Corporate Presentation: Annual Shareholder Meeting
Corporate Presentation: Corporate Presentation: Annual Shareholder MeetingAnnual Shareholder Meeting
Tim Ruane, CEOInSite Vision
May 31, 2012
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Our Approach: Novel Products, Reduced Risk, Efficient Development
Our Approach: Novel Products, Reduced Our Approach: Novel Products, Reduced Risk, Efficient DevelopmentRisk, Efficient Development
DuraSite®: Polymer drug delivery technology• Increases efficacy• Improves dosing and compliance
Low safety and regulatory risks • FDA approved technology• Combine with known agents
Shorter development timelines• Target indications with high unmet need• Leverage existing data on platform and products
Reduced development costs• Streamline clinical trial programs• Work closely with FDA to define expectations and program
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Undervalued Company with Strong Focus and Investment Fundamentals
Undervalued Company with Strong Focus Undervalued Company with Strong Focus and Investment Fundamentalsand Investment Fundamentals
Significant royalties from two partnered commercial products• Merck• Bausch + Lomb
Three Phase 3 product candidates advancing • AzaSite Plus™
& DexaSite™• BromSite™
(ISV‐303)
Proven platform technology
Multiple partnering opportunities• Own global rights to the three Phase 3 products & Phase I/2 product
Strong cash position and oversight of resources
Management team focus on execution
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InSite Vision’s PipelineInSite VisionInSite Vision’’s Pipelines Pipeline
Phase 3/SPA Enrolling
Phase 3 Starting Soon
Phase 1/2 On-hold
New IND Planned
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AzaSite®
in North America OpportunityAzaSiteAzaSite®®
in North America Opportunityin North America Opportunity
Partner: Merck (via 2011 acquisition of Inspire Pharmaceuticals)• Approved in U.S. & Canada for bacterial conjunctivitis
InSite Vision receives 25% royalty• 2012 minimum royalty guarantee: $17M• Escalating 2013 minimum royalty guarantee• Includes AzaSite Xtra™
(ISV‐405; 2% azithromycin
in DuraSite) as “life cycle management”
opportunity
2011 Royalties of $13.9M• Merck intends to grow in bacterial conjunctivitis
Patent protection• AzaSite: Issued IP to March 2019• AzaSite Xtra: Issued IP to October 2027
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Besivance®
OpportunityBesivanceBesivance®®
OpportunityOpportunity
Partner: Bausch + Lomb
Approved in U.S. for bacterial conjunctivitis• Launched in mid‐2009 in U.S.• Asia/Latin America/ROW launches in 2011• Additional filings end‐2011/early 2012
InSite Vision receives middle single‐digit royalty on global sales• 2011 Royalties: $1.2M (vs. $0.5M in 2010)
“Besivance Global Commercialization” ongoing
Patent protection to 2021
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Blepharitis: Acute and/or Chronic Inflammation of the Eyelids
BlepharitisBlepharitis: Acute and/or Chronic : Acute and/or Chronic Inflammation of the EyelidsInflammation of the Eyelids
Blepharitis(also known as Lid Margin Disease)
Image Source: WebMD.com
Signs & Symptoms
• Redness• Flaking skin• Crusting• Cysts• Irritation
• Gritty sensation• Itching• Vision impairment• Discomfort
Possible Causes
• Bacteria• Viruses• Allergy• Environmental conditions• Systemic disease
Prevalence
• Estimated 34 million people in the U.S. alone
