A Topical Treatment to Correct Presbyopia Results from A Phase I-II Study of EV06 Ophthalmic Solution for the Treatment of Presbyopia Bill Burns Chief Executive Officer
A Topical Treatment to
Correct Presbyopia
Results from A Phase I-II Study of EV06 Ophthalmic Solution
for the Treatment of Presbyopia
Bill BurnsChief Executive Officer
2 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Higher proportion of EV06 subjects had gain of 10 letters or more (DCNVA) compared to placebo
Note: Preliminary analysis based on LOCF in study eye only
0
5
10
15
20
25
30
35
40
45
50
Day 8 Day 15 Day 31 Day 61 Day 91
% o
f Su
bje
cts
Percent of Subjects with Gain of ≥10 Letters in DCNVA
Placebo
EV06
P=0.04
P-value is based on Fisher’s exact test
P=0.003
DCNVA=Distance-corrected near visual acuity
3 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Presbyopia is the MOST prevalent eye condition
In the US, almost 90 MILLION will have presbyopia by 2020…
…which will rise to over 120 MILLION by 20501
1.3B
2011 20502005
1B
1.8B
2020
1.4B
Globally, nearly 2 BILLION people will have presbyopia by 2050
1. Holden BA, Fricke TR, Ho SM, et al. Global Vision Impairment Due to Uncorrected Presbyopia. Arch Ophthalmol. 2008;126(12):1731-1739. doi:10.1001/archopht.126.12.1731.
4 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Aging EyeYoung Eye
How Is Accommodation Lost?Why Does Presbyopia Happen?
Cytosol Displacement Centrally = Accommodation
Lens Stiffening = Compromised
Accommodation
Oxidation induced disulfide bonds form between crystalline proteins -
a Leading Potential Cause
↓
↑
5 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
What is EV06?How Does it Work?
• EV06 (Lipoic Acid Choline Ester, 1.5%) is a prodrug
Choline Lipoic Acid
Lipoic Acid Choline Ester
• EV06 penetrates cornea - metabolized into Choline & Lipoic Acid, two naturally occurring substances
Dihydrolipoic Acid
• Enzymes within
lens fiber cells
chemically reduce
Lipoic Acid to
active form
Dihydrolipoic Acid
6 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
How Does EV06 Work?
Dihydrolipoic Acid Chemically Reduces
Disulfide Bonds
Dihydrolipoic Acid
Disulfide Bonds
LENS ELASTICITY IS REGAINED
Cytosol Displacement Centrally = Accommodation
↓
↑
7 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Study Design
• Prospective, randomized, double-masked, placebo-controlled multicenter Phase I/II study
• 75 subjects with hyperopia, myopia, or emmetropia and a diagnosis of presbyopia randomized 2:1 to receive EV06 BID or placebo BID
Objective: Evaluate safety and efficacy of EV06 in improving DCNVA in
subjects with presbyopia
DCNVA=Distance-corrected near visual acuity
-7 Days Day 0 Day 1 Day 1 Day 7 Day 7 Day 90
SCREENING
Key inclusion criteria:• 45-55 years of age• Binocular DCNVA worse than
20/40• BCDVA of 20/20 or better in
each eye• A difference of ≤ 0.50 D
between manifest refraction spherical equivalent and cycloplegic refraction spherical equivalent
Ra
nd
om
iza
tio
n
(2:1
,EV
06
: P
lace
bo
)
Unilateral Dosing Bilateral Dosing
EV06 1.5% BIDN=50
EV06 1.5% BIDN=50
PLACEBO BIDN=25
PLACEBO BIDN=25
8 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Study Details
Demographics
Category Value
Age; Mean (range) 50.5 yrs (45-55)
Gender Female 71%
Race Caucasian 70.7%
Patient Type Emmetropes 68%Myopes 20%Hyperopes 12%
• Four Study Sites across US• Visual Assessments included:
• Manifest Refraction
• Best Corrected Distance Visual Acuity (BCDVA)
