An Open-Label, Multi-Center, Clinical Study Evaluating the Effect of the NDE L68 StableFit® Punctal Plug on the Tear Lake
Phase: NA
Conditions: Dry Eye Syndromes
Sponsor: Mati Therapeutics Inc.

 
 
 
 
 
An Open-Label, Multi-Center, Clinical Study Evaluating the Effect 
of the NDE L68 StableFit® Punctal Plug on the Tear Lake 
 
 
 
Clinical Study Protocol-NDE 68-19-01 
NCT Number: NCT04280653 
Protocol Version 1: July 31, 2019 

Mati Therapeutics Inc. 
CONFIDENTIAL 
The following contains confidential, proprietary information which is the 
property of Mati Therapeutics 
 
Clinical Study Protocol - NDE68-19-01 
 
An Open-Label, Multi-Center, Clinical Study Evaluating the Effect 
of the NDE L68 StableFit® Punctal Plug on the Tear Lake 
 
Protocol Version 1: July 31, 2019 
 
 
 
 
 
 
 
This document is a confidential communication of Mati Therapeutics Inc. Acceptance of this 
document constitutes an 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 

Mati Non-Drug Eluting L68 StableFit® Punctal Plug 
Clinical Study Protocol NDE68 -19-01 
·PROTOCOL APPROVAL 
Protocol Number: NDE68-19-01 
Title of Protocol: An Open-Label, Multi-Center, Clinical Study Evaluating the Effect of the NDE 
L68 StableFit® Punctal Plug on the Tear Lake 
· 
Prepared by: 
Study Director: 
Approved by: 
Approved by: 
Daniel Schwob, Consultant 
D'Ellis Group Inc. 
Robert Williams, MD 
Clinical Consultant 
Deepank Utkhede 
Chief Scientific Officer, 
Mati Therapeutics Inc. 
Robert Butchof~y 
President, 
Mati Therapeutics Inc. 
Version 1: July 31, 2019 
Date 
Date 
7-30-/'f 
Date 
2 
Mati Therapeutics Inc. -CONFIDENTIAL 

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Clinical Study Protocol NDE68 -19-01 
 
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STATEMENT OF COMPLIANCE 
Mati Therapeutics Inc. Protocol NDE68-19-01 
An Open-Label, Multi-Center Clinical Study Evaluating the Effect of the  
NDE L68 StableFit® Punctal Plug on the Tear Lake 
Protocol Version Date: July 31, 2019 
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.  
b. 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. 
c. 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. 
d. Obtain authorization for use/disclosure of health information (HIPAA authorization). 
e. Maintain reliable study device dispensing log, receipt and return shipping records, and to store 
study supplies in a secure, locked facility accessible only to authorized study personnel. 
f. Maintain  adequate  and  accurate  source  documents  in  accordance  with  Food  and  Drug 
Administration (FDA) regulations (e.g., CRFs, consent forms, ADE/SADE 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, notify the Sponsor 
immediately if any documents are to be destroyed, transferred to a different facility or owner. 
g. 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. 
h. Attempt to complete the study within the time designated. 
i. 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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Signature of Investigator:  _________________________________Date:__________________ 
 
Print Name of Investigator: _______________________________
 
Acknowledged By/Sponsor’s Representative Signature:  
 
 
Signature of Sponsor’s Representative:  ______________________Date:__________________ 
 
Print Name of Sponsor’s Representative: _______________________ 
 
 

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TABLE OF CONTENTS 
PROTOCOL APPROVAL .....................................................................................................2 
ABBREVIATIONS AND DEFINITIONS 
............................................................................8 
STUDY SYNOPSIS .................................................................................................................9 
1 
KEY ROLES 
................................
................................
..............................................14 
2 
INTRODUCTION:  BACKGROUND AND RATIONALE 
..................................15
 
2.1 
Background Information 
.............................................................................................15 
2.2 
Rationale 
................................
................................
......................................................15 
2.3 
Potential Risks and Benefits 
................................
........................................................15 
3 
OBJECTIVES AND PURPOSE 
..............................................................................16 
4 
STUDY DESIGN AND ENDPOINTS 
.....................................................................16 
4.1 
Description of the Study Design 
................................
..................................................16 
4.2 
Study Endpoints 
................................
................................
...........................................16 
4.2.1 Primary Study Endpoint 
..............................................................................................16 
4.2.2 Secondary Study Endpoints 
................................
.........................................................16 
4.2.3 Safety Endpoints 
................................
................................
..........................................16 
5 
STUDY ENROLLMENT AND WITHDRAWAL 
..................................................16
 
5.1 
Study Population 
........................................................................................................16 
5.2 
Study Subject Inclusion Criteria 
................................
..................................................16 
5.3 
Study Subject Exclusion Criteria 
................................
.................................................17 
5.4 
Strategies for Recruitment and Retention 
................................
....................................17 
5.5 
Study Subject Withdrawal or Termination Criteria 
.....................................................18
 
5.5.1 Reasons for Termination, Discontinuation or Disqualified 
.........................................18 
5.6 
Premature Termination or Suspension of Study or Study Site 
....................................19 
6 
STUDY DEVICE .......................................................................................................20 
6.1 
Mati’s Non-Significant Risk, Non-Drug Eluting (NDE) L68 StableFit® punctal plug20 
6.2 
Procedure for Insertion of the NDE L68 StableFit® Punctal Plug 
..............................21 
6.3 
Instruction for Study Subjects 
.....................................................................................22 
6.4 
Procedure for Removal of Punctal a Plug 
...................................................................22 
6.5 
Punctal Plug – Unable to Insert / Extruded 
.................................................................23 
6.5.1 Unable to Insert a Punctal Plug in Either Punctum......................................................23 
6.5.2 Extrusion of the Punctal Plug after the Baseline Visit 
.................................................23
 
6.6 
Study Plug Accountability and Storage Procedures 
....................................................23 
7 
STUDY PROCEDURES AND SCHEDULE 
...........................................................23
 
7.1 
Protocol Amendments 
................................................................................................23 
7.2 
Study Procedures/Evaluations .....................................................................................24 
7.2.1 Study Specific Procedures 
................................
...........................................................24 
7.3 
Study Visit Schedule 
..................................................................................................25 

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7.3.1 Visit 1: Day 0 - Screening (Prior to punctal plug insertion) 
........................................25 
7.3.2 Visit 1: Baseline - Day 0 
.............................................................................................25 
7.3.3 Visit 2:  Follow-Up (Day 7 + 1 post plug insertion) 
....................................................26 
7.3.4 Visit 3: Follow-Up (Day 28 + 4 post plug insertion) 
...................................................26 
7.3.5 Early Exit 
................................
................................
.....................................................27 
7.3.6 Unscheduled Visit 
......................................................................................................28 
8 
ASSESSMENT OF SAFETY 
...................................................................................28 
8.1 
Safety Variables 
................................
................................
...........................................28 
8.2 
Definitions....................................................................................................................29 
8.2.1 Adverse Device Event (ADE) 
.....................................................................................29 
8.2.2 Serious Adverse Device Event (SADE) ......................................................................29 
8.2.3 Unexpected Adverse Device Event .............................................................................29 
8.3 
Adverse Device Event Descriptions 
................................
............................................29 
8.3.1 Intensity........................................................................................................................29 
8.3.2 Relationship to Study Device.......................................................................................30 
8.4 
Follow-up for Adverse Device Event 
................................
..........................................30 
8.5 
Reporting Procedures 
.................................................................................................30 
8.5.1 Adverse Device Event Reporting 
................................................................................31 
8.5.2 Serious Adverse Device Event Reporting 
...................................................................31 
8.5.3 Unanticipated Problem Reporting................................................................................31 
8.6 
Reporting of Technical Complaints about Investigational Device 
..............................31 
8.6.1 Definitions....................................................................................................................31
 
