A Single-Center, Double-Masked Evaluation of the Efficacy and Safety of PRX-100 in the Treatment of Early to Moderate Presbyopia
Phase: PHASE2
Conditions: Presbyopia
Sponsor: LENZ Therapeutics, Inc



03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
0(',&$/ 021,725
0HGLFDO 0RQLWRU
25$ 3(56211(/
'HSDUWPHQW 9LFH 3UHVLGHQW
3URMHFW 0DQDJHU
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
dermatologic, hematologic, neurologic, or 
psychiatric disease.
6WXG\ 7UHDWPHQWV
x
PRX-100 (aceclidine 
 and tropicamide 
) Ophthalmic Solution 
x
 Aceclidine Ophthalmic Solution
x
Vehicle Ophthalmic Solution (for PRX-100)
(YDOXDWLRQ &ULWHULD
(IILFDF\ 0HDVXUHV
3ULPDU\ (IILFDF\ 9DULDEOH
x
Percentage of subjects who achieve a 3-line (15-
letters) or greater improvement from pre-treatment in 
the measurement of monocular best-corrected 
distance VA at 45 cm at 1h post-treatment in the 
study eye.
6HFRQGDU\ (IILFDF\ 9DULDEOH
x
The percentage of subjects who achieve a 1-line (5-
letter) to 3-line (15-letters) or greater improvement 
from pre-treatment by 1-letter increments in the 
measurement of monocular best-corrected distance 
VA at 45 cm in the study eye at each time point
o
0.5, 1, 3, 4, 5 and 7h post-treatment
x
Percentage of subjects with at least a 3-line (15-
letter) improvement in the study eye in the 
measurement of post-treatment monocular best-
corrected distance VA at 
compared to pre-
treatment monocular best-corrected distance VA  
 
x
Mean monocular best-corrected distance logMAR 
VA at near distances in the study eye
o
Post-treatment assessments compared to 
pre-treatment assessment
o
Two near testing distances will be 
assessed: 45 cm (all post-treatment time 
points [0.5, 1, 3, 4, 5 and 7h]) and 
x
Percentage of subjects with at least a 3-line (15-
letter) improvement in the measurement of post-
treatment binocular best-corrected distance VA at 45 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
cm compared to pre-treatment binocular best-
corrected distance VA at 45 cm
o
0.5, 1, 3, 4, 5 and 7h post-treatment
x
Percentage of subjects with at least a 3-line (15-
letter) improvement in the measurement of post-
treatment binocular best-corrected distance VA 
 
compared to pre-treatment binocular best-
corrected distance VA 
 
x
Mean binocular best-corrected distance logMAR VA
at near distance
o
Post-treatment assessments compared to 
pre-treatment assessment
o
Two near testing distances will be 
assessed: 45 cm (all post-treatment time 
points [0.5, 1, 3, 4, 5 and 7h]) and 
 
([SORUDWRU\ (IILFDF\ 9DULDEOHV
x
 
 
 
 
 
 
 
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
o
 
 
 
 
 
 
6DIHW\ 0HDVXUHV
x
Best-corrected VA
x
Low-luminance best-corrected VA
x
Slit lamp biomicroscopy
x
Conjunctival redness
x
IOP
x
Adverse events (AEs) (reported, elicited, and 
observed)
2WKHU 0HDVXUHV
x
Pupillometry
*HQHUDO 6WDWLVWLFDO 0HWKRGV DQG 7\SHV RI $QDO\VHV
*HQHUDO &RQVLGHUDWLRQV
In general, quantitative/continuous data will be summarized using descriptive statistics (n, 
mean, SD, median, min, and max). Qualitative/categorical data will be summarized using 
frequencies and percentages. Statistical testing, unless otherwise indicated, will be performed 
at a 2-sided 0.10 significance level.  
The study eye, defined in section 8.3.1, will be used for all monocular analyses. The fellow 
eye will inherently be included in all binocular analyses.  Both eyes will be displayed and 
analyzed for all ophthalmic safety variables.
The primary and monocular secondary efficacy analyses will be conducted in the modified
intent-to-treat (mITT) population using statistical models which implicitly impute missing 
data.  The mITT population is defined in section 10.2.1.
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
x
Random effect measure: subject within sequence, to account for the correlation 
between treatments and periods within a subject. 
x
Repeated measures correlation will be estimated with an unstructured variance-
covariance matrix in the GEE model. 
Standard errors and CIs (80 and 90%) will also be presented for each treatment group and the 
difference between treatment groups. Separate models will be built for each distance (with 45 
cm being primary and 
 being secondary) and time points. Pairwise comparisons among 
treatment groups will also be made at each distance and time point using McNemar’s tests. 
6HFRQGDU\ (IILFDF\ $QDO\VLV
For the secondary efficacy variable of monocular assessment of best-corrected distance VA, 
the percentage of subjects who achieve a 1-line (5-letter) to 3-line (15-letters) or greater 
improvement from pre-treatment by 1-letter increments in the measurement of monocular 
best-corrected distance VA will be evaluated at 45 cm for each time point (0.5, 1, 3, 4, 5 and 
7h post-treatment) using the mITT population.  Analyses will be repeated using the ITT 
population.
In addition,
will be compared to pre-treatment 
assessments in the study eye.
Descriptive statistics will be presented for each time point and distance as well as for the 
change from pre-dose at each time point and distance by treatment group. The same logistic 
regression models developed for the primary analyses will be used to test these secondary 
endpoints.  
For continuous secondary endpoints, similar mixed effect models will be employed.  Two-
sided one-sample t-tests from a mixed effects linear model with binocular best-corrected 
distance VA at near distance change from pre-dose as the response variable; sequence, period, 
and treatment as fixed effects; and subject within sequence as a random effect term with a 
variance component covariance matrix to account for the correlation among measures within 
a subject using α = 0.1. Two-sided 80% and 90% CI will be provided as additional descriptors 
of the data. Separate models will be constructed for each distance and time point separately. 
Pairwise comparisons between treatment groups will also be made at each distance and time 
point using one-sample t-tests.
([SORUDWRU\ (IILFDF\ $QDO\VLV
Exploratory efficacy endpoints will be analyzed for all available data similarly to the primary 
and secondary endpoints in the mITT population and in the ITT population for sensitivity. All 
exploratory variables will include percentage based and mean based analyses, similar to the 
primary and secondary endpoints. Pairwise treatment comparisons will be calculated where 
possible, along with changes from pre-treatment; otherwise, analyses will be limited to within 
treatment statistics. 
2WKHU $QDO\VLV
Pupil diameter will be analyzed using similar statistical methods to that of the secondary 
efficacy variable best-corrected distance VA at near distance for each time point separately.  

