
10.4.6 Baseline Descriptive Statistics 
....................................................................................53 
10.4.7 Planned Interim Analyses 
................................
............................................................54 
10.4.8 Multiple Comparison/Multiplicity 
................................
...............................................54 
10.4.9 Tabulation of Individual Response Data......................................................................54 
10.4.10Exploratory Analyses 
.................................................................................................54 
10.5 Sample Size 
................................................................................................................54 
10.6 Measures to Minimize Bias .........................................................................................54 
10.6.1 Enrollment/ Randomization/Masking Procedures 
.......................................................54 
10.6.2 Evaluation of Success of Blinding 
..............................................................................54 
10.6.3 Breaking the Study Blind/Participant Code 
................................................................55 
11 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
................................
...............................................................55 
11.1 Source Documentation 
...............................................................................................55 
11.2 Access and Retention of Study Records 
................................
......................................55 
11.3 Subject Confidentiality 
................................
................................
................................56 
11.4 Case Report Form Completion 
................................
....................................................56 
11.5 Investigator Study Summary........................................................................................57
 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
.......................................57
 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
..............................................57
 
13.1 Ethical Standard 
................................
................................
...........................................57 
13.2 Institutional Review Board 
................................
..........................................................57 
13.3 Informed Consent Process 
................................
...........................................................58 
13.3.1 Consent Procedures and Documentation 
................................
.....................................58 
13.3.2 Other Informational Documents Provided to Participants 
...........................................58 
13.4 Participant and Data Confidentiality 
...........................................................................58 
13.4.1 Research Use of Stored Human Samples, Specimens or Data ....................................59
 
13.5 Future Use of Stored Specimens 
.................................................................................59 
14 
DATA HANDLING AND RECORD KEEPING 
....................................................59
 
14.1 Data Collection and Management Responsibilities 
.....................................................59
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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14.2 Study Records Retention..............................................................................................59 
14.3 Protocol Deviations 
....................................................................................................60 
14.4 Publication and Data Sharing Policy 
................................
...........................................60 
15 
LITERATURE REFERENCES 
................................
...............................................61 
16 
APPENDICES 
................................
................................
............................................61 
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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ABBREVIATIONS AND DEFINITIONS 
ACCF  
 
Anterior Chamber Cells and Flare 
ADE   
Adverse Device Effect 
AE    
Adverse Event  
AI   
Arcuate Incision 
BCDVA  
Best-Corrected Distance Visual Acuity 
BCVA  
Best-Corrected Visual Acuity  
CE   
Cataract Extraction 
CFR    
Code of Federal Regulations  
CRF   
Case Report Form  
CRC   
Clinical Research Coordinator 
FDA     
Food and Drug Administration  
GCP    
Good Clinical Practice  
HIPAA   
Health Insurance Portability and Accountability Act  
IB    
Investigator’s Brochure  
ICH     
International Conference on Harmonisation  
ICH E6   
International Conference on Harmonisation Guidance for Industry, Good 
Clinical Practice: Consolidated Guidance  
IEC    
Independent Ethics Committee  
IND   
Investigational New Drug Application  
IOL   
Intraocular Lens 
IRB    
Investigational Review Board  
LRI   
Limbal Relaxing Incision 
LSMEANS Least-squares Means  
NCR     
No Carbon Required  
N-PPDS 
Nepafenac Punctal Plug Deliver System 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
p-PPDS  
placebo Punctal Plug Delivery System (plug does not contain an active drug 
core) 
PCO   
Posterior Capsule Opacity 
PI    
Principal Investigator  
PP    
Punctal Plug 
PPDS   
 
Punctal Plug Delivery System 
QC     
Quality Control  
SAE     
Serious Adverse Event  
SOIS   
Summed Ocular Inflammation Score  
Study Subject  An individual that has signed a HIPAA form and an IRB approved study 
consent form 
SubjectIndividual being considered for enrollment in to the study  
UP    
Unanticipated Problem  
 
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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STUDY SYNOPSIS 
Title: A clinical study evaluating the safety and efficacy of punctal plug delivery system (Evolute
®) of 
Nepafenac (N-PPDS) compared with a Placebo Punctal Plug Delivery System (p-PPDS) in Controlling Post-
Operative Ocular Pain and inflammation in Subjects undergoing Routine Unilateral Cataract Surgery 
Sponsor: Mati Therapeutics Inc. 
Clinical Phase: 2 
Investigational Masked Product: N-PPDS (Nepafenac Punctal Plug Deliver System) is an L-shaped, silicone 
punctal plug with a drug eluting core that contains nepafenac (active) 
Comparator Masked Product: p-PPDS (placebo Punctal Plug Delivery System) is an L-shaped, silicone 
punctal plug with a drug insert that contains no active ingredient (placebo). 
Number of Sites: up to 3 sites in the USA. 
Study Population: Approximately 75 qualified subjects (75 eyes) who have given written consent, have met 
all study inclusion/exclusion criteria and are scheduled to undergo unilateral cataract surgery with the 
implantation of an intraocular lens (IOL) will be enrolled in to the study. 
Study Objectives: To evaluate the safety and ocular efficacy of N-PPDS in controlling post-operative ocular 
pain and inflammation associated with cataract surgery. 
Study Design: This is a Phase 2, multi-center, randomized, parallel-arm, double-masked, placebo-controlled 
study.  One (1) to 2 days prior to their scheduled cataract surgery, each study subject will be randomized 
(2:1) in to one of two treatment groups: 
Group A: 
A total of 50 study subjects (50 eyes) will have an N-PPDS inserted in the lower punctum 
of their scheduled surgical eye.   
Group B: 
A total of 25 study subjects (25 eyes) will have a p-PPDS inserted in the lower punctum of 
their scheduled surgical eye.   
All plugs will remain in the study subject’s lower punctum for a period of 2 weeks following cataract 
surgery. 
Subject Selection: 
The following are inclusion and exclusion criteria for a prospective study subject: 
 
Study Inclusion Criteria: 
1. A male or female subject in good general health, > 22 years of age at the time of the screening visit  
2. A patient must be able to read, comprehend and willing to give HIPAA & informed consent. 
3. A woman of child-bearing potential must not be pregnant or lactating, must have a negative pregnancy 
test at screening and must be practicing an adequate method of birth control.  Acceptable methods of 
birth control include intrauterine device (IUD); oral, dermal (“patch”), implant or injected 
contraceptives; tubal ligation; and barrier methods with spermicide. 
4. A subject has the availability, willingness and sufficient cognitive awareness to comply with exam 
procedures and able to return for all scheduled study visits 
5. A subject with a cataract for which routine phacoemulsification extraction and implantation of an 
intraocular lens has been planned 
6. A subject has a preoperative corneal astigmatism of 3.0 D or less in their scheduled operative eye  
7. A subject with clear ocular media other than cataract in their scheduled operative eye 
8. A subject has the potential for a post-operative Snellen BCDVA of 20/30 or better in their scheduled 
surgical eye 
9. A subject has a lower puncta that can be dilated to 1.0 mm in their scheduled surgical eye 
10. A subject with a dry eye condition being treated with a marketed punctal plug, where the marketed plug 
will be replaced by a masked study plug.  
 

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Clinical Study Protocol NPIF-2018-01 
 
 
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Study Pre-Operative Exclusion Criteria: 
1. A subject with a history of complications, adverse events, trauma or disease in the nasolacrimal area, 
whether or not it was due to punctal plug wear, including but not limited to dacryocystitis, inflammation 
or canaliculitis in either eye  
2. A subject with structural lid abnormalities (e.g., ectropion, entropion) in their scheduled surgical eye  
3. A subject with a puncta >0.9 mm prior to dilation in their scheduled surgical eye 
4. A subject experiencing any ocular pain in either eye at the screening visit or on the day the plug is to be 
inserted  
5. A subject with any moderate to severe lid, conjunctival or corneal findings in either eye at the screening 
visit  
6. A subject with any signs of intraocular inflammation (cells/flare) in either eye at the screening visit  
7. A subject with a known sensitivity to nepafenac or any inactive ingredient of the punctum plug, silicone, 
fluorescein, topical anesthetic, or any other products required for study procedures or cataract surgery 
8. A subject with a history as a steroid responder  
9. A subject with a known or suspected allergy or hypersensitivity to non-steroidal anti-inflammatory drugs 
(NSAIDs), or to any component of the test article 
10. A subject with only one eye with potentially good vision  
11. A subject with a known pathology that may affect visual acuity (as determined by the Investigator); 
particularly retinal changes that affect vision (macular degeneration, cystoid macular edema, 
proliferative diabetic retinopathy, etc.) in their scheduled surgical eye 
12. A subject that has a condition associated with the fluctuation of hormones that could lead to refractive 
changes 
13. A subject with amblyopia or strabismus 
14. A subject with capsule or zonular abnormalities with preoperative lens tilt and/or decentration (e.g., 
Marfan
's syndrome), or may affect postoperative centration or tilt of the lens (e.g. pseudoexfoliation 
syndrome) 
15. A subject has a history of ocular trauma in their scheduled surgical eye  
16. A subject that has undergone prior intraocular surgery in the scheduled surgical eye within the last 6 
months or laser surgery within three months prior to screening 
17. A subject with pupil abnormalities (non-reactive, tonic pupils, abnormally shaped pupils, or pupils that 
do not dilate at least 3.5 mm under mesopic/scotopic conditions) in their scheduled surgical eye. 
18. A subject with a corneal abnormality (e.g., stromal, epithelial or endothelial dystrophies) in their 
scheduled surgical eye 
19. A subject with evidence of clinically significant keratoconus in their scheduled surgical eye 
20. A subject with evidence of Epithelial Basement Membrane Dystrophy on slit-lamp exam 
21. A subject that has been wearing PMMA lenses within 6 months, gas permeable lenses within one month, 
or extended-wear or daily soft contact lens within 7 days of their scheduled surgery 
22. A subject with an inability to achieve keratometric stability for contact lens wearers 
23. A subject with a history of chronic/recurrent inflammatory eye disease (e.g., scleritis, uveitis, herpes 
keratitis) in either eye 
24. A subject with uncontrolled glaucoma 
25. A subject that requires an LRI or AI procedure before, during or after cataract surgery  
26. A subject that may or is expected to undergo surgical intervention prior to or during the study period 
other than cataract surgery 
27. A subject that requires the use of systemic or ophthalmic NSAIDs or corticosteroid medications during 
the study period, 
with the exception of a subject who has been prescribed and has been taking a baby 
aspirin (<81mg/daily), (Note:  All other NSAIDs or corticosteroid medications must be discontinued at 
least 48 hours prior to the insertion of the punctal plug) 
28. A subject that requires the use of systemic or ocular medications that may affect vision, ocular 
inflammation or pain 
29. A subject with an acute or chronic disease, or illness, that would increase risk or confound study results 
(e.g., autoimmune disease, connective tissue disease, immunocompromised, suspected glaucoma, 
glaucomatous changes in the fundus or visual field, ocular inflammation, etc.) 
30. A subject with an uncontrolled systemic disease:  A potential subject in whom therapy for a systemic 
disease is not yet stabilized will not be considered for entry into the study 

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31. A subject with diabetes that is poorly controlled 
32. A subject currently participating or has participated in another clinical trial within 30 days prior to 
enrollment.  
33. A subject that requires a stent implant during cataract extraction, with the exception of the implantation 
of the iStent® by GLAUKOS® 
Intra-Operative Exclusion Criteria (Surgical Complications): 
1. Sulcus-sulcus or bag-sulcus fixation 
2. Posterior capsular rupture or zonular dialysis 
3. Disruption of anterior hyaloids face 
4. Vitreous loss 
5. Capsulorhexis tear 
6. Floppy iris syndrome 
7. Requirement for the use of trypan blue, capsular tension ring or other intraocular device other than the 
IOL 
8. Inability to place IOL in capsular bag 
9. Significant anterior chamber hyphema 
10. Zonular rupture. 
Study Duration: The project study duration is approximately six months.  The study is projected to start in 
the 1st quarter of 2018. 
Study Variables: At the study pre-op and each scheduled post-op visits, the following procedures will be 
performed and recorded: 
a. Uncorrected distance visual acuity testing (Visit 1, 5, 6 and 7 only) 
b. Manifest Refraction (Visit 1, 6 and 7 only) 
c. Slit Lamp Examination [Lid, conjunctiva, cornea, anterior chamber cells and flare (ACCF)] 
NOTE: The Investigator that performs the slit-lamp evaluation at Visit 4 (Day 1 post-op) should perform the 
slit-lamp evaluation at ALL post-op visits  
d. Record the use of permitted concomitant medication(s), alteration in use or addition of any open-label 
medication(s) during the study period. 
e. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviews and record the subject’s response to ocular pain at Visit 4 (Day 1 
post-op) should interview the subject at ALL post-op visits (Visits 4, 5, 6 and 7). 
f. Assessment of any reported Adverse Events 
Additional procedures will be performed and recorded at Visit 1 (Screening/Baseline, Day -30 to -1), Visit 2 
(Punctal Plug Insertion Visit, 1-2 days pre-op), Visit 3 (Surgical day, Day 0) and Visit 7 (Final study visit, 
Day 14 post-op) 
a. Visit 1: 
- Grade Cataract Density (scale: 1 to 4) 
- Fundus examination 
- Evaluation of lower puncta 
b. Visit 2: 
- Insertion of masked study punctal plug 
- Inspection of the punctal plug via the slit-lamp in addition, performed at each follow-up visit. 
NOTE: All NSAIDs or corticosteroid medications, with the exception of a subject who has been prescribed 
and has been taking a baby aspirin (<81mg/daily), must be discontinued at least 48 hours prior to 
the insertion of the punctal plug. 

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c. Visit 3: 
- Pupil measurements (prior to and immediately following surgery) 
- Monocular cataract extraction/IOL implantation 
● Indicate the incision Type, Location and Size (mm) 
● Nucleus removal time  
● Ease Cortex removal 
● Effective Phaco Power (Phaco Time and Power) 
● Type of IOL (e.g., monofocal, toric etc.) and lens power 
●  Record any surgical complications 
- Subject reported AEs prior to or after surgery 
d. Visit 7: 
- Fundus examination 
Study Efficacy Variables:  
Primary:  Investigator evaluation of study subject post-op ocular pain at visits 4, 5, 6 and 7. 
Secondary: Mean anterior chamber scores for cells and flare at visits 4, 5, 6 and 7 
Study Safety Variables: Safety outcome measures include 
a. Distance visual acuity 
b. Slit Lamp Examination (Lid, conjunctiva, cornea) 
c. Fundus Examination 
d. Use of concomitant (rescue) medication(s) 
e. Incidents of reported Adverse Events 
Sample Size Determination: Since this is a pilot study, no formal sample size estimation was performed.   
 