8.6.2 Reporting of Technical Complaints 
................................
.............................................32 
8.6.3 Punctal Plug SADE and Technical Complaints 
...........................................................33 
8.6.4 Anticipated Adverse Device Events 
................................
............................................33 
8.7 
Study Halting Rules 
................................
................................
.....................................33 
8.8 
Safety Oversight...........................................................................................................33
 
9 
CLINICAL MONITORING 
................................
.....................................................33 
10 
STATISTICAL CONSIDERATIONS 
................................
.....................................35 
10.1 Statistical and Analytical Plans 
...................................................................................35 
10.2 Statistical Hypotheses 
................................
................................
..................................35 
10.2.1 Primary Hypotheses 
................................
................................
.....................................35 
10.2.2 Secondary Hypotheses 
................................
................................
.................................35 
10.3 Analysis Datasets 
................................
................................
.........................................35 
10.4 Description of Statistical Methods 
..............................................................................36 
10.4.1 General Approach 
................................
................................
........................................36 
10.4.2 Analysis of the Primary Endpoint(s)............................................................................36 
10.4.3 Analysis of the Secondary Endpoint(s)........................................................................36 
10.4.4 Safety Analyses 
..........................................................................................................36 
10.4.5 Baseline Descriptive Statistics 
....................................................................................37 
10.4.6 Planned Interim Analyses 
................................
............................................................37 
10.5 Sample Size 
................................................................................................................37 
10.5.1 Enrollment Procedures 
...............................................................................................37 
11 
SOURCE DOCUMENTS AND ACCESS ...............................................................37 

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11.1 Source Documentation 
...............................................................................................37 
11.2 Access and Retention of Study Records 
................................
......................................38 
11.3 Subject Confidentiality 
................................
................................
................................38 
11.4 Case Report Form Completion 
................................
....................................................38 
11.5 Investigator Study Summary........................................................................................39
 
12 
QUALITY ASSURANCE AND QUALITY CONTROL 
.......................................39
 
13 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
..............................................39
 
13.1 Ethical Standard 
................................
................................
...........................................39 
13.2 Institutional Review Board 
................................
..........................................................40 
13.3 Informed Consent Process 
................................
...........................................................40 
13.3.1 Consent Procedures and Documentation 
................................
.....................................40 
13.3.2 Other Informational Documents Provided to Participants 
...........................................40 
13.4 Participant and Data Confidentiality 
...........................................................................40 
14 
DATA HANDLING AND RECORD KEEPING 
....................................................41
 
14.1 Data Collection and Management Responsibilities 
.....................................................41
 
14.2 Study Records Retention..............................................................................................41 
14.3 Protocol Deviations 
....................................................................................................42 
14.4 Publication and Data Sharing Policy 
................................
...........................................42 
15 
REFERENCES 
.........................................................................................................42 
 
 
 
 

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ABBREVIATIONS AND DEFINITIONS 
ADE     Adverse Device Effect 
CRA      Clinical Research Associate  
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  
ICF       Informed Consent Form 
ICH       International Conference on Harmonisation  
ICH E6     International Conference on Harmonisation Guidance for Industry, Good Clinical 
Practice: Consolidated Guidance  
IEC       Independent Ethics Committee  
IDE      Investigational Device Exemption 
IRB       Investigational Review Board  
ITT       Intent-to-treat 
L68 StableFit®Mati punctal plug design 
MedDRA   Medical Dictionary for Regulatory Activities 
NCR       
No Carbon Required  
NDE     Non-drug eluting 
NSR     Non-Significant Risk 
PP       Per Protocol 
QC        
Quality Control  
SADE  
   Serious Adverse Device Event  
Study Subject  An individual that has signed a HIPAA form and an IRB approved study consent 
form 
Subject    Individual being considered for enrollment in to the study  
UP       
Unanticipated Problem  
 
 

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STUDY SYNOPSIS 
Study Protocol Number: NDE68-19-01 
Study Protocol Title: An Open-Label, Multi-Center Clinical Study Evaluating the Effect of the 
NDE L68 StableFit® Punctal Plug on the Tear Lake 
Sponsor: Mati Therapeutics Inc. 
Investigational Product, Open-Label: Mati’s Non-Significant Risk, Non-Drug Eluting (NDE) 
L68 StableFit® punctal plug design. The NDE L68 StableFit® punctal plug is pre-loaded onto a 
disposable inserter and individually packaged and sterilized to prevent contamination. The L68 
StableFit® plug consists of medical grade silicone and 2% green colorant. The L68 StableFit® 
plug is stored at room temperature.  
Number of sites: Up to 4 sites within the U.S.A. 
Study  Population: Up  to  40  male  or  female  subjects  in  good  general  health  with  a  mild  to 
moderate  dry  eye  condition. A  subject  will  be  allowed  to  use  ocular  drops  during  the  study 
however,  
the  subject  must  discontinue  
the  use  of  all  drops  at  
least  one  hour  prior  
to  a  study 
examination. 
Study Objective: To evaluate the effect of the NDE L68 StableFit® punctal plug on the tear lake. 
In addition, evaluate the insertion/removal characteristics and the investigator’s evaluation of the 
subjects’ acceptance of the NDE L68 StableFit® punctal plug. 
Study  Design: This  
is  a  Non-Significant  Risk  
(NSR)  medical  device,  multi-center,  open-label 
clinical  study. Each  study  subject  
that  qualifies  at  
the  baseline  visit  will  
receive  an  NDE  L68 
StableFit® punctal plug in the lower punctum in one of their eyes. All study plugs will remain in 
the study subject’s lower punctum for a period of 28 + 4 days after insertion. 
Note: The investigator has the option of inserting the plug in either the left or right eye of 
the subject. However, if the investigator is unable to insert the plug in the first eye chosen, 
the investigator can insert the plug in the fellow eye as long as the fellow eye meets all 
study inclusion/exclusion criteria.  
Subject  Selection: The  following  are  
inclusion  and  exclusion  criteria  for  a  prospective  study 
subject 
Study  Inclusion  Criteria: The  following  are  inclusion  criteria  for  potential study  subjects’ 
wishing to participate in this study 
a. A male or female subject, 18 years of age or older, in good general health at the time of the 
baseline examination, who may or may not have a mild to moderate dry eye condition 
b. A subject must be able to read, comprehend and be willing to give HIPAA authorization and 
informed consent  