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
TABLE OF CONTENTS 
6<1236,6 
/LVW RI $EEUHYLDWLRQV  
 
,1752'8&7,21 
 
678'< 2%-(&7,9(6 
 
&/,1,&$/ +<327+(6(6  
 
29(5$// 678'< '(6,*1 
 
678'< 3238/$7,21  
 
1XPEHU RI 6XEMHFWV DSSUR[LPDWH 
 
6WXG\ 3RSXODWLRQ &KDUDFWHULVWLFV  
 
,QFOXVLRQ &ULWHULD  
 
([FOXVLRQ &ULWHULD 
 
:LWKGUDZDO &ULWHULD LI DSSOLFDEOH 
 
678'< 3$5$0(7(56 
 
(IILFDF\ 0HDVXUHV 
6.1.1 
Primary Efficacy Variable ................................................................24 
6.1.2 
Secondary Efficacy Variable ............................................................24 
6.1.3 
Exploratory Efficacy Variables: .......................................................25 
6.1.4 
Criteria for Effectiveness ..................................................................26 
 
6DIHW\ 0HDVXUHV 
 
2WKHU 0HDVXUHV  
 
678'< 0$7(5,$/6 
 
6WXG\ 7UHDWPHQWV 
7.1.1 
Study Treatment(s)/ Formulation(s) .................................................26 
7.1.2 
Instructions for Use and Administration ...........................................27 
 
2WKHU 6WXG\ 6XSSOLHV  
 
678'< 0(7+2'6 $1' 352&('85(6  
 
6XEMHFW (QWU\ 3URFHGXUHV 
8.1.1 
Overview ...........................................................................................28 
8.1.2 
Informed Consent..............................................................................28 
8.1.3 
Washout Intervals .............................................................................28 
8.1.4 
Procedures for Final Study Entry ......................................................29 
8.1.5 
Pregnancy ..........................................................................................29 
8.1.6 
Methods for Assignment to Treatment Groups: ...............................29 
 
&RQFXUUHQW 7KHUDSLHV 
8.2.1 
Prohibited Medications/Treatments ..................................................30 
8.2.2 
Escape Medications ..........................................................................30 
8.2.3 
Special Diet or Activities ..................................................................30 
 
([DPLQDWLRQ 3URFHGXUHV 
8.3.1 
Procedures to be performed at the Study Visit with Regard to Study 
Objective(s) ....................................................................................................30 
 
6FKHGXOH RI 9LVLWV 0HDVXUHPHQWV DQG 'RVLQJ  

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
8.4.1 
Scheduled Visit .................................................................................34 
8.4.2 
Unscheduled Visits ...........................................................................34 
 
&RPSOLDQFH ZLWK 3URWRFRO 
 
6XEMHFW 'LVSRVLWLRQ 
8.6.1 
Completed Subjects ..........................................................................34 
8.6.2 
Withdrawn Subjects ..........................................................................34 
8.6.3 
Discontinued Subjects .......................................................................35 
 
6WXG\ 7HUPLQDWLRQ  
7KH VWXG\ PD\ EH WHUPLQDWHG DW DQ\ WLPH E\ WKH ,QYHVWLJDWRU WKH VSRQVRU
DQGRU 2UD ZLWK DSSURSULDWH QRWLILFDWLRQ 
 
6WXG\ 'XUDWLRQ  
 
0RQLWRULQJ DQG 4XDOLW\ $VVXUDQFH  
 
$'9(56( (9(176  
 
$GYHUVH (YHQW 
9.1.1 
Severity .............................................................................................36 
9.1.2 
Relationship to Investigational Product ............................................36 
9.1.3 
Expectedness .....................................................................................37 
 
6HULRXV $GYHUVH (YHQWV 
 
3URFHGXUHV IRU 5HSRUWLQJ $GYHUVH (YHQWV 
9.3.1 
Reporting a Suspected Unexpected Adverse Reaction .....................39 
9.3.2 
Reporting a Serious Adverse Event ..................................................39 
 
3URFHGXUHV IRU 8QPDVNLQJ LI DSSOLFDEOH  
 
7\SH DQG 'XUDWLRQ RI WKH )ROORZXS RI 6XEMHFWV DIWHU $GYHUVH (YHQWV 
 
67$7,67,&$/ +<327+(6(6 $1' 0(7+2'6 2) $1$/<6(6 
 *HQHUDO &RQVLGHUDWLRQV  
 6WXG\ 3RSXODWLRQV 
10.2.1 Modified Intent-to-Treat Population .................................................41 
10.2.2 Intent-to-Treat Population .................................................................42 
10.2.3 Modified Per Protocol Population ....................................................42
10.2.4 Per Protocol Population ....................................................................42 
10.2.5 Safety Population ..............................................................................42 
 *HQHUDO ,PSXWDWLRQ 0HWKRGV 
 3ULPDU\ (IILFDF\ 9DULDEOH 
 6HFRQGDU\ (IILFDF\ 9DULDEOHV 
 ([SORUDWRU\ (IILFDF\ 9DULDEOHV  
 2WKHU 0HDVXUHV  
 6DPSOH 6L]H  
 'HPRJUDSKLF DQG %DVHOLQH &KDUDFWHULVWLFV  
 3ULPDU\ (IILFDF\ $QDO\VHV  
 6HFRQGDU\ (IILFDF\ $QDO\VLV 
 ([SORUDWRU\ (IILFDF\ $QDO\VLV 
 2WKHU 0HDVXUHV  
 $GMXVWPHQW IRU 0XOWLSOLFLW\  
 6DIHW\ $QDO\VLV 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
 
&203/,$1&( :,7+ *22' &/,1,&$/ 35$&7,&(6 (7+,&$/
&216,'(5$7,216 $1' $'0,1,675$7,9( ,668(6 
 3URWHFWLRQ RI +XPDQ 6XEMHFWV 
11.1.1 Subject Informed Consent.................................................................47 
11.1.2 IRB Approval ....................................................................................48 
 (WKLFDO &RQGXFW RI WKH 6WXG\  
 6XEMHFW &RQILGHQWLDOLW\  
 'RFXPHQWDWLRQ 
11.4.1 Retention of Documentation .............................................................49 
 /DEHOLQJ 3DFNDJLQJ 6WRUDJH $FFRXQWDELOLW\ DQG 5HWXUQ RU 'LVSRVDO RI
,QYHVWLJDWLRQDO 3URGXFW 
11.5.1 Labeling/Packaging...........................................................................49 
11.5.2 Storage of Investigational Product ....................................................50 
11.5.3 Accountability of Investigational Product ........................................50 
11.5.4 Return or Disposal of Investigational Product ..................................50 
 5HFRUGLQJ RI 'DWD RQ 6RXUFH 'RFXPHQWV DQG (OHFWURQLF &DVH 5HSRUWV
)RUPV H&5)V 
 +DQGOLQJ RI %LRORJLFDO 6SHFLPHQV 
 3XEOLFDWLRQV 
 
