ocularis presentation 0908[2]
DESCRIPTION
Updated presentation on first drop for improvement of night vision.TRANSCRIPT
April 11, 2023 ConfidentialConfidential
© 2008 Ocularis Pharma - Confidential March, 2008 Page 2
Ocularis Pharma: Overview
• Developing Nyxol® Eye Drops to Treat Night Vision Complaints– Night Myopia– Post-IOL surgery– Post-LASIK surgery
• Retasking an approved drug for a new indication– Lower risk, lower cost, faster to market– $400+ million market potential (US)– Large ophthalmic companies now entering market
• Experienced management team and field-leading advisors
© 2008 Ocularis Pharma - Confidential March, 2008 Page 3
Management Group• Al Meyer, CEO
– Former EVP & CFO, PathoGenesis
• Charlie Hoffmann, Principal, Business Development– Investment banker Prudential Vector Healthcare, First Boston,
Goldman Sachs
• Jerry Horn, MD, Principal, Scientific & Medical– Ophthalmic surgeon specializing in LASIK– Inventor of Nyxol Eye Drops
• Bill Pitlick, PhD, Principal, Product Development – Chief Scientific Officer, Avera Pharma– Former VP, Clinical/Regulatory Affairs, PathoGenesis
• Keith Terry, Principal, Market Development– Director, Strategic Marketing, Immunology, Abbott Labs– Former Managing Director, International, PathoGenesis
© 2008 Ocularis Pharma - Confidential March, 2008 Page 4
Advisory Board
• Glen Bradley, Retired CEO, CIBA Vision
• Bill Gantz, Executive Chairman, Ovation Pharma– Founder & CEO, PathoGenesis– Former President & COO, Baxter
• Stephen Klyce, PhD, Professor, LSU– Expert on corneal aberrations and pupil size
• Marguerite McDonald, MD, OCLI– LASIK pioneer
• Peter Drake, PhD, Founder & EVP, Vector Securities_______________________________________________
• Art Ginsburg, PhD, Chairman, Vision Sciences Corp– Expert on contrast sensitivity
© 2008 Ocularis Pharma - Confidential March, 2008 Page 5
Night Vision Complaints (“NVCs”)
• NVCs include several conditions– Glare– Halos– Starbursts– Poor depth perception
• Significant unmet need, increasingly recognized– 20+% of patients complain to eye docs about NVCs– 6-7% have moderate/severe condition, i.e. night vision worse
than 20/45
• No medications indicated to treat NVCs today
© 2008 Ocularis Pharma - Confidential March, 2008 Page 6
Nyxol Eye Drops to Treat Night Vision Complaints
Typical Night Vision Disturbance Clear Night Vision
© 2008 Ocularis Pharma - Confidential March, 2008 Page 7
Cause of Night Vision Complaints
• Imperfections exist in periphery of cornea – “higher order aberrations”
• In dim light, pupil dilates more than needed
• Light enters through periphery and scatters
• Treatment thesis:
Limit pupil dilation to improve night vision
© 2008 Ocularis Pharma - Confidential March, 2008 Page 8
● Mechanism of Action– Alpha 1 antagonist– Inhibits iris dilator muscle– Limits pupil dilation
Nyxol Eye Drops: Manage Pupil Dilation
TypicalDilation
ManagedDilation
© 2008 Ocularis Pharma - Confidential March, 2008 Page 9
Nyxol Eye Drops: Manage Pupil Dilation Before After
© 2008 Ocularis Pharma - Confidential March, 2008 Page 10
• Phentolamine mesylate– Long used as intravenous hypotensive– Recently approved (5/08) as injection to reverse oral anesthesia– Reformulated as an eye drop to improve night vision
• Nyxol activity– Use as needed– One drop in each eye– Works in < 30 minutes, lasts 8 hours
• Nyxol safety– Topical use, no systemic effect observed– Very well tolerated in the eye, very comfortable– Some users experience redness, manage w/ OTC redness
reducer
Nyxol Eye Drops: Drug Profile
© 2008 Ocularis Pharma - Confidential March, 2008 Page 11
• Established Intellectual Property – Four U.S. patents issued for use to improve dim light vision
– Five patents pending