 
 

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Schedule of Assessments, Events 
 
EXAM PARAMETERS 
 v1  v2  v3  v4  v5  v6  v7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Inform Consent/HIPPA 
    
          
 Demographic data/Medical Hx
  
  A             
 Concomitant Medication 
              
 Urine Pregnancy Test (if applicable) 
  B             
 Subject Randomization to Treatment 
  
            
 Investigator Evaluation of Ocular Pain 
  C       F   F   F   F 
 Uncorrected  Distance VA 
  C              
 Manifest Refraction 
  C              
 Best-Corrected Distance VA 
  C              
 Slit Lamp Examination 
  C       F   F   F   F 
 Insertion of Masked Punctal Plug 
  
            
 Inspection of Masked Punctal Plug 
  
 D  E  D  D  D  D 
 Evaluation of lower puncta 
              
 Pupil Measurements 
  
    G          
 Type and Grade Cataract 
              
 Monocular Cataract Extraction/IOL Implantation 
  
            
 Fundus Examination 
               
 Removal of Masked Punctal Plug 
  
             H 
 Adverse Event Recording 
  
             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Keys to Abbreviations: 
Visit Schedule: 
 
 
 
A  = Prior 12 months 
v1  = Day -30 to -1 
B  = Pregnancy test (women of childbearing potential) 
v2  = 1 to 2 days prior to surgery 
C  = Evaluation of Both Eyes 
v3  = Surgery Day 
D  = Evaluation using slit-lamp 
v4  = 1 day post-op 
E  = Visual inspection after surgery 
v5  =  3 + 1 days post-op 
F  = Investigator that performs the slit-lamp and/or ocular pain evaluation 
v6  = 7 + 1 days post-op 
     at Visit 4 (Day 1 post-op) should perform ALL post-op visit evaluations 
v7  = 14 + 2 days post-op 
G  = Measurement to occur prior to surgery and immediately after surgery 
H  = All masked punctal plugs must be removed at the subject last visit 
  
 
 
 
 

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1 KEY ROLES 
Investigators:   
Eric Donnenfeld, MD 
ericdonnenfeld@gmail.com 
Site 1: Ophthalmic Consultants of Long Island 
711 Stewart Ave 
Garden City, NY 11530 
516 500-4200 
Site 2: Island Eye Surgicenter – Carle Place 
1500 Jericho Turnpike 
Westbury, NY 11590 
516 877-2400 
 
Edward Holland, MD 
eholland@holprovision.com 
Cincinnati Eye Institute – Edgewood 
580 South Loop Road, Suite 200 
Edgewood, KY 41017 
859 331-9000 
 
Kerry Solomon, MD 
kds@cepmd.com 
Site 1:  Carolina Eyecare Physicians, LLC. 
1101 Clarity Rd., Suite 100 
Mt. Pleasant, SC  29464 
843 881-3937 
Site 2: The Physician
's Eye Surgery Center 
2060 Charlie Hall Blvd, Suite 301 
Charleston, SC 29414 
843 203-5799 
 
Medical Monitor: 
Robert Williams, MD 
89 Wilks Way 
Friday Harbor, WA 98250 
360 378-7916 
iopdoc1@gmail.com  
 
Sponsor:  
 
Mati Therapeutics Inc. (Headquarters) 
4317 Dunning Lane 
Austin, TX 78746 
512 329-6360 
 
Sponsor Personnel 
Clinical Trial Coordinator:  Deepank (Deeps) Utkhede 
Chief Scientific Officer 

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Mati Therapeutics Canada Inc. (R&D Branch) 
201-4475 Wayburne Drive 
Burnaby, BC V5G 4X4 
778 991-3301 
dutkhede@matitherapeutics.com 
 
Study Monitor/Biostatistician:  
Daniel Schwob 
D’Ellis Group, Inc. 
26741 Portola Pkwy, Ste 1E 717 
Foothill Ranch, CA 92610 
949 916-2800/949 735-1320 
dschwob@dellisgroup.com 
 
Regulatory Specialist: 
  
  
Caroline Stokl, Ph.D., 
Consultant, Regulatory Affairs 
201-4475 Wayburne Drive 
Burnaby, BC V5G 4X4 
604 983-9103 
cstokl@matitherapeutics.com 
 
Emergency Telephone Numbers:  
24 hour Adverse Event FAX 
number 
360 282-6871 
Robert Williams, MD 
Office: 360.378-7916 
Cell:  360.298-5325 
Deepank Utkhede 
Cell:  778.991-3301 
Daniel Schwob 
Office: 949.916-2800 
Cell:  949.735-1320 
 
 
 

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2 INTRODUCTION: BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
This  study  will  be  conducted  
in  compliance  with  
the  protocol,  
International  Conference  on 
Harmonization  (ICH),  Good  Clinical  Practice  (GCP)  guidelines  and  applicable  regulatory 
requirements. 
2.1 Background Information 
Punctal plugs are medical devices designed to block the drainage of tear fluid from the eye; 
several models are approved and commercially available.  Punctal plugs are classified by the 
FDA as a Class II Pre-Amendment medical device.  Furthermore, plugs are not identified as 
significant  risk  devices  on  the  FDA  Information  Sheet  titled “Significant  Risk  and  Non-
Significant Risk Medical Device Studies.”   
Mati  Therapeutics  Inc.  
is  
the  first  
to  use  punctal  plugs  as  an  anchoring  device  for  a  drug 
delivery  platform.    A  drug-eluting  core  is  inserted  into  Mati’s  proprietary  punctal  plug 
(Evolute® PPDS), which allows medication to be continuously released into the tear film of 
the eye over a period of time.  This platform has the potential to become a viable alternative to 
eye  drop  
therapy  and  could  address  significant  compliance  
issues  
that  currently  exist  with 
patients who will not or cannot properly self-administer eye drop medications. 
Cataract surgery is the most commonly performed surgery in the nation, with more than 3.5 
million of these procedures done annually in the United States.  Multiple studies have reported 
noncompliance  and  self-administration  difficulties  with  
topical  medications  among  cataract 
surgery  patients  (Kholdebarin  2008; Winfield  1990). A  2014  study  showed  
that  92.6%  of 
patients incorrectly administered topical medications after cataract surgery (An 2014). 
Although  recent  advances  
in  cataract  extraction  (CE)  surgery  have  decreased  
the  physical 
trauma associated with ocular surgery, disruption of the blood–aqueous barrier during surgery 
can  
lead  
to  
the  
release  of  
inflammatory  mediators,  
increasing  
the  risk  of  secondary  ocular 
complications.    Favorable  post-operative  outcome  depends  on  the  proper  use  of  topical 
medications  
to  shorten  
the  
inflammatory  
response  
induced  by  cataract  surgery.  
  Untreated, 
post-operative inflammation can increase the risk of mild iritis with increased cells and flare 
in the anterior chamber (AC) and can interfere with the patient’s visual rehabilitation.  In rare 
cases,  inflammation  can  lead  to  complications  such  as  cystoid  macular  edema,  posterior 
capsule fibrosis, keratopathy, fibrin reaction, or chronic uveitis.  Therefore, anti-inflammatory 
agents are routinely prescribed to resolve post-op signs and symptoms of cataract surgery more 
rapidly and to improve patient comfort. 
The  US  Food  and  Drug  Administration  approved  Nepafenac ophthalmic  suspension  0.1% 
(NEVANAC ®) in 2005 and Nepafenac ophthalmic suspension 0.3% (ILVERO®) in 2005 
from  Alcon  Laboratories,  Fort  Worth,  Texas,  USA.    Both  ophthalmic  suspension 
concentrations received an indication for the treatment of pain and inflammation associated 
with cataract surgery. 

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NEVANAC® ophthalmic suspension was compared with its vehicle in two double-masked, 
randomized clinical trials in which patients were dosed three-times-daily beginning one day 
prior to cataract surgery, continued on the day of surgery and for the first two weeks of the 
postoperative period.  Nepafenac 0.1% treated patients were less likely to have ocular pain and 
measurable signs of inflammation (cells and flare) in the early postoperative period through 
the end of treatment than those treated with its vehicle.  For ocular pain, both studies had a 
significantly  higher  percentage  of  patients  (approximately  80%)  in  the Nepafenac  group 
reporting no ocular pain on the day following cataract surgery (Day 1) compared to those in 
the vehicle group (approximately 50%).  
ILEVRO®  ophthalmic  suspension  was  compared  with  its  vehicle  in  two  double-masked, 
randomized clinical trials in which patients were dosed once a day beginning one day prior to 
cataract  surgery,  continued  on  the  day  of  surgery  and  for  the  first  two  weeks  of  the 
postoperative period.  Nepafenac 0.3% treated patients were less likely to have ocular pain and 
measurable signs of inflammation (aqueous cells and flare) in the early postoperative period 
through  to  the  end  of  treatment  than  those  treated  with  its  vehicle.    In  the  two  studies, 
Nepafenac cleared  inflammation  at  day  14  post  operation  in  65%  and 61%  of  patients 
compared to 32% and 24% of patients on vehicle.  Pain free rates in the Nepafenac group were 
86%  and 84%  compared  
to 46%  and 38%  of  patients  on  vehicle.  The  Day  14  results  for 
reduction of both pain and inflammation were statistically significantly superior to the vehicle. 
This study will enroll approximately 75 qualified subjects (75 eyes) who have given written 
consent, have met all study inclusion/exclusion criteria and are scheduled to undergo unilateral 
cataract surgery with the implantation of an intraocular lens (IOL) will be enrolled in to the 
study. 
2.2 Rationale 
Past  clinical  studies  with  topical  dosing  of  0.1%  and  0.3%  ophthalmic  suspensions of 
Nepafenac (NEVANAC®/ILEVRO®)  have  demonstrated  the  safety  and  efficacy  of 
Nepafenac in  
the  
treatment  of  pain  and  
inflammation  associated  with  ocular  surgery.  
  The 
objective for this study is to evaluate the use of a punctal plug drug delivery device that can 
deliver  a  sustained,  safe  and  effective  concentration  of Nepafenac to  a  subject  undergoing 
cataract surgery, for the treatment of post-operative ocular pain and inflammation.   
Placebo has been selected as the control group.  This will allow the results obtained from this 
study  
to  be  compared to treatment  
results  
from  similarly  design  Phase  3  and  3B  studies  of 
Nepafenac. 
2.3 Potential Risks and Benefits 
2.3.1 Known Potential Risks 
A study subject randomized to receive N-PPDS may have unforeseen risk and could exhibit 
moderate  
to  severe  post-op  
inflammation  and/or  ocular  pain.  
  However,  
the  
risk  associated 
with using N-PPDS to deliver a sustain release of Nepafenac are anticipated to be similar, if 
not less than, those of commercially available topical 0.1% and 0.3% ophthalmic suspension 

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of Nepafenac and  silicone  punctal  plug  products.    In  ocular  surgery  clinical  studies  with 
Nevanac®,  adverse  reactions  that  occurred  in  5-15%  of  study  patients  included capsular 
opacity,  decreased  visual  acuity,  
foreign  body  sensation,  
increase  
intraocular  pressure,  and 
sticky  sensation.  Adverse  reactions  that  occurred  in  1-5%  of  study  patients  included 
conjunctival  edema,  corneal  edema,  dry  eye,  
lid  margin  crusting,  ocular  discomfort,  ocular 
hyperemia, ocular pain, ocular pruritus, photophobia, tearing and vitreous detachment.  Some 
of these reactions may have been the consequence of the surgical procedure.  A summary of 
known  potential  risks  to  humans  of  topical  0.1%  and  0.3%  ophthalmic  suspension  of 
Nepafenac can  be  
found  
in  
the  NEVANAC®  and  ILEVRO®  prescribing  
information  
(see 
Appendices 4 and 5). 
A study subject randomized to receive a placebo Punctal Plug Delivery System (p-PPDS) could 
exhibit moderate to severe post-op inflammation and/or ocular pain.  Other risks associated 
with using a p-PPDS are anticipated to be similar to commercially available punctal plugs use 
in humans.  A study subject could experience ocular discomfort, epiphora, loss of plug, ocular 
inflammation, and subconjunctival hemorrhage.  Less common, but serious, side effects are 
pyogenic granuloma, damage to the muscle at the opening of the punctum, canaliculitis, or 
migration of the plug into the canaliculus requiring irrigation or surgery.   
2.3.2 Known Potential Benefits 
The  potential  benefit  associated  with  the  use  of  N-PPDS  to  deliver  a  sustain  release  of 
nepafenac is the reduction of post-operative ocular inflammation and ocular pain.  In addition, 
the use of N-PPDS eliminates the subject non-compliance issue with daily dosing of an anti-
inflammatory drug.   
A summary of known benefits to humans of topical 0.1% and 0.3% ophthalmic suspensions of 
nepafenac can  be  found  
in  
the  NEVANAC®  and  ILEVRO®  prescribing  
information  (see 
Appendices 4 and 5). 
3 OBJECTIVES AND PURPOSE 
To evaluate the safety and efficacy of N-PPDS in the treatment of post-operative ocular pain 
and inflammation associated with cataract surgery. 
4 STUDY DESIGN AND ENDPOINTS 
4.1 Description of the Study Design 
This is a Phase 2, multi-center, randomized, parallel-arm, double-masked, placebo-controlled 
study.  One (1) to 2 days prior to their scheduled cataract surgery, each study subject will be 
randomized (2:1) in to one of two treatment groups: 
Group A: A total of 50 study subjects (50 eyes) will have an N-PPDS inserted in the lower 
punctum of their scheduled surgical eye.   

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Group  B:  A  
total  of  25  study  subjects  
(25  eyes)  will  have  a  p-PPDS  
inserted  
in  
the  
lower 
punctum of their scheduled surgical eye.   
All plugs will remain in the study subject’s lower punctum for a period of 2 weeks following 
cataract surgery. 
4.2 Study Endpoints 
The study will be complete when 75 study subjects (75 eyes) have been evaluated at Visit 7 
(Day 14 post-op) or have been terminated from the study. 
4.2.1 Primary Efficacy Endpoint 
The  primary  effectiveness  endpoint  will  analyze  the  Investigator’s  evaluation  of  study 
subject’s ocular pain following cataract surgery compared with placebo at 1, 3, 7 and 14 days 
post-op. 
4.2.2 Secondary Efficacy Endpoints 
The  secondary  effectiveness  will  analyze  the  complete  (CR)  and  partial  response  (PR)  to 
therapy regarding the Summed Ocular Inflammation Score (sum of the mean anterior chamber 
cells and flare) following cataract surgery compared with placebo at 3, 7 and 14 days post-op. 
4.2.3 Safety Endpoints  
Safety  assessments  will  include  the  incidence  and  severity  of  reported  AEs  after 
randomization, distance visual acuity, slit-lamp biomicroscopy findings, fundus findings, and 
use of concomitant rescue medications. 
5 STUDY ENROLLMENT AND WITHDRAWAL 
5.1 Subject Inclusion Criteria  
The following are inclusion criteria for a prospective study subject: 
1. A  male  or  female  subject  
in  good  general  health,  ≥22  years  of  age  at  
the  
time  of  
the 
screening visit  
2. A  patient  must  be  able  to  read,  comprehend  and  willing  to  give  HIPAA  &  informed 
consent. 
3. A woman of child-bearing potential must not be pregnant or lactating, must have a negative 
pregnancy test at screening and must be practicing an adequate method of birth control.  
Acceptable  methods  of  birth  control  include  intrauterine  device (IUD);  oral,  dermal 
(“patch”),  implant  or  injected  contraceptives;  tubal  ligation;  and  barrier  methods  with 
spermicide. 