5()(5(1&(6 
$SSHQGL[  6FKHGXOH RI 9LVLWV DQG 0HDVXUHPHQWV 
$SSHQGL[  ([DPLQDWLRQ 3URFHGXUHV 7HVWV (TXLSPHQW DQG 7HFKQLTXHV  
$SSHQGL[  +DQGOLQJ RI %LRORJLFDO 6SHFLPHQV  
$SSHQGL[  3URWRFRO $PHQGPHQW 6XPPDU\  
 *HQHUDO &RQVLGHUDWLRQV 
o 
 6WXG\ 3RSXODWLRQV 
 0RGLILHG ,QWHQWWR7UHDW 3RSXODWLRQ...............................................81 
Intent-to-Treat Population ..............................................................................82 
Modified Per Protocol Population ..................................................................83 
o 
 *HQHUDO ,PSXWDWLRQ 0HWKRGV 
o 
 3ULPDU\ (IILFDF\ 9DULDEOH 
o 
 6HFRQGDU\ (IILFDF\ 9DULDEOHV 
o 
 6DPSOH 6L]H  
o 
 3ULPDU\ (IILFDF\ $QDO\VHV  

 
[…] 6.1.2 Secondary Efficacy Variable .........................................................98 
 ([SORUDWRU\ (IILFDF\ 9DULDEOHV .....................................................100 
6.1.4 Criteria for Effectiveness .....................................................................101 
 *HQHUDO &RQVLGHUDWLRQV 
>«@  6HFRQGDU\ (IILFDF\ 9DULDEOHV  
 2WKHU 0HDVXUHV 
>«@  6HFRQGDU\ (IILFDF\ $QDO\VLV  
 2WKHU 0HDVXUHV 
 *HQHUDO &RQVLGHUDWLRQV 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
>«@  6HFRQGDU\ (IILFDF\ 9DULDEOHV  
 ([SORUDWRU\ (IILFDF\ 9DULDEOHV 
 2WKHU 0HDVXUHV 
>«@  6HFRQGDU\ (IILFDF\ $QDO\VLV  
 ([SORUDWRU\ (IILFDF\ $QDO\VLV 
 2WKHU 0HDVXUHV 
$SSHQGL[  6SRQVRU DQG 2UD $SSURYDOV  
$SSHQGL[  ,QYHVWLJDWRU¶V 6LJQDWXUH  
/LVW RI $EEUHYLDWLRQV
ADHD
Attention-Deficit/Hyperactivity Disorder
AE
adverse event
cd/m2
candela per square meter
CFR
Code of Federal Regulations
CI
confidence interval
CST
Clinical Trial Suite
eCRF
electronic case report form
D
diopter
EKG
electrocardiogram
ETDRS
Early Treatment of Diabetic Retinopathy Study
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GEE
Generalized Estimating Equation
ICF
informed consent form
IEC
independent ethics committee
IND
investigational new drug application
IOL
intraocular lens
IOP
intraocular pressure
IP
investigational product
IRB
institutional/independent review board
ITT
intent to treat
LASEK
laser-assisted sub-epithelial keratectomy
LASIK
laser in situ keratomileusis
LOCF
last observation carried forward
logMAR
logarithm of the minimum angle of resolution
MAX
maximum
MedDRA
Medical Dictionary for Regulatory Activities
MIN
minimum
mmHg
millimeters of mercury
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
NCS
not clinically significant
OD
right eye
OS
left eye
OU
both eyes
OTC
over the counter
PP
per protocol
PRK
photorefractive keratectomy
QD
once daily
RGP
rigid gas permeable
SAE
serious adverse event
SAP
statistical analysis plan
SD
standard deviation
SOP
standard operating procedure
VA
visual acuity

,1752'8&7,21
Presbyopia is defined by a loss in the ability of the eye to adjust its focal length so that objects at 
different distances produce focused images on the retina. As the eye ages, the lens of the eye 
becomes less able to change shape. Hardening of the lens, along with weakening of the ciliary 
muscles, plays a major role in the pathogenesis of presbyopia and leads to symptoms such as 
blurred vision, eye strain and headache after reading or computer use (Truscott 2009; Helmholtz
1855; Ostrin and Glasser 2007; Scarcelli 2011).  
Presbyopia affects most people over 45 years of age and continues to worsen until approximately 
65 years of age. Based on data from 228 countries, it was estimated that in 2005, presbyopia 
affected more than 1 billion people worldwide. Presbyopia is projected to increase to 1.78 billion 
people by 2050.  More than half of the people with this condition do not have adequate treatment 
options, which results in some level of disability when performing tasks that require near visual 
acuity (Holden 2008).  
Current treatments available for presbyopia include the use of reading glasses, contact lenses, or 
refractive (including laser) or intraocular lens (IOL) surgery. Pharmaceutical therapies have been 
explored but, thus far, continue to be limited in treating presbyopia without being associated with 
undesirable adverse effects (Gilmartin 1995).  
PRX-100 is an ophthalmic solution that contains a low dose of aceclidine 
 and 
tropicamide 
. Both aceclidine and tropicamide have been used extensively in humans for 
ophthalmic indications. Aceclidine is a parasympathomimetic miotic agent that is approved for 
lowering IOP in Europe. In 1969, a 2% solution of aceclidine was approved in several European 
countries for the treatment of glaucoma. Furthermore, aceclidine has been used at concentrations 
of up to 4% in humans. Tropicamide is an anticholinergic drug that was approved for human use 
in the US in 1960. Tropicamide induces mydriasis (pupil dilation) and cycloplegia (paralysis of 
the ciliary muscle) and is used to facilitate ophthalmic patient examinations. Tropicamide is 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
b. bladder medication (eg Urecholine®, bethanechol) 
c.
antipsychotics 
d. antidepressants 
e.
attention –deficit/hyperactivity disorder (ADHD) medications 
f.
alpha-blockers (eg, tamsulosin, Flomax®, Jayln®, Uroxatral®, Rapaflo®) 
g. anticholinergics (eg, atropine, belladonna, benztropine, dicyclomine, donepezil, 
hyoscyamine, propantheline, scopolamine, trihexphenidyl) 
h. muscarinic receptor agonists or cholinergic agonists (eg, Salagen®, Evoxac®)
i.
over-the-counter (OTC) or prescription antihistamines or decongestants 
j.
any prescribed topical ophthalmic medications 
k. recreational drug use (eg, marijuana, methadone, heroin, cocaine); 
20. Have a diagnosis of diabetes mellitus or a history of elevated blood sugar; 
21. Have a condition or a situation, which in the Investigator’s opinion, may put the 
subject at increased risk, confound study data, or interfere significantly with the 
subject’s study participation, including but not limited to unstable: cardiovascular, 
hepatic, renal, respiratory, gastrointestinal, endocrine, immunologic, dermatologic, 
hematologic, neurologic, or psychiatric disease.  
5.5
:LWKGUDZDO &ULWHULD LI DSSOLFDEOH
Subjects will be withdrawn from the study if any of the following criteria are met: 
1. 
Be a female of childbearing potential who is currently pregnant, nursing or 
planning a pregnancy; tests positive to a urine pregnancy test at visit 2, 3 
or 4; or refuses to use an adequate method of contraception for the 
duration of the study; 
2. 
Have an active ocular infection at visit 2, 3 or 4 (bacterial, viral or fungal), 
positive history of an ocular herpetic infection, preauricular
lymphadenopathy, or ongoing, active ocular inflammation (eg, moderate 
to severe blepharitis, allergic conjunctivitis, peripheral ulcerative keratitis, 
scleritis, uveitis) in either eye.  
Subjects may also be withdrawn from the study for the following reasons: 
x
AE
x
Lost to follow-up 
x
Withdrawal of consent by subject 
x
Investigator discretion 
x
Death 
x
Subject not following required study procedures 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
x
Study terminated by the Sponsor 
x
Other 
Subject withdrawals will be documented clearly on the subject’s source 
document.   