• Established Market Dimension– External market research – 3 Health Advances studies
– Internal market research – 4 Patient, M.D. and O.D. studies
– Conclusion: Nyxol is a $400+ million market in US
• Established Regulatory Pathway with FDA– Acknowledged serious unmet medical need
– Stated no systemic tox required
– Discussed pivotal study design
– Agreed on primary endpoint (contrast sensitivity)
Nyxol Eye Drops: Milestones Achieved
© 2008 Ocularis Pharma - Confidential March, 2008 Page 12
• Proved Treatment Thesis - NOVA Study– 100 patients with NVCs in 5 patient groups
• Night myopia• Post-LASIK• High myopia• Contact lens• Cataract
– Employed consensual pupillary light reflex to make pupils smaller
– Measured night vision (LCVA) before and after– Study shows conclusively
Making pupils smaller improves night vision
Nyxol Eye Drops: Milestones Achieved
© 2008 Ocularis Pharma - Confidential March, 2008 Page 13
• Completed 4 Phase 1/2 clinical trials– Investigator INDs– 101 subjects in total– Single dose, 4 concentrations, placebo controlled
• Demonstrated that Nyxol is a viable drug– Clinically & statistically significant improvement in night vision
• Contrast Sensitivity
• Low Contrast Visual Acuity
• Wavefront Aberrometry
• Subjective Questionnaire
– Well tolerated in the eye – very comfortable– No systemic effects
Nyxol Eye Drops: Milestones Achieved
© 2008 Ocularis Pharma - Confidential March, 2008 Page 14
• In 12 months - Conduct multiple dose (14 day) Phase 2 study– Company IND– 40 subjects with severe night vision complaints– Full panel of objective and subjective evaluations
• In 18 months - Initiate Phase 3 clinical trial– Broad indication – moderate/severe NVCs– 2 pivotal studies– 500 patients in each– 6 month treatment– Follow 100 patients for full year
Nyxol Eye Drops: Development Plan Overview
© 2008 Ocularis Pharma - Confidential March, 2008 Page 15
Nyxsol Recent Milestone
• Received Term Sheet From Major Pharmaceutical Company For $28M
© 2008 Ocularis Pharma - Confidential March, 2008 Page 16
• Developed comprehensive formulation strategy: existing patents precede FDA approved use & formulation same drug for different medical application
• Plan:
• 1 Corporate IND (animal tox, formulation/stability) $500k
• 2 Definitive Phase II study: 60 pts, 14 days $500k
• 3 Manufacturing: Ready fill, blowfill seal, pf free $500k
• 4 Comprehensive NOVA, other marketing study $500k
• 5 Management, overhead, other $500k
• Result: $400 M market drug w Corp IND; Phase I, II completed. Valuation expected: $50M - $100M.
Nyxol Eye Drops: 2009 - 2010
© 2008 Ocularis Pharma - Confidential March, 2008 Page 17
Comparable Phase 3 Programs
Product Nyxol® Restasis® Alphagan P®
IndicationModerate to Severe NVC
Moderate to Severe Dry Eye
Open Angle Glaucoma
# of Patients 1,000 1,200 926
Duration 6 months 6 months 1 year
© 2008 Ocularis Pharma - Confidential March, 2008 Page 18
Ocularis Strategy: Next Steps• Attain value-creating milestones
– Conduct investigator IND studies• 7 day use study/focus group• Population study in normals/incidence & severity of NVCs• 28 day use study/focus group
– Obtain formulation license
– Obtain company IND• Conduct formulation/28 day stability study• Conduct 28 day topical animal tox study
– Complete multi-dose Phase 2 study
– Initiate pivotal Phase 3 study
• Partner, license or sell to major ophthalmic companyAlcon AMOAllergan Bausch & Lomb
© 2008 Ocularis Pharma - Confidential March, 2008 Page 19
Ocularis: Investment Summary
• Experienced, successful management group • Strong intellectual property protection
• Strong clinical evidence that Nyxol works
• Large unmet market
• No competitive drug product
• Clear execution planLow cost / Low risk / Fast to market
• Clear Exit Strategy
