OIS 2014 Year in Review

2014 – The Year in Review

Emmett Cunningham M.D., Ph.D., M.P.H.

Partner, Clarus Ventures, LLC

Save the Dates

7th Annual OIS@AAOLas Vegas, NevadaNovember 12th, 2015

4rd Annual OIS@ASCRSSan Diego, CaliforniaApril 16th, 2015

HASHTAG: #OISAAO

6th Annual OIS@AAO> 750 Attendees; 32 States & 22 Countries

29%

30%

7%

19%

15%

Corporate / Strategic Executive

Private Company Executive

Investment Professionals

Physician / Clinician

Media / Press / Consultants

OIS@AAO Advisory Board

K. Angela MacfarlaneForSight Labs

Sabri Markabi, MDAlcon

James MazzoAcuFocus

David W. Parke, MDAAO

Jane RadyAbbott Medical Optics

Calvin Roberts, MDBausch + Lomb

Murthy V. Simhambhatla, PhDAbbott Medical Optics

Richard L. Lindstrom, MDMinnesota Eye Consultants

Anthony P. AdamisGenentech

Mark S. Blumenkranz, MDStanford University

Eugene de Juan, MDForSight Labs

Andy CorleyYelroc

Malvina B. Eydelman, MDFDA

David R. Guyer, MDOphthotech

David KarcherASCRS

Michael Kaschke, MDCarl Zeiss

William J. Link, PhDVersant Ventures

Gilbert H. Kliman, MDInterWest Partners

Emmett T. Cunningham, MD, PhD, MPHClarus Ventures

Ellen Strahlman, MD, MHScBecton Dickinson

Scott M. Whitcup, MDAllergan

George Yancopoulos, MD, PhDRegeneron

Co-Chairs:

HASHTAG: #OISAAO

Drugs

0

20

40

60

80

100

120

140

19

88

19

89

19

90

19

91

19

92

19

93

19

94

19

95

19

96

19

97

19

98

19

99

20

00

20

01

20

02

20

03

20

04

20

05

20

06

20

07

20

08

20

09

20

10

20

11

20

12

20

13

20

14

Total Ophthalmic Approvals Total Approvals

Linear (Total Ophthalmic Approvals) Linear (Total Approvals)

Original NDA/BLA Approvals – 1988 to 2014Center for Drug Evaluation and Research

Data provided by :

Wiley A. Chambers, MDSupervisory Medical OfficerDivision of Transplant and Ophthalmology Products

• Range: 0 – 9• Mean: 4.4• Median: 4

Ophthalmic / Year: Stable

Original NDA/BLA ApprovalsCenter for Drug Evaluation and Research - FY2014

Data provided by :

Wiley A. Chambers, MDSupervisory Medical OfficerDivision of Transplant and Ophthalmology Products

October 1, 2013 thru September 30, 2014• Travoprost ophthalmic solution (IZBA®), 0.003%, for the reduction of elevated intraocular

pressure in patients with open-angle glaucoma or ocular hypertension, May 15, 2014 (NDA) – Alcon.

• Phenylephrine and ketorolac injection (Omidria®), 1% / 0/3%, to be added to an

ophthalmic irrigation solution used during cataract surgery or intraocular lens replacement; indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain, June 2, 2014 – Omeros

• Atropine ophthalmic solution, 1%, for cycloplegia, mydriasis and penalization of healthy eye

in the treatment of amblyopia, July 18, 2014 – Akorn

• Fluocinolone acetonide intravitreal insert (Iluvien®), 0.19 mg, for the treatment of

diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure, September, 29, 2014, Alimera Sciences

3.8% Ophthalmic

102

4

0

20

40

60

80

100

120

Ophthalmic

Non-Ophthalmic

Noteworthy Approvals …

Fluocinolone acetonide intravitreal insert (Iluvien®), 0.19 mg

FDA Approved, September, 29, 2014

EU Approved, 2012

Fluocinolone acetonide

Global Diabetic Macular Edema Patients

16.9% CAGR - Treated

•Improved Access to

Care

•New Products

0

5

10

15

20

25

30

2013 2020

Rest of World

Latin America

India

China

Other Wealthy Nations

Japan

Western Europe

United States

Market Scope ®Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/

27 M

23 M

2.5% CAGR

http://market-scope.com/

FAME Study Efficacy: Percentage of Patients With ≥ 15-Letter Improvement (Pooled Data)