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4. A subject has the availability, willingness and sufficient cognitive awareness to comply 
with exam procedures and able to return for all scheduled study visits 
5. A subject with a cataract for which routine phacoemulsification extraction and implantation 
of an intraocular lens has been planned 
6. A  subject  has  a  preoperative  corneal  astigmatism  of  3.0  D  or  less  in  their  scheduled 
operative eye  
7. A subject with clear ocular media other than cataract in their scheduled operative eye 
8. A subject has the potential for a post-operative Snellen BCDVA of 20/30 or better in their 
scheduled surgical eye 
9. A subject has a lower puncta that can be dilated to 1.0 mm in their scheduled surgical eye. 
10. A patient with a dry eye condition being treated with a marketed punctal plug, where the 
marketed punctal plug will be replaced by a masked study plug. 
5.2 Subject Pre-Operative Exclusion Criteria 
The following are pre-surgical exclusion criteria for a prospective study subject: 
1. A  subject  with  a  history  of  complications,  adverse  events,  trauma  or  disease  in  the 
nasolacrimal area, whether or not it was due to punctal plug wear, including but not limited 
to dacryocystitis, inflammation or canaliculitis in either eye  
2. A  subject  with  structural  
lid  abnormalities  
(e.g.,  ectropion,  entropion)  
in  
their  schedule 
surgical eye  
3. A subject with a puncta >0.9 mm prior to dilation in their scheduled surgical eye 
4. A subject experiencing any ocular pain in either eye at the screening visit or on the day the 
plug is to be inserted  
5. A subject with any moderate to severe lid, conjunctival or corneal findings in either eye at 
the screening visit  
6. A  subject  with  any  signs  of  intraocular  inflammation  (cells/flare)  in  either  eye  at  the 
screening visit  
7. A subject with a known sensitivity to nepafenac or any inactive ingredient of the punctum 
plug,  silicone,  fluorescein,  
topical  anesthetic,  or  any  other products  required  for  study 
procedures or cataract surgery 
8. A subject with a history as a steroid responder  

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9. A  subject  with  a  known  or  suspected  allergy  or  hypersensitivity  
to  non-steroidal  anti-
inflammatory drugs (NSAIDs), or to any component of the test article 
10. A subject with only one eye with potentially good vision  
11. A  subject  with  a  known  pathology  
that  may  affect  visual  acuity  
(as  determined  by  
the 
Investigator); particularly retinal changes that affect vision (macular degeneration, cystoid 
macular edema, proliferative diabetic retinopathy, etc.) in their scheduled surgical eye 
12. A subject that has a condition associated with the fluctuation of hormones that could lead 
to refractive changes 
13. A subject with amblyopia or strabismus 
14. A  subject  with  capsule  or  zonular  abnormalities  with  preoperative  lens  tilt  and/or 
decentration (e.g., Marfan’s syndrome), or may affect postoperative centration or tilt of the 
lens (e.g. pseudoexfoliation syndrome) 
15. A subject has a history of ocular trauma in their scheduled surgical eye  
16. A subject that has undergone prior intraocular surgery in the scheduled surgical eye within 
the last 6 months or laser surgery within three months prior to screening 
17. A subject with pupil abnormalities (non-reactive, tonic pupils, abnormally shaped pupils, 
or  pupils  
that  do  not  dilate  at  
least  3.5  mm  under  mesopic/scotopic  conditions)  
in  
their 
scheduled surgical eye. 
18. A subject with a corneal abnormality (e.g., stromal, epithelial or endothelial dystrophies) 
in their scheduled surgical eye 
19. A subject with evidence of clinically significant keratoconus in their scheduled surgical 
eye 
20. A subject with evidence of Epithelial Basement Membrane Dystrophy on slit-lamp exam 
21. A  subject  
that  has  been  wearing  PMMA  
lenses  within  6  months,  gas  permeable  
lenses 
within one  month,  or  extended-wear  or  daily  soft  contact  lens  within  7  days  of  their 
scheduled surgery 
22. A subject with an inability to achieve keratometric stability for contact lens wearers 
23. A  subject  with  a  history  of  chronic/recurrent  inflammatory  eye  disease  (e.g.,  scleritis, 
uveitis, herpes keratitis) in either eye 
24. A subject with uncontrolled glaucoma 
25. A subject that requires an LRI or AI procedure before, during or after cataract surgery  

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26. A subject that may or is expected to undergo surgical intervention prior to or during the 
study period other than cataract surgery 
27. A  subject  that  requires  the  use  of  systemic  or  ophthalmic  NSAIDs  or  corticosteroid 
medications  during  the  study  period,  with  the  exception  of  a  subject  who  has  been 
prescribed and has been taking a baby aspirin (<81mg/daily), (Note:  All other NSAIDs or 
corticosteroid medications must be discontinued at least 48 hours prior to the insertion of 
the punctal plug) 
28. A subject that requires the use of systemic or ocular medications that may affect vision, 
ocular inflammation or pain 
29. A subject with an acute or chronic disease, or illness, that would increase risk or confound 
study results (e.g., autoimmune disease, connective tissue disease, immunocompromised, 
suspected  glaucoma,  glaucomatous  changes  in  the  fundus  or  visual  field,  ocular 
inflammation, etc.) 
30. A subject with an uncontrolled systemic disease:  A potential subject in whom therapy for 
a systemic disease is not yet stabilized will not be considered for entry into the study 
31. A subject with diabetes that is poorly controlled 
32. A subject currently participating or has participated in another clinical trial within 30 days 
prior to enrollment. 
33. A subject that requires a stent implant during cataract extraction, with the exception of the 
implantation of the iStent
® by GLAUKOS®. 
5.3 Intra-Operative Exclusion Criteria (Surgical Complications) 
If any of the following surgical complication occurs during cataract surgery, the study subject 
will be discontinued from the study (see Section 5.5.2.2 regarding handling of discontinued 
study subjects), have their study punctal plug removed and excluded from further participation 
in the study:  
1. Sulcus-sulcus or bag-sulcus fixation 
2. Posterior capsular rupture or zonular dialysis 
3. Disruption of anterior hyaloids face 
4. Vitreous loss 
5. Capsulorhexis tear 
6. Floppy iris syndrome 

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7. Requirement for the use of trypan blue, capsular tension ring or other intraocular device 
other than the IOL 
8. Inability to place IOL in capsular bag 
9. Significant anterior chamber hyphema 
10. Zonular rupture. 
5.4 Strategies for Recruitment and Retention 
To  increase  study  subject  enrollment  and  retention  in  the  study,  sites  should  dedicate  an 
individual [Clinical Research Coordinator (CRC)] who is well informed regarding the study 
design,  
required inclusion/exclusion  criteria  and  visit  schedule,  as  
the  main  contact  who  
is 
readily available to answer all potential subject questions and/or concerns about participating 
in the clinical study.  The CRC should be prepared to discuss with a potential study subject the 
differences  in  the  amount  of  time,  examination  procedures  and  visit  schedule  they  would 
experience if they agreed to participate in the study.  In addition, should a subject agree to 
participate  
in  
the  study,  
the  CRC  would  be  
readily  available  and  
their  main  contact  person 
while participating in the study. 
To  encourage  recruitment  and  retention  of  a  study  subject,  sites  should  offer  a  subject 
reimbursement for transportation cost and a stipend for their time and effort for participation, 
offer less  waiting  time  in  the  doctor’s  office  by  scheduling  more  flexible  and  reliable 
appointment times.   
In addition, discuss the advantages  of  participating in the study by not 
having to remember or instilling one less drop prior to or after cataract surgery.   
5.5 Study Subject Withdrawal or Termination Criteria 
Each study subject will be informed that they are free to withdraw from the study at any time.  
The Investigator, the  
Investigator in consultation with the Medical Monitor, or the Medical 
Monitor may exercise his or her medical judgment to terminate a study subject’s participation 
in the study if it is in the best interest of the study subject.  A terminated study subject will be 
followed through Day 14 or until the condition has resolved or has become medically stable. 
Medical Monitoring for this study will be conducted by: 
Robert Williams, MD 
Phone (Office): 360-378-7916 
Phone (Cell): 360-298-5325 
Email: iopdoc1@gmail.com 
 
The name of the Medical Monitor and contact information will be provided to each study site.  
Mati Therapeutics Inc. reserves the right to terminate the study at any time.  Every effort will 
be made to collect all data required by the protocol during or following the study subject’s 
early termination visit. 

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5.5.1 Reasons for Termination, Discontinuation or Disqualified 
At  a  study  subject  
last  visit  (scheduled  or  unscheduled),  they  will  have  their  masked 
punctal plug removed and a study exit case report form (CRF) must be completed, whether 
or not the study subject completed the final study visit (Visit 7, day 14 post-op).  The reason 
for any early exiting from the study will be indicated on the study exit form and all efforts will 
be made to complete and report the observations as thoroughly as possible. 
 The primary reason 
for  a  study  subject  early  exiting  
the  study  should  be  selected  from  
the  following  standard 
categories (see Sections 5.5.1.1 – 5.5.1.3 below). 
5.5.1.1 Reason for Termination 
A study subject will be terminated from the study if in the Investigators medical judgment, it 
was in the best interest of the study subject that developed or reported: a) moderate to severe 
signs or symptoms of ocular inflammation or pain, b) reported a serious AEs, regardless of 
relation to the study drug/device or has died.  
5.5.1.2 Reason for Discontinued 
A study subject will be discontinued from the study if the  
Investigator is unable to insert a 
punctal plug in to the study subject’s lower punctum, they have experienced a complication 
(intra-operative exclusion criteria) during surgery, the punctal plug has been extruded after the 
surgical  visit  (Visit3),  study  subject  has  used  a  prohibited  concomitant  therapy,  is  non-
compliant, has missed scheduled study visits, has personal reasons, has relocated out of the 
area or has a desired to withdraw from further participation in the study in the absence of a 
medical  need  as  determined  by  the  Investigator.    Other  reason – the  study  subject  was 
discontinued for a reason other than those listed above, the Investigator must specify the reason 
5.5.1.3 Reason for Disqualification 
A  study  subject  will  be  disqualified  
from  
the  study  
if  
there  was  a  
failure  
to  obtain  written 
informed  consent  or  HIPAA  Authorization,  improper  entry  (did  not  meet  all 
inclusion/exclusion criteria), had a positive pregnancy test (after Visit 1).  
5.5.2 Handling of Study Subject Termination, Discontinued or Disqualified 
5.5.2.1 Handling of Terminated Study Subject 
A terminated study subject will return to the clinic for an end of study safety evaluation and 
the  removal  of  the  masked  punctal.    A  terminated  study  subject  will  receive  appropriate 
treatment  at  
the  discretion  of  
the  Investigator.  
 Notification  of  
termination  will  be  clearly 
documented on the appropriate Case Report Form.  A terminated study subject is considered 
to have completed the study and will NOT be replaced. 

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5.5.2.2 Handling of Discontinued Study Subject 
A  study  subject  may  voluntarily  discontinue  (withdraw)  from  the  study  at  any  time  they 
choose.  Notification of discontinuation will be clearly documented on the appropriate Case 
Report Form.  If a study subject elects to withdraw from the study during the study follow-up 
period, the Investigator will make every effort to have the study subject return to the clinic for 
an end of study safety evaluation and the removal of the masked punctal plug.  A study subject 
who is discontinued from the study will be replaced. 
5.5.2.3 Handling of Disqualified Study Subject 
Notification  of  disqualification  will  be  clearly  documented  on  
the  appropriate  Case  Report 
Form.  If a study subject was inserted with a masked punctal plug, the Investigator will make 
every effort to have the study subject return to the clinic for an end of study safety evaluation 
and the removal of the masked punctal plug.  A study subject disqualified from the study will 
be replaced. 
5.6 Premature Termination or Suspension of Study or Study Site 
Mati Therapeutics Inc. reserves the right to terminate or suspended the study at any time. 
 Every 
effort will be made to collect all data required by the protocol during or following the study 
subject’s early termination visit. 
If  representatives  of  Mati  Therapeutics  Inc.,  
the  Principal  Investigator,  
the  Study  Monitor 
(Clinical  Research  Associate  [CRA]),  
the  Medical  Monitor,  or  
the  FDA  officials  discover 
conditions  arising  during  the  study  that  indicate  that  the  study  will  be  halted  or  that 
participation by the study center will be terminated, this action may be taken after appropriate 
consultation  with  representatives  of  Mati  Therapeutics  Inc.,  
the  Principal  Investigator,  
the 
CRA, and the Medical Monitor.  Conditions that may warrant termination of the study include, 
but are not limited to the following: 
a. The discovery of an unexpected, serious, or unacceptable risk to a study subject enrolled 
in the study 
b. A  decision  on  the  part  of  Mati  Therapeutics  Inc.  to  suspend  or  discontinue  testing, 
evaluation, or development of the product 
c. Failure of the Principal Investigator to enroll study subjects into the study at an acceptable 
rate 
d. Failure of the Principal Investigator to comply with pertinent FDA regulations and ICH 
Guidelines 
e. Submission of knowingly false information from the research facility to Mati Therapeutics 
Inc., or designee, the CRA, the Medical Monitor, or the FDA 
f. Insufficient adherence to protocol requirements.   

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Study termination and follow-up will be performed in compliance with the conditions set forth 
in 21 CFR 312.50 and 21 CFR 312.56. 
6 STUDY AGENT 
6.1 Study Treatments 
6.1.1 Route of Administration 
Each qualified study subject as they are enrolled in to the study will be sequentially assigned 
a  Subject  ID  number.    Treatment  assignments  for  this  study  have  been  randomized  (see 
Section  10.6.1 for  details  on  
treatment  randomization)  
to  determine  which  one  of  
the  
two 
masked punctal plug drug delivery systems a study subject will receive for the duration of the 
study. 
6.1.2 Formulation, Appearance, Packaging and Labeling 
The N-PPDS and p-PPDS consist of a drug insert that is placed in to the bore of an L-shaped 
punctum plug (Figure 1).  The plug component for both the N-PPDS and p-PPDS products 
consists of an inactive medical grade silicone and 2% green colorant.  The drug insert of the 
N-PPDS contains 204 µg of nepafenac (active ingredient) dispersed within a solid sustained 
release matrix.  The drug insert for the p-PPDS consist of the same excipients as the N-PPDS 
however contains no active (nepafenac) ingredient (see Appendix 6 for details). 
Figure 1: Component of the N-PPDS and p-PPDS inserts   
 
 
Both the N-PPDS and the p-PPDS are provided pre-loaded on an insertion tool (see Figure 2).   