• Widely considered bothunder-diagnosed and misdiagnosed
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Blepharitis: Global Landscape OverviewBlepharitisBlepharitis: Global Landscape Overview: Global Landscape Overview
No approved agents
Clear market need• Ophthalmologists see worst patients; many “silent sufferers”
Off‐label prescribing by ophthalmologists• Scant reimbursement; patients pay out‐of‐pocket
High FDA hurdle: traditional endpoint• Onerous in chronic settings of inflammation/infection (blepharitis)
Industry “Holy Grail”: front‐of‐eye focus
Classic first‐to‐market opportunity• Only company in Phase 3 development with SPA in place
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AzaSite Plus™
(ISV‐502) for BlepharitisAzaSite PlusAzaSite Plus™™
(ISV(ISV‐‐502) for 502) for BlepharitisBlepharitis
Intended to rapidly reduce signs and symptoms of acute and chronic blepharitis
Combines low doses of azithromycin and dexamethasonewith DuraSite to address both infection and inflammation
Administered twice‐daily for 14 days
Safety and superior efficacy established in 2008 Phase 3 clinical trial versus AzaSite
Issued patents to 2019; potential exclusivity to 2031 based on 2011 intellectual property filings
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DexaSite™
(ISV‐305) for BlepharitisDexaSiteDexaSite™™
(ISV(ISV‐‐305) for 305) for BlepharitisBlepharitis
Low‐dose dexamethasone in DuraSite
Administered twice‐daily for 14 days
Originally intended to rapidly reduce acute inflammation in the treatment of non‐microbial blepharitis
Safety and efficacy established in 2008 Phase 3 clinical trial versus AzaSite Plus
Phase 3 results indicate unanticipated high activity of BID dexamethasone in DuraSite• Basis for 2009 intellectual property filings• Potential exclusivity to 2029
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Special Protocol Assessment (SPA) Approval: DOUBle
Phase 3 for AzaSite Plus & DexaSite
Special Protocol Assessment (SPA) Approval: Special Protocol Assessment (SPA) Approval: DOUBleDOUBle
Phase 3 for AzaSite Plus & Phase 3 for AzaSite Plus & DexaSiteDexaSite
DOUBle
(Dual Ophthalmic agents Used in Blepharitis)Simultaneous evaluations of AzaSite Plus, AzaSite, DexaSite and DuraSite (vehicle)• Valuable data on our two agents ‐
and AzaSite
‐
in one Phase 3 study
Four‐arm Study of 900 Patients Design and Statistical Analysis PlanN= 900
Randomized
Blinded
Powered at 80%
2‐sided Fisher’s Exact Test
AzaSite PlusN= 300
AzaSite PlusN= 300
AzaSiteN= 150
AzaSiteN= 150
DexaSiteN= 300
DexaSiteN= 300
DuraSiteN= 150
DuraSiteN= 150
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DOUBle
(Dual Ophthalmic agents Used in Blepharitis)
SPA Agreed Primary Endpoints: May 2011
Traditional EndpointComplete (100%) resolution of all clinical signs & symptoms (cure)
New Endpoint #1Time to recurrence:
Patients with complete (100%) resolution of clinical signs & symptoms
(cure)
Other EndpointsImprovement in clinical signs & symptoms: All other patients
Exacerbation of clinical signs & symptoms: All other patients
Special Protocol Assessment (SPA) Approval: DOUBle
Phase 3 for AzaSite Plus & DexaSite
Special Protocol Assessment (SPA) Approval: Special Protocol Assessment (SPA) Approval: DOUBleDOUBle
Phase 3 for AzaSite Plus & Phase 3 for AzaSite Plus & DexaSiteDexaSite
vs.AzaSite PlusAzaSite Plus
AzaSiteAzaSite
vs.DexaSiteDexaSite
DuraSite (Vehicle)DuraSite (Vehicle)
vs.AzaSite PlusAzaSite Plus
DexaSiteDexaSitevs.