Primary readout

28.7%

16.2%

P = .002

Campochiaro PA, et al. Ophthalmol. 2011;118:626-635; Campochiaro PA, et al. Ophthalmol. 2012;119:2125-2132. ILUVIEN Prescribing Information.

0

5

10

15

20

25

30

35

40

0 3 6 9 12 15 18 21 24 27 30 33 36

Control (n = 185)

0.2 µg/d FAc (ILUVIEN; n = 376)

> 15 Letters (%)

Cataract

IOP

Approved Dose

Global Ophthalmic Pharmaceutical Market Revenues by Specialty

7.910.3

4.3

5.02.8

3.63.9

4.1

0

5

10

15

20

25

2014 2019

Rev

enu

es B

illio

ns

US$

All Other

Dry Eye

Glaucoma Pharmaceuticals

IVT Anti-VEGF (AMD, DME, RVO, Etc.)

$18.9 Bn

$23.0 Bn

CAGR

0.5% Other

5.4% Dry Eye

3.1% Glaucoma

5.6% Anti-VEGF



IVT Injections….

Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz

-

2,000,000

4,000,000

6,000,000

8,000,000

10,000,000

12,000,000

14,000,000

16,000,000

18,000,000

2006 2007 2008 2009 2010 2011 2012 2013 2014

US OUS Total

Global IVT a – VEGF Injections

IVTa – VEGF Injections

Source: Market Scope Estimates Market Scope ®

16.4M

12.2M

4.2M

Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/

Most Growth OUS


IVT Injection vs Cataract ProceduresUSA , 2001 – 2016E

Williams GA. IVT injections: health policy implications. Review of Ophthalmology 2014; June:62-64.

IVT Injection > 2x Cataract

Wet AMD

Anti-VEGF for nAMD, DME, RVO

Market Scope ®

US Retina Specialist Treatment for Wet AMD

Usage Stable

Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/

2Q2013 2Q2014


Similar to abflibercept, conbercept (KH902; ChengduKanghong Biotech Co., Ltd., Sichuan, China) consists ofThe VEGF binding domains of the human VEGFR-1 andVEGFR-2 combined with the Fc portion of the humanImmunoglobulin….

Approved in ChinaDecember 6, 2013

Conbercept(Lumitin®)

(朗沐)

FovistaTM Phase 3 TrialsIn Wet AMD

Actively Recuriting

Fovista 1.5mg + Lucentis (N=311) Consistent w/Lucentis dosing schedule Q4W approved in EU*

Lucentis 0.5mg (N=311) Consistent w/Lucentis dosing scheduleQ4W approved in EU*

OPH1002N = 622

Year 1

Fovista 1.5mg + Lucentis (N=311) Q8W (pre-specified PRN therapy during Q4W non-treating months)

Lucentis 0.5mg (N=311) Q8W (pre-specified PRN therapy during Q4W non-treating months)

Fovista 1.5mg + Avastin 1.25mg /Eylea 2mg (N=311) Avastin: Q4W / Eylea: Q8WAvastin Q4W / Eylea Q4W for 3 months, then Q8W

Avastin 1.25mg / Eylea 2mg (N=311) Avastin Q4W / Eylea Q8WAvastin Q4W / Eylea Q4W for 3 months, then Q8W

Year 2

OPH1003N = 622

OPH1004N = 622

PrimaryEndpoint

DME

Courtesy Dr. David Sarraf

ScreeningHigh Risk PDR (71A)

Month 36Mild NPDR (35E)

24 Months - Ranibizumab:

• ~36% 2-Step improvement in

EDTRS DR severity

• ~ 3 Fold reduction in

progression to PDR

sBLA submitted August 7, 2014Action date February 6, 2015 (Priority Review)