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Figure 2: Pre-Loaded masked study product on an Insertion Tool 
 
The pre-loaded masked punctum delivery systems will be supplied in a sealed sterilized tray, 
labeled with investigational drug statement in accordance with applicable regulations.   
6.1.3 Product Storage and Stability 
All used and unused study punctum delivery system products must be stored in a secure area 
with controlled access.  All plugs must be refrigerated between 36 – 46°F (2 – 8°C).  All study 
punctum delivery system products have a retest date of 6 months. 
A daily temperature log will be maintained documenting appropriate investigational product 
and required  concomitant medication storage conditions and will  be  made available for the 
study monitor to inspect. 
6.1.4 Starting Dose 
One (1) to 2 days prior to their scheduled cataract surgery, a subject will be randomized (2:1) 
in to one of two treatment groups.  The assigned punctal plug will be inserted in their lower 
punctum of their scheduled surgical eye.   
NOTE: All systemic, topical and ophthalmic NSAIDs or corticosteroid medications, with the 
exception of a subject who has been prescribed and has been taking a baby aspirin 
(<81mg/daily), must be discontinued at least 48 hours prior to the insertion of the punctal 
plug. 
6.1.5 Preparation for Insertion of Masked Punctal Plug 
a. A study subject will be placed in a recline position 
b. To anesthetize the area around the lower punctum, use a proparacaine or lidocaine soaked 
cotton-tipped  swab,  placing  the  swab  directly  on  the  lower  punctum  of  the  scheduled 
surgical  eye  
for  ~30  
to  60  seconds  
(proparacaine  or  
lidocaine  can  be  
irrigated  
into  
the 
canaliculus for better anesthesia if desired) 
c. The dilator is engaged vertically in the punctum with a gentle twisting motion.  The dilator 
is  moved  
to  a  horizontal  position  passing  
it  
into  
the  proximal  canaliculus  dilating  
the 
punctum 

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d. The punctum is dilated to at least 1.0 mm.  Once the punctum is dilated to 1.0 mm, leave 
dilator in place for 15 to 30 seconds to allow the sphincter to fully relax 
NOTE: For smaller puncta, hold and rotate the dilator in the punctum and canaliculus for a 
longer period of time (1 – 2 minutes or longer).  Dilation may require very firm pressure.  
Add more anesthesia if needed. 
6.1.6 Masked Punctal Plug Insertion 
a. While dilating, prep the plug to insert it in the punctum 
b. Remove dilator and immediately attempt to insert the plug before the sphincter starts to 
close 
NOTE: The punctum may constrict before the plug can be inserted, additional dilation would 
then be required.  If a plug is partially inserted (e.g., cap not flush with the lid) the plug should 
be removed and the punctum re-dilated or dilated to a larger diameter.  Placement of the plug 
can then be re-attempted.  Multiple attempts are sometimes necessary. 
c. After  insertion  the  punctal  opening  should  be  visually  inspected  using  a  slit-lamp  to 
confirm the  
retention and correct placement of the plug, with the  cap still  visible.  The 
position of the study plug may be adjusted with forceps, if necessary.  
NOTE: Any questions or concerns regarding the insertion or removal of a punctal plug contact: 
Robert Williams, MD  
Phone (Office): 360-378-7916  
Phone (Cell): 360-298-5325 
Email: iopdoc1@gmail.com 
 
6.1.7 Unable to Insert/Extruded/Lost Masked Punctal Plug 
6.1.7.1 Unable to insert masked punctal plug 
If the plug cannot be inserted after a few attempts with gentle dilation, the subject will not be 
eligible for the study.  Lubricants are not to be used.  
6.1.7.2 Punctal Plug extruded pre-operative 
If a study subject extrudes their plug prior to surgery, a new plug will be inserted in the lower 
punctum of the subject’s schedule surgical eye.  The study subject will then be rescheduled for 
surgery in 1 to 2 days after re-insertion of the new plug.  The punctal plug will remain in the 
study subject’s lower punctum during cataract surgery and for a period of 2 weeks following 
surgery. 

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6.1.7.3 Punctal Plug extruded during surgery 
If a study subject extrudes their plug during the surgical procedure, a new plug will be inserted 
in to the lower punctum of the subject’s surgical eye upon completion of the surgery.  The 
punctal plug will remain in the study subject’s lower punctum for a period of 2 weeks following 
surgery. 
6.1.7.4 Punctal Plug extruded after surgery 
A study subject that has noticed a plug has been extruded or lost during the follow-up period 
after surgery should immediately contact the Investigator and/or his/her staff and return to the 
Investigator’s office as soon as possible.  The Investigator will discontinue the study subject 
from the study and place them on open-label post-op medication(s) deemed necessary for the 
patient’s welfare by the Investigator.   
For any study subject where the plug has been lost, the Investigator will retro-illuminate or 
palpate  the  canaliculi  to  confirm  the  plug  has  not  migrated  into  the  canal.    Information 
regarding  the  loss  of  any  plug  must  be  recorded  in  the  source  documents,  CRFs  and 
Accountability Logs. 
NOTE: If an extruded plug can be located by a study subject, the plug should be returned and 
collected by the Investigator and/or his/her staff.  If the plug tears or has separated, report this 
as  a  
technical  complaint  
(Section  8.6). Retain  
the  plug  
for  accountability  of  
investigational 
supplies. 
6.1.8 Duration of Therapy 
All plugs will be inserted in to the lower punctum of the subject’s schedule surgical eye 1 to 2 
days prior to surgery and will remain in  
the study subject’s lower punctum during cataract 
surgery and for a period of 2 weeks following surgery. 
6.1.9 Removal of a Masked Punctal Plug 
The  masked  punctal  plug  can  be  removed  from  
the  study  subject’s  punctum  using  sterile 
ophthalmic forceps and a gentle tugging motion.  A drop of anesthetic may be administered if 
necessary.   
a. Stabilize/constrain eyelid with fingers or with help from assistant 
b. It  
is  recommended  
that  a  0.12  1x2  
teeth  Castroviejo  Suture  forceps  or  similar  
toothed 
forceps with platforms should be used for plug removal.  NOTE – using a jewelers forceps 
is not advisable 
c. Teeth should be placed on the far side of the plug with the blades straddling the neck 
d. Care must be taken not to grasp the outermost edge of the cap on the punctal plug as this 
may cause the cap to tear and separate, making it difficult to remove the plug from the 
canaliculus and/or causing plug intrusion.  

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e. The teeth should not be used to grasp the plug but are used instead to prevent the blades of 
the forceps from sliding off the neck.  Grasping the plug with the teeth may fracture it 
f. The motion to remove should be towards the medial canthus (not up or temporally), which 
is necessary to disengage the heel of the plug. 
If  the  cap  becomes  separated, try  to  remove  the  plug  using  toothed  0.12  forceps  (0.12 
Castroviejo forceps or similar) by grasping the neck of the plug through the punctum.  If this 
is not possible, and it doesn’t seem as if the plug will lodge in the canal, and only if you feel 
comfortable doing so, you may attempt to irrigate the canal until the plug flushes out of the 
nasolacrimal duct.   
NOTE: Study plugs are larger than commercially available silicone plugs and may become 
lodged  
in  
the  canal  more  easily.  
  Clinical  
judgment  should  be  exercised  when  proceeding.  
Referral  to  tertiary  care  is  advised  in  cases  where  the  plug  cannot  be  retrieved  by 
massaging/milking through the punctal opening or by irrigation.  
NOTE: Removal of a masked punctal plug immediately after insertion may result in the 
cap of the plug being torn off; the Investigator should wait at least 24 hours after insertion 
before attempting to remove a masked punctal plug.  However, if the plug tears or separates, 
report  
this  as  a  
technical  complaint.  
  Retain  
the  plug  for  accountability  of  
investigational 
supplies. 
6.2 Study Plug Accountability Procedures 
The  Investigator  is  responsible  for  maintaining  the  study  treatment  (punctal  plugs) 
accountability  log,  which  will  contain  inventory  records  acknowledging  the  receipt  and 
dispensing of all study plugs.  The study center will keep a complete accounting of all used, 
unused,  damaged,  extruded  and  lost  study  plugs.  All  lost/extruded  study  plugs  must  be 
recorded into the accountability log and on the CRFs of the study subject who lost/extruded 
their masked study plug, noting the suspected date the study plug was lost/extruded.   
All used and unused masked study plugs must be accounted for and kept in the designated 
secure area at the study center until the Sponsor provides instructions for the return of all study 
materials.  Final accountability for investigational study plugs will be verified by the Sponsor 
and/or their  representatives  and  considered  complete  when  the  study  plugs  are  no  longer 
actively used and all study plugs (used, unused, extruded, lost) have been accounted for and 
returned to the Sponsor.   
7 STUDY PROCEDURES AND SCHEDULE 
Data will be captured  and compiled using procedures developed by  
representatives of Mati 
Therapeutics Inc.  All requested study data must be recorded clearly on study NCR CRFs and 
other study forms, as required.  An explanation must be provided for all missing data.  Only 
the  Investigator  or  his/her  staff  members  who  are  identified  on  the  Study  Personnel 
Identification List may enter or correct data on a CRF.  Incomplete or inconsistent data on the 
CRFs will result in data queries that will require resolution by the Investigator. 

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7.1 Protocol Amendments 
Modification of the protocol is prohibited without prior  written  agreement in the form of a 
protocol amendment.  All amendments will be created by the Sponsor and must be approved 
by the IRB prior to implementation except when required to mitigate immediate safety risks or 
when the changes involve only logistical or administrative revisions. 
7.2 Study Procedures/Evaluations 
7.2.1 Study specific procedures 
Procedures that will be required during the course of the study include (see Section 7.4 for 
details): 
a. Informed consent and HIPAA authorization: The Investigator and or qualified staff will 
review and answer any questions a potential study subject may have regarding the study, 
the consent or HIPAA authorization forms.  Prior to the initiation of any study specific 
activities, the subject must sign both documents 
b. Record subject’s medical history for the previous 12 months and demographic data 
c. Investigator evaluation of ocular pain: The Investigator will interview and record subject 
responses in regards to any ocular pain they may be experiencing 
NOTE: The Investigator that interviews and record subject responses to ocular pain at Visit 
4 (Day 1 post-op) should interview the subject at ALL post-op visits (Day 3, 7, and 14). 
d. Concomitant Medication use: All prescription systemic, ophthalmic and over-the-counter 
concomitant medications used during the study, including all pre-, intra- and post-operative 
medications,  including  intravenous  solutions,  dilating  drops,  irrigations,  viscoelastics, 
antimicrobials/anti-infective, miotics, etc. related to the surgery, will be documented.  The 
medication name, start and stop dates, indication, dose, route of administration and any 
dosing  alterations  must  be  documented  on  
the  Concomitant  Medications  CRF  
through 
completion of the last study visit. 
e. Distance Visual Acuity testing: Visual acuity with and without correction, will be measured 
using  a  Snellen  chart.    The  test  distance  and  lighting  conditions  specified  for  the 
Investigator’s chart must be used and kept constant throughout the study (see Appendix 3 
for details). 
f. Manifest Refraction: A poropter or an auto refractor will be used to determine the study 
subject’s best visual acuity with correction 
g. Slit-Lamp  Examination:    Slit-lamp  examination  will  include  assessment  of  the  lid, 
conjunctiva,  cornea  and  anterior  chamber.  
  Evaluation  of  
the  anterior  chamber  will  be 
performed using a slit beam of 1 mm height and 1 mm width with maximum luminance 

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through the highest powered lens using the Investigator’s standard slit lamp equipment and 
procedure.  Grading of any slit lamp findings is defined in Appendix 2. 
NOTE: The investigator that performs the slit-lamp evaluation at Visit 4 (Day 1 post-op) 
should perform the slit-lamp evaluation at ALL post-op visits (Day 3, 7, and 14). 
h. Evaluation of lower punctum size 
i. Insertion of the study punctal plug, see Section 6.1.6 of the protocol for details. 
j. Removal of the study punctal plug, see Section 6.1.9 of the protocol for details. 
k. Fundus examination: The back part of the eye (fundus), including the retina, optic disc, 
choroid and blood vessels, will be examined using an ophthalmoscope (see Appendix 3 for 
details) 
l. Adverse  Event  Reporting,  see Sections  8.3.1  and  8.3.2 of  the  protocol  for  details:  To 
optimize  consistency  of  AE  
reporting  across  centers,  
the  study  subject  will  be  asked  a 
standard question to elicit any AEs. 
 At each study visit or telephone evaluation of the study 
subject, study personnel (non-observer) will ask the following question:   
“Have you had any problems since your last visit?” 
7.2.2 Standard of care Study Procedures  
At Visit 1 (Screening/Baseline), in addition to study specific examinations, the Investigator 
will  perform  pre-operative  examinations  that  are  part  of  the  Investigator’s  standard  pre-
operative evaluations for a potential subject being considered for cataract surgery.   
At the operative visit (Visit 3) for each study subject, the Surgeon/Investigator will use their 
standard  surgical  procedure  for  the  extraction  of  the  cataract.    The  procedure  for  the 
implantation of an  
IOL  will be based upon  
the  package  
insert of the intraocular lens being 
implanted.  The procedures use for the extraction of the cataract and implantation of an IOL 
should be consistent for all study related cases. 
Pre-,  
intra- and  post-operative  open-label  medications  will  be  used  as  
is  customary  
for  
the 
Surgeon/Investigator and should be consistent for all cases. 
 However the use of any pre-, intra- 
or post-operative NSAID or corticosteroid is prohibited.   
At the conclusion of the study,  a study  
subject  may  be scheduled for additional, non-study 
related, post-operative examinations based upon the Surgeon/Investigator’s standard of care. 
7.3 Laboratory Procedures/Evaluations 
N/A. 

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7.4 Study Visit Schedule 
7.4.1 Visit 1:  (Screening/Baseline Visit, Day -30 to -1) 
A potential study subject qualifications will be assessed according to the inclusion/exclusion 
criteria listed in the protocol (see Sections 5.1, 5.2 and 5.3).  Prior to undergoing any study-
specific procedures, both the study Informed Consent and Authorization for Use/Disclosure of 
Health Information forms (HIPAA authorization) must be signed by a potential subject who 
has  agreed  
to  participate  
in  
the  study.  
  During  
this  visit,  
the  
following  
information  will  be 
collected/evaluated and recorded in the appropriate sections of the study case report forms for 
both eyes: 
a. Obtain informed consent and HIPAA release 
b. Record the subject’s demographic data and prior 12 month medical history 
c. Record the use of all systemic, topical and/or ophthalmic concomitant medications over 
the previous 30 days 
d. Urine pregnancy test (if applicable) 
e. Investigator evaluation of ocular pain 
f. Monocular Distance Visual Acuity, Uncorrected and Best-Corrected  
g. Manifest Refraction 
h. Slit-lamp examination  
i. Evaluation of lower punctum (scheduled study eye only) 
j. Type and grade of cataract (scheduled study eye only) 
k. Fundus examination (scheduled study eye only) 
A subject who meets all of the study inclusion/exclusion criteria will be scheduled for surgery.  
Each qualified subject will be scheduled to return to the Investigators office 1 to 2 days before 
their scheduled surgery for the insertion of the study punctal plug. 
7.4.2 Visit 2: (Masked Punctal Plug Insertion Visit, 1-2 days pre-op) 
Each qualified study subject as they are enrolled in to the study will be sequentially assigned 
an ID number. 
 Treatment assignments for this study have been randomized (see Section 10.6.1 
for details on treatment randomization) to determine which one of the two treatments the study 
subject will receive during the study.  In addition, the ID number and the study subject initials 
will be recorded on study case report forms, in lieu of recording their name, in order to maintain 
subject confidentiality. 

