OPHTHALMOLOGY INNOVATION SHOWCASE - Encore Vision

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


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.


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

↓

↑


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


How Does EV06 Work?

Dihydrolipoic Acid Chemically Reduces

Disulfide Bonds

Dihydrolipoic Acid

Disulfide Bonds

LENS ELASTICITY IS REGAINED

Cytosol Displacement Centrally = Accommodation

↓

↑

http://en.wikipedia.org/wiki/File:Dihydrolipoic-acid-2D-skeletal.png

http://en.wikipedia.org/wiki/File:Dihydrolipoic-acid-2D-skeletal.png


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


-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


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


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


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


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



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



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


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


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


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


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)

Healthcare

OPHTHALMOLOGY INNOVATION SHOWCASE - Encore Vision