AzaSite PlusAzaSite Plus
AzaSiteAzaSite
vs.DexaSiteDexaSite
DuraSite (Vehicle)DuraSite (Vehicle)
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DOUBle Study Execution UpdateDOUBle Study Execution UpdateDOUBle Study Execution Update
Update as of May 24th• All 45 sites up and running• 44/45 sites have enrolled at least 1 patient
626 patients (~70%) enrolled since November 16th FPO• 95 patients have now completed the study• 26 patients dropped out early
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The InSite Vision OpportunityThe InSite Vision OpportunityThe InSite Vision Opportunity
Classic first‐to‐market advantage
Potential for broad payor strategy, reimbursement, promotion and use upon approval
SPA discussions/agreement reveal FDA interest in an approved blepharitis drug • Well aware of acute vs. chronic disease endpoint issue• Clearly understand reality of ophthalmology clinical practice
Two InSite “pipeline shots on goal”• AzaSite Plus needs superiority over AzaSite and DexaSite• DexaSite
needs only be superior to DuraSite
(vehicle)
Third potential “BD shot on goal” with AzaSite vs. Vehicle• Potential 1st
positive Phase 3 to support AzaSite blepharitis
NDA path• Merck owns no rights to these data
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AzaSite Plus and DexaSite: Substantial Market Opportunities
AzaSite Plus and AzaSite Plus and DexaSiteDexaSite:: Substantial Market OpportunitiesSubstantial Market Opportunities
Assuming moderate market penetration and current pricing of drugs prescribed for blepharitis, possible sales ranges are:• AzaSite Plus
$500M to $1B
[Based on 10% at $120/prescription]
• DexaSite
$200M to $400M [Based on 5% at $90/prescription]
• AzaSite
We haven’t examined possible $ effects of a
positive outcome for AzaSite via this study
Reiterated 2011 Guidance for 2012 • Fully accrued in 2H 2012• Results end‐2012/early 2013
We believe our blepharitis program will allow us to file one and, hopefully, two NDAs in the U.S. in 2013
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BromSite™
(ISV‐303) for Reduction of Inflammation and Pain Post‐Cataract Surgery
BromSiteBromSite™™
(ISV(ISV‐‐303) for Reduction of 303) for Reduction of Inflammation and Pain PostInflammation and Pain Post‐‐Cataract SurgeryCataract Surgery
Lower dose formulation of bromfenac (0.075%) in DuraSite• Preclinical data indicate superior performance to bromfenac
IND filed July 2010
Phase 1/2 clinical study completed January 2011• Four‐arm study evaluating safety and efficacy
Top‐line results reported March 2011• Final/full results to be presented and/or published in future
Superior PK performance reported October 2011• Phase 2 PK study vs. Ista’s
Bromday
–
the current market leader
Anticipate exclusivity into 2029 based on 2009 filings
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Confirm BromSite
Regulatory Pathway with FDA Following Surprisingly Strong Phase 1/2 Data
Confirm Confirm BromSiteBromSite
Regulatory Pathway with FDA Regulatory Pathway with FDA Following Surprisingly Strong Phase 1/2 DataFollowing Surprisingly Strong Phase 1/2 Data
Phase 1/2 design evaluated BromSite administered once‐and twice‐daily against ISTA’s Xibrom™ and DuraSite
RN=169
53.3%
19.0%
p=0.0016
53.3%
42.2%
p=NS
BromSite (BID)BromSite (BID)
BromSite (QD)BromSite (QD)
XiBrom (BID)XiBrom (BID)
DuraSite (BID)DuraSite (BID)
All statistically significant
superiority @ Days 8, 15 & 29
Primary Endpoint Secondary EndpointsAbsence of cells in anterior chamber of
the eye at Day 15
Reduction of: • Flare • Pain & discomfort from inflammation • Others
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BromSite
vs. Bromday
Phase 2 PK StudyBromSiteBromSite
vs. vs. BromdayBromday
Phase 2 PK StudyPhase 2 PK Study
Phase 2 pharmacokinetic study designed to evaluated BromSite against ISTA’s Bromday™ (market leader)• Statistically compared mean aqueous humor concentrations of
bromfenac
for the 2 treatment arms
Study Design & AnalysisRandomizedDouble‐blindMulti‐center (N=3)Patients dosed QD• Day ‐2 & ‐1 pre‐surgery• Day 0 of surgery100‐200 µl fluid extractedHPLC‐MS analysis
RN=58
BromSite (0.075% bromfenac in DuraSite)
BromSite (0.075% bromfenac in DuraSite)
Bromday(0.09% bromfenac)
Bromday(0.09% bromfenac)
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BromSite
vs. Bromday
Phase 2 PK StudyBromSiteBromSite
vs. vs. BromdayBromday
Phase 2 PK StudyPhase 2 PK Study
BromSite achieves >2x the tissue concentration in the eye vs. Bromday• Potential benefits in avoiding cystoid
macular edema