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At this visit the following will be performed and recorded: 
a. Investigator evaluation of ocular pain 
b. Insertion  of  
the  assigned  masked  punctal  plug  
in  
to  
the  
lower  punctum  of  
the  schedule 
surgical eye 
c. Inspection  of  
the  masked  punctal  plug  via  
the  slit  
lamp  
to  ensure  
the  plug  
is  properly 
positioned, with the cap still visible and secured in place.   
NOTE: The position of the masked punctal plug may be adjusted with forceps 
d. Recording of any reported adverse event(s). 
e. Concomitant medication 
7.4.3 Visit 3:  (Surgical Visit, Day 0) 
Cataract surgery (e.g., corneal incision, anterior capsulotomy, fragmentation/removal of the 
lens/cataract) may be performed with the assistance of a femtosecond laser.  It is recommended 
the surgeon use a standard phacoemulsification extraction surgical  
technique.  
 The anterior 
capsulotomy should be a well centered continuous curvilinear capsulorhexis approximately 5.5 
mm in diameter and the lens must be placed in the capsular bag.  A viscoelastic should be used 
to protect the endothelium.  At this visit the following surgical data will be recorded: 
a. Surgical Eye Pupil measurements (prior to and immediately following surgery) 
b. Monocular cataract extraction/IOL implantation recording the following information: 
• Indicate the incision Type (clear cornea, limbal, sclera), Location (nasal, temporal, 
superior, other) and Size (mm) 
• Nucleus removal time (< 1min, 1 - < 2 min, 2 - < 3 min, 3 - < 4 min, >4 min)  
• Ease of Cortex removal (Very Easy, Easy, Difficult, Very Difficult) 
• Effective Phaco Power (recording of phaco time and power) 
• Type of IOL (e.g., monofocal, toric, etc.) and lens power 
• Record any surgical complications 
c. Visual Inspection of the masked punctal plug at the conclusion of surgery 
d. Subject reported AEs prior to or after surgery 
e. Concomitant medication 

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Should  a  surgical  complication  occur,  
implantation  of  
the  
lens  will  be  at  
the  
Investigator’s 
discretion.  If  any  of  the  surgical  complications  occur,  as  listed  in Section  5.3,  the  study 
subject’s punctal plug will be removed after surgery and the subject terminated from the study. 
Pre-,  
intra- and  post-operative  open-label  medications  will  be  used  as  
is  customary  
for  
the 
Surgeon/Investigator, and should be consistent for all cases.  All pre-, intra- and post-operative 
open-label medications must be recorded on the Concomitant Medication CRF.  However the 
use  of  any  pre-,  intra- or  post-operative  NSAID  or  corticosteroid  is  prohibited,  with  the 
exception  of  a  subject  who  has  been  prescribed  and  has  been  taking  a  baby  aspirin 
(<81mg/daily). An LRI or AI procedure required for any sphere/cylinder correction before, 
during or after cataract surgery is prohibited during the study period. 
Each study subject will be scheduled to return within 1, 3, 7 and 14 days after their surgical 
procedure.  The Surgeon/Investigator and/or his/her staff will review with each study subject 
the  proper  use  or  discontinuation  of  any  post-op  open-label  medications  prescribed  by  
the 
Investigator.   
7.4.4 Visit 4 through Visit 6: Follow-up visits  
7.4.4.1 Visit 4:  (Day 1 Post-Op) 
At this visit the following will be performed on the surgical eye only: 
a. Investigator evaluation of ocular pain 
b. Inspection of the masked punctal plug via the slit lamp 
c. Slit-Lamp examination. 
d. Recording of any reported adverse event(s). 
e. Concomitant medication 
Each study subject will be scheduled to return in 2 days for a follow-up study examination 
(Visit  5,  day  3  post-op).  
  The  
Investigator  and/or  his/her  staff  will  
review  with  each  study 
subject the proper use or discontinuation of any post-op open-label medications prescribed by 
the Investigator. 
 Any changes, discontinuation or addition of an open-label medication(s) must 
be recorded on the Concomitant Medication CRF. 
7.4.4.2 Visit 5:  (Day 3 ± 1 Post-Op) 
At this visit the following will be performed on the surgical eye only: 
a. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviewed and record the subject’s response to ocular pain 
at Visit 4 (Day 1 post-op) should interview the subject at this visit 

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b. Monocular Distance Visual Acuity (Uncorrected)  
c. Inspection of the masked punctal plug via the slit lamp 
d. Slit-Lamp examination 
NOTE: The  
Investigator that performed slit-lamp evaluation at Visit 4 (Day 1 post-op) 
should perform the slit-lamp evaluation at this visit. 
e. Recording of any reported adverse event(s). 
f. Concomitant medication 
Each study subject will be scheduled to return in 4 days for a follow-up study examination 
(Visit  6,  day  7  post-op).  
  The  
Investigator  and/or  his/her  staff  will  
review  with  each  study 
subject the proper use or discontinuation of any post-op open-label medications prescribed by 
the Investigator.  Any changes, discontinuation or addition of an open-label medication(s) must 
be recorded on the Concomitant Medication CRF. 
7.4.4.3 Visit 6:  (Day 7 ± 1 day Post-Op) 
At this visit the following will be performed on the surgical eye only: 
a. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviewed and record the subject’s response to ocular pain 
at Visit 4 (Day 1 post-op) should interview the subject at this visit 
b. Monocular Distance Visual Acuity (Uncorrected and Best-Corrected)  
c. Manifest Refraction 
d. Inspection of the masked punctal plug via the slit lamp  
e. Slit-Lamp examination   
NOTE: The Investigator that performed the slit-lamp evaluation at Visit 4 (Day 1 post-op) 
should perform the slit-lamp evaluation at this visit. 
f. Recording of any reported adverse event(s). 
g. Concomitant medication 
Each study subject will be scheduled to return in 7 days for a follow-up study examination 
(Visit 7, day 14 post-op).  The Investigator and/or his/her staff will review with each study 
subject the proper use or discontinuation of any post-op open-label medications prescribed by 
the Investigator. 
 Any changes, discontinuation or addition of an open-label medication(s) must 
be recorded on the Concomitant Medication CRF. 

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7.4.5 Visit 7:  (Final Study Visit, Day 14 ± 2 days Post-Op) 
At the final scheduled study visit the following will be performed on the surgical eye only: 
a. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviewed and record the subject’s response to ocular pain 
at Visit 4 (Day 1 post-op) should interview the subject at this visit 
b. Monocular Distance Visual Acuity (Uncorrected and Best-Corrected)  
c. Manifest Refraction 
d. Inspection of the masked punctal plug via the slit lamp  
e. Slit-Lamp examination 
NOTE: The  
Investigator that performed slit-lamp evaluation at Visit 4 (Day 1 post-op) 
should perform the slit-lamp evaluation at this visit. 
f. Fundus examination 
g. Removal of the masked punctal plug 
h. Recording of any reported adverse event(s). 
i. Concomitant medication 
An exit form will be completed at this final study examination (Visit 7), or whenever the study 
subject completes or leaves the study for any reason.  The Investigator and/or his/her staff will 
review with each study  subject the proper use  or discontinuation of any  post-op open-label 
medications prescribed by the Investigator.  Any changes, discontinuation or addition of an 
open-label medication(s) must be recorded on the Concomitant Medication CRF. 
7.4.6 Early Exit Visit 
Any study subject exiting the study early, the  
Investigator must remove the study subject’s 
masked punctal plug.  In addition, the Investigator should record the following: 
a. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviewed and record the subject’s response to ocular pain 
at Visit 4 (Day 1 post-op) should interview the subject at this visit 
b. Monocular Distance Visual Acuity (Uncorrected and Best-Corrected)  
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d. Inspection of the masked punctal plug via the slit lamp  
e. Slit-Lamp examination 
NOTE: The  
Investigator that performed slit-lamp evaluation at Visit 4 (Day 1 post-op) 
should perform the slit-lamp evaluation at this visit. 
f. Fundus examination 
g. Removal of the masked punctal plug 
h. Recording of any reported adverse event(s). 
i. Concomitant medication 
Any changes, discontinuation or addition of an open-label medication(s) must be recorded on 
the Concomitant Medication CRF. 
7.4.7 Unscheduled Visit 
The Investigator has the option of bringing a study subject back in for an unscheduled visit 
during the treatment period for safety reasons [e.g., study subject complaint of moderate to 
severe  ocular  symptom(s),  an  AE].  
  An  unscheduled  visit  CRF  should  be  completed.  
  At 
minimum, the Investigator should record the following: 
a. Investigator evaluation of ocular pain 
NOTE: The Investigator that interviewed and record the subject’s response to ocular pain 
at Visit 4 (Day 1 post-op) should interview the subject at this visit 
b. Inspection of the masked punctal plug via the slit lamp, if applicable 
c. Monocular Distance Visual Acuity (Uncorrected) 
d. Slit-Lamp examination  
NOTE: The Investigator that slit-lamp evaluation at Visit 4 (Day 1 post-op) should perform 
the slit-lamp evaluation at this visit. 
e. Recording of any reported adverse event(s). 
f. Concomitant medication 
Any changes, discontinuation or addition of an open-label medication(s) must be recorded on 
the Concomitant Medication CRF. 

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Table 1: Schedule of Assessments, Events 
 
EXAM PARAMETERS 
 v1  v2  v3  v4  v5  v6  v7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Inform Consent/HIPPA 
    
          
 Demographic data/Medical Hx
 /Medication Use 
  A             
 Concomitant Medication 
              
 Urine Pregnancy Test (if applicable) 
  B             
 Subject Randomization to Treatment 
  
            
 Investigator Evaluation of Ocular Pain 
  C       F   F   F   F 
 Uncorrected  Distance VA 
  C              
 Manifest Refraction 
  C              
 Best-Corrected Distance VA 
  C              
 Slit Lamp Examination 
  C       F   F   F   F 
 Insertion of Masked Punctal Plug 
  
            
 Inspection of Masked Punctal Plug 
  
 D  E  D  D  D  D 
 Evaluation of lower puncta 
              
 Pupil Measurements 
  
    G          
 Type and Grade Cataract 
              
 Monocular Cataract Extraction/IOL Implantation 
  
            
 Fundus Examination 
               
 Removal of Masked Punctal Plug 
  
             H 
 Adverse Event Recording 
  
             
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Keys to Abbreviations: 
Visit Schedule: 
 
 
 
A  = Prior 12 months 
v1  = Day -30 to -1 
B  = Pregnancy test (women of childbearing potential) 
v2  = 1 to 2 days prior to surgery 
C  = Evaluation of Both Eyes 
v3  = Surgery Day 
D  = Evaluation using slit-lamp 
v4  = 1 day post-op 
E  = Visual inspection after surgery 
v5  =  3 + 1 days post-op 
F  = Investigator that performs the slit-lamp and/or ocular pain evaluation 
v6  = 7 + 1 days post-op 
     at Visit 4 (Day 1 post-op) should perform ALL post-op visit evaluations 
v7  = 14 + 2 days post-op 
G  = Measurement to occur prior to surgery and immediately after surgery
 
H  = All masked punctal plugs must be removed at the subject last visit 
  
 
 
 
 

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7.5 Emergency Anaphylactic or Overdose Procedures, Dose Modification 
Dose modification of the study drug/device is not required in this study.   
NOTE: Use caution when administering nepafenac to a subject  who has previously 
exhibited sensitivities to phenylacetic acid derivatives and salicylate hypersensitivity 
as the potential for cross-sensitivity exists.  This study is not expected to cause AEs 
different  in  type  or  intensity  from  those  previously  reported  in  published  clinical 
research  literature  regarding  the  use  of  topical  nepafenac  (NEVANAC®  or 
ILEVRO®).  Refer to the Investigator Brochure and Appendices 4 and 5 for additional 
information. 
Should a subject experience a significant medical issue, the subject may be treated according 
to the Investigator’s medical judgment.  Any changes, discontinuation or addition of a post-op 
medication(s) must be recorded on the Concomitant Medication CRF. 
7.6 Concomitant Medications 
7.6.1 Pre-Study Concomitant Medication Use 
Pre-study  concomitant  medications  are  defined  as  all  prescription  and  over-the-counter 
medications taken within 30 days (whether continuing or not) prior to Visit 3 (Day 0).  All 
prior medications must be documented on the Concomitant Medications CRF. 
7.6.2 Concomitant Medication Use 
Each study subject will be instructed not to use any other ocular drops, gels or ointments in his 
or her eyes that have not been prescribed by the Investigator.  Systemic medications being used 
at Visit 1 that are permitted by the study protocol (see inclusion/exclusion criteria for details), 
are considered necessary for the study subject’s welfare, and will not interfere with the study 
may be used.   
All  prescription  systemic,  ophthalmic  and  over-the-counter  concomitant  medications  used 
concurrently (from Day -30 to Day 14), that are considered necessary for the study subject’s 
welfare, and will not interfere with the study, may be used but must be documented on the 
Concomitant  Medication  CRF.  
  The  use  of  all  concomitant  medications  during  
the  study, 
including  all  pre -,  
intra- and  post-operative  medications,  
including  
intravenous  solutions, 
dilating drops, irrigations, viscoelastics, antimicrobials/ anti-infectives, miotics, etc. related to 
the surgery, will be documented.  The medication name, start and stop dates, indication, dose, 
route of administration and any dosing alterations must be documented on the Concomitant 
Medications CRF through completion of the last study visit. 
In case of intolerable irritation due to standard post-op open-label medication(s) prescribed by 
their Investigator, a study subject is to notify the Investigator immediately.  If necessary, the 
open-label treatment regimen may be temporarily altered, or the treatment may be stopped and 
appropriate therapy administered at the Investigator
's discretion. 
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or addition of an open-label medication(s) must be recorded on the Concomitant Medication 
CRF. 
7.7 Prohibited Medications, Treatments and Procedures 
7.7.1 Prohibited Medications 
The use of any systemic, topical and/or ophthalmic NSAID or corticosteroid within 48 hours 
of Visit 2 or during the course of the study (Visit 2 to Visit 7) is not allowed unless medically 
necessary.  If an NSAID, corticosteroid or an immunosuppressant is required for any condition 
(ocular or systemic), the study subject will be terminated from the study, have their masked 
punctal plug removed and will be followed through Visit 7 (Day 14) or if required until the 
condition has resolved or has become medically stable. 
Investigational/experimental/off-label usages of drugs or devices are not permitted during the 
study, except as described in the protocol.   
7.7.2 Prohibited Procedures 
The following procedures are prohibited during the study period: 
a. An LRI or AI procedure before, during or after cataract surgery  
b. A blepharoplasty before or after cataract surgery 
c. Nd:YAG capsulotomy (e.g., for PCO) 
7.8 Prophylactic Medications 
The pre- and post-operative use of antimicrobial/anti-infective and the cohesive and dispersive 
viscoelastics use during surgery will be used at the discretion of the Surgeon/Investigator.  The 
use of Miochol at the conclusion of cataract surgery is recommended but can be avoided at the 
discretion of the Surgeon/Investigator.  The use of any of the above mention medications will 
be documented on the Concomitant Medication CRF. 
7.9 Rescue Medications 
During  
the  study  some  patients,  as  determined  by  
the  
investigator,  may  require  additional 
rescue medications in the study eye due to post-op ocular pain and/or inflammation the patient 
is  experiencing.    Rescue  treatment  will  be  allowed  per  pre-specified  rescue  criteria 
(Section 7.9.1); if the rescue criteria are not met, the medications will be considered prohibited 
medications.    Prohibited  medications,  though  discouraged,  could  be  used  but  would  be 
considered protocol deviations.   