Dry AMD

IVT Lampalizumab (Anti-Factor D Fab - 10mg) For Geographic Atrophy

Rate limiting enzyme in alternative complement cascade

Factor D

Anti-Factor D Fab

Phase 2 RCT (129 pts)

CFI + Biomarker44% Reduction in GA growth

CFI - BiomarkerNo Apparent Reduction in GA growth

IVT Lampalizumab(Anti-Factor D Fab)

For Geographic Atrophy

Sham

injection

Q4 weeks

10 mg

lampalizumab

Q6 weeks

10 mg

lampalizumab

Q4 weeks

Phase III GA populationN = 936 per study

Randomized 2:1:2:1

Sham

injection

Q6 weeks

N = 312CFI+: 188CFI: 124

N = 156CFI+: 94CFI: 62

N = 312CFI+: 188CFI: 124

N = 156CFI+: 94CFI: 62

‘Chroma’ and ‘Spectri’ Global Phase 3 TrialsActively Recruiting

Phase III Trials

Opus-2 and Sonata Phase 3 Results of Lifitegrast 5.0%

for Dry EyeTo be Submitted to the

FDA 1Q2015

> 1800 Patients

Lifitegrast 5.0%LFA Inhibitor

Dry Eye

Corneal Staining

Phase 2 Dry Eye Data*

39% Change from Baseline in Sign

Mean Change in Total CFS (EE50 Population)

CF

S C

hang

e fr

om B

asel

ine

Weeks on Treatment

61% Change from Baseline in Symptom

Vehicle Control (n=15)

Combined EBI-005 Treatment (n=20)

Mean Change in Score on Painful or Sore Eyes OSDI Question (EE50 Population)

Weeks on Treatment

Pai

n C

hang

e fr

om B

asel

ine

* Not statistically significant at 6 weeks

Receptor

EBI-005

Phase 3 Dry Eye Trials Recruiting(data 1H2015)

Positive Phase 2 data inAllergic Conjunctivitis†

Topical IL-1R Blocker

†Secondary and Exploratory Endpoints

EBI - 005

Humira®

(Adalimumab)

International Phase 3 Studies Recruiting in Non-Infectious Intermediate, Posterior, and

Panuveitis / Behcet’s Disease

IgG1 Fc

Fab

Anti - TNFa

Gevokizumab ( anti-IL-1b ) Non-Infectious and Behcet’s Uveitis

Four Phase 3 Trials Actively Recruiting• > 700 patients • Active and Controlled

Non-Infectious intermediate, posterior, and panuveitis

• Active and Controlled Behcet’s Disease

• Data 1H2015

RhopressaTM

Triple MOAROCKi /NETi, EVP Reduction

Data mid-2015

Phase 2b (221 Patients)0.01% Rhopressa TM vs 0.02% Rhopressa TM vs Latanoprost

Majority of Glaucoma Patients

RhopressaTM & LatanoprostClinically and

Statistically Equivalentat Days 14 and 28

Pre-Specified Subgroup Analysis

Baseline Day 14 Day 28 Baseline Day 14 Day 28

Phase 3 Studies Recruiting

15.0

17.0

19.0

21.0

23.0

25.0

27.0

Diurnal Average IOP (Entire Cohort; Entry IOP 22-36 mmHg)

( n = 221 )

0.01% AR-13324 0.02% AR-13324 Latanaprost

15.0

17.0

19.0

21.0

23.0

25.0

27.0

Diurnal Average IOP (Moderate IOP; Entry IOP 22-26 mmHg)

( n = 106 )

0.01% AR-13324 0.02% AR-13324 Latanaprost

Gene Therapy in Ophthalmology At the Tipping Point ?