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c. A subject must be willing to have a punctal plug inserted in the lower punctum of one of their 
eyes  
d. A  subject  must  be  willing  
to  comply  with  all  study  
instructions,  agree  to  make  all  office 
appointments, and complete the entire course of the study 
Subject  Exclusion  Criteria: The  
following  are  exclusion  criteria  
for  potential  study  subjects’ 
wishing to participate in this study: 
a. 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 the planned study eye  
b. A subject with a history of intolerance to punctal plugs 
c. A subject with structural lid abnormalities (e.g., ectropion, entropion) in the planned study eye 
d. A subject with any clinically significant lid, conjunctival or corneal findings in the planned 
study eye at the baseline visit 
e. A subject with a puncta >0.9 mm prior to dilation in the planned study eye 
f. A subject with a severe dry eye condition 
g. A subject experiencing epiphora in the planned study eye 
h. A subject experiencing any clinically significant ocular pain or discomfort in or around either 
eye at the baseline visit  
i. A  subject  with  a  known  sensitivity  
to  any  
inactive  
ingredient  of  
the  punctal  plug,  silicone, 
topical anesthetic, or any other products required for the study  
j. A subject currently participating or has participated in a clinical trial involving the use of an 
investigational medication within 30 days prior to enrollment. 
Study Duration: The approximate study duration is eight months. The study is projected to start 
the 3rd quarter of 2019 
Study Variables: The following will be performed and/or recorded during the course of the study 
Visit 1: Screening/Baseline (Day 0) 
a. Obtain written Consent and HIPAA 
b. Subject demographic data and medical history for past 7 days 
c. Verify a subject has not used any ocular drops within the last hour prior to their baseline visit 

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d. Record subject reports of any ocular signs or symptoms they are currently experiencing, prior 
to the sizing and dilation of the lower punctum  
e. Slit-Lamp examination of the planned study eye, prior to the sizing and dilation of the lower 
punctum  
f. Tear lake  evaluation of the planned study  eye,  prior  
to the sizing  and dilation of the lower 
punctum  
g. Size evaluation of the lower puncta of the planned study eye, prior to dilation of the lower 
punctum 
h. After dilation of the punctum to at least 1.0 mm, insert the study punctal plug 
i. Inspection of the punctal plug after insertion via slit-lamp 
j. Record any Adverse Device Events 
k. After  a  study  subject  has  been  inserted  with  the  NDE  L68  StableFit®  punctal  plug,  the 
Investigator will evaluate the insertion characteristics of the punctal plug 
NOTE: After the last study subject has been inserted with a study punctal plug, based on all 
subjects enrolled in the study, the investigator will give an overall assessment on the insertion 
characteristics of the study punctal plug. 
Visit 2: Follow-up (Day 7 + 1 post plug insertion) 
a. Verify a subject has not used any ocular drops, in their study eye, within the last hour prior to 
their scheduled visit  
b. Slit Lamp examination  
c. Inspection of the plug via slit-lamp  
d. Tear lake evaluation 
e. Record any Adverse Device Events 
Visit 3: Follow-up (Day 28 + 4 post plug insertion) 
a. Verify a subject has not used any ocular drops, in their study eye, within the last hour prior to 
their scheduled visit 
b. Investigator evaluation of the subject’s acceptability of the punctal plug, prior to removal of 
the study plug  
c. Slit Lamp examination, prior to removal of the study plug 
d. Inspection of plug via slit-lamp, prior to removal of the study plug 

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e. Tear lake evaluation, prior to removal of the study plug 
f. Remove study punctal plug 
g. After the plug has been removed, the Investigator will evaluate the removal characteristics of 
the inserted punctal plug 
h. Record any Adverse Device Events 
NOTE: After the last study subject has had their punctal plug removed, based on all subjects 
that  completed  
the  study,  
the  
investigator  will  give  an  overall  assessment  on  
the  removal 
characteristics of the punctal plug. 
Study Outcome Variables:  
Primary Study Endpoint:   Investigators’ evaluation of the tear lake  
Secondary Study Endpoint:  Investigator’s  evaluation  of  epiphora,  insertion/  removal 
characteristics  and  Investigators’  evaluation  of  the  subject’s 
acceptance of the NDE L68 StableFit® punctal plug. 
Study Safety Variables:   Safety assessments will include any clinically significant slit-lamp 
biomicroscopy  findings,  any  extrusions  of  a  punctal  plug  and 
incidence  and  severity  of  any  reported  ADEs  after  punctal  plug 
insertion. 
Sample Size Determination: 
Since  
this  
is  a  pilot  study,  no  formal  sample  size  estimation  was 
performed.  
 
 

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Schedule of Assessments, Events 
  E
XAM PARAMETERS 
  v1     v2     V3 
    
 
   
    
    
 Inform Consent/HIPAA 
     
  
 Demographic Data/Medical Hx 
   A   
   
 Subject Reports of any Ocular Signs or Symptoms 
   B    
  
 Verify No Ocular Drop use One Hour Prior to Visit 
        
 Inv. Evaluation of Subject’s Acceptance of Study Plug 
        
   C 
 Slit Lamp Examination 
   B      C 
 Tear Lake Evaluation 
   B      C 
 Size Evaluation of Lower Puncta, Prior to Dilation 
   B    
   
 Dilation of Lower Puncta 
      
  
 Insertion of a Punctal Plug 
      
   
 Inspection of the Placement of the Punctal Plug 
   D      C 
 Investigator Device Assessment of Insertion 
   E    
   
 Removal of Punctal Plug 
       
   
 Investigator Device Assessment of Removal 
        
   F 
 Adverse Device Event Recording 
        
    
    
    
    
 
Keys to Abbreviations: 
Visit Schedule: 
 
 
A  = Record medical history for the past 7 days 
v1  = Screening/Baseline 
B  = PRIOR to INSERTION of punctal plug 
v2  = 7 + 1 days post plug insertion 
C  = PRIOR to REMOVAL of punctal plug 
v3  = 28 + 4 days post plug insertion 
D  = Slit-Lamp Evaluation of Punctal Plug AFTER INSERTION 
 
E  = After EACH Study Subject and after ALL Study Subjects have had their Punctal Plug Inserted 
F = After EACH Study Subject and after ALL Study Subjects have had their Punctal Plug Removed  
 
 
 