© 2008 Ocularis Pharma - Confidential March, 2008 Page 20
Ocularis PharmaAppendices
1. Recent Night Vision Market Developments
2. Night Vision Complaint Market
3. Results of Recent Phase II Trial
4. NOVA Study Results
5. Optometrist Survey Results
6. Recent Phentolamine Approval
7. Clinical Study: HOA Analysis
© 2008 Ocularis Pharma - Confidential March, 2008 Page 21
Ocularis Pharma
Appendix 1
Recent Night Vision Market Developments
© 2008 Ocularis Pharma - Confidential March, 2008 Page 22
Accidents at Night
• National Highway Traffic Safety Administration & National Safety Council say
– 90% of driver’s reaction depends on vision
– Fatality rate at night 3 times daytime rate
– Pedestrians 3 to 7 times more vulnerable at night than daytime
– 25% of travel occurs during darkness
– 49% of fatal crashes occur at night
© 2008 Ocularis Pharma - Confidential March, 2008 Page 23
Bausch & Lomb IntroducesNew Contact Lens
• B&L introduced PureVision® Contact Lenses in January, 2008
– Improves vision in low-light conditions
– 74,000 patient on-line study confirmed night vision and night driving were improved with PureVision CLs
– Aspheric design of PureVision CLs reduces spherical aberration and improves night vision
© 2008 Ocularis Pharma - Confidential March, 2008 Page 24
“Shedding Light on Driving in the Dark”
• Study conducted by Kelton Research September, 2007
• Sponsored by– ACUVUE® Contact Lenses (Johnson & Johnson)– Road & Travel Magazine (women’s automotive and travel issues)
• Published by Johnson & Johnson Vision Care late 2007
• Sample– 515 nationally representative Americans– 18 years old and older– Vision corrected
• Rx Eyeglasses 83%• Rx Contact Lenses 25%• Reading Glasses 14%• LASIK 4%
– “Driving in the dark” - driving in low-light conditions• Early AM• Night
© 2008 Ocularis Pharma - Confidential March, 2008 Page 25
Driving in the Dark
• Percent of 150 million vision corrected Americans who– Have difficulty driving in the dark 32%
all or most of time
– Experience glare 48%
– See halos or starburst patterns 28%
– Have difficulty seeing signs or exits 26%
– Have difficulty judging distances 22%
© 2008 Ocularis Pharma - Confidential March, 2008 Page 26
How They Feel Behind the Wheel in the Dark
Men Women
• Uncomfortable 17% 27%– Not confident in the dark
• Unsafe 17% 25%– Could not see signs
• Anxious 16% 25%– Do not want to drive
© 2008 Ocularis Pharma - Confidential March, 2008 Page 27
Younger vs Older Drivers in the Dark
18-49 50+
• Difficulty driving in the dark 36% 22%
• Hard time seeing signs & exits 30% 17%
© 2008 Ocularis Pharma - Confidential March, 2008 Page 28
Market Summary• B&L product introduction proves there is a night vision
market
• J&J study proves the market is larger than our estimates– 1/3 have difficulty driving in the dark– More women than men experience night vision problems– More younger people than older people have night vision
problems
• J&J is poised to launch their new contact lens for night vision shortly
• Other companies are launching night vision products (contact lenses and spectacle lenses)– Wavetouch– Ophthonics– Essilor
© 2008 Ocularis Pharma - Confidential March, 2008 Page 29
Ocularis Pharma
Appendix 2
Night Vision Complaint Market
© 2008 Ocularis Pharma - Confidential March, 2008 Page 30
Night Vision Complaint Market:Summary Conclusions
• Total potential NVC market exceeds $420 million
• Nyxol can achieve sales of over $150 million
• Nyxol will be used to improve vision performance
• Optometrists will be the primary prescribers of Nyxol
• Nyxol will be marketed by a major ophthalmic company salesforce to 35,000 ODs and 18,000 MDs
© 2008 Ocularis Pharma - Confidential March, 2008 Page 31
Night Vision Complaint Market:Market Research and Analysis