678'< 3$5$0(7(56
6.1
(IILFDF\ 0HDVXUHV
6.1.1
Primary Efficacy Variable 
x
Percentage of subjects who achieve a 3-line (15-letters) or greater 
improvement from pre-treatment in the measurement of monocular best-
corrected distance VA at 45 cm at 1h post-treatment in the study eye. 
6.1.2
Secondary Efficacy Variable 
x
The percentage of subjects who achieve a 1-line (5-letter) to 3-line (15-
letters) or greater improvement from pre-treatment by 1-letter 
increments in the measurement of monocular best-corrected distance VA 
will be evaluated at 45 cm for each time point 
o
0.5, 1, 3, 4, 5 and 7h post-treatment 
x
Percentage of subjects with at least a 3-line (15-letter) improvement in 
the study eye in the measurement of post-treatment monocular best-
corrected distance VA at 
 compared to pre-treatment monocular 
best-corrected distance VA at 
 
 
x
Mean monocular best-corrected distance logMAR VA at near distances 
in the study eye 
o
Post-treatment assessments compared to pre-treatment 
assessment 
o
Two near testing distances will be assessed: 45 cm (all post-
treatment time points [0.5, 1, 3, 4, 5 and 7h]) and 
 
  
x
Percentage of subjects with at least a 3-line (15-letter) improvement in 
the measurement of post-treatment binocular best-corrected distance VA 
at 
 compared to pre-treatment binocular best-corrected distance 
VA at 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
o
 
x
Percentage of subjects with at least a 3-line (15-letter) improvement in 
the measurement of post-treatment binocular best-corrected distance VA 
at 
 compared to pre-treatment binocular best-corrected distance 
VA at 
 
  
x
Mean binocular best-corrected distance logMAR VA at near distance 
o
Post-treatment assessments compared to pre-treatment 
assessment 
o
Two near testing distances will be assessed: 45 cm (all post-
treatment time points [0.5, 1, 3, 4, 5 and 7h]) and 
 
 
6.1.3
Exploratory Efficacy Variables: 
x
 
 
   
 
 
  
  
 
 
  
 
 
 
 
 
 
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
o
 
 
 
  
 
 
 
  
 
6.1.4
Criteria for Effectiveness 
Changes in best-corrected distance VA at near distance will be calculated as 
the difference, in logMAR units, between the post-treatment monocular (study 
eye) and binocular best-corrected distance VA measurements at near (45 cm
and 
 minus the pre-treatment monocular (study eye) and binocular best-
corrected distance VA measurements at near (45 cm and 
  A 3-line 
improvement in VA is considered clinically meaningful. 
6.2
6DIHW\ 0HDVXUHV
x
Urine pregnancy test  
x
Best-corrected distance VA 
x
Low-luminance best-corrected distance VA 
x
Slit-lamp biomicroscopy 
x
Conjunctival redness 
x
IOP 
x
AEs (reported, elicited, and observed)  
6.3
2WKHU 0HDVXUHV
x
Pupillometry 

678'< 0$7(5,$/6
7.1
6WXG\ 7UHDWPHQWV
7.1.1
Study Treatment(s)/ Formulation(s) 
The study treatments are as follows: 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
•
Muscarinic receptor agonists or cholinergic agonists (eg, Salagen®,
Evoxac®): 2 weeks
•
Over-the-counter and prescription antihistamines or decongestants: 2 
weeks
•
Artificial tears: on the day of or during visit 1, 2, 3 or 4  
•
Any prescribed topical ophthalmic medications: 2 weeks 
8.1.4
Procedures for Final Study Entry 
Subjects must satisfy all inclusion and none of the exclusion criteria in order 
to be entered into the study. 
8.1.5
Pregnancy 
Females must have a negative urine pregnancy test at visit 1, if female of 
childbearing potential (those who have experienced menarche and who are not 
surgically sterilized [bilateral tubal ligation, hysterectomy or bilateral 
oophorectomy] or post-menopausal [12 months after last menses]) and must 
use adequate birth control throughout the study period. Adequate birth control 
is defined as hormonal – oral, implantable, injectable, or transdermal 
contraceptives; mechanical – spermicide in conjunction with a barrier such as 
condom or diaphragm; intrauterine device (IUD); or surgical sterilization of 
partner. For non-sexually active females, abstinence may be regarded as an 
adequate method of birth control. 
In the event a female has a positive urine pregnancy test at visit 2, 3 or 4, the 
subject will be withdrawn from the study and the Investigator will notify Ora 
and the sponsor within 24 hours of knowledge of the event. 
8.1.6
Methods for Assignment to Treatment Groups: 
Each subject who signs an informed consent form will be assigned a screening 
number.  Screening numbers will be assigned in sequential order beginning 
with 001.  Once a subject meets all qualification criteria, he/she will be 
randomized in a 1:1:1 ratio to one of three Latin square design sequences 
[(1,2,3), (2,3,1), and (3,1,2)] detailing the order in which treatments (1: PRX-
100, 2: aceclidine, 3: vehicle) will be administered over the three study visits 
and will be assigned a 4-digit subject number.  Subject numbers will be 
assigned in a sequential order starting at the lowest number available.  No 
numbers will be skipped or omitted. Randomization will be used to avoid bias 
in the assignment of subjects to treatment, to increase the likelihood that 
known and unknown subject attributes (e.g., demographics and baseline 
characteristics) are evenly balanced across treatment groups, and to enhance 
the validity of statistical comparisons across treatment groups.  Masked 
treatment will be used to reduce potential of bias during data collection and 
evaluation of clinical endpoints.  

