Analysis of the US Retinal Therapeutics Market

Improvements in Administration and Efficacy Drive Growth

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December 2013

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This research service examines the US market for age-related macular degeneration

(AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) therapeutics.

Topics covered include the following:

• US market sizing and forecasting including breakdown by disease segment

• Competitive landscape including comprehensive product and development pipeline

analysis

• Launch timelines and patent expirations

• Important trends, unmet needs, opportunities and risks in retinal disease therapeutics

• Conclusions, recommendations, and companies to watch

Contents

Source: Frost & Sullivan

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• The information contained in this research service was derived from a variety of relevant

primary and secondary sources.

• Secondary data sources include company publications (annual reports, US Securities

and Exchange Commission (SEC) filings, investor presentations, earnings transcripts,

and press releases); US government public sources (clinicaltrials.gov, FDA.gov, Orange

Book); pharmaceutical industry databases; and published articles in scientific and

medical journals.

• Revenue forecasting is performed using a robust, data-driven, bottom-up, patient-based

approach. Marketed drugs and potential new entrants in Phase 3 of development and

beyond are individually forecast, and aggregate figures are provided.

• Revenue from off-label usage is not included, but is accounted for in forecast models.

Methodology

Source: Frost & Sullivan

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Scope and Segmentation

• This research service evaluates the United States market for pharmaceutical treatments for the

following retinal diseases: AMD, DME, and RVO.

• Units are defined as patients. Treated patient numbers, when estimated, are derived from annual

sales revenue and annual cost of therapy.

• The price is the annual cost of therapy, and the average annual cost of therapy is based on the

average wholesale price (AWP) per drug, as reported in Thomson Reuters Red Book. Hospital or

clinic-associated expenses are not included in the cost of therapy.

• Indication-specific annual revenue, as reported, is used when available. Otherwise, estimates are

used.

Geographic Coverage US

Study Period 2009–2017

Base Year 2012

Forecast Period 2013–2017

Monetary Unit US Dollars

Source: Frost & Sullivan

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Key Questions This Study Will Answer

Is the market growing, how long will it continue to grow, and at what rate?

Are the existing competitors structured correctly to meet customer needs?

What pipeline candidates have the greatest potential? When are they expected to reach market?

Which treatments are set to dominate the market? How much market share for each competitor?

What is the peak sales potential for AMD, DME, and RVO market?

What the strengths and weaknesses of current and future therapies?

Source: Frost & Sullivan

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Market Segmentation

This research service evaluates the US markets for prescription medications for the retinal disorders

age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. It does not

include other retinal disorders, such as Stargardt’s disease, retinitis pigmentosa, retinopathy of

prematurity, or cytomegalovirus retinitis.

DME

Total Retinal Therapeutics Market

RVO

Total Retinal Therapeutics Market: Market Segmentation, US, 2012

AMD

Market Segmentation

Source: Frost & Sullivan

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New Market Opportunities

Unmet Needs

• Although new treatments are highly efficacious,

all VEGF treatments are administered via

intravitreal injection, an invasive procedure.

• Further improvements are needed to drug

administration methods to reduce the

frequency of intravitreal injection, such as with

Allergan’s AGN-150998 which has the potential

to be dosed every 3 months.

• New treatments which can be administered

orally or topical drops would revolutionize

treatment and garner significant market

adoption in place of intravitreal injections.

• Combination treatment to further increase

efficacy such as Ophthotech’s Fovista (PDGF

inhibitor) with a VEGF inhibitor such as Avastin

are promising.

Current Participant Strategies

• As is typical with treatment decisions, efficacy

trumps all other measures and VEGF

treatments dominate the market due to their

high efficacy.

• There is very limited competition for VEGF

treatments such as Eylea and Lucentis.

• Eylea differentiates from Lucentis on the

promise of less frequent dosing; hence the

focus of their marketing strategy on dose

frequency.

• Compounding pharmacies continue to get high

demand for their low cost Avastin VEGF

treatment.

Source: Frost & Sullivan

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Marketed

Pre-

registration

Phase 2

Phase 1

Phase 3 AMD DME

RVO

Competitive Landscape

Total Retinal Therapeutics Market: Competitive Landscape, US, 2013

Eylea

(Regeneron)

Lucentis

(Genentech)

Macugen

(Valeant Pharmaceuticals/

Pfizer)

Lucentis

(Genentech)

Lucentis

(Genentech) Ozurdex

(Allergan)

Eylea

(Regeneron)

Fovista

(Archemix, Ophthotech)

Sirolimus

(MacuSight)

Sonepcizumab

(Lpath)

Squalamine

(Ohr Pharmaceutical)

Ruboxistaurin

(Eli Lilly)

Triamcinolone

(Allergan)

Eylea

(Regeneron)

Macugen

(Valeant Pharmaceuticals/

Pfizer)