• Ocularis has commissioned or conducted seven market research studies– Optometrists– Ophthalmologists– Patients
• Key conclusions– 20+% of patients visiting eye doctors complain about night vision– Moderate/Severe NVCs comprise about one third of these
patients (~6.5%)– Optometrists would prescribe an eye drop indicated for NVCs– Patients would buy and use eye drops at the forecast price point
© 2008 Ocularis Pharma - Confidential March, 2008 Page 32
NVC Patients Seen by ODs
• Avg patient visits per mo 250
• Night vision complaints 20%
• Treatable 65%
• Treatable NVC patients per month 32.5
• Months per year 12
• Treatable NVC patients per year 390
• ODs in US 35,000
• Annual Treatable NVC patients in US 13.7 mm
• Moderate to Severe NVC patients in US 4.5 mm
© 2008 Ocularis Pharma - Confidential March, 2008 Page 33
Nyxol Eye Drops: Target Prescribers• Primary – Optometrists (ODs), whose focus is
visual function of the eye:– Myopia– Astigmatism– Hyperopia– Presbyopia
• Secondary – Ophthalmologists (MDs), whose focus is diseases of the eye: – Glaucoma– Macular degeneration– Cataracts
• Rationale– ODs are more attuned to night vision complaints than MDs– ODs will embrace a new prescription opportunity
© 2008 Ocularis Pharma - Confidential March, 2008 Page 34
Night Vision Complaint Market
Moderate/Severe NVC Market Segments
Night Myopia (Non-Surgical) $327 mm
Post-Surgical $95 mmIOLs & LASIK
Total $422 mm
© 2008 Ocularis Pharma - Confidential March, 2008 Page 35
Night Vision Complaint Market:Night Myopia Market Potential
NightMyopia(000's)
Population 118,931
Incidence of Mod/Sev NVCs 6.6%Patients w/ Mod/Sev NVCs 7,849
Patients Treatable 65%
Patients Seeking Therapy 40%
Target Mod/Sev NVC Patients 2,041
Annual Rx Price (4 Rxs/Yr @ $40) $160
Mod/Sev NVC Market Potential $326,536
Penetration 40%
Nyxol Sales Projection $130,615
© 2008 Ocularis Pharma - Confidential March, 2008 Page 36
Night Vision Complaint Market:Summary Market Potential
NightMyopia IOL LASIK Total
Population 118,931 11,529 10,200 140,659
Incidence of Mod/Sev NVCs 6.6% 7.5% 6.4% 6.7%Patients w/ Mod/Sev NVCs 7,849 866 655 9,370
Patients Treatable 65% 65% 65%
Patients Seeking Therapy 40% 60% 60%
Target NVC Patients 2,041 338 255 2,634 % of Population 1.7% 2.9% 2.5% 1.9%
Rx Frequency/Rx Price 4/$40 4/$40 4/$40
Mod/Sev NVC Market Potential $326,536 $54,013 $40,872 $421,422
Penetration 40% 40% 40% 40%
Nyxol Sales Projection $130,615 $21,605 $16,349 $168,569
Nyxol Market Potential 2015 (000's)
Post Surgical
NightMyopia IOL LASIK Total
Population 118,931 11,529 10,200 140,659
Incidence of Mod/Sev NVCs 6.6% 7.5% 6.4% 6.7%Patients w/ Mod/Sev NVCs 7,849 866 655 9,370
Patients Treatable 65% 65% 65%
Patients Seeking Therapy 40% 60% 60%
Target NVC Patients 2,041 338 255 2,634 % of Population 1.7% 2.9% 2.5% 1.9%
Rx Frequency/Rx Price 4/$40 4/$40 4/$40
Mod/Sev NVC Market Potential $326,536 $54,013 $40,872 $421,422
Penetration 40% 40% 40% 40%
Nyxol Sales Projection $130,615 $21,605 $16,349 $168,569
Nyxol Market Potential 2015 (000's)
Post Surgical
© 2008 Ocularis Pharma - Confidential March, 2008 Page 37
• Study parameters– 380 patients with no serious eye pathology– Photopic (normal light) corrected vision was 20/25 or better– “Night myopia” – defined as 20/45 or worse
• Findings– 16.6% incidence of “night myopia”– “Moderate to severe” NVCs about 6.6%
• Ocularis correlates “night myopia” with pupil diameter
Fejer Study - 1992: Incidence of “Night Myopia”
Incidence Est Avgof Night Scotopic
Age Myopia Pupil (mm)
16-25 32.7% 7.0
26-45 15.7% 6.0
46-65 5.5% 5.0
>65 3.1% 4.5
Total 16.6% ~6.0
Incidence Est Avgof Night Scotopic
Age Myopia Pupil (mm)
16-25 32.7% 7.0
26-45 15.7% 6.0
46-65 5.5% 5.0
>65 3.1% 4.5
Total 16.6% ~6.0