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7.9.1 Administration of a Rescue Medication 
Following  cataract  surgery,  a  rescue  treatment  with  an  ocular  topical  corticosteroid 
(prednisolone acetate 1% q.i.d.) should be administered in the study eye, at the discretion of 
the physician, if any of the following rescue criteria apply: 
a. Anterior Chamber Cell grade is 3 (grade 3 = 16-30+ cells) or greater 
b. Anterior Chamber Flare grade is 3 (grade 3 = moderate intensity) or greater 
c. Subject reports moderate to severe ocular pain 
A study subject will be followed through Visit 7 (Day 14) or until the study subject’s post-op 
ocular pain and/or inflammation in the study eye has resolved or has become medically stable.  
The  use  of  a  rescue  medication  during  
the  study  will  be  documented  on  
the  Concomitant 
Medication CRF. 
8 ASSESSMENT OF SAFETY 
8.1 Safety Variables 
Safety variable for this study include any reported AE after screening, visual acuity, slit lamp 
biomicroscopy  finding, fundus examination  findings,  use  of  concomitant  and/or  rescue 
medications.  To optimize consistency of AE reporting across centers, the study subject will 
be asked a standard question to elicit any AEs.  At each study visit or telephone evaluation of 
the study subject, study personnel will ask the following question:   
"Have you had any problems since your last visit?" 
8.2 Definitions 
8.2.1 Adverse Event 
Adverse  Event  (AE):  any unanticipated sign  (including  a  clinically  significant  abnormal 
laboratory finding), symptom, or disease temporally associated with the administration of a 
medicinal product, whether or not considered related to the investigational product or device.  
Medical  conditions  or  diseases  present  before  a  subject  starts  study  treatment  are  only 
considered AEs if they worsen after the subject starts study treatment.  
8.2.2 Serious Adverse Events  
Serious Adverse Event (SAE): defined as any AE that (at any dose): 
• Results in death 

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• Is  
life-threatening.  NOTE: The  
term  "life-threatening"  refers  
to  an  event  
in  which  
the 
subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more intense 
• Requires inpatient hospitalization or prolongs existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• May jeopardize the subject or may require intervention to prevent one of the outcomes 
listed  above.  Medical  and  scientific  
judgment  should  be  exercised  
in  deciding  
if  
these 
events should be considered 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 
In addition, an AE that results in overdose or produces congenital abnormality or cancer is 
always considered an SAE. 
A subject admitted to a hospital as a result of an AE, even if released on the same day, would 
qualify for inpatient hospitalization. An emergency room visit that results in admission to the 
hospital would also qualify for inpatient hospitalization. However, emergency room visits that 
do not result in admission to the hospital would not qualify for inpatient hospitalization and, 
instead, should be evaluated for one of the other criteria for SAEs (e.g., life-threatening AE or 
medically significant event). 
Hospitalization  scheduled  before  a  subject  enrolls  in  the  study  is  not  the  result  of  a 
treatment-emergent  AE,  and  therefore  events  leading  to  such  hospitalization  will  not  be 
considered  study  AEs  or  SAEs.  During  the  study,  if  a  subject  has  elective  surgery  for  a 
condition present at inclusion into the study, and the condition did not worsen during the study, 
the  reason  for  elective  surgery  (and  resulting  hospitalization,  if  applicable)  should  not  be 
considered or reported as an SAE. (Surgery or hospitalization should always be reported as an 
outcome  of  an  AE.)  For  AEs  that  result  in  persistent  or  significant  disability/incapacity, 
disability/incapacity refers to a substantial disruption of a subject
's ability to carry out normal 
life functions. 
The investigator must also submit documentation of the following to the Institutional Review 
Board, Ethics Committee, or Research Ethics Board (collectively referred to as an IRB): 
• Center-specific  SAEs and follow-up: The type of serious event that must  be submitted 
(e.g., all or only suspected), as well as the required timing of submission (e.g., within 10 
days  of  occurrence),  is  defined  by  the  IRB  and  regulations/guidance  from  regulatory 
authorities.  
• Any documentation provided by the Sponsor regarding reportable SAEs from the study: 
The  Sponsor  will  provide  documentation  of  reportable  events  to  the investigator,  as 
specified in Section 8.7. 
The investigator should ensure that the subject receives appropriate medical treatment and that 
the subject is followed up until the SAE resolves or becomes chronic, as defined in Section 8.4. 

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8.3 Adverse Event Descriptions 
8.3.1 Intensity 
The intensity of AEs will be characterized as mild, moderate, or severe, as follows: 
• Mild:  Usually  
transient,  requiring  no  special  
treatment,  and  does  not  
interfere  with  
the 
subject
's daily activities 
• Moderate:  Introduces  a  
low  
level  of  
inconvenience  or  concern  
to  
the  subject  and  may 
interfere with daily activities, but is usually ameliorated by simple therapeutic measures 
• Severe: Significantly interferes with a subject
's usual daily activities and requires systemic 
drug therapy or other treatment, if available 
8.3.2 Relationship to Study Treatment 
The  causal  relationship  to  study  drug  or  treatment  will  be  determined  by  the  investigator 
according to best medical judgment, as follows: 
• Suspected: There is a reasonable possibility that the AE is associated with use of the study 
treatment, such as a temporal relationship of the event to study treatment administration, 
or when other drugs, therapeutic interventions, or underlying conditions do not provide a 
sufficient explanation for the observed event. 
• Not suspected: A relationship between the AE and the study treatment can reasonably be 
ruled  out  based  on  lack  of any  temporal  relationship  of  the  event  to  study  treatment 
administration,  or  when  the  subject
's  underlying  condition,  medical  history,  or  other 
therapy provide sufficient explanation for the observed event. 
8.4 Follow-up for Adverse Events Definitions 
Throughout the study to the final study contact, all AEs will be followed until they resolve or 
become chronic (as judged by the investigator).  
At the final study visit, new AEs, as well as follow-up information for continuing AEs, will be 
recorded in the CRF and source document. If an SAE (defined in Section 8.2) is unresolved at 
the final study visit, it will be followed by the investigator until it resolves or becomes chronic 
(as judged by the investigator). Follow-up data for such SAEs will be recorded in the source 
document and reported to the safety monitors (refer to Section 8.7). Non-serious ongoing AEs 
will be followed beyond the final study visit at the discretion of the investigator and recorded 
in the source documents.   
8.5 Pregnancy Follow-up 
If a subject becomes pregnant during the study, the investigator must inform the Sponsor and 
collect follow-up data regarding the pregnancy, birth, and status of the child. The Sponsor will 
provide  special  CRFs  for  data  collection  in  the  case  of  pregnancy.  Follow-up  should  be 

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continued  until  study  close-out  at  the  study  center.  After  close-out,  the  Sponsor
's  Safety 
designee will continue to obtain follow-up information. 
Pregnancy should be recorded as a protocol deviation. Pregnancy is not an AE; however, any 
complication related to pregnancy would be considered an AE. 
8.6 Reporting of Technical Complaints  
8.6.1 Definitions 
A quality complaint is one that is received in writing, electronically, or orally that involves the 
use or attempted use of a N-PPDS, p-PPDS 
that identified any defects in the physical properties 
of the drug product (color, precipitates, viscosity, etc.) or its packaging. Technical complaints 
also include any identified customer dissatisfaction with the physical characteristic(s) of the 
study product (dispensing characteristics, labeling, packaging, etc.). 
8.6.2 Reporting of Technical Complaints 
Any technical complaint should be reported by fax to the Sponsor
's Chief Scientific Officer 
(contact  information below)  within  24  hours.  The  complaint  report  should  include  the 
following information: 
• Name of the study product 
• Strength of study product 
• Batch/lot number of study product 
• Investigator name, study center name, and contact number 
• Date the complaint occurred 
• Brief description of the complaint 
• Study subject or other individual involved (yes/no):  
o If yes and a study subject, the investigator should report whether any AEs were 
associated with the complaint (yes/no; if a subject AE was associated with the 
complaint, refer to Section 8 and attach the AE CRF page to the complaint) 
o If yes and another individual, the investigator should describe the situation and 
any ill effects on the health of the individual 
o If no, in the investigator
's judgment, the investigator should report whether the 
complaint could reasonably  cause an SAE if it  
recurred  under  circumstances 
that did involve a study subject or other person (yes/no) 
• Identity of any other investigational or commercial devices involved 
The study product and associated packaging that initiated the complaint should be returned to 
the Chief Scientific Officer (address below) for analysis. 

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Mati Therapeutics Inc.  
Attn: Chief Scientific Officer 
Deepank Utkhede 
201 – 4475 Wayburne Drive 
Burnaby, BC 
Canada V5G 4X4 
  
Fax:    
604-637-8747 
Telephone:  778-991-3301 
 
Any  complaint  about  a study product  must  be  
reported  
regardless  of  whether  
the  defect  or 
deficiency had any effect on a subject or on study personnel. 
8.6.3 Punctal Plug Serious Adverse Events and Technical Complaints  
The Sponsor will evaluate all SAE reports and technical complaints received in the study to 
determine if the report meets the definition of an unanticipated ADE. Unanticipated ADEs are 
defined as follows: 
• any serious adverse effect on the health or safety or any life-threatening problem or death 
caused by, or associated with, a device, if that effect, problem, or death was not previously 
identified  in  nature,  severity,  or  degree  of  incidence  in  the  investigational  plan  or 
application or any other unanticipated serious problem associated with a device that relates 
to the rights, safety, or welfare of subjects. 
If  the  Sponsor  determines  that  any  SAE  or  technical  report  is  an  unanticipated  ADE,  an 
investigation  will  be  begun  
immediately. The  Sponsor  will  
inform  
the  
investigator  of  any 
additional reporting requirements beyond those stated in Section 8.7, as applicable. 
If the Sponsor determines that an unanticipated ADE presents an unreasonable risk to subjects, 
the Sponsor will terminate the study as soon as possible. Termination will occur not later than 
five working days after the Sponsor makes this determination and not later than 15 working 
days after the Sponsor first received notice of the effect. The Sponsor will report the results of 
any investigations to the FDA and to investigators, who will also submit the reports to their 
IRBs, within 10 working days after the Sponsor first received notice of the effect. 
8.6.4 Anticipated Adverse Events 
The following is a list including, but not limited to, ocular adverse events that are anticipated.  
Any  event that is unlikely but  anticipated must  have  an adverse event form completed  and 
reported to Mati Therapeutics Inc. (see Section 8.7 for reporting details). 
• Endophthalmitis/Intraocular infection 
• Hypopyon 
• IOL dislocation 

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• Cystoid macular edema 
• Pupillary block 
• Retinal detachment/tear 
• Corneal edema 
• Iritis 
• Raised IOP requiring treatment 
• Visual symptoms requiring lens removal 
• Tilt and decentration requiring repositioning 
• Residual refractive error resulting in a secondary intervention 
NOTE: Wound  burps  during  the  first  week  postoperatively  and  suture  removal  are  not 
considered adverse events for this study. 
8.7 Reporting Procedures 
Adverse events that occur from Visit 2 (1-2 days pre-op) through completion of the end-of-
study visit must be documented.  The Investigator will assess the AE severity and relationship 
of the AE to the study drug/device.  
  The  
Investigator will follow the progress of the study 
subject until the AE either resolves or becomes medically stable.  Treatments and medications 
required to treat AEs must be recorded.   
All adverse events, regardless of severity and whether  or not attributed to the drug or drug 
delivery device, are to be reported to Mati Therapeutics Inc.  Adverse events are also to be 
reported to the site IRB per the IRB’s reporting requirements.   
8.7.1 Adverse Event Reporting 
An adverse event that is not serious or related to the study drug or drug delivery device is to 
be reported to the designated Medical Monitor within 10 working days of the Investigator first 
becoming aware of the event.  Notification will occur by recording on the appropriate CRF(s), 
scanning and email or faxing the CRF(s) of  
the  visit in which the event  
is first noted.  
 An 
adverse event is also to be reported to the reviewing IRB/IEC per their reporting requirements. 
8.7.2 Serious Adverse Event Reporting 
All SAEs, regardless of cause(s) or relationship to the study drug or the drug delivery device, 
must be reported within 24 hours of becoming aware of the event to the designated Medical 
Monitor by telephone, facsimile, or email.  Additional contact numbers and AE/SAE reporting 
information will be provided to each site in a separate document.  

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All SAEs will be reported to: 
Robert Williams, MD 
Mati Therapeutics Inc. 
iopdoc1@gmail.com 
Phone: 360.378-7916 
Phone: 360.298-5325 (cell) 
Fax:  360.282-6871 
 
The Investigator must complete the SAE Report Form and send it with other relevant pages of 
the CRF to the designated Medical Monitor within 24 hours of discovery of the SAE.  The 
Investigator will also compile with urgent priority other relevant documentation (copies of test 
results,  hospital  discharge  summary,  autopsy  report, etc.)  and  send  
this  
information  
to  
the 
designated Medical Monitor. 
 Any SAE will be reported to the Investigator’s IRB/IEC per their 
reporting requirements. 
8.7.3 Unanticipated Problem Reporting 
If during the study  an adverse event occurs  
that may reasonably be  
regarded as study drug 
and/or study-device-related and was not previously expected in nature, severity, or degree of 
incidence in the investigation plan, the Investigator is to report the unanticipated adverse event 
to the designated Medical Monitor within 48 hours, and to the Investigator’s IRB as soon as 
possible,  but  no  later  than  10  working  days,  after  learning  of  the  event  as  required  by 
21CFR812.  
8.7.4 Events of Special Interest 
N/A 
8.7.5 Unmasking Study Treatment 
Masked information on the identity of the assigned test article will be provided for each study 
subject. If the treatment code needs to be broken in the interest of the study subject’s safety, 
the Investigator is encouraged to contact the Medical Monitor prior to unmasking if there is 
sufficient time.  Dependent upon the individual circumstances (i.e., medical emergency), the 
individual code  may  be  broken  prior  to  contact  with  the  Medical  Monitor.  
 The  Medical 
Monitor must be informed in all cases in which the code was broken and of the circumstances 
involved. 
The Medical Monitor for this study is:  
Robert Williams, MD 
Phone: 360.378-7916 (office) 
 
Phone: 360.298-5325 (cell) 
 
Additionally,  the  Medical  Monitor may  be  required  to  unmask a  study subject’s  masked 
treatment if  the  AE  meets  criteria  of  a  Suspected  Unexpected  Serious  Adverse  Reaction 
(SUSAR) in order to fulfill expedited regulatory reporting requirements. 