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1 KEY ROLES 
Sponsor: 
Mati Therapeutics Inc. (Headquarters) 
4317 Dunning Lane 
Austin, TX 78746 
512 329-6360 
Sponsor Personnel: 
Clinical Trial    Deepank (Deeps) Utkhede 
  Coordinator:   Chief Scientific Officer 
Mati Therapeutics Canada Inc. (R&D Branch) 
201-4475 Wayburne Drive 
Burnaby, BC V5G 4X4 
778 991-3301 
dutkhede@matitherapeutics.com 
Study Monitor/    Daniel Schwob 
   Biostatistician:   D’Ellis Group, Inc. 
26741 Portola Pkwy, Ste 1E 717 
Foothill Ranch, CA 92610 
949 916-2800/949 735-1320 
dschwob@dellisgroup.com 
Regulatory    
Caroline Stokl, Ph.D., 
   Specialist:    
Consultant, Regulatory Affairs 
201-4475 Wayburne Drive 
Burnaby, BC V5G 4X4 
604 983-9103 
cstokl@matitherapeutics.com 
Medical Monitor:   Robert Williams, MD 
89 Wilks Way 
Friday Harbor, WA 98250 
360 378-7916 
iopdoc1@gmail.com  
Emergency    
24 hour Adverse Event FAX Number: 
Telephone No.:   
FAX:   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 AND 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 
A punctal plug, also known as tear duct plug or lacrimal plug, is a small medical device that is 
inserted into the nasolacrimal duct (puncta) of an eye to block (occlude) the drainage of tear fluid. 
Over  the  years  several  models  of  punctal  plugs  have  been  approved  and  are  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.”  
Occlusion of the puncta with punctal plugs has been a treatment for lacrimal deficiency in patients 
with dry eye for over the last 30 years (Freeman 1975). Since then, punctal plugs have been used 
extensively in primary eye care and are considered safe and effective in the treatment of dry eye 
(Freeman 1975; Willis et al. 1987; Tuberville et al. 1982; Fayet et al. 1990). Since the inception 
of  punctal plugs,  several  materials  and  designs  have  been  developed  with  a  host  of  products 
available  on  the  market.  While  the  designs  have  slight  differences  in  architecture,  the  basic 
mechanism of action in treating dry eye with punctal plugs is basically the same, the conservation 
of naturally produced tears by physical occlusion of the lacrimal punctum.  
Although Mati’s punctal plug designs are novel, the types of materials and techniques for insertion 
of the plugs are the same as other commercially marketed punctal plugs. Therefore Mati punctal 
plugs do not represent any more  
risk to  human subjects than the risk associated with currently 
marketed punctal plugs however; the unique design of Mati punctal plug has shown a significant 
improvement in plug retention when compared to other marketed plugs. 
2.2 Rationale 
To  evaluate  
the  effect  of  Mati’s  non-significant  risk,  non-drug  eluting  (NDE)  L68  StableFit® 
punctal  plug  on  the  tear  lake. In  addition,  evaluate  the  insertion/removal  characteristics  and 
subjects’ acceptance of Mati’s NDE L68 StableFit® punctal plugs.  
2.3 Potential Risks and Benefits 
The risks of the NDE L68 StableFit® punctal plug is not fully known but are expected to be similar 
to  
those  observed  for  commercial  punctal  plugs,  which  are  considered  
to  be  
low.  Some  risks 
associated  with  punctal  plug  use  are  discomfort,  epiphora,  loss  of  plug,  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 canalicula, requiring irrigation or surgery. In controlled clinical trials of the Mati punctal plugs, 
rates of serious adverse device events have been less than 1 percent (Fayet 1990, Balaram 2001, 
Kim 2005). 
There are no treatment benefits to study participants. Study subjects will receive regular eye exams. 

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3 OBJECTIVES AND PURPOSE 
To  evaluate  
the  effect  of  
the  NDE  L68  StableFit®  punctal  plug  on  
the  
tear  
lake. In  addition, 
evaluate the insertion/removal characteristics and assess the subjects’ acceptance of the NDE L68 
StableFit® punctal plug. 
4 STUDY DESIGN AND ENDPOINTS 
4.1 Description of the Study Design 
This is a Non-Significant Risk (NSR) medical device, multi-center, open-label clinical study. Each 
study subject that qualifies at the baseline visit will receive an NDE L68 StableFit® punctal plug 
in the lower punctum in one of their eyes. All study plugs will remain in the study subject’s lower 
punctum for a period of 28 + 4 days after insertion. 
4.2 Study Endpoints 
The study will be complete when up to 40 study subjects (40 eyes) have been evaluated at Visit 3 
(28 + 4 days post-insertion) or have been terminated from the study. 
4.2.1 Primary Study Endpoint 
The primary study endpoint will be the comparison of the tear lake volume at baseline with the 
tear lake volume at each follow-up visit. 
4.2.2 Secondary Study Endpoints 
Secondary  study  endpoints  will  evaluate  the  investigator’s  evaluation  of  epiphora, 
insertion/removal  characteristics  of  the  NDE  L68  StableFit®  punctal  plug,  and  Investigators’ 
evaluation of the study subjects’ acceptance of the NDE L68 StableFit® punctal plug. 
4.2.3 Safety Endpoints  
Safety assessments will include any clinically significant slit-lamp biomicroscopy findings, any 
extrusions of a punctal plug, and incidence and severity of any reported ADEs after punctal plug 
insertion. 
5 STUDY ENROLLMENT AND WITHDRAWAL  
5.1  Study Population 
Up to 40 normal healthy volunteers who meet all study inclusion/exclusion criteria will be enrolled 
in to the study. A subject will be allowed to use ocular drops during the study however, the subject 
must discontinue the use of all drops at least one hour prior to a study examination. 
5.2  Study Subject Inclusion Criteria  
The  following  are  
inclusion  criteria  for  potential  study  subjects’  wishing  
to  participate  
in  
this 
study: 

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a. A male or female subject, 18 years of age or older, in good general health at the time of the 
baseline examination, who may or may not have a mild to moderate dry eye condition 
b. A subject must be able to read, comprehend and be willing to give HIPAA authorization and 
informed consent  
c. A subject must be willing to have a punctal plug inserted in the lower punctum of one of their 
eyes  
d. Subject  must  be  willing  to  comply  with  all  study  instructions,  agree  to  make  all  office 
appointments, and complete the entire course of the study. 
5.3  Study Subject Exclusion Criteria 
The  
following  are  exclusion  criteria  
for  potential  study  subjects’  wishing  
to  participate  
in  
this 
study: 
a. 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  
b. A subject with a history of intolerance to punctal plugs 
c. A subject with structural lid abnormalities (e.g., ectropion, entropion) in either eye  
d. A subject with any clinically significant lid, conjunctival or corneal findings in either eye at 
the baseline visit 
e. A subject with a puncta >0.9 mm prior to dilation in either eye 
f. A subject with a severe dry eye condition 
g. A subject experiencing epiphora in either eye  
h. A subject experiencing any clinically significant ocular pain or discomfort in or around either 
eye at the baseline visit  
i. A  subject  with  a  known  sensitivity  
to  any  
inactive  
ingredient  of  
the  punctal  plug,  silicone, 
topical anesthetic, or any other products required for the study  
j. A subject currently participating or has participated in another clinical trial within 30 days prior 
to enrollment. 
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, study 
specific 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. 

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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 as his/her 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 his/her time and effort for participation, 
offer less waiting time in the doctor’s office by scheduling more flexible and reliable appointment 
times.  
5.5  Study Subject Withdrawal or Termination Criteria 
After insertion of a study plug, the Investigator may withdraw a study subject from the study if in 
their medical judgment it is in the study subject’s best interest. 
Each study subject will be informed that they are free to withdraw from the study at any time. If a 
study  subject  
is  prematurely  withdrawn  from  
the  study,  
the  reason(s)  for  withdrawal  must  be 
recorded  on  the  relevant  page  of  the  subject’s  case  report  form  (CRF). Study  subjects  who 
withdraw from the study will be replaced. 
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 Visit 3 (28 days after insertion of the punctal plug) 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 termination of a study 
subject. 
5.5.1 Reasons for Termination, Discontinuation or Disqualified 
At a study subject last visit (scheduled or unscheduled), they will have their 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 3, 28 days after plug insertion). The reason for any early exit 
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’s 
early exit from the study should be selected from the following standard categories. 