Sirolimus

(MacuSight)

CNTO 2476

(Janssen)

Danazol

(Ampio)

Danazol

(Ampio)

Eculizumab

(Alexion)

Emixustat

(Acucela)

ESBA 1008

(Alcon)

ICO-007

(Isis)

Mecamylamine

(CoMentis)

Mecamylamine

(CoMentis)

MP 0112

(Molecular Partners)

MP 0112

(Allergan/Molecular

Partners)

Pazopanib

(GSK)

AAV2sFLT 01

(Genzyme / AGTC)

ACU 3223

(Acucela)

AKB 9778

(Aerpio

Therapeutics)

NOVA63035

(Novagali)

hI-con1

(Iconic

Therapeutic)

LD22-4

(Advanced Refractive

Technologies)

P 529

(Paloma)

Triamcinolone

(Icon Bioscience)

Triamcinolone

(Icon Bioscience) Volociximab

(Ophthotech)

X 82

(Tyrogenex)

Intravitreal Injection

Oral

Topical

ARC1905

(Ophthotech)

Source: Frost & Sullivan

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Marketed Product Analysis

Product Company Class Indication

US

Launch

Patent

Expiry Administration

Eylea

(aflibercept) Regeneron VEGFR1

AMD,

RVO 2011 2020

Intravitreal Injection/Bi-

monthly

Ozurdex

(dexamethasone) Allergan Steroid RVO 2009 2020–2024

Intravitreal

Injection/Monthly

Macugen

(pegaptanib)

Valeant

Pharmaceuticals/

Pfizer

VEGF-A AMD 2004 2017 Intravitreal Injection

Lucentis

(ranibizumab) Genentech

VEGFR1,

VEGFR2

AMD,

DME,

RVO

2006 2017, 2019 Intravitreal

Injection/Monthly

Total Retinal Therapeutics Market: Marketed Product Analysis, US, 2013

Source: Frost & Sullivan

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Pipeline Analysis

Total Retinal Therapeutics Market: Pipeline Analysis, US, 2013

Product Company Class Phase Indication Administration

Fovista

(E 10030) Archemix, Ophthotech PDGF-B 3 AMD Intravitreal Injection

Ruboxistaurin Eli Lilly PKC beta 3 DME Oral

Triamcinolone Allergan Steroid 3 DME Intravitreal Injection

Eylea

(aflibercept) Regeneron VEGFR1 3 DME Intravitreal Injection

Macugen

(pegaptanib)

Valeant

Pharmaceuticals / Pfizer VEGF-A 3 DME Intravitreal Injection

Sirolimus MacuSight mTOR 2 AMD, DME Intravitreal Injection

Sonepcizumab Lpath S1P 2 AMD Intravitreal Injection

Squalamine Ohr Pharmaceutical Angiogenic 2 AMD Topical

Source: Frost & Sullivan

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Pipeline Analysis (continued)

Source: Frost & Sullivan

Product Company MOA/Class Phase Indication Dose/Administration

CNTO 2476 Janssen Unknown 2 AMD Intravitreal Injection

Danazol Ampio Pharmaceuticals Antiangiogenic 2 AMD, DME Oral

Eculizumab Alexion C5 2 AMD Intravitreal Injection

Emixustat Acucela REP65 2 AMD Oral

ESBA1008 Alcon (Novartis) VEGF 2 AMD Intravitreal Injection

ICO 007 Isis/iCo Therapeutics c-Raf 2 DME Intravitreal Injection

Mecamylamine

(ATG 003) CoMentis

Nicotinic

acetylcholine

/Antiangiogenic

2 AMD, DME Topical

MP 0112 (AGN-

150998)

Allergan/Molecular

Partners VEGF-A 2 AMD, DME Intravitreal Injection

Pazopanib GlaxoSmithKline VEGFR2, PDGFR,

c-kit 2 AMD Intravitreal Injection

AAV2sFLT 01 Genzyme/AGTC Gene therapy 1 AMD Intravitreal Injection

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Pipeline Analysis (continued)

Product Company MOA/Class Phase Indication Dose/Administration

ACU 3223 Acucela Vitamin A derivative 1 AMD Oral

AKB 9778 Aerpio Therapeutics

HPTPβ

inhibitor/Tie-2

activator

1 DME Oral

NOVA63035 Novagali Steroid 1 DME Intravitreal Injection

hI-con1 Iconic Therapeutics hI-con1 1 AMD Intravitreal Injection

LD22-4 Advanced Refractive

Technologies Antiangiogenic 1 AMD Intravitreal Injection

P 529 Paloma

Pharmaceuticals

Dual TORC1/2

inhibitor 1 AMD Intravitreal Injection

Triamcinolone Icon Bioscience Steroid 1 AMD, RVO Intravitreal Injection

Volociximab Ophthotech Anti-α5β1 1 AMD Intravitreal Injection

ARC1905 Ophthotech Anti-C5 aptamer 1 AMD Intravitreal Injection

X 82 Tyrogenex VEGF 1 AMD Intravitreal Injection

Source: Frost & Sullivan

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Timeline of Key Events

2017 2016 2015 2014 2013 2012 2009 2010 2011

Fovista Approval

(Ophthotec)

Iluvien Approval

(Alimera)

RVO DME AMD

Total Retinal Therapeutics Market: Timeline of Key Events, US, 2009–2017

Source: Frost & Sullivan

Key Takeaway: Ophthotech’s Fovista has the potential to become an add-on therapy to VEGF

treatment in 2017.