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8.8 Study Halting Rules 
Collaboration between representatives of Mati Therapeutics Inc., Investigators and statisticians 
may stop the study if there is evidence of a lack of safety or efficacy associated with the study 
drug/device or if there is sufficient evidence of efficacy to warrant phase III testing. 
8.9 Safety Oversight 
This study will utilize a Medical Monitor for safety monitoring.  The Medical Monitor will 
remain masked regarding the study treatment until the study has been completed.  The Medical 
Monitor will review and assess any reports of adverse events and, if necessary, to discuss these 
with the reporting Investigator(s).  The medical monitor will also be available to answer all 
questions from Investigators. 
9 CLINICAL MONITORING 
Mati  Therapeutics  Inc.  representative  will  ensure  that  the  investigation  is  conducted  in 
accordance with the following:  
a. GCPs as specified in ICH E6 (R1) and E8 (8.2) and 21 CFR. Part 50, 54, 56 and 312 
b. The signed Investigators
' Agreement 
c. The signed protocol for the study 
d. Any conditions imposed by the IRB 
e. The requirements of the regulations for the Protection of Human Patients (21CFR50) and 
all other applicable regulations 
Prior to initiation of the study at a site, the CRA will conduct a visit with the Investigator(s) 
and the study staff to ensure the following 
a. The  Investigator  understand  the  investigational  status  of  the  study  material  and  the 
requirements for its accountability 
b. The Investigator understands the protocol and understands and accepts their obligations in 
conducting the clinical investigation 
c. The  Investigator has  adequate  facilities  for  conducting  the  study,  and  equipment  and 
instrumentation required by the protocol 
d. The Investigators and their staff have sufficient time and access to an adequate number of 
subjects to conduct the clinical investigation. 
During the course of the investigation, the CRA will conduct periodic site visits and maintain 
telephone  contact  with  the  Investigators  and  their  staff  to  ensure  that  the  study  is  being 
conducted in accordance with the protocol, and with any specific conditions of the IRB and 

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clinical  
requirements.  
  At  such  visits, the  CRA will  ensure  
that  
informed  consent  has  been 
obtained and documented for each study subject, in accordance with 21 CFR parts 50 and 56, 
and  
the  requirements  of  
the  overseeing  IRB  and  
the  Sponsor.  The  CRA  will  review  and 
compare CRFs to source records and supporting documents to ensure that data recorded on the 
CRFs are complete, accurate, and legible, and that any corrections to the CRFs are made with 
a single line strike-through of the incorrect entry, and entry of the correct information adjacent 
with initials of the individual making the correction and date of corrected entry.  The CRA will 
further  ensure  
that  
there  are  no  data  omissions  and  
that  any  study  subject  withdrawals  are 
documented.  The CRA will review CRFs and source records for any unanticipated AEs, and 
ensure that the Investigators are complying with FDA and Sponsor requirements for reporting 
AEs and SAEs.  The CRA will ensure that the Investigators are carrying out the agreed upon 
activities  and  have  not  delegated  them  to  unauthorized  staff,  that  the  facilities  and  staff 
continue to be acceptable for the study, and that the Investigators are properly tracking study 
inventory and are accounting for the disposition of all study drug. 
The CRA shall prepare and maintain records of each site visit, significant telephone discussion, 
and written communications with the site. These records will include such information as: 
a. Date, name, and address of the Investigators and names of other staff members present at 
each meeting 
b. A summary of the findings of the visit 
c. A statement of any action taken by the CRA or Investigators to correct any deficiencies 
noted. 
10 STATISTICAL CONSIDERATIONS 
10.1 Statistical and Analytical Plans 
The primary analysis population will be an ITT (Intent-to-Treat) analysis for all study subjects 
randomized to treatment that have completed at least on post-operative follow-up visit and had 
no major protocol violations.  Individual study subjects or individual visits may be excluded if 
a major protocol violation occurs (such as violation of inclusion/exclusion criteria, the use of 
prohibited medications or non-compliance with protocol requirements that can potentially have 
significant impact on efficacy).   
10.2 Statistical Hypotheses 
a. First Hypotheses  
The Null Hypothesis:  There are no differences between patients receiving an active treatment 
(N-PPDS) vs. a placebo (p-PPDS) in controlling post-operative ocular pain associated with 
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Alternative Hypothesis: There are differences between patients receiving an active treatment 
(N-PPDS) vs. a placebo (p-PPDS) in controlling post-operative ocular pain associated with 
cataract surgery 
b. Secondary Hypotheses  
The Null Hypothesis: There are no differences between patients receiving an active treatment 
(N-PPDS) vs. a placebo (p-PPDS) in controlling post-operative ocular inflammation associated 
with cataract surgery 
Alternative  Hypothesis: There  are  no  differences  between  patients  receiving  an  active 
treatment (N-PPDS) vs. a placebo (p-PPDS) in controlling post-operative ocular inflammation 
associated with cataract surgery. 
10.3 Analysis Datasets 
Data will be pooled from all study centers for data analysis, unless otherwise specified.  Study 
dataset will be generated (keypunched) from original (white) case report forms that have been 
reviewed and collected from clinical sites. 
 Dataset will contain rows of individual subject data; 
each row will be clear labeled with the study subject randomized study number and initials.  
Each column of the dataset will contain a specific parameter for all study subjects.  Unmasking 
the treatment code will not occur until the dataset has been keypunched, data has been verified, 
and codes or classifications have been assigned. 
10.4 Description of Statistical Methods 
10.4.1 General Approach 
All statistical tests will be two-sided and interpreted at a 5% significance level.  Descriptive 
statistics (i.e., mean, standard deviation, etc.) will be provided for all continuous variables and 
frequency distributions will be generated for all categorical variables collected in this study. 
10.4.2 Analysis of the Primary Efficacy Endpoint(s) 
The primary efficacy variable will be the severity of ocular pain report at visit 4, 5, 6 and 7 
(post-op days 1, 3, 7 and 14).  For analyses using the intent-to-treat (ITT) data set, all data from 
all subjects with at least one post-operative follow-up pain evaluation will be included.  For 
the per protocol (PP) analyses dataset, data from subjects or visits with significant protocol 
deviations will be excluded.   
10.4.3 Analysis of the Secondary Endpoint(s) 
The secondary efficacy variable will be the severity of ocular inflammation (anterior chamber 
cells and flare) report at visit 4, 5, 6 and 7 (post-op days 3, 7 and 14).  For analyses using the 
intent-to-treat (ITT) data set, all data from all subjects with at least one post-operative follow-
up inflammation evaluation will be included.  For the per protocol (PP) analyses dataset, data 
from subjects or visits with significant protocol deviations will be excluded. 

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Efficacy analysis of primary and secondary endpoints will be based on observed data only.  In 
the case of a significant amount of missing data, Last Observation Carried Forward may be 
used for sensitivity analysis. 
10.4.4 Safety Analyses 
All study subjects who are exposed or deemed exposed to study medication will be evaluable 
for safety analysis.  A subject is deemed exposed to study medication if they discontinue the 
study prior to surgery visit and were implanted with a masked PPDS.   
The safety endpoints in this study are adverse events, visual acuity, slit-lamp parameters (Lid, 
conjunctiva, cornea), fundus findings, and use of rescue medication.  Safety variables will be 
summarized using descriptive statistics. 
The type, severity, duration and frequency of reported adverse events will be tabulated for each 
treatment group, by visit.  Adverse events will also be summarized for events and a comparison 
of the proportion of study patients reporting adverse events between groups will be made using 
a  chi-square  test.  
  Additionally,  any  adverse  event  experienced  by  a  subject  after  signing 
informed consent and before exposure will be presented separately in the safety analysis. 
Adverse  events  will  be  coded  using  the  Medical  Dictionary  for  Regulatory  Activities 
(MedDRA).  Treatment emergent AEs (those occurring after insertion of a study PPDS) will 
be summarized descriptively:  The number and percentage of study subjects who experienced 
an AE and the total number of AEs will be summarized by system organ class and preferred 
term.  Associated AEs, defined as AEs suspected to be treatment related by the investigator, 
SAEs and serious associated AEs will also be summarized, if necessary.  Summaries of each 
type of event will be prepared by severity and for all severities combined. 
Concomitant medication recorded and used during the study will be coded using the World 
Health Organization Drug Dictionary and listed by subject.  Ocular concomitant medications 
will be identified by each eye in the listing. 
10.4.5 Adherence and Retention Analyses 
N/A 
10.4.6 Baseline Descriptive Statistics 
Demographic and baseline characteristics will be summarized by treatment group and overall.  
Counts and percentages will be presented for categorical variables such as sex, age group (by 
decade),  race,  ethnicity,  cataract  density  and  type.    Mean,  standard  deviation,  median, 
minimum and maximum will be presented for continuous variables such as age, punctum size 
(non-dilated) and visual acuity scores. 

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10.4.7 Planned Interim Analyses 
An  interim  analysis  will  be  performed  to  confirm  that  positive  efficacy  trends  are  being 
observed and that the enrolment should continue. The interim analysis will be performed after 
a minimum of 25 subjects have completed visit 7 in the study. The data will be unmasked and 
analysis of primary and secondary endpoints will be completed along with baseline descriptive 
statistics.  
Sites will remain masked to treatment for the remainder of the study. A summary of the results 
may be shared with the sites but no individual site data will be generated or shared.  
10.4.8 Multiple Comparison/Multiplicity 
N/A 
10.4.9 Tabulation of Individual Response Data 
Reports of ocular pain will be tabulated by treatment group, by number of patients reporting 
ocular  pain  as  either  “No  Pain”  or  “Pain”  
(trace to  severe)  at  each  
follow-up  visit (Visit  4 
through Visit 7). 
10.4.10Exploratory Analyses 
N/A  
10.5 Sample Size 
Since this is a pilot study, no formal sample size estimation was performed.   
10.6 Measures to Minimize Bias 
To minimize bias, the study has been designed as a randomized, double blind study. 
10.6.1 Enrollment/ Randomization/Masking Procedures 
Randomization will be stratified (or balanced) by study center.  Patients will be randomized in 
a ratio of 2:1, 2 active (N-PPDS) for each placebo (p-PPDS).  Treatment assignments for this 
study have been randomized in blocks of three (each sequential group of three, two lines are 
active treatment, and one line is placebo treatment), 25 blocks total.  Using a random number 
generator (JMP 10.0 statistical software), each block is assigned three randomized numbers.  
The dataset is then sorted by ascending order  by block, by random number.  By ascending 
order,  each  line  is  assigned  a  subject  number  (e.g.  101-175).    As  a  subject  qualifies  for 
enrollment,  they  will  be  sequentially  assigned  a  subject  number.    The  subject  numbers 
designated what treatment group the subject will be assigned. 
10.6.2 Evaluation of Success of Blinding 
N/A 

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10.6.3 Breaking the Study Blind/Participant Code 
Prior  
to  
locking  
the  database  and  breaking  
the  masked  study  medication code,  each  study 
subject  and  visit  will  be  assessed  regarding  the  qualification  for  evaluation  of  safety  and 
efficacy parameters. 
11 SOURCE DOCUMENTS AND ACCESS TO SOURCE DATA/DOCUMENTS  
11.1 Source Documentation 
The Investigator must maintain adequate and accurate source documents upon which CRFs for 
each study subject are based.  They are to be separate and distinct from the CRFs, except for 
cases in which the Sponsor has predetermined that direct data entry into specified pages of the 
subject
's CRF is appropriate.  Study source documents should include detailed notes on: 
a. Study protocol number 
b. The oral and written communication with the study subject regarding the study treatment 
(including the risks and benefits of the study).   
c. The date that informed consent and HIPAA forms were signed must be recorded in the 
source documentation 
d. The study subject
's medical history prior to participation in the study 
e. The  study  subject
's  basic  
identifying  
information,  such  as  demographics,  
that  
links  
the 
subject
's source documents with the CRFs 
f. Date of all study subject visit and surgery throughout the duration of the study 
g. Date the punctal plug was first inserted, removed and if applicable, dates of any plug that 
was extruded/loss and a new plug was re-inserted 
h. Anterior chamber cells and flare values at each visit 
i. Subject reports of ocular pain at each visit 
j. All AEs 
k. The subject
's exposure to any concomitant therapy (including start and stop dates, route of 
administration, and dosage) 
l. All relevant observations and data on the condition of the subject throughout the study. 
11.2 Access and Retention of Study Records 
The  study  is  subject  to  audits  by  the  Sponsor/designee,  third  parties,  or  by  regulatory 
authorities.  If such an audit occurs, the Investigator must agree to allow access to all required 

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study subject records.  The Investigator will notify Sponsor promptly of any FDA audits that 
are scheduled, and must forward copies of any resultant Form 483 and/or audit reports to the 
Sponsor promptly. 
All study records will be maintained by the Investigator at the site for a minimum of 2 years 
following the date a marketing application is approved for the drug for which the indication 
was being investigated.  If no application is to be filed or the application is not approved for 
such indication, study records must be retained for at least 2 years after the investigation is 
discontinued and the FDA is notified:  
11.3 Subject Confidentiality 
Records identifying the study subject by name will be kept confidential.  The Investigator will 
ensure the study subject’s anonymity is maintained throughout the course of the study. 
 A study 
subject will be assigned a site/subject ID number to maintain study subject confidentiality.  In 
particular,  the  Investigator  will  keep  an  enrollment  log  with  confidential  identifying 
information that corresponds to the subject numbers and initials of each study subject.  A study 
subject  name  may  possibly  be  disclosed  to  Mati  Therapeutics  Inc.  or  regulatory  agencies 
during inspection of medical records related to the study, but reasonable precautions will be 
taken to maintain confidentiality of personal information to the extent permitted by applicable 
laws and regulations.  If the results of the study are published, the study subject’s identity will 
remain confidential. 
11.4 Case Report Form Completion 
The  Investigator  
is  responsible  for  ensuring  
that  data  are  properly  recorded  on  each  study 
subject’s  case  report  forms  and  related  documents.    An  Investigator  who  has  signed  the 
protocol signature page should personally sign completed case report forms to ensure that the 
observations  and  findings  are  recorded  on  
the  case  report  forms  correctly  and  completely.  
Following study examination, investigative sites should complete and remove the yellow NCR 
copy of the CRF from the study subjects’ booklet leaving the white copy of the CRF intact 
inside the booklet.  Yellow copies of completed CRFs will be mailed in on a weekly basis to 
the following: 
D’Ellis Group, Inc. 
Attn:  Daniel Schwob 
26741 Portola Pkwy, Suite 1E 717 
Foothill, Ranch, CA   92610 
 
The CRF data will be reviewed against the subject’s source data by the study monitors to ensure 
completeness and accuracy.  After monitoring has occurred at the clinical sites and the CRFs 
have  been  submitted,  additional  data  clarifications  and/or  additions  may  be  needed.  
  Data 
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11.5 Investigator Study Summary 
A  final  Investigator’s  summary  will  be  provided  to  Mati  Therapeutics  Inc.  within 
approximately  
three  months  after  
the  completion  of  
the  study.  
  The  Investigator  summary 
should include: 
a. Investigator name and title 
b. Title if the protocol 
c. Date the clinical study began (1st enrolled study subject) and the date the last study subject 
exited the study 
d. Number  of  study  subjects enrolled  
into  
the  study,  completed,  discontinued,  
terminated, 
withdrew 
e. Brief discussion regarding any reported AEs/SAEs 
f. Brief discussion of clinical findings during the study. 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
Investigator must grants permission to personnel from the Sponsor, its representatives, third 
parties  and  appropriate  regulatory  authorities  for  on-site  monitoring  and  review  of  all 
appropriate study documentation, as well as on-site review of the procedures employed in data 
collection, where clinically appropriate. 
 Study auditing, data entry, verification and validation, 
and  subsequent  analysis  will  be  performed  by  the  Sponsor  or  Sponsor’s  designees  in 
accordance with GCPs and established Standard Operating Procedures. 
13 ETHICS/PROTECTION OF HUMAN SUBJECTS 
13.1 Ethical Standard 
The Investigator agrees to conduct the study in accordance with United States Investigational 
New  Drug  regulations  specified  under  21  CFR  11,  50,  54,  56,  and  312,  the  International 
Conference  on  Harmonization  (ICH)  Harmonized  Tripartite  Guideline  for  Good  Clinical 
Practice  (GCP),  and  the  Guidelines  of  the  Declaration  of  Helsinki,  Finland,  1964  and  its 
subsequent  amendments  (Tokyo,  Japan,  1975;  Venice,  Italy,  1983;  Hong  Kong,  1989; 
Republic of South Africa, 1996; Scotland, 2000).  The Investigator will conduct all aspects of 
the  study  
in  accordance  with  all  national,  state,  and  
local  
laws  of  
the  pertinent  regulatory 
authorities. 
13.2 Institutional Review Board 
The protocol, Informed Consent Form (ICF), and any study subject information sheet must be 
approved in writing by the appropriate IRB before the study can be initiated at a site.  A copy 
of the IRB approval must be sent to the Sponsor (or designee) along with a list of the IRB 
members  and  their  occupations/affiliations.    Institutional  Review  Board  approval  is  also 