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5.5.1.1 Termination from the study 
A study subject will be terminated from the study if in the Investigator’s medical judgment, it was 
in the best interest of the study subject that developed or reported: a) a clinically significant ocular 
sign(s) or symptom(s) b) reported serious ADE, regardless of relation to the study device or has 
died or c) extrusion of a punctal plug. 
A terminated study subject will return to the clinic for an end of study safety evaluation and the 
removal of the punctal plug. 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. 
5.5.1.2  Discontinued from the study 
A study subject will be discontinued from the study if the Investigator is unable to insert the study 
punctal plug in to either eye of the study subject’s lower punctum, has personal reasons, 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 – if the study subject was discontinued for a reason 
other than those listed above, the Investigator must specify the reason. 
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 must make every effort to have the study subject return to the clinic for an end of 
study safety evaluation and the removal of their punctal plug. A study subject who is discontinued 
from the study will be replaced. 
5.5.1.3  Disqualification from the study 
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).  
Notification of disqualification will be clearly documented on the appropriate Case Report Form. 
The Investigator must make every effort to have the study subject return to the clinic for an end of 
study safety evaluation and the removal of the 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 

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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. 
Study termination and follow-up will be performed in compliance with the conditions set forth in 
21 CFR 812.40 and 21 CFR 812.43. 
6 STUDY DEVICE 
6.1  Mati’s Non-Significant Risk, Non-Drug Eluting (NDE) L68 StableFit® punctal plug 
The NDE L68 StableFit® punctal plug consists of inactive medical grade silicone and 2% green 
colorant. The  NDE  L68  StableFit®  punctal  plug  design  
is  shown  
in  Figure  1. The  NDE  L68 
StableFit® punctal plug is provided pre-loaded on an insertion tool, packaged in a preformed rigid 
tray with a foil laminate lid heat sealed onto the tray and sterilized. 
Figure 1: Proprietary NDE L68 StableFit® Punctal Plug Design
 
 

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6.2  Procedure for Insertion of the NDE L68 StableFit® Punctal Plug 
The  procedure  
for  
inserting  a  Mati’s  NDE  L68  StableFit®  punctal  plug  
is  similar  
to  
those  
for 
commercial plugs. In preparation for the insertion of the NDE L68 StableFit® punctal plug, the 
subject may be seated at the slit lamp, or placed in a reclined position: 
a. To anesthetize the area around the lower punctum, place a drop of topical anesthetic such as 
proparacaine  or  
lidocaine  on  
the  eye. Then  use  a  proparacaine  or  
lidocaine  soaked  cotton-
tipped swab. Place the swab directly on the lower punctum of the eye to be inserted for ~30 to 
60 seconds (proparacaine or lidocaine can be irrigated into the canaliculus for better anesthesia 
if desired) 
b. Using  
the  Coroneo  punctal  dilator,  
the  dilator  
is  engaged  vertically  (straight  down)  
in  
the 
punctum with a gentle twisting motion. The dilator is then quickly moved 90 degrees parallel 
to the lid margin passing it into the proximal canaliculus dilating the punctum 
c. The punctum must be 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. It is very important 
to fully dilate the punctum to 1.0 mm.  
While  dilating,  prep  
the  study  punctal  plug  
to  be  
inserted  
in  
the  
lower  punctum  of  
the  study 
subject’s eye. 
NOTE: For small puncta, hold and rotate the dilator in the punctum and canaliculus for as long 
as required to achieve dilation to 1.0 mm. This may take some considerable time. Dilation may 
require very firm pressure. Add more anesthesia if needed. 
d. Remove dilator and immediately attempt to insert the plug before the sphincter starts to close 
e. Position the plug end of the insertion instrument over the study subject’s punctum 
f. Gently insert the plug, coming straight down perpendicular to the punctum until the cap of the 
plug is flush with the lid margin 
g. Once the plug is in the proper position, press the release button and pull the insertion instrument 
away from the study subject’s punctum 
h. After insertion, the punctal opening should be visually inspected using a slit-lamp to confirm 
the retention and proper placement of the study punctal plug, with the cap still visible. The 
position of the study punctal plug may be adjusted with forceps, if necessary. 
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 margin) 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 however; lubricants 
are not to be used.  
Any questions or concerns regarding the insertion or removal of a punctal plug contact: 

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Robert Williams, MD  
Phone (Office): 360-378-7916  
Phone (Cell):    360-298-5325 
Email: iopdoc1@gmail.com 
 
6.3  Instruction for Study Subjects 
Instruct each study subject not to attempt to remove or adjust the punctal plug on his/her own. If a 
punctal  plug  
is  extruded  and  
the  subject  can  
recover  
it,  
the  plug  must  be  
returned  
to  
the  study 
center. In addition, encourage each study subject to restrict eye rubbing and be mindful of his/her 
study eye when swimming or in other activities.  
6.4  Procedure for Removal of Punctal a Plug 
The punctal plug can be removed from the study subject’s punctum using 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 jeweler’s forceps is not advisable 
c. Teeth should be placed on the far side of the plug with the blades straddling the neck of the 
plug just under the cap 
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 
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: Please  exercise  clinical  
judgment  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. Plug migrations are to be reported as an ADE however, a 
superficial migration, in which the plug is temporarily displaced, is visible with the slit 
lamp and can be easily repositioned, is not considered an ADE. 

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Removal of the study punctal plug immediately after insertion may result in the cap of the 
plug being torn off; if possible the Investigator should wait 30 to 60 minutes after insertion before 
attempting to remove a study punctal plug. However, if the plug tears or separates, report this as a 
technical complaint. Retain the plug for accountability of investigational supplies. 
6.5  Punctal Plug – Unable to Insert / Extruded 
6.5.1 Unable to Insert a Punctal Plug in Either Punctum 
If  a  punctal  plug  cannot  be  inserted  in  to  each  eye  after  dilation,  the  study  subject  will  be 
discontinued from the study and replaced. 
6.5.2 Extrusion of the Punctal Plug after the Baseline Visit 
A study subject that has noticed a plug has been extruded or lost during the follow-up period should 
immediately contact the Investigator and/or his/her staff and return to the Investigator’s office as 
soon as possible. The Investigator will terminate the study subject from the study and will NOT 
be replaced.  
6.6  Study Plug Accountability and Storage Procedures 
The Investigator is responsible for maintaining the study treatment (punctal plug) 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 his/her study plug, noting the suspected 
date the study plug was lost/extruded.  
All used and unused 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 study plugs will be verified by the Sponsor and/or his/her 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  Delegation  of 
Authority form 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. 
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 