© 2008 Ocularis Pharma - Confidential March, 2008 Page 38
Night Vision ComplaintsResults of Initial Optometrist Survey
• Incidence of NVCs
– Patients complain about night vision• Unprompted 20%• Prompted >20%
© 2008 Ocularis Pharma - Confidential March, 2008 Page 39
Night Vision ComplaintsResults of Initial Optometrist Survey
• Nyxol™ Eye Drops to Treat NVCs– 70% of patients with NVCs would benefit– ODs would readily adopt a product that was safe and
effective– ODs would prescribe empirically to patients– ODs would be primary prescribers– Patients would be willing to pay $30/month or
$360/year for such a product
© 2008 Ocularis Pharma - Confidential March, 2008 Page 40
Night Vision ComplaintsResults of Initial Optometrist Survey
• Optometrists today are not prescribing drugs to treat NVCs– Alphagan P is rarely prescribed because
• Side effects• Declining efficacy• Confusion with pharmacist over using a glaucoma med for
night vision complaints– Do not prescribe pilocarpine for NVCs because of serious side
effects– Prescribe glasses, rewetting drops or tell patient to look away
from glare source, all with limited results
© 2008 Ocularis Pharma - Confidential March, 2008 Page 41
Why Would ODs Treat NVCs?
• New, value added therapy for patients
– ODs get a new therapeutic tool to improve night vision– ODs get a continuing, regular revenue stream vs periodic
eyeglass/contact lens update every year or two– Example - dry eye therapy is taking off with Restasis
• ODs writing Rxs
• Simple diagnosis and treatment
• No capital investment required
© 2008 Ocularis Pharma - Confidential March, 2008 Page 42
• No drugs approved for treating NVCs
• Several existing drugs have pupil constricting side effects– Alphagan P– Pilocarpine
• For treating NVCs, these drugs have– Limited effectiveness– Unacceptable side effects
Nyxol Eye Drops: Competition
© 2008 Ocularis Pharma - Confidential March, 2008 Page 43
Ocularis Pharma
Appendix 3
Nyxol – Results of Recent Phase II Trial
© 2008 Ocularis Pharma - Confidential March, 2008 Page 44
• Single dose, Phase II study– 24 subjects (16 on drug, 8 on placebo)– Severe night vision complaints– Positive effect on LCVA with consensual pupillary light reflex
• Measurement– Primary endpoint - Contrast Sensitivity– High & low contrast visual acuity– Wavefront aberrometry– Subjective questionnaire– Pupil size
• Study goals– Demonstrate Nyxol Eye Drops work and are safe– Compare measurement techniques
Nyxol Eye Drops: OP-NYX-SNVLatest Study Completed – 10/08
© 2008 Ocularis Pharma - Confidential March, 2008 Page 45
• Co-Principal Investigators– Dr. Marguerite McDonald– Dr. Eric Donnenfeld
• Study Site - Ophthalmic Consultants of Long Island– 25 eye docs, 7 offices– Largest ophthalmic practice in New York– Full time clinical research staff
• Study status– 47 subjects screened, 24 enrolled– First subject enrolled 8/14/07– Last subject completed 10/30/07– Data analysis continuing– Study report available early 2008
Nyxol Eye Drops: OP-NYX-SNV
© 2008 Ocularis Pharma - Confidential March, 2008 Page 46
Study Demographics - 24 Total Subjects– Gender
• 7 Male• 17 Female
– Age• 14 45 & Under• 10 Over 45
– Type• 19 Night Myopes• 5 Post-surgical
– 3 LASIK
– 1 RK
– 1 IOL
Preliminary Analysis OP-NYX-SNV
© 2008 Ocularis Pharma - Confidential March, 2008 Page 47
• Female, 38 years old, night myopia (no surgery)
• Night vision problems– Glare– Halos– Depth perception
• Limits night driving
Nyxol Eye Drops: OP-NYX-SNVSubject 002 Demographics
© 2008 Ocularis Pharma - Confidential March, 2008 Page 48
OP-NYX-SNV: Subject 002Pre- and Post-Dose
OD OSPre-Dose Pupil Size (mm) 7.5 7.8
LCVA 20/53 20/53
Ability to See?
Post-Dose Pupil Size (mm) 5.2 5.1
LCVA 20/17 20/15
Change in Ability to See?