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
x
Informed consent and HIPAA 
x
Demographics 
x
Medical/medication history 
x
Urine pregnancy test (for females of child-bearing potential) 
x
Inclusion/exclusion criteria review 
x
Screening assessments:  
o
Screening monocular best-corrected distance visual acuity (VA) at 45 cm* 
o
Screening monocular best-corrected distance VA* 
x
Slit-lamp biomicroscopy 
x
Fluorescein staining 
o
Subjects should wait at least 30 minutes with his/her eyes closed following 
fluorescein staining 
 
 
 
  
 
 
  
 
 
 
9LVLWV    'D\V   
x
Medical and medication history update  
x
Urine pregnancy test (for females of child-bearing potential) 
x
Subjects will be asked to read printed instructions about what will be completed at 
each visit prior to beginning baseline/pre-treatment assessments. 
x
Baseline/pre-treatment assessments:  
o
Pupillometry 
  
o
Monocular best-corrected distance VA at 
 
o
Binocular best-corrected distance VA at 
 
o
Monocular best-corrected distance visual acuity at 
* 
o
Binocular best-corrected distance VA at 
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
o
Monocular best-corrected distance VA* 
o
Binocular best-corrected distance VA* 
o
Monocular low-luminance best-corrected distance VA* 
o
Binocular low-luminance best-corrected distance VA* 
o
 
  
  
  
  
 
  
o
Slit-lamp biomicroscopy
o
Conjunctival redness assessment 
x
Randomization will occur at visit 2 for all qualified subjects. All randomized 
subjects will receive each treatment once at each visit 2, 3 and 4 (crossover study 
design). Subjects randomization will dictate which treatment will be administered 
at each study visit. 
7UHDWPHQW $GPLQLVWUDWLRQ
x
Instillation of PRX-100, aceclidine, or vehicle OU 
o
 
 
 
 
3RVWWUHDWPHQW DVVHVVPHQWV
o
AE query post-treatment and 1 hour post-treatment 
o
The following assessments will be made 0.5, 1, 3, 4, 5 and 7 hours post-
treatment:  

Conjunctival redness assessment 

Pupillometry 
  

Monocular best-corrected distance VA at 
 

Binocular best-corrected distance VA at 
 

Monocular best-corrected distance VA*

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 

Binocular best-corrected distance VA* 

Monocular low-luminance best-corrected distance VA* 

Binocular low-luminance best-corrected distance VA* 
o
The following assessments will be made 1, 4 and 5 hours post-treatment:  

Monocular best-corrected distance VA at 
 

Binocular best-corrected distance VA at 
 

All best-corrected distance VA at 
 assessments to be assessed 
immediately following best-corrected distance VA at 45 cm 
assessments 
o
The following assessments will be made 1 and 5 hours post-treatment 
following binocular low-luminance best-corrected distance VA:

 
  
  
  
  
 
 
o
Following the 7-hours post-treatment assessments: 

Slit lamp biomicroscopy 

IOP 

AE query 
$VVHVVPHQW IRU 6WXG\ ([LW
x Subjects will be assessed for study exit. Study exit can occur at either visit 1, 2, 3, 
or 4. If a subject completes the study, Study exit will occur at Visit 4. 
* VA to be assessed with best distance correction 
 
  
** Best effort will be made to adhere to 
 assessment time points. No 
minimum/maximum windows are defined for any post-treatment assessment time point. 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
8.4
6FKHGXOH RI 9LVLWV 0HDVXUHPHQWV DQG 'RVLQJ
8.4.1
Scheduled Visit 
Refer to Appendix 1 for a schedule of measurements at the Visit. 
8.4.2
Unscheduled Visits 
In the case of an AE, an Unscheduled Visit may be performed by the 
Investigator. Unscheduled Visit assessments can include any of the following: 

Medical/medication history 

Urine pregnancy test 

VA assessments 

Slit-lamp biomicroscopy 

Conjunctival redness 

IOP 

Fluorescein staining 

AE query 
The Investigator may perform additional assessments, if needed. All 
additional assessments will be documented in the subject’s source document. 
8.5
&RPSOLDQFH ZLWK 3URWRFRO
This study will be conducted in compliance with the protocol, the ethical principles 
that have their origin in the Declaration of Helsinki, the International Conference on 
Harmonisation (ICH) consolidated Guideline E6 for Good Clinical Practice (GCP) 
(CPMP/ICH/135/95), and applicable regulatory requirement(s), such as Food and 
Drug Administration (FDA) GCP Regulations and Code of Federal Regulations Title 
21, parts 11, 50, 54, 56 and 312, as appropriate. 
8.6
6XEMHFW 'LVSRVLWLRQ
8.6.1
Completed Subjects 
A completed subject is one who has not been discontinued from the study. 
8.6.2
Withdrawn Subjects 
A subject may be withdrawn for meeting any of the withdrawal criteria as 
described in Section 5.5. 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
8.6.3
Discontinued Subjects 
A discontinued subject is one who does not complete the four (4) protocol defined 
study visits. A subject MAY be discontinued at the discretion of the Investigator, 
Sponsor, and/or the IRB/IEC. Subjects will also be discontinued if the following 
criteria is met:
x
 
Prior to discontinuing a subject, every effort should be made to obtain as much 
follow-up data as possible, and to retrieve all study materials.  Adverse events 
(AEs) will be followed as described in Section 9.
8.7
6WXG\ 7HUPLQDWLRQ
7KH VWXG\ PD\ EH WHUPLQDWHG DW DQ\ WLPH E\ WKH ,QYHVWLJDWRU WKH
VSRQVRU DQGRU 2UD ZLWK DSSURSULDWH QRWLILFDWLRQ
8.8
6WXG\ 'XUDWLRQ
This study is comprised of 4 visits over a total duration of approximately 7 weeks. 
8.9
0RQLWRULQJ DQG 4XDOLW\ $VVXUDQFH
During the course of the study an Ora, Inc. monitor, or designee, will make routine 
site visits to review protocol compliance, assess study drug accountability, and ensure 
the study is being conducted according to the pertinent regulatory requirements. The 
review of the subjects’ medical records will be performed in a manner that adequately 
maintains subject confidentiality. Further details of the study monitoring will be 
outlined in a monitoring plan. 
Regulatory authorities of domestic and foreign agencies, Ora, Inc. quality assurance 
and/or its designees may carry out on-site inspections and/or audits which may 
include source data checks. Therefore, direct access to the original source data will be 
required for inspections and/or audits. All inspections and audits will be carried out 
giving consideration to data protection as well as subject confidentiality to the extent 
that local, state, and federal laws apply. 