• M&S Vision testing system – all sites
• Distance Corrected Near Visual Acuity (DCNVA)
• Defocus Curve Testing
• iTrace Aberrometer Wavefront Measures – one site only
9 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
EV06 Safety & Tolerance Results
• No Subjects Discontinued For Adverse Events, Safety Concerns, or Tolerability
• No Sight Related Adverse Events
• Upon Instillation
– Mean EV06 Comfort Rating 3.0
– Mean Placebo Comfort Rating 2.7
• (Scale 0 – 10; “0” = Very Comfortable)
• No Change In Best Corrected Distance Visual Acuity
10 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
EV06 Efficacy Results
• Achieved both Primary Efficacy Results:
– Improvement in Distance Corrected Near Vision Acuity (DCNVA) in the Study Eye after treatment, which continued throughout the dosing period
– Higher proportion of subjects with gain of ≥10 letters in DCNVA in the study eye vs. placebo
11 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
0
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
0.45
0.5
0 20 40 60 80 100
LogM
AR
Sco
re
Treatment Day
DCNVA LogMAR - OU
Placebo
EV06
P=0.017
P=0.022P=0.027 P=0.005
P-values for two sample t-test, EV06 vs. Placebo
Improvement in Distance Corrected Near Vision Acuity
DCNVA=Distance-corrected near visual acuity
12 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Gain of ≥ 10 Letters - DCNVA
Note: Preliminary analysis based on LOCF in study eye only
0
5
10
15
20
25
30
35
40
45
50
Day 8 Day 15 Day 31 Day 61 Day 91
% o
f Su
bje
cts
Percent of Subjects with Gain of ≥10 Letters in DCNVA
Placebo
EV06
P=0.04
P-value is based on Fisher’s exact test
P=0.003
DCNVA=Distance-corrected near visual acuity
13 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
EV06 DCNVA Snellen score - Day 1 & Day 91
0 0
8
22
36
22
12
0
12
24 2422
8 8
0 0
20/20 20/25 20/32 20/40 20/50 20/63 20/80 20/100
% S
ub
ject
s
Day 1 EV06 Day 91 EV06
Poly. (Day 1 EV06) Poly. (Day 91 EV06)
Improved shift in Snellen Scores
14 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Placebo DCNVA Snellen score - Day 1 & Day 91
0 0
8
20
40
16
12
14
12
8
24
32
8
4 0
20/20 20/25 20/32 20/40 20/50 20/63 20/80 20/100
% S
ub
ject
s
Day 1 Placebo Day 91 Placebo
Poly. (Day 1 Placebo ) Poly. (Day 91 Placebo)
No material shift in Snellen Scores
15 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
Conclusions and Next Steps
• EV06 restores near vision in presbyopic patients
• EV06 demonstrated an acceptable safety and
tolerability profile
• Additional study is warranted
• Follow-on study of subjects from just completed
trial to determine duration of treatment effect at:
−120 days post-dosing
−270 days post-dosing
16 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
THANK YOU
Clinical Sites
Sall Research Medical Center, Inc.Artesia, California
North Valley Eye Medical GroupMission Hills, California
Comprehensive Eye Care, Ltd. Washington, Missouri
Total Eye Care Memphis, Tennessee
17 | CONFIDENTIAL-PLEASE DO NOT DISTRIBUTE
THANK YOU
Advisors
Jerry Cagle, PhD Dan Durrie, MDDennis Dean, PhDAdrian Glasser, PhD
David Gooden, PhDMarjorie Lou, PhDStella Robertson, PhD
Encore Vision Team
Kathryn Crawford, PhDShikha Barman, PhDJudy Gordon, DVMJerry Stein, PhD
William Garner, PhDMargaret Garner, PhDDennis Dean, PhDLexitas Pharma Services, IncRegulatory Professionals, Inc (RPI)
Board of Directors
Peter BennettWilliam BurnsAdrienne Graves, PhDJohn Hunkeler, MD
Les KreisRichard Lindstrom, MDEd Tyler (Chairman)