Lot of difficulty
Much better
OD OSPre-Dose Pupil Size (mm) 7.5 7.8
LCVA 20/53 20/53
Ability to See?
Post-Dose Pupil Size (mm) 5.2 5.1
LCVA 20/17 20/15
Change in Ability to See?
Lot of difficulty
Much better
© 2008 Ocularis Pharma - Confidential March, 2008 Page 49
Contrast Sensitivity Methodology
© 2008 Ocularis Pharma - Confidential March, 2008 Page 50
Contrast Sensitivity Subject 002 ODFACT Pre Dose FACT Post-Dose
© 2008 Ocularis Pharma - Confidential March, 2008 Page 51
Contrast Sensitivity Subject 002 OSFACT Pre Dose FACT Post Dose
© 2008 Ocularis Pharma - Confidential March, 2008 Page 52
• Subject 002 went from being functionally blind at night to being able to see well
• Substantial improvement in all measures– Contrast Sensitivity Well below normal to high normal
Exceeds FDA efficacy criteria
– LCVA 20/53 to 20/17 or better– Snellen acuity 1 line of improvement– Subjective “Lot of difficulty” to “much better”
Nyxol Eye Drops: OP-NYX-SNV Subject 002
© 2008 Ocularis Pharma - Confidential March, 2008 Page 53
OP-NYX-SNV StudyContrast Sensitivity – Active Pre vs Post
0
1
2
3
4
5
6
7
1.5 3 6 12 18
Pre
Post
Spatial Frequency – Cycles/DegreeSpatial Frequency – Cycles/Degree
Pat
ch U
nit
sP
atch
Un
its
P < .05P < .05
P < .001P < .001
P < .05P < .05
P < .001P < .001
P < .001P < .001
© 2008 Ocularis Pharma - Confidential March, 2008 Page 54
Contrast Sensitivity Active Subjects FACT Pre-Dose FACT Post-Dose
© 2008 Ocularis Pharma - Confidential March, 2008 Page 55
Contrast Sensitivity Active Subjects45 & Under
FACT Pre Dose FACT Post Dose
© 2008 Ocularis Pharma - Confidential March, 2008 Page 56
Individual Subject AnalysisChange in FACT Patch Units
Contrast Sensitivity - Active
-3
-2
-1
0
1
2
3
4
5
6
7
8
1 2 3 4 5
Frequencies
Del
ta P
atch
es-P
re v
s P
ost
Contrast Sensitivity - Placebo
-3
-2
-1
0
1
2
3
4
5
6
7
8
1 2 3 4 5
Frequencies
Del
ta P
atch
es-P
re v
s P
ost
© 2008 Ocularis Pharma - Confidential March, 2008 Page 57
Mesopic Low Contrast Visual Acuity
0
2
4
6
8
10
12
Pre vs Post Active vs Placebo Pre vs Post <45
Ch
ang
e in
Let
ters
Rea
dC
han
ge
in L
ette
rs R
ead
p < .001p < .001
p < .05p < .05
p < .001p < .001
© 2008 Ocularis Pharma - Confidential March, 2008 Page 58
Wavefront Acuity Map RMS Error
0
0.25
0.5
0.75
1
1.25
1.5
Placebo Active
Pre
Post
P < .001P < .001 NS NS
RM
S E
rro
r U
nit
s µ
RM
S E
rro
r U
nit
s µ
© 2008 Ocularis Pharma - Confidential March, 2008 Page 59
Subjective Change in Night Vision
0%
20%
40%
60%
80%
100%
MuchBetter
Better Same Worse MuchWorse
Placebo
Active
© 2008 Ocularis Pharma - Confidential March, 2008 Page 60
Reduction in Pupil Diameter
0.00
0.25
0.50
0.75
1.00
1.25
1.50
Pre vs Post Active vs Placebo
Red
uct
ion
in P
up
il D
iam
mm
Red
uct
ion
in P
up
il D
iam
mm p < .0001 p < .0001
p<.0001 p<.0001
© 2008 Ocularis Pharma - Confidential March, 2008 Page 61
Redness
None
Trace
Slight
Moder-
Severe
NS
p<0.001
Placebo Active 0
25
50
75
100
Units0-100
Pre
Post
© 2008 Ocularis Pharma - Confidential March, 2008 Page 62
Intraocular Pressure
0
2
4
6
8
10
12
14
Placebo Active
Pre
Post
P < .001P < .001 NS NS
IOP
mm
Hg
IOP
mm
Hg
© 2008 Ocularis Pharma - Confidential March, 2008 Page 63
Systolic Blood Pressure
0
25
50
75
100
125
150
Placebo Active
Pre
PostBP
mm
Hg
BP
mm
Hg
© 2008 Ocularis Pharma - Confidential March, 2008 Page 64
Diastolic Blood Pressure
0
20
40
60
80
100
Placebo Active
Pre
Post
BP
mm
Hg
BP
mm
Hg
© 2008 Ocularis Pharma - Confidential March, 2008 Page 65
OP-NYX-SNV
• Study Summary– Nyxol Eye Drops improve night vision
• Clinically meaningful• Statistically significant