$'9(56( (9(176
9.1
$GYHUVH (YHQW
An AE is defined as any untoward medical occurrence associated with the use of an 
investigational product (IP) in humans, whether or not considered IP-related. An AE 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
can be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an investigational product, 
without any judgment about causality. An AE can arise from any use of the 
investigational product (e.g., off-label use, use in combination with another drug or 
medical device) and from any route of administration, formulation, or dose, including 
an overdose. An AE can arise from any delivery, implantation, or use of a medical 
device, including medical device failure, patient characteristics that may impact 
medical device performance (e.g., anatomical limitations), and therapeutic parameters 
(e.g., energy applied, sizing, dose release) associated with a medical device. 
All AEs spontaneously reported by the subject and/or in response to an open question 
from study personnel or revealed by observation, physical examination or other 
diagnostic procedures will be recorded in the subject’s source document and eCRF. 
Any clinically relevant deterioration in clinical finding is considered an AE and must 
be recorded. When possible, signs and symptoms indicating a common underlying 
pathology should be noted as one comprehensive event. 
Documentation regarding the AE should be made as to the nature, date of onset, end 
date, severity, relationship to investigational product, expectedness, action(s) taken, 
seriousness, and outcome of any sign or symptom observed by the physician or 
reported by the patient upon indirect questioning. 
All AEs will be collected from the time a subject signs the informed consent form 
through the subject’s study exit visit. 
9.1.1
Severity 
Severity of an AE is defined as a qualitative assessment of the degree of 
intensity of an AE as determined by the Investigator or reported to him/her by 
the patient/subject.  The assessment of severity is made irrespective of 
relationship to investigational product or seriousness of the event and should 
be evaluated according to the following scale: 
x
Mild: Event is noticeable to the subject, but is easily tolerated and does 
not interfere with the subject’s daily activities.
x
Moderate:  Event is bothersome, possibly requiring additional therapy, 
and may interfere with the subject’s daily activities.
x
Severe:  Event is intolerable, necessitates additional therapy or alteration 
of therapy, and interferes with the subject’s daily activities.
9.1.2
Relationship to Investigational Product 
The relationship of each AE to the investigational product should be 
determined by the Investigator using these explanations: 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
x
Suspected:  A reasonable possibility exists that the investigational product 
caused the AE.
x
Not Suspected: A reasonable possibility does not exist that the 
investigational product caused the AE. 
Suspected adverse reaction means any AE for which there is a reasonable 
possibility that the investigational product caused the AE.  “Reasonable 
possibility” means there is evidence to suggest a causal relationship between 
the investigational product and the AE.  Types of evidence that would suggest 
a causal relationship between the investigational product and the AE include:  
a single occurrence of an event that is uncommon and known to be strongly 
associated with investigational product exposure (e.g., angioedema, hepatic 
injury, Stevens-Johnson Syndrome); one or more occurrences of an event that 
is not commonly associated with investigational product exposure, but is 
otherwise uncommon in the population exposed to the investigational product 
(e.g., tendon rupture); an aggregate analysis of specific events observed in a 
clinical trial (such as known consequences of the underlying disease or 
condition under investigation or other events that commonly occur in the 
study population independent of drug therapy) that indicates those events 
occur more frequently in the investigational product-treatment group than in a 
concurrent or historical control group. 
9.1.3
Expectedness 
The expectedness of an AE should be determined based upon existing safety 
information about the investigational product using these explanations: 
x
Unexpected:  an AE that is not listed in the Investigator’s Brochure (IB) or 
is not listed at the specificity or severity that has been observed. 
x
Expected:  an AE that is listed in the IB at the specificity and severity that 
has been observed. 
x
Not applicable: an AE unrelated to the investigational product. 
Adverse events that are mentioned in the IB as occurring with a class of 
products or as anticipated from the pharmacological (or other) properties of 
the product, but are not specifically mentioned as occurring with the particular 
product under investigation are to be considered unexpected. 
The Investigator should initially classify the expectedness of an AE, but the 
final classification is subject to the Medical Monitor’s determination.

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
9.2
6HULRXV $GYHUVH (YHQWV
An AE is considered serious if, in the view of either the Investigator or sponsor, it 
results in any of the following outcomes: 
x
Death; 
x
A life-threatening AE; 
o
Note:  An AE is considered “life-threatening” if, in the view of either the 
Investigator or sponsor, its occurrence places the patient or subject at 
immediate risk of death.  It does not include an AE that, had it occurred in a 
more severe form, might have caused death. 
x
Inpatient hospitalization or prolongation of existing hospitalization; 
o
Note:  The term “inpatient hospitalization” refers to any inpatient admission 
(even if less than 24 hours).  For chronic or long-term inpatients, inpatient 
admission includes transfer within the hospital to an acute/intensive care 
inpatient unit.  Inpatient hospitalization does not include:  emergency room 
visits; outpatient/same-day/ambulatory procedures; observation/short stay 
units; rehabilitation facilities; hospice facilities; nursing homes; or clinical 
research/phase 1 units. 
o
Note:  The term “prolongation of existing hospitalization” refers to any 
extension of an inpatient hospitalization beyond the stay anticipated or 
required for the reason for the initial admission as determined by the 
Investigator or treating physician. 
x
A persistent or significant incapacity or substantial disruption of the ability to 
conduct normal life functions; 
o
Note:  A serious adverse event (SAE) specifically related to visual threat 
would be interpreted as any potential impairment or damage to the subject’s 
eyes (e.g., hemorrhage, retinal detachment, central corneal ulcer or damage to 
the optic nerve). 
x
A congenital anomaly/birth defect. 
Important medical events that may not result in death, are life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
9.3
3URFHGXUHV IRU 5HSRUWLQJ $GYHUVH (YHQWV
All AEs and their outcomes must be reported to Ora, the study sponsor, and the 
IRB/IEC as required by the IRB/IEC, federal, state, or local regulations and 
governing health authorities and recorded on the appropriate subject source document 
and eCRF. 
9.3.1
Reporting a Suspected Unexpected Adverse Reaction 
All AEs that are ‘suspected’ and ‘unexpected’ are to be reported to Ora, the 
study sponsor and the IRB/IEC as required by the IRB/IEC, federal, state, or 
local regulations and governing health authorities. 
9.3.2
Reporting a Serious Adverse Event 
To ensure subject safety, all SAEs, regardless of relationship to the 
investigational product, must be immediately reported by the Investigator to 
Ora and the sponsor within 24 hours of becoming aware of the event.  All 
information relevant to the SAE must be recorded on the appropriate source 
document, SAE Report Form and eCRF.  The Investigator is obligated to 
pursue and obtain information requested by Ora and/or the sponsor in addition 
to the information reported on the source document, SAE Report Form and 
eCRF.  All subjects experiencing a SAE must be followed up and the outcome 
reported. 
In the event of a SAE, the Investigator must notify Ora and the sponsor 
immediately; obtain and maintain in his/her files all pertinent medical records, 
information, and medical judgments from colleagues who assisted in the 
treatment and follow-up of the subject; provide Ora and the study sponsor 
with a complete case history, which includes a statement as to whether the 
event was or was not suspected to be related to the use of the investigational 
product; and inform the IRB of the AE within their guidelines for reporting 
SAEs. 
Contact information for reporting SAEs: 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
9.4
3URFHGXUHV IRU 8QPDVNLQJ LI DSSOLFDEOH
When medically necessary, the Investigator may need to determine what treatment 
has been assigned to a subject.  When possible (i.e., in non-emergent situations), Ora 
and/or the study sponsor should be notified before unmasking investigational product. 
A two-panel clinical label with scratch offs will be used for unmasking.  
9.5
7\SH DQG 'XUDWLRQ RI WKH )ROORZXS RI 6XEMHFWV DIWHU $GYHUVH
(YHQWV
The Investigator will follow unresolved AEs to resolution, until the subject is lost to 
follow-up or until the AE is otherwise explained.  Resolution means the subject has 
returned to baseline state of health or the Investigator does not expect any further 
improvement or worsening of the AE.  If the subject is lost to follow-up, the 
Investigator should make 3 reasonable attempts to contact the subject via telephone, 
post, or certified mail.  All follow-up will be documented in the subject’s source 
document. Non-serious AEs identified on the last scheduled contact must be recorded 
on the source document with the status noted.  
If the Investigator becomes aware of any new information regarding a SAE (i.e. 
resolution, change in condition, or new treatment), a new Serious Adverse Event 
Report Form must be completed and faxed to Ora and/or the study sponsor within 24 
hours.  The original SAE Report Form is not to be altered.  The Report Form should 
describe whether the event has resolved or continues and how the event was treated. 
 67$7,67,&$/ +<327+(6(6 $1' 0(7+2'6 2) $1$/<6(6
10.1
*HQHUDO &RQVLGHUDWLRQV
All quantitative/continuous study assessments will be summarized by treatment (or 
treatment sequence) and visit and time point (as applicable) using descriptive 
statistics (n, mean, SD, median, minimum, and maximum.  All qualitative/categorical 
study assessments will be summarized by treatment (or treatment sequence), visits, 
and time point (as applicable) using frequency counts and percentages.   
Statistical testing, unless otherwise indicated, will be performed at a 2-sided 0.10 
significance level.  When applicable, two-sided 80% and 90% CIs will be reported.  
All p-values (P) will be displayed to four decimal places, with P less than 0.0001 
presented as '< 0.0001' and P greater than 0.9999 presented as ‘> 0.9999’.  