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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 are required during the course of the study include: 
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 demographic data and medical history for the previous 7 days  
c. Record any subject reports of any ocular signs or symptoms they may be experiencing 
d. Slit-Lamp Examination: Slit-lamp examination will include assessment of the lid, conjunctiva 
and cornea as normal or abnormal. If a finding is indicated as abnormal, the investigator will 
indicate if the finding is clinically significant. If the finding is considered clinical significant, 
the investigator will describe the finding in the section provided on the Case Report form  
e. Evaluation  of  
the  subject  
tear  
lake: Using  a  slit  
lamp  micrometer,  
the  micrometer  will  be 
oriented vertically and centered on the lower lid margin at the middle of the lower lid. The tear 
lake will be measured using the slit lamp micrometer from the lid margin to the superior border 
of the lower tear lake and measured to 0.1 mm. 
f. Punctum size evaluation prior to dilation: Using the Coroneo punctum dilator, the narrow end 
of the dilator has calibrated rings that correspond to punctum diameters of 0.5, 0.6 and 0.7 mm. 
The rings on the wide end of the dilator correspond to punctum diameters of 0.8, 0.9 and 1.0 
mm. Prior to measuring the punctum diameter, the eye should be anesthetized (see Section 6.2 
of the protocol for details) with a topical anesthetic. The narrow end of the dilator is them 
introduced vertically into the punctum and advanced until the punctum starts to invert. The 
diameter is recorded as the nearest ring to the edge of the punctum when inversion begins. If 
the punctum diameter is larger than 0.7 mm, the narrow end of the dilator is removed, and the 
wider  end  
inserted  and  advanced  
in  
the  same  way. Again,  
the  diameter  
is  recorded  as  
the 
nearest ring when inversion begins. 
g. Insertion of a study punctal plug (see Section 6.2 of the protocol for details) 
h. Removal of a study punctal plug (see Section 6.6 of the protocol for details) 
i. Adverse  Device  Event  reporting,  see Section  8.5 of  the  protocol  for  details: To  optimize 
consistency  of  ADE  reporting  across  centers,  the  study  subject  will  be  asked  a  standard 
question to elicit any ADEs. At each study visit or telephone evaluation of the study subject, 
study personnel will ask the following question: 

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“Have you had any problems since your last visit?” 
7.3  Study Visit Schedule 
7.3.1 Visit 1: Day 0 - Screening (Prior to punctal plug insertion) 
A  potential  study  subject  qualifications  will  be  assessed  according  to  the  inclusion/exclusion 
criteria listed in the protocol (see Sections 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 of a subject, prior to the 
sizing and dilation of the lower punctum for the planned study eye. 
a. Obtain informed consent and HIPAA authorization release 
b. Record the subject’s demographic data and prior 7 days medical history 
c. Verify a subject has not used any ocular drops within the last hour prior to their baseline visit 
d. Record any subject reports of ocular signs or symptoms they are currently experiencing  
e. Slit-lamp examination of the planned study eye 
7.3.2 Visit 1: 
Baseline - Day 0 (Insertion of a punctal plug - refer to Section 6.2 for details 
regarding the insertion of the NDE punctal plug) 
After  
the  screening  examination,  a  qualified  study  subject  will  be  sequentially  assigned  an  
ID 
number. In addition, the ID number and the study subject initials will be recorded on study case 
report forms, in lieu of recording his/her name, in order to maintain subject confidentiality. 
Note: The investigator has the option of inserting the plug in either the left or right eye of the 
subject. However, if the investigator is unable to insert the plug in the first eye chosen, the 
investigator  can  
insert  
the  plug  
in  
the  
fellow  eye  as  
long  as  
the  
fellow  eye  meets  all  study 
inclusion/exclusion criteria.  
f. Tear  
lake  evaluation  of  
the  planned  study  eye  prior  
to  
the  sizing  and  dilation  of  
the  
lower 
punctum  
g. Size  evaluation  of  
the  punctum  of  
the  planned  study  eye  prior  
to  
the  dilation  of  
the  
lower 
punctum  
h. After dilation, the study punctal plug is inserted in to the lower punctum of study eye, inspect 
the punctal plug using the slit-lamp, the position of a study punctal plug may be adjusted with 
forceps. 
i. Record any reported adverse device event(s) 

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j. After  
the  study  plug  has  been  
inserted  
in  
the  
lower  puncta,  
the  
investigator  will  assess  
the 
insertion characteristics of the plug. 
NOTE: After the last study subject has been inserted with a study punctal plug, based on all 
subjects enrolled in the study, the investigator will give an overall assessment on the insertion 
characteristics of the study punctal plug. 
7.3.3 Visit 2: Follow-Up (Day 7 + 1 post plug insertion) 
At this visit the following will be performed and recorded: 
a. Verify a subject has not used any ocular drops, in their study eye, within the last hour prior to 
their scheduled visit 
b. Slit-lamp examination of the study eye 
c. Inspection of the punctal plug via the slit lamp 
d. Tear lake evaluation of the study eye 
e. Recording of any reported adverse device event(s) 
7.3.4 Visit 3: Follow-Up (Day 28 + 4 post plug insertion) 
At this visit the following will be performed and recorded: 
a. Verify a subject has not used any ocular drops, in their study eye, within the last hour prior to 
their scheduled visit 
b. Investigator evaluation of subject’s acceptability of the punctal plug, prior to the removal of 
the punctal plug 
c. Slit-lamp examination, prior to the removal of the punctal plug 
d. Inspection of the punctal plug via the slit lamp, prior to removal of the plug 
e. Tear lake evaluation of the eye prior the removal of the punctal plug 
f. Removal of the punctal plug (refer to Section 6.6 for details regarding the removal of a punctal 
plug) 
g. Recording of any reported adverse device event 
h. After  removal  of  the  study  subject  punctal  plug,  the  investigator  will  assess  the  removal 
characteristics of the plug. 
NOTE: After the last study subject has had their punctal plug removed, the investigator will 
give an overall assessment on the removal characteristics of all punctal plugs that 
were inserted 
during the study. 

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An exit form will be completed at the final study examination (Visit 3), or whenever the study 
subject completes or leaves the study for any reason. 
 Schedule of Assessments, Events 
  E
XAM PARAMETERS 
  v1     v2     V3 
    
 
   
    
    
 Inform Consent/HIPAA 
     
  
 Demographic Data/Medical Hx 
   A   
   
 Subject Reports of any Ocular Signs or Symptoms 
   B    
  
 Verify No Ocular Drop use One Hour Prior to Visit 
        
 Inv. Evaluation of Subject’s Acceptance of Study Plug 
        
   C 
 Slit Lamp Examination 
   B      C 
 Tear Lake Evaluation 
   B      C 
 Size Evaluation of Lower Puncta, Prior to Dilation 
   B    
   
 Dilation of Lower Puncta 
      
  
 Insertion of a Punctal Plug 
      
   
 Inspection of the Placement of the Punctal Plug 
   D      C 
 Investigator Device Assessment of Insertion 
   E    
   
 Removal of Punctal Plug 
       
   
 Investigator Device Assessment of Removal 
        
   F 
 Adverse Device Event Recording 
        
    
    
    
    
 
Keys to Abbreviations: 
Visit Schedule: 
 
 
A  = Record medical history for the past 7 days 
v1  = Screening/Baseline 
B  = PRIOR to INSERTION of punctal plug 
v2  = 7 + 1 days post plug insertion 
C  = PRIOR to REMOVAL of punctal plug 
v3  = 28 + 4 days post plug insertion 
D  = Slit-Lamp Evaluation of Punctal Plug AFTER INSERTION 
 
E  = After EACH Study Subject and after ALL Study Subjects have had their Punctal Plug Inserted 
F = After EACH Study Subject and after ALL Study Subjects have had their Punctal Plug Removed  
 
7.3.5 Early Exit 
Any study subject exiting the study early, the Investigator must record/perform the following: 
a. Verify a subject has not used any ocular drops, in their study eye, within the last hour prior to 
their scheduled visit 
b. Investigator evaluation of subject’s acceptability of the punctal plug, prior to the removal of 
the punctal plug, if the plug has not been extruded 
c. Slit-lamp  examination,  prior  to  the  removal  of  
the  punctal  plug,  if  the  plug  has  not  been 
extruded 