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required for any advertising or other material used for subject recruitment.  If the protocol is 
amended, the Investigator must sign the revised protocol and submit the amendment to the IRB 
for review and approval prior to implementation of the changes specified in the amendment.  
The Investigator must report promptly to the IRB all changes in the research activity and all 
unanticipated problems involving risk to human  subjects or  others, including  all SAEs that 
have resulted in an expedited safety report to the FDA.  No drug will be shipped to a site until 
IRB approval has been granted and the Sponsor or designee has been notified of this in writing. 
The Investigator is responsible for obtaining continued review of the clinical study, at intervals 
not to exceed 1 year or otherwise specified by the IRB.  The  
Investigator must provide the 
Sponsor (or designee) with written documentation of the continued review. 
13.3 Informed Consent Process 
13.3.1 Consent Procedures and Documentation 
Each subject must provide written Informed Consent before any study-related procedures are 
started.  It is the responsibility of the Investigator or designated staff member(s) to give a copy 
of  
the  
Informed  Consent  
to  each  potential  study  subject  and  
to  be  available  
to  answer  any 
questions the subject may have about the nature of the study and his or her participation in it.  
The  
individual  
responsible  
for  explaining  
the  consent  
form  
to  
the  subject  must  witness  
the 
subject’s signature on the form.  It is the responsibility of the Investigator to provide a copy of 
the IRB-approved consent form to the Sponsor (or designee) prior to the start of the study.  If 
a protocol amendment substantially alters a study design or increases the potential risk to the 
study subject, the consent form must be revised and submitted to the IRB(s) for review and 
approval prior to implementation.  The revised consent form must be used to obtain consent 
from each study subject currently in the study if they are affected by the amendment and from 
new subjects prior to their enrollment in the study.  See Appendix 7 for further details 
13.3.2 Other Informational Documents Provided to Participants 
A  subject  
to  be  enrolled  
in  
to  
the  study  
is  
required  
to  
review  and  sign  a Health  Insurance 
Portability  and  Accountability  Act  (HIPAA)  of  1996  authorization  document.  
  Each  study 
subject will receive copies of all applicable informational documents for their records. 
13.4 Participant and Data Confidentiality 
Any party (e.g., domestic and foreign regulatory authorities, sponsor
's monitors and auditors) 
with direct access will be required to take all reasonable precautions within the constraints of 
the applicable regulatory requirement(s) to maintain the confidentiality of subjects
' identities 
and sponsor’s proprietary information. 
The  confidentiality  of  
records  
that  could  
identify  subjects  will  be  protected,  
respecting  
the 
privacy and confidentiality rules in accordance with applicable regulatory requirement(s). 

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13.4.1 Research Use of Stored Human Samples, Specimens or Data 
N/A 
13.5 Future Use of Stored Specimens 
N/A 
14 DATA HANDLING AND RECORD KEEPING 
14.1 Data Collection and Management Responsibilities 
The nature and location of all source documents will be identified to ensure that original data 
required to complete the CRFs exist and are accessible for verification by the site monitor.  At 
a  minimum,  source  documents  should  include specific  data,  as  indicated  in Section  11.1 
(source documentation) of the protocol, for each subject. 
14.2 Study Records Retention 
The Investigator must arrange for retention of study records at the site for 2 years after the last 
approval  of  a  marketing  application  in  an  ICH  region  and  until  there  are  no  pending  or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since 
the formal discontinuation of clinical development of the study drug/device.  These documents 
should  be  retained  for  a  longer  period,  however,  if  required  by  the  applicable  regulatory 
requirements  or  by  agreement  with  the  Sponsor.    The  Sponsor  will  inform  the 
Investigator/Institution  as  to  when  these  documents  no  longer  need  to  be  retained.    The 
Investigator  will  
take  measures  
to  prevent  any  accidental  or  premature  destruction  of  
these 
documents. 
a. All adverse event information (adverse event forms, follow-up letters, etc.) 
b. Study subject records (source documents/CRFs) 
c. Investigational supply records/inventory 
d. IRB and regulatory approval documentation 
e. All study related correspondence 
f. All study agreements 
g. Site visit documentation 
h. Protocols and the reason for any deviations from the protocol 
i. Study Subject log 
j. Clinical Investigator’s Brochure 

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k. Completed study subject informed consent and HIPAA forms 
l. Study subject medical chart/clinic notes. 
It is required that the author of an entry in the source documents be identifiable.  Direct access 
to source documentation (medical records) must be allowed for the purpose of verifying that 
the data recorded on the CRF are consistent with the original source data. 
NOTE: These  documents  should  be  
retained  
for  a  
longer  period  
if  
required  by  
the 
applicable  regulatory  requirements  or  by  agreement  with  the  Sponsor.    It  is  the 
responsibility  of  
the  Sponsor  
to  
inform  
the  
Investigator/Institution  as  
to  when  
these 
documents no longer need to be retained.  The Investigator should take measures to 
prevent any accidental or premature destruction of these documents. 
Mati Therapeutics Inc. requires notification if the Investigator wishes to relinquish ownership 
of the data so that mutually agreed-upon arrangements can be made for transfer of ownership 
to a suitably qualified, responsible person. 
14.3 Protocol Deviations 
Any  deviation  
from  
the  protocol  done  
to  protect  
the  
life  or  physical  well-being  of  a  study 
subject  in  an  emergency  must  be  reported  to  Mati  Therapeutics  Inc.  and  the  reviewing 
Institutional Review Board (IRB) as soon as possible, but no later than five working days after 
the  deviation  occurs.  
  Unless  
it  
is  an  emergency,  
if  
the  Investigator  desires  
to  modify  any 
procedure  and/or  deviate  from  
the  design  of  
the  study,  he  or  she  must  contact  and  obtain 
consent from Mati Therapeutics Inc. regarding the proposed changes prior to implementation 
(refer to Section 7.1 for details).  If the modifications may affect the scientific soundness of 
the study, or the rights, safety, or welfare of the study participants, approval by the FDA and 
all appropriate regulatory agencies as well as approval of the IRB is also required. 
14.4 Publication and Data Sharing Policy 
All information related to this study is considered confidential information belonging to Mati 
Therapeutics  Inc.  
  Data  on  
the  use  of  
the  study  drug/device  and  results  of  all  clinical  and 
laboratory studies are considered private and confidential.  None of the details, results, or other 
information for this study shall be published or made known to a third party without written 
consent from Mati Therapeutics Inc., except for disclosure to regulatory agencies if required 
by law. 
 
 

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15 LITERATURE REFERENCES 
Kholdebarin R, et al. Multicenter study of compliance and drop administration in glaucoma. 
Can J Ophthalmol. 2008;43:454–461.  
Winfield AJ, et al. A study of the causes of non-compliance by patients prescribed eyedrops. 
Br J Ophthalmol. 1990;74:477– 480.  
An  JA,  et  al.  Evaluation  of  eyedrop  administration  by  
inexperienced  patients  after  cataract 
surgery. J Cataract Refract Surg. 2014;40:1857–1861. 
16 APPENDICES 
 

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Appendix 1 
PUNCTAL SIZING TECHNIQUE 
With the Coroneo Punctal Gauge 
 
 
 

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Appendix 2 
SLIT-LAMP  EXAMINATION  GRADING  SYSTEMS: The  biomicroscopic  slit-lamp 
exam should be performed by the same evaluator at each study visit.  Adherence to the grading 
scales listed below will improve consistency across study sites. 
A.  
Evaluation of Biomicroscopy Findings (Lid/Lid Margin, Conjunctiva, Cornea) 
The severity of a sign will be graded by the investigator based on the appearance at each study 
visit  The  following  four-point  grading  scales  are  to  be  used  to  rate  Lid/Lid  Margin, 
Conjunctiva, and Corneal findings: 
Severity 
Score 
Description 
None 
0 
Finding is NORMAL 
Mild 
+1 
Finding is FAINT but discernible and diffuse 
Moderate  
+2 
Finding is DISTINCIVE 
Severe  
+3 
Finding is VERY DISTINCTIVE and dense 
 
B.  
Evaluation of Anterior Chamber Cells and Flare (Anterior Chamber Cells and Flare) 
The severity of Anterior Chamber Cells and Flare will be graded by the investigator based on 
the appearance at each study visit.  The following five-point grading scales are to be used to 
rate the following: 
i. Anterior Chamber CELLS 
Severity 
Score 
Description 
None 
0 
No cells seen 
Trace  
+1  
1-5 cells seen 
Mild 
+2  
6-15 cells seen 
Moderate  
+3 
16-30 cells seen 
Severe  
+4 
>30 cells seen 
 
ii. Anterior Chamber FLARE 
Severity 
Score Description 
None  
0 
No Tyndall effect 
Trace  
+1 
Tyndall effect barely discernible 
Mild 
+2 
Tyndall effect in anterior chamber is clearly visible 
Moderate  
+3 
Tyndall effect in anterior chamber is moderately intense 
Severe  
+4 
Tyndall effect in anterior chamber is very intense. The aqueous humour has a white 
milky appearance 

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Appendix 3 
GRADING SYSTEMS AND METHODOLOGIES 
A. 
Visual Acuity 
Visual acuity will be measured using a Snellen chart both with (BCVA) and without correction 
(UCVA).  The test distance and lighting conditions specified for the investigator’s chart must 
be used and kept constant throughout the study.   
B.  
Fundus Exam 
Using  an  ophthalmoscope,  
the  
investigator  will  examine  
the  back  part  of  
the  eye  
(fundus), 
including the retina, optic disc, choroid and blood vessels.  Findings will be recorded as either 
“Within Normal Limits” or “Abnormal”.  If findings are abnormal, investigator will rate the 
findings  as  either  “Not  Clinically  Significant”  or  “Clinical  Significant”.    For  all  Fundus 
Findings  indicated  as  Clinical  Significant  the  investigator  will  describe  the  finding  in  the 
appropriate section of the Case Report Form: 
C. 
Cataract Density 
Severity 
Score 
Description 
None 
0 
No cataract 
Trace  
+1 
Early lens opacity 
Mild 
+2 
Intermediate lens opacity 
Moderate  
+3 
Advanced lens opacity 
Severe  
+4 
Hypermature lens opacity 
 
D. 
Ocular Pain Evaluation 
Severity 
Score 
Description 
None 
0 
Absence of pain 
Trace  
+1 
A slight, occasional awareness of an ocular sensation 
Mild 
+2 
A noticeable, intermittent awareness of an ocular 
sensation that has no impact on daily activities 
Moderate  
+3 
A prolonged, moderate ocular aching that occasionally 
interferes with normal daily activities 
Marked (Severe)  
+4 
A prolonged, intense ocular pain that interferes with 
normal daily activities 
Severe (Intolerable) 
+5 
A definite, continuous, unbearable ocular or periocular 
pain that prohibits performing normal daily activities 
 

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Appendix 4 
NEVANAC® (nepafenac ophthalmic suspension) 0.1% Package Insert 
 

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Appendix 5 
ILEVRO® (nepafenac ophthalmic suspension) 0.3% Package Insert

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Appendix 6 
Study Product Components 
Nepafenac Punctal Plug Delivery System (N-PPDS) Components 
Component 
Description 
Nepafenac 
GMP grade, micronized powder 
poly (ξ-caprolactone) 
GMP grade, pellets 
PEG400 
NF grade, liquid 
Tyloxapol 
USP grade, viscous liquid 
Tubing 
Polyimide tube length (0.0220" inner diameter, 
with 0.0010" wall–medical grade) 
Loctite
® 4305™ Cyanoacrylate 
adhesive 
Medical grade ethyl cyanoacrylate with 
photoinitiator 
L67 Punctal Plug 
 
Silicone punctal plug 
(Silicone –MED-4870, colorant MED-4800-6) 
 
Placebo Punctal Plug Delivery System (p-PPDS) Components 
Component 
Description 
poly (ξ-caprolactone) 
GMP grade, pellets 
PEG400 
NF grade, liquid 
Tyloxapol 
USP grade, viscous liquid 
Tubing 
Polyimide tube length (0.0220" inner diameter, 
with 0.0010" wall–medical grade) 
Loctite
® 4305™ Cyanoacrylate 
adhesive 
Medical grade ethyl cyanoacrylate with 
photoinitiator 
L67 Punctal Plug 
 
Silicone punctal plug 
(Silicone –MED-4870, colorant MED-4800-6) 
 
 
 

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Appendix 7 
GUIDELINES FOR INFORMED CONSENT 
Both the written informed consent form and the discussion of informed consent with a potential 
study subject should include explanations of the following: 
a. The study involves research 
b. The purpose of the study 
c. The study treatment(s) and the probability for random assignment to each treatment 
d. The study procedures to be followed, including all invasive procedures 
e. The subject
's responsibilities 
f. The aspects of the study that are experimental 
g. The  reasonably  foreseeable  risks  or  inconveniences  to  the  study  subject  and,  when 
applicable, to an embryo, fetus, or nursing infant 
h. The reasonably expected benefits.  When there is no intended clinical benefit to the study 
subject, the study subject should be made aware  
i. The alternative procedure(s) or course(s) of treatment that may be available to the subject, 
and their important potential benefits and risks 
j. The compensation and/or treatment available to the study subject in the event of study-
related injury 
k. The anticipated prorated payment, if any, to the study subject for participating in the study 
l. The anticipated expenses, if any, to the subject for participating in the study 
m. The  study  subject
's  participation  
in  
the  study  
is  voluntary  and  
that  
they  may  refuse  
to 
participate or withdraw from the study, at any time, without penalty or loss of benefits to 
which they are otherwise entitled 
n. The  monitor(s),  the  auditor(s),  the  IRB/Independent  Ethics  Committee  (IEC),  and  the 
regulatory authority(ies) will be granted direct access to the study subject
's original medical 
records  for  verification  of  clinical  study  procedures  and/or  data,  without  violating  the 
confidentiality of the subject, to the extent permitted by the applicable laws and regulations 
and that, by signing a written informed consent form, the subject or the subject
's legally 
acceptable representative is authorizing such access 

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o. The  records  identifying  the  study  subject  will  be  kept  confidential  and,  to  the  extent 
permitted by the applicable laws and/or regulations, will not be made publicly available. If 
the results of the study are published, the subject’s identity will remain confidential. 
p. The study subject or their legally acceptable representative will be informed in a timely 
manner if information becomes available that may be relevant to the subject
's willingness 
to continue participation in the study. 
q. The person(s) to contact for further information regarding the study and the rights of study 
subjects, and whom to contact in the event of study-related injury 
r. The foreseeable circumstances and/or reasons under which the subject
's participation in the 
study may be terminated 
s. The expected duration of the study subject
's participation in the study 
t. The approximate number of study subjects involved in the study.