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
x
Percentage of subjects with at least a 3-line (15-letter) improvement in the study 
eye in the measurement of post-treatment monocular best-corrected distance VA
 compared to pre-treatment monocular best-corrected distance VA 
 
 
x
Mean monocular best-corrected distance logMAR VA at near distances in the 
study eye 
o
Post-treatment assessments compared to pre-treatment assessment 
o
Two near testing distances will be assessed: 
 (all post-treatment time 
points [0.5, 1, 3, 4, 5 and 7h]) and 
 
x
Percentage of subjects with at least a 3-line (15-letter) improvement in the 
measurement of post-treatment binocular best-corrected distance VA at 45 cm 
compared to baseline binocular best-corrected distance VA at 45 cm
o
0.5, 1, 3, 4, 5 and 7h post-treatment  
x
Percentage of subjects with at least a 3-line (15-letter) improvement in the 
measurement of post-treatment binocular best-corrected distance VA at 
 
compared to baseline binocular best-corrected distance VA at 
 
  
x
 Mean binocular best-corrected distance logMAR VA at near 
o
Post-treatment assessments compared to pre-treatment assessment 
o
Two near testing distances will be assessed: 
 (all post-treatment time 
points [0.5, 1, 3, 4, 5 and 7h]) and 
 
10.6 ([SORUDWRU\ (IILFDF\ 9DULDEOHV
The exploratory efficacy variables are: 
x
   
  
  
 
  
 
 
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
Descriptive statistics will be presented for each time point and distance by treatment 
group. Testing of the percentage of subjects with at least a 3-line (15-letter)
improvement in the study eye from pre-dose will be completed accounting for the 
correlations between treatments and periods within a subject using a logistic 
(binomial error and logit link) model estimated by generalized estimating equation 
methods. Aspects of the model include: 
• Response measure: indicator of whether the subject had at least a 3-line (15-letter) 
improvement in the study eye from pre-dose in the monocular assessment of best-
corrected distance VA at 
. 
• Fixed effect explanatory measures: sequence, period, and treatment.  
• Random effect measure: subject within sequence, to account for the correlation 
between treatments and periods within a subject. 
• Repeated measures correlation will be estimated with an unstructured variance-
covariance matrix.  
Standard errors and CIs (80 and 90%) will also be presented for each treatment 
group and the difference between treatment groups. Separate models will be built for 
each distance (with 45 cm being primary and 
 being secondary) and time point 
separately. Pairwise comparisons among treatment groups will also be made at each 
distance and time point using McNemar’s tests. 
10.11
6HFRQGDU\ (IILFDF\ $QDO\VLV
Descriptive statistics will be presented for each time point and distance as well as 
for the change from pre-dose at each time point and distance by treatment group. 
The same logistic regression models developed for the primary analyses will be used 
to test secondary proportion endpoints.  For continuous secondary endpoints, similar 
mixed effect models will be employed.  Two-sided one-sample t-tests from a mixed 
effects linear model with monocular best-corrected distance VA at near from pre-
dose as the response variable; sequence, period, and treatment as fixed effect 
variables; and subject within sequence as a random effect term with a variance 
component covariance matrix to account for the correlation among measures within 
a subject using α = 0.10 and two-sided 80% and 90% CI will be provided as 
additional descriptors of the data.  Separate models will be built for each distance 
and time point separately. Pairwise comparisons among treatment groups will also 
be made at each distance and time point using one-sample t-tests.  
10.12
([SORUDWRU\ (IILFDF\ $QDO\VLV
Exploratory efficacy endpoints will be analyzed for all available data similarly to 
the primary and secondary endpoints in the mITT population and in the ITT 
population for sensitivity. All exploratory variables will include percentage based 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
enrollment into the study.  If the subject is under the legal age of consent, the 
consent form must be signed by a legal guardian or as required by state and/or 
local laws and regulations. 
All informed consent/assent forms must be approved for use by the sponsor 
and receive approval/favorable opinion from an IRB/IEC prior to their use.  If 
the consent form requires revision (e.g., due to a protocol amendment or 
significant new safety information), it is the Investigator’s responsibility to 
ensure that the amended informed consent is reviewed and approved by Ora 
prior to submission to the governing IRB/IEC and that it is read, signed and 
dated by all subjects subsequently enrolled in the study as well as those 
currently enrolled in the study. 
If informed consent is taken under special circumstances (oral informed 
consent), then the procedures to be followed must be determined by Ora 
and/or study sponsor and provided in writing by Ora and/or study sponsor 
prior to the consent process. 
11.1.2 IRB Approval 
This study is to be conducted in accordance with IRB regulations (U.S. 21 
CFR Part 56.103).  The Investigator must obtain appropriate IRB approval 
before initiating the study and re-approval at least annually. 
Only an IRB/ERC approved version of the ICF will be used. 
11.2
(WKLFDO &RQGXFW RI WKH 6WXG\
This study will be conducted in accordance with the ethical principles that originated 
with the Declaration of Helsinki. 
11.3
6XEMHFW &RQILGHQWLDOLW\
All personal study subject data collected and processed for the purposes of this study 
should be maintained by the Investigator and his/her staff with adequate precautions 
as to ensure that the confidentiality of the data in accordance with local, state, and 
federal laws and regulations. 
Monitors, auditors and other authorized representatives of Ora, the sponsor, the 
IRB/IEC approving this study, the Food and Drug Administration (FDA), the 
Department of Health and Human Services (DHHS), other domestic government 
agencies, and other foreign regulatory agencies will be granted direct access to the 
study subject’s original medical and study records for verification of the data and/or 
clinical trial procedures.  Access to this information will be permitted to the 
aforementioned individuals to the extent permitted by law. 
A report of the results of this study may be published or sent to the appropriate health 
authorities in any country in which the investigational product may ultimately be 
marketed, but the subject’s identity will not be disclosed in these documents.