Eylea Approval

(Regeneron)

Ozurdex Approval

(Allergan)

Lucentis Approval

(Genentech)

Eylea Approval

(Regeneron)

Eylea Approval

(Regeneron)

Lucentis Approval

(Genentech)

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Included below please find the detailed Table of Contents for Analysis of the US Retinal Therapeutics

Market: Improvements in Administration and Efficacy Drive Growth

For more information, please refer to the following slide for contact details.

Additional Sources of Information on Ophthalmic Disorders

• U.S. Retinal Therapeutics Market

• Analysis of the United States Glaucoma Pharmaceuticals Market

• Breakthroughs in Ophthalmic Devices and Drug Delivery Technologies (Technical Insights)

Additional Frost & Sullivan offerings:

• Talk to an analyst

• Take our DNA Survey

• Arrange a Growth Workshop

• Explore the Growth Excellence Matrix 2.0

• Attend a relevant live or virtual event

• Explore Healthcare Growth Consulting opportunities

Learn More—Next Steps

Source: Frost & Sullivan

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For More Information

Jennifer Carson Corporate Communications

(+1) 210.247.2450

jennifer.carson@frost.com

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Contents

Section Slide Number

Executive Summary 8

Market Overview 18

Competitive Playbook 21

Total Retinal Therapeutics Market –

• Drivers and Restraints 24

• Forecasts and Trends 27

Competitive Environment 36

AMD Segment Breakdown 50

DME Segment Breakdown 58

RVO Segment Breakdown 66

Key Companies to Watch 74

The Last Word 79

Appendix 85

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List of Exhibits

Exhibit Slide Number

Total Retinal Therapeutics Market: Market Engineering Measurements, US, 2012 13

Total Retinal Therapeutics Market: Market Segmentation, US, 2012 19

Total Retinal Therapeutics Market: Game-changing Strategies, US, 2013 23

Total Retinal Therapeutics Market: Key Market Drivers, US, 2012–2017 25

Total Retinal Therapeutics Market: Key Market Restraints, US, 2012–2017 26

Total Retinal Therapeutics Market: Market Engineering Measurements, US, 2012 28

Total Retinal Therapeutics Market: Revenue Forecast, US, 2009–2017 32

Total Retinal Therapeutics Market: Average Wholesale Price per Injection, US,

2009–2017 34

Total Retinal Therapeutics Market: Competitive Landscape, US, 2013 37

Total Retinal Therapeutics Market: Marketed Product Analysis, US, 2013 38

Total Retinal Therapeutics Market: Pipeline Analysis, US, 2013 39

Total Retinal Therapeutics Market: Absolute Market Share Trend by Revenue US, 2012

and 2017 43

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List of Exhibits (continued)

Exhibit Slide Number

Total Retinal Therapeutics Market: Company Market Share Analysis of Top 4 Participants,

US, 2012 44

Total Retinal Therapeutics Market: SWOT Analysis, US, 2013 44

Total Retinal Therapeutics Market: Timeline of Key Events, US, 2009–2017 46

Total Retinal Therapeutics Market: Patent Expirations, US, 2000–2030 47

Total Retinal Therapeutics Market, AMD Segment: Comparative Best Corrected Visual

Acuity from Baseline for Select Marketed Drugs, US, 2012 48

AMD Segment: Market Engineering Measurements, US, 2012 49

AMD Segment: Revenue Forecast, US, 2009–2017 52

AMD Segment: Prevalence and Treated Patient Forecast, US, 2009–2017 54

AMD Segment: Penetration Analysis, US, 2009–2017 56

DME Segment: Market Engineering Measurements, US, 2012 59

DME Segment: Revenue Forecast, US, 2009–2017 60

DME Segment: Prevalence and Treated Patient Forecast, US, 2009–2017 62

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List of Exhibits (continued)

Exhibit Slide Number

DME Segment: Penetration Analysis, US, 2009–2017 64

RVO Segment: Market Engineering Measurements, US, 2012 67

RVO Segment: Revenue Forecast, US, 2009–2017 68

RVO Segment: Prevalence and Treated Patient Forecast, US, 2009–2017 70

RVO Segment: Penetration Analysis, US, 2009–2017 72