(CME), a potentially serious adverse event post‐surgery• Demonstrated superiority over current market leader
P=0.0032RN=58
BromSite (0.075% bromfenac in DuraSite)
BromSite (0.075% bromfenac in DuraSite)
Bromday(0.09% bromfenac)
Bromday(0.09% bromfenac)
Mean concentrations of bromfenac in the aqueous humor Measured ~3 hours after last dose
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BromSite
SummaryBromSiteBromSite
SummarySummary
February 2012 pre‐Phase 3 FDA meeting• Finalized Phase 3 protocols• Standard endpoints (same as 2010 Phase 1/2 Study)• BromSite
need only show superiority vs. DuraSite
(vehicle)• 2 Phase 3 Studies (n=240 each)• Clinical trial material now manufactured
Reiterated 2011 Guidance • Fully accrued in 2H 2012• Results end‐2012/early 2013
We believe our BromSite program will give us an opportunity to file an additional NDA in 2013• IND to potential NDA filing: 3 years• Ideal model for future InSite development plans
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Europe: Expanding our Commercial Footprint
Europe: Expanding our Commercial Europe: Expanding our Commercial FootprintFootprint
February 2012 EU Regulatory Meetings (2 Countries)• InSite blepharitis
programs: AzaSite Plus & DexaSite• Covered 2008 Phase 3 data & ongoing DOUBle
study
Key Results• U.S. efficacy/safety data sufficient to support EU filings; there is
NO de facto need for EU patient data• EU/North American formulation differences (preservative levels)
are a non‐issue; we simply need appropriate EU CMC package• Centralized filing/review procedure should be available to us
We are evaluating opportunities to file in EU first
We believe these principles should apply to AzaSite & BromSite
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European Regulatory Pathways: ContinuedEuropean Regulatory Pathways: ContinuedEuropean Regulatory Pathways: Continued
Q2 2012 EU Regulatory Meetings• BromSite
Phase 3 program: Package submitted; meetings
scheduled• AzaSite NDA filing pathway: Package submitted; awaiting
scheduled
Key Questions• Seeking agreement in BromSite
Phase 3 clinical program• Seeking agreement that AzaSite NDA data sufficient to support EU
filings; no need for additional EU patient dataInformal inputs: AzaSite Xtra as sNDA to AzaSite or full NDA
• CMC issues on EU/North American formulation differences; seek
agreement for appropriate EU CMC package• Is centralized filing/review procedure available for AzaSite and
BromSite?
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R&D Pipeline –
What’s Next?R&D Pipeline R&D Pipeline ––
WhatWhat’’s Next?s Next?
ISV‐101: Bromfenac solution in DuraSite• IND filed and Phase 1/2 study approved; on hold due to pipeline
prioritization
AzaSite Xtra™ (ISV‐405): Azithromycin (2.0%) solution in DuraSite• “Double strength”
AzaSite with issued global IP through end‐2027• Completed all formulation/stability data and all GLP toxicology work to support
global IND and/or IND‐equivalent filings
ISV‐102: Tetracycline‐based solution in DuraSite• Completed formulation/stability studies• Potential therapy for the treatment of ocular infections
ISV‐620: Prostaglandin analog solution in DuraSite• Completed formulation/stability studies• Potential therapy for cosmetic eyelash enhancement
ISV‐215: Prostaglandin analog solution in DuraSite• Completed formulation/stability studies• Potential therapy for treatment and/or prevention of Glaucoma
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IP UpdateIP UpdateIP Update
November 2011: USPTO definitively rules against UCSF in AzaSite patent interference• USCF files appeal end‐2011; we just received basis of appeal filing• Our case; Merck in monitoring role
Merck continues its prosecution of paragraph IV/ANDA case vs. Sandoz• Merck’s case; InSite monitoring role• Likely Q1 2013 trial date
Continued close coordination of AzaSite IP/legal issues by Merck/InSite
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InSite Vision: Strong Fundamentals, Near‐Term Catalysts, Undervalued Opportunity
InSite Vision: Strong Fundamentals, InSite Vision: Strong Fundamentals, NearNear‐‐Term Catalysts, Undervalued OpportunityTerm Catalysts, Undervalued Opportunity
Two partnered commercial products• Merck• Bausch & Lomb
Three Phase 3 product candidates advancing• AzaSite Plus™
• DexaSite™
• BromSite™
(ISV‐303)
Multiple NDA/registration plans• North America: AzaSite Plus & DexaSite, and BromSite• Europe now fully on our radar screen
AzaSite, AzaSite Plus, DexaSite, BromSite
Potential for multiple 2013 NDA filings in U.S. and/or Europe
Thank youThank youThank you
www.insitevision.com