– Results consistent across all endpoints• Contrast Sensitivity• High & Low Contrast Visual Acuity• Wavefront• Subjective questionnaire• Pupil size
– Nyxol Eye Drops safe and well tolerated
© 2008 Ocularis Pharma - Confidential March, 2008 Page 66
Ocularis Pharma
Appendix 4
NOVA Study Results
© 2008 Ocularis Pharma - Confidential March, 2008 Page 67
Night Optics and Vision Assessment (NOVA) Study Design
• Non-therapeutic epidemiological study• 100 subjects (20 in each of 5 groups) with complaints of
night vision disturbances– Post refractive surgery– High myopia/astigmatism– Contact lens wearers– Glasses only at night– Cataracts
• Endpoints measured prior to and during illumination of the contralateral eye (consensual pupillary light reflex)– Pupil diameter– High and low contrast visual acuity– Subjective questionnaire
© 2008 Ocularis Pharma - Confidential March, 2008 Page 68
NOVA Study Result
• 4 of 5 groups show significant improvement with smaller pupils in dim light– Post refractive surgery– High myopia/astigmatism– Contact lens wearers– Glasses only at night (night myopia)
• Small fraction of cataract patients reported improvement
© 2008 Ocularis Pharma - Confidential March, 2008 Page 69
NOVA StudySmaller Pupils Improve Night Vision
© 2008 Ocularis Pharma - Confidential March, 2008 Page 70
NOVA StudySmaller Pupils Improve Visual Acuity
© 2008 Ocularis Pharma - Confidential March, 2008 Page 71
Population Study Design• Epidemiological study
• Objectives are to determine– Incidence of night vision disturbances in the normal population– Spectrum of severity of night vision disturbances– Benefit derived from making pupils smaller
• Endpoints measured prior to and during illumination of the contralateral eye (consensual pupillary light reflex)– Contrast sensitivity– High and low contrast visual acuity– Pupil size – Subjective questionnaire
• Study size, centers, timing - TBD
© 2008 Ocularis Pharma - Confidential March, 2008 Page 72
Ocularis Pharma
Appendix 5
Optometrist Survey Results
© 2008 Ocularis Pharma - Confidential March, 2008 Page 73
Optometrist Night Vision Survey
• 13 questions asked on optometrist experience with night vision complaints
• 35 optometrists in Milwaukee area surveyed• Conducted by Milwaukee Market Research• Completed March, 2008
© 2008 Ocularis Pharma - Confidential March, 2008 Page 74
Average Patients Seen Per Month
0
50
100
150
200
250
300
Survey National Average
© 2008 Ocularis Pharma - Confidential March, 2008 Page 75
Services Provided
79%
9%
4%
3% 5%
Eyeglasses/Contacts
Allergy/Dry Eye
Glaucoma
Pre/Post Surgery
Other
© 2008 Ocularis Pharma - Confidential March, 2008 Page 76
Night Vision Complaints
0%
5%
10%
15%
20%
25%
30%
Unprompted Prompted
© 2008 Ocularis Pharma - Confidential March, 2008 Page 77
Symptoms Cited by Patients with NVCs
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
NightDriving
Difficulty
Glare Halos Starbursts Sensitivity DepthPerception
Ghosting
© 2008 Ocularis Pharma - Confidential March, 2008 Page 78
Potential Causes of NVCs
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
NightMyopia
Cataracts Dry Eye Post-LASIK
Post-IOL Back ofthe Eye
© 2008 Ocularis Pharma - Confidential March, 2008 Page 79
What Drugs Do ODs Prescribe
0%
10%
20%
30%
40%
50%
60%
70%
80%
Alphagan P Pilocarpine Artificial Tears None
© 2008 Ocularis Pharma - Confidential March, 2008 Page 80
What Devices Do ODs Prescribe
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
50%
Eyeglasses TintedGlasses
Anti ReflectiveCoating
Look Away
© 2008 Ocularis Pharma - Confidential March, 2008 Page 81
What Percent Would Benefit?What Percent Would OD Prescribe?