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d. Inspection of the punctal plug via the slit lamp, prior to removal of the plug, if the plug has not 
been extruded 
e. Tear lake evaluation of the study eye prior the removal of the punctal plug, if the plug has not 
been extruded 
f. Removal of the punctal plug (refer to Section 6.6 for details regarding the removal of a punctal 
plug), if the plug has not been extruded 
g. Recording of any reported adverse device event(s) 
h. After a study subject has had the punctal plug removed, the investigator will assess the removal 
characteristics of the plug. 
An exit form will be completed whenever the study subject completes or leaves the study for any 
reason.   
A study subject that has exited the study due to an adverse device event will be followed by the 
investigator until the ADE has resolved or has become medically stable.   
7.3.6 Unscheduled Visit 
The investigator has the option of bringing a study subject back in for an unscheduled visit during 
the course of the study for safety reasons (e.g., subject complaint of moderate or severe ocular 
symptoms,  and  ADE). An  unscheduled  visit  CRF  should  be  completed. At  minimum  the 
investigator should record the following” 
a.    Inspection of the punctal plug via the slit-lamp, if applicable 
b.   Slit-Lamp examination 
c.   Recording of any reported adverse device events 
8 ASSESSMENT OF SAFETY 
8.1  Safety Variables 
Safety variable for this study include any clinically significant slit-lamp biomicroscopy findings, 
any extrusions of a punctal plug, and incidence and severity of any reported ADEs after punctal 
plug insertion. To optimize consistency of ADE reporting across centers, the study subject will be 
asked by study personnel the following question:   
"Have you had any problems since your last visit?" 
All ADEs either observed by the Investigator or one of his/her medical collaborators, or reported 
by the subject spontaneously, or in response to the direct question above, will be noted in the ADEs 
section of the subject
's CRF and in the source document. Only treatment emergent ADEs (those 
occurring during or after the insertion of the investigational punctal plug) should be recorded as 
ADEs. Events reported before the initial screening period should be recorded as medical history. 

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If any ADE is reported, the date of onset, intensity, relationship to study device or treatment, action 
taken, date of resolution (or the fact that it is still continuing or has become chronic), and whether 
the ADE is serious or not will be recorded (see Section 8.5). 
Plug migrations are to be reported as an ADE; however, a superficial migration, in which the plug 
is temporarily displaced, is visible with the slit lamp and can be easily removed, is not considered 
an ADE. 
8.2  Definitions 
8.2.1 Adverse Device Event (ADE) 
Any unfavorable and unintended effect on health or safety of a study subject involving the use of 
a medical device. Medical conditions or diseases present before a subject starts the study are only 
considered adverse device events if they worsen during or after use of the medical device. Any 
new medical conditions or diseases that present during the course of the study will be recorded as 
an adverse device event.  
8.2.2 Serious Adverse Device Event (SADE) 
Defined as any ADE that: 
• Results in death 
• Is life-threatening even if temporary in nature.  
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 permanent impairment of a body function or permanent damage to a body structure  
• Necessitates medical or surgical intervention to prevent a life-threatening situation or preclude 
permanent impairment of a body function or permanent damage to a body structure  
8.2.3 Unexpected Adverse Device Event 
An ADE that is not identified in nature, instructions for use or clinical study protocol.  
8.3  Adverse Device Event Descriptions 
8.3.1 Intensity 
The intensity of ADEs 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 

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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 Device 
The causal relationship to study device will be determined by the investigator according to his/her 
best medical judgment, as follows: 
Suspected:  There is a reasonable possibility that the ADE is associated with use of the study 
device, such as a temporal relationship of the event to study device insertion, 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 ADE and the study device can reasonably be ruled out 
based on lack of any temporal relationship of the event to study device insertion, 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 Device Event 
Throughout the study to the final study contact, all ADEs will be followed until they resolve or 
become chronic (as judged by the investigator).  
At the final study visit, new ADEs, as well as follow-up information for continuing ADEs, will be 
recorded in the CRF and source document. If an SADE (defined in Section 8.2.2) 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  SADEs  will  be  recorded  in  the  source 
document and reported to the safety monitors (refer to Section 8.5.2). Non-serious ongoing ADEs 
will be followed beyond the final study visit at the discretion of the Investigator and recorded in 
the source documents. 
8.5  Reporting Procedures 
Adverse device events that occur from Visit 1 through completion of the end-of-study visit must 
be documented. The Investigator will assess the ADE severity and relationship of the ADE to the 
study device. The Investigator will follow the progress of the study subject until the ADE either 
resolves or becomes medically stable. Treatments and medications required to treat ADEs must be 
recorded.  
All adverse device events, regardless of severity and whether or not attributed to the device are to 
be reported to Mati Therapeutics Inc. Adverse device events are also to be reported to the site IRB 
per the IRB’s reporting requirements.  

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8.5.1 Adverse Device Event Reporting 
An adverse device event that is not serious or related to the study 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 device event is also to 
be reported to the reviewing IRB/IEC per his/her reporting requirements. 
8.5.2 Serious Adverse Device Event Reporting 
All SADEs, regardless of cause(s) or relationship to the study 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 ADE/SADE reporting information will be provided to 
each site in a separate document.  
All SADEs will be reported to: 
Robert Williams, MD or    Deepank (Deeps) Utkhede 
Mati Therapeutics Inc.   Mati Therapeutics Canada Inc. (R&D Branch) 
iopdoc1@gmail.com   
    dutkhede@matitherapeutics.com 
Phone: 360.378-7916  
    Phone: 778 991-3301 
Phone: 360.298-5325 (cell)   
Fax:   360.282-6871  
 
 
The Investigator must complete the SADE Report Form and send it with other relevant pages of 
the  CRF  
to  
the  designated  Medical  Monitor  within  24  hours  of  discovery  of  
the  SADE.  
  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 SADE will be reported to the Investigator’s IRB/IEC per his/her 
reporting requirements. 
8.5.3 Unanticipated Problem Reporting 
If  during  
the  study  an  adverse  device  event  occurs  
that  may  
reasonably  be  
regarded  as  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  device  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.  
8.6  Reporting of Technical Complaints about Investigational Device 
8.6.1 Definitions 
A quality complaint received in writing, electronically, or orally that alleges deficiencies related 
to  
the  
identity,  quality,  durability,  
reliability,  safety,  effectiveness,  or  performance  of  a  device 
product. (In this definition, "effectiveness" refers to the actual function of the device, not to how 

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the subject responds to the action of the device. Also in this definition, "device product" refers 
only to devices provided by the Sponsor for clinical studies and to investigational devices.)  
In this definition, safety includes the safety of a subject, user, or other person associated with the 
use of a medical device.  
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 device 
• Model of the study device 
• Identification numbers (i.e. serial or part number) for a device  
• 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  ADEs  were 
associated  with  the  complaint  (yes/no;  if  a  subject  ADE  was  associated  with  the 
complaint, refer to Section 8 and attach the ADE 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 SADE 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 device and associated packaging that initiated the complaint should be returned to the 
Chief Scientific Officer (address below) for analysis. 
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 