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
Clinical label texts for the primary packaging (glass vials) and secondary 
packaging (clinical kits) meet applicable regulatory requirements and include 
the statement “Caution: New Drug-Limited by Federal Law to Investigational 
Use.”     
11.5.2 Storage of Investigational Product 
Investigational drug must be stored in a secure area of the investigative site, 
accessible only to Investigator or designees, at room temperature between 15° 
- 25°C (59-77°F).  The investigational product will be administered only to 
subjects entered into the clinical study, in accordance with the conditions 
specified in this protocol.  All investigational drugs will be returned to 
inventory after use. 
11.5.3 Accountability of Investigational Product 
The investigational product is to only be administered by the principal 
Investigator or his/her named sub Investigator(s), and is to only be used in 
accordance with this protocol.  The investigational product must only be 
distributed to subjects properly qualified under this protocol to receive 
investigational product. 
The Investigator must keep an accurate accounting of the investigational 
product received from the supplier.  This includes the amount of 
investigational product administered to subjects and the amount returned or 
disposed upon the completion of the study.  A detailed inventory must be 
completed for the investigational product. 
11.5.4 Return or Disposal of Investigational Product 
All investigational products will be returned to the sponsor or their designee 
or destroyed.  The return or disposal of investigational product will be 
specified in writing. 
11.6 5HFRUGLQJ RI 'DWD RQ 6RXUFH 'RFXPHQWV DQG (OHFWURQLF &DVH
5HSRUWV )RUPV H&5)V
The Investigator is responsible for ensuring that study data is completely and 
accurately recorded on each subject’s source document, eCRF and all study-related 
material.  All study data should also be attributable, legible, contemporaneous, and 
original.  Recorded datum should only be corrected in a manner that does not 
obliterate, destroy, or render illegible the previous entry (e.g., by drawing a single line 
through the incorrect entry and writing the revision next to the corrected data).  An 
individual who has corrected a data entry should make clear who made the correction 
and when, by adding to the correction his/her initials as well as the date of the 
correction. 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
11.7 +DQGOLQJ RI %LRORJLFDO 6SHFLPHQV
Not applicable 
11.8 3XEOLFDWLRQV
Authorship and manuscript composition will reflect cooperation among all parties 
involved in the study. Authorship will be established before writing the manuscript.  
Ora and the study sponsor will have the final decision regarding the manuscript and 
publication. 
 5()(5(1&(6
Francois J. and Goes F. Ultrasonic study of the effect of different miotics on the eye components. 
Ophthalmologica Basel 1977;175(6):328-338. 
Gilmartin B, Amer A, Ingleby S. Reversal of tropicamide mydriasis with single instillations of 
pilocarpine can induce substantial pseudo-myopia in young adults. Ophthalmic & Physiological 
Optics 1995;15(5):475-479. 
Helmholtz, H.v. Uber die akkommodation des auges. A. v. Graefe’s Arch. Klin. Ophthalmol. 
1855;1, 1–74.
Holden B, Fricke T, Ho S, Wong R, Schlenther G, Cronje´ S, Burnett A, Papas E, Naidoo K, 
Frick K. Global vision impairment due to uncorrected presbyopia. Archives of Ophthalmology 
2008;126(12):1731-1739. 
Ostrin, L.A. and Glasser, A Edinger-Westphal and pharmacologically stimulated accommodative 
refractive changes and lens and ciliary process movements in rhesus monkeys. Experimental Eye 
Research 2007;84: 302-313. 
Randazzo A, Nizzola F, Rossetti L, Orzalesi N, Vinciquerra P. Pharmacological management of 
night vision disturbances after refractive surgery – Results of a randomized clinical trial. J Cataract 
Refract Surg 2005;31(9): 1764-1772.  
Romano, J. H. Double-blind cross-over comparison of aceclidine and pilocarpine in open-angle 
glaucoma. British Journal of Ophthalmology 1970;54: 510-521.
Scarcelli, G., Kim, P., and Yun, S.H. In vivo measurement of age-related stiffening in the 
crystalline lens by brillouin optical microscopy. Biophysical Journal 2011;101: 1539-1545. 
Truscott, R. J. Presbyopia. Emerging from a blur towards an understanding of the molecular 
basis for this most common eye condition. Experimental Eye Research 2009;88: 241-247. 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
$SSHQGL[  +DQGOLQJ RI %LRORJLFDO 6SHFLPHQV
Not applicable 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

03Jul2018 
CONFIDENTIAL 
Page  of 
 
 
 
 
$SSHQGL[  6SRQVRU DQG 2UD $SSURYDOV
3URWRFRO 7LWOH
A Single-Center, Double-Masked Evaluation of the Efficacy and 
Safety of PRX-100 in the Treatment of Early to Moderate Presbyopia
3URWRFRO 1XPEHU
PRX100.FDAIIb
)LQDO 'DWH
03Jul2018
This clinical study protocol was subject to critical review and has been approved by the sponsor.  
The following personnel contributed to writing and/or approving this protocol. 
Signed
Signed