0%
5%
10%
15%
20%
25%
30%
35%
40%
% Benefit % Prescribe
© 2008 Ocularis Pharma - Confidential March, 2008 Page 82
Price and Prescriber
• Price– Our market model assumes $13 per month– Survey says patients would pay $24 per month for this product,
almost double our assumed price
• Likely Prescribers1 Optometrist
2 Refractive Surgeon
3 Ophthalmologist
© 2008 Ocularis Pharma - Confidential March, 2008 Page 83
Optometrist Survey Summary• 28% of patients would complain about night
vision, if asked• Treat NVCs with drugs
– 70+% Artificial tears– <25% Glaucoma meds with pupil reduction side effect
• Treat NVCs with devices– 45% Eyeglasses– 45% Antireflective coating– 26% Tinted glasses
• Who would benefit from Nyxol™ Eye Drops?– 35% of NVC sufferers
• Who would get Nyxol scrips?– 39% of NVC sufferers
© 2008 Ocularis Pharma - Confidential March, 2008 Page 84
Ocularis Pharma
Appendix 6
Recent Phentolamine Approval
© 2008 Ocularis Pharma - Confidential March, 2008 Page 85
Novalar Pharma & Phentolamine Mesylate
• Novalar Pharma– San Diego based, founded in 2000– Financed by Domain, NEA, SR One and Montreux– Focused on drugs for dentristry
• OraVerse® for Injection (phentolamine mesylate)– Approved for use by FDA May, 2008– Indicated for reversal of dental anesthesia– Labeled for adults and pediatrics (>6 years old)– Lifestyle drug, reduces time of numbness by 50%– 4 use patents, 1 formulation patent– Will launch in October, 2008 with own sales/marketing team– Injectable dosage form distinct from Nyxol® Eye Drops
© 2008 Ocularis Pharma - Confidential March, 2008 Page 86
Implications for Nyxol® Eye Drops Program
• Novalar’s success with OraVerse demonstrates phentolamine mesylate can be:– Formulated in solution with 3 year stability
– Manufactured (API and drug product) under cGMP
– Shown to be safe in animals and man• Approved for adults and children (6 and older)• FDA required tox and safety to be “squeaky clean” for
approval of this lifestyle drug
– Approved by FDA under modern regulations (last approved in 1952)
Conclusion: Results in a major reduction in risk, cost and time to
market for Nyxol Eye Drops development
© 2008 Ocularis Pharma - Confidential March, 2008 Page 87
Phentolamine MesylateComparison of Dosage Forms & Systemic Safety
Conclusion: Nyxol Eye Drops should have systemic safetybetter than or equal to OraVerse
Conclusion: Nyxol Eye Drops should have systemic safetybetter than or equal to OraVerse
Nyxol® Eye Drops OraVerse® Injection Regitine® Injection
Indication Treatment of Reversal of Diagnosis ofnight vision complaints dental anesthesia pheochromocytoma
Concentration 1.0% solution 0.0235% solution 0.5% solution10 mg/mL 0.235 mg/mL 5 mg/mL
Route of Admin Corneal surface Submucosal Intravenous
Delivered Dose 1.0 mg 0.4 mg 5.0 mg
Systemic Take Up % 10% (est) 100% 100%Systemic Dose 0.1 mg 0.4 mg 5.0 mg
Fraction of IV Dose % 2% 8% 100%
© 2008 Ocularis Pharma - Confidential March, 2008 Page 88
Ocularis Pharma
Appendix 7
Clinical Study: HOA Analysis
© 2008 Ocularis Pharma - Confidential March, 2008 Page 89
HOA AnalysisAvg Change Pre- to Post- Drug