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Any complaint about a study device 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 SADE and Technical Complaints  
The  Sponsor  will  evaluate  all  SADE  
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  SADE  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 8.5.3 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 his/her IRBs, 
within 10 working days after the Sponsor first received notice of the effect. 
8.6.4 Anticipated Adverse Device Events 
Due to the duration of the study, the only anticipated ADE would be extrusion of the punctal plug. 
Any event that is unlikely but anticipated must have an adverse device event form completed and 
reported to Mati Therapeutics Inc. (see Section 8.5 for reporting details). 
8.7  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 associated with the study device. 
8.8  Safety Oversight 
This study will utilize a Medical Monitor for safety monitoring. The Medical Monitor will review 
and assess any reports of adverse device 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:  

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a. GCPs as specified in ICH E6 (R1) and E8 (8.2) and 21 CFR. Parts 50, 54, 56 and 812 
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 his/her 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 his/her 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 may  conduct  periodic  site  visits  and maintain 
telephone contact with the Investigators and his/her staff to ensure that the study is being conducted 
in  accordance  with  the  protocol,  and  with  any  specific  conditions  of  the  IRB  and  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 ADEs, and ensure that the Investigators are 
complying with FDA and Sponsor requirements for reporting ADEs and SADEs. 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 devices. 
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: 

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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 
who had a lower puncta inserted with a study punctal plug 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 or non-compliance with protocol requirements 
that can potentially have significant impact on study outcomes).  
10.2 Statistical Hypotheses 
10.2.1 Primary Hypotheses 
The Null Hypothesis:  There  are  no  differences  between  baseline  and  follow-up  tear  lake 
evaluations 
Alternative  Hypothesis:  There  are  differences  between  baseline  and  follow-up  tear  lake 
evaluations  
10.2.2 Secondary Hypotheses  
The Null Hypothesis: There  are  no  differences  in  the  frequency  or  severity  of  study  subjects 
exhibiting of epiphora 
Alternative  Hypothesis:  There  are  differences  in  the  frequency  or  severity  of  study  subjects 
exhibiting of epiphora 
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 clearly labeled with the study subject ID number and initials. Each column of the 
dataset will contain a specific parameter for all study subjects.  

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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 Endpoint(s) 
The  primary  study  variable  will  be  based  on  
the  change from  baseline  
in  
tear  
lake  values. For 
analyses, using the intent-to-treat (ITT) data set, all data from all subjects with at least one follow-
up evaluation of the tear lake will be evaluated. 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) 
Secondary endpoints will be based on changes from baseline in the severity of epiphora. For the 
investigator’s evaluation of the subject’s acceptance of the punctal plug, data from all subjects will 
be evaluated. Investigator evaluation of insertion and removal characteristics will be tabulated by 
study subject and overall evaluation. For analyses using the intent-to-treat (ITT) data set, all data 
from all subjects with at least one assessment of epiphora, subject acceptability and punctal plug 
characteristics evaluations will be included. For the per protocol (PP) analyses dataset, data from 
subjects or visits with significant protocol deviations will be excluded. 
10.4.4 Safety Analyses 
All study subjects who were inserted with a punctal plug will be evaluable for safety analysis. The 
safety  endpoints  in  this  study  are  clinically  significant  slit  lamp  biomicroscopy  findings  (lid, 
conjunctiva, and cornea), incident rate of plug extrusions, and the frequency and severity of any 
reported adverse device events. Safety variables will be summarized using descriptive statistics. 
The type, severity, duration and frequency of reported adverse device events will be tabulated by 
visit. Additionally,  any  adverse  device  event  experienced  by  a  subject  after  signing  informed 
consent and before exposure will be presented separately in the safety analysis. 
Adverse  device  events  will  be  coded  using  the  Medical  Dictionary  for  Regulatory  Activities 
(MedDRA). Treatment emergent ADEs (those occurring after insertion of a study punctal plug) 
will be summarized descriptively: The number and percentage of study subjects who experienced 
an ADE and the total number of ADEs will be summarized by system organ class and preferred 
term. Associated ADEs, defined as ADEs suspected to be treatment related by the investigator, 
SADEs and serious associated ADEs 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. 

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10.4.5 Baseline Descriptive Statistics 
Demographic  and  baseline  characteristics  will  be  summarized. Counts  and  percentages  will  be 
presented for categorical variables such as sex, age group (by decade), race and ethnicity. Mean, 
standard deviation, median, minimum and maximum will be presented for continuous variables 
such as age and non-dilated punctum size. 
10.4.6 Planned Interim Analyses 
Data will be analyzed on an ongoing basis. The final analyses will be completed after the last study 
subject has completed his/her final visit and the study database has been closed. 
10.5 Sample Size 
Since this is a pilot study, no formal sample size estimation was performed.  
10.5.1 Enrollment Procedures 
Qualified subjects that meet all inclusion and exclusion criteria and complete the screening process 
will be sequentially assigned a study number. 
11 SOURCE DOCUMENTS AND ACCESS  
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 visits  
g. Date a punctal plug was first inserted, removed and if applicable, dates of any plug that was 
extruded/loss 
h. Subject reports of signs and symptoms at each visit 

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i. All ADEs and SADE 
j. The  subject
's  exposure  
to  any  concomitant  
therapy  
(including  start  and  stop  dates,  
route  of 
administration, and dosage) 
k. 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 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 device 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 
 

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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 clarifications 
and/or additions are documented and are part of each subject’s CRFs. 
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 of 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 ADEs/SADEs 
f. Brief discussion of clinical findings during the study. 
12 QUALITY ASSURANCE AND QUALITY CONTROL 
Investigator must grant 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 regulations specified 
under  21  CFR  11,  50,  54,  56,  and  812,  
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. 

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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 his/her occupations/affiliations. Institutional Review Board approval is also 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 SADEs that have resulted in an expedited 
safety report to the FDA. No device 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 his/her enrollment in 
the study. See Section 7.1 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 his/her 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. 

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The confidentiality of records that could identify subjects will be protected, respecting the privacy 
and confidentiality rules in accordance with applicable regulatory requirement(s). 
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 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 device event information (adverse device 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. Investigator Brochure 
k. Completed study subject informed consent and HIPAA forms 
l. Study subject medical chart/clinic notes. 

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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 of the IRB is 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  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. 
 
15 REFERENCES 
Balaram M, Schaumberg DA, Dana MR. 2001. Efficacy and tolerability outcomes after punctal 
occlusion with silicone plugs in dry eye syndrome. Am J Ophthalmol. 131(1):30-36. 
Fayet B, Bernard JA, Ammar J, et al. 1990. Treatment of chronic dry eye with temporary punctal 
plugs. J Fr Ophthalmol. 13(3):123-133.  
Freeman JM. 1975. The punctum plug: evaluation of a new treatment for the dry eye. Trans Am 
Acad Ophthalmol Otolaryngol. 79:OP874-878.  
Kim BM, Osmanovic SS, Edward DP. 2005. Pyogenic granulomas after silicone punctal plugs: a 
clinical and histopathologic study. Am J Ophthalmol. 139:678-684. 

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Tuberville AW, Frederick WR, Wood TO. 1982. Punctal occlusion in tear deficiency syndrome. 
Ophthalmology. 89:1170-1172.  
Willis RM, Folberg R, Krachmer JH, et al. 1987. The treatment of aqueous-deficient dry eye with 
removable punctal plugs. A clinical and impression-cytologic study. Ophthalmology. 94:514-518.