Sisyphus Snowball

Tipping Point

Devices

0

20

40

60

80

100

120

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

510(k) Original and Panel Track PMA

Linear (510(k)) Linear (Original and Panel Track PMA)

Original 510(k) & PMA Received – 2004 to 2014Center for Devices and Radiological Health

Data provided by :Malvina B. Eydelman, MDDirectorDivision of Ophthalmic, and Ear, Nose and Throat Devices, FDA

• Range: 1 – 9• Mean: 4.2• Median: 4

PMAs Stable

• Range: 53 - 104• Mean: 70• Median: 63

510(k)s Increasing

3.1% of Total


2414

76

0

500

1000

1500

2000

2500

Ophthalmic

Non-Ophthalmic

510(k) ClearancesCenter for Devices and Radiological Health - FY2014

5.6% of Total

October 1, 2013 thru September 30, 2014• ReSure® Sealant, for use in stopping fluid from leaking through the incision in a

patient’s cornea after cataract surgery with intraocular lens placement in adults –Ocular Therapeutix.


17

1

0

2

4

6

8

10

12

14

16

18

20

Ophthalmic

Non-Ophthalmic

PMA ApprovalsCenter for Devices and Radiological Health - FY2014

Noteworthy Approvals …

Clinical Trial Results:

• Superiority over sutures for prevention of wound leaks (p<0.0001)

• Significantly less AEs in ReSure group vs. suture group (p<0.0001)

• Well tolerated

• Commercial launch 1Q2014

FDA ApprovedJanuary 8, 2014

4.1%

34.1%

0%

10%

20%

30%

40%

50%

ReSure Sealant(n=295)

Suture(n=176)

Leak Rate (PMA)

* P<0.0001

HeliosTM Insert

Punctal Plug

Punctal Plug

Sustained ReleaseDrugs for Glaucoma

Funding

$651$665 $660 $666

$670

$688$706 $701 $702

$656

$674 $675

$820$810

$779$764

$740

$763$770

$741

$727

$670

$500

$550

$600

$650

$700

$750

$800

$850

2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015E

NEI (Actual) NEI (2014$)

NEI Funding Flat, but …Down ~25% after Inflation (2014$)

28% of RO1s Funded

Inflation Calculatorhttp://data.bls.gov/cgi-bin/cpicalc.pl

Data provided by :

Matthew McMahon, Ph.D.Director, Office of Translational Research, NEI

$0

Source: PricewaterhouseCoopers, Silicon Valley Bank

Total VC vs BioPharma vs Medical Device Investments (2000-2013)

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

$-

$10

$20

$30

$40

$50

2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013

Bill

ion

s

Total VC $ BioPharma Device

$99 Bn Healthcare ~ $4Bn

Courtesy Jon Norris, SVB

Lifescience Venture Capital Funding Gap

$6.0

$7.3

$9.1

$8.6

$6.6 $6.3

$7.7

$6.7

$6.7

$3.4

$6.6

$7.9

$6.1

$5.2

$1.8

$3.7 $3.6

$3.9

$0.0

$1.0

$2.0

$3.0

$4.0

$5.0

$6.0

$7.0

$8.0

$9.0

$10.0

2005 2006 2007 2008 2009 2010 2011 2012 2013

Invested ($Bn)Fundraised ($Bn)

Source: PricewaterhouseCoopers, Silicon Valley Bank Courtesy Jon Norris, SVB

$2.8 Bn(1.7x Gap)

0

100

200

300

400

500

600

0

5

10

15

20

25

30

Total D

ollars In

veste

d ($

M)

Nu

mb

er

of

Ve

ntu

re D

eal

s fo

r D

rug

and

Dev

ice

# Rx Deals # Device Deals VC Investment ($USD, Millions)

business intelligence*2014 figures through SeptemberSOURCE: Strategic Transactions

Ophthalmic Investments by VCs Over Time1999 – 2014*

VC Funding Stable• ~ $400M / year• 15 – 20 deals

VC Investment By Ophthalmic Indication (1999-2014*)

*2014 figures through SeptemberSOURCE: Strategic Transactions

47

36

2118

12 118 7

12

73 4

0

5

10

15

20

25

30

35

40

45

50

0

100

200

300

400

500

600

700

800

900

1,000

1,100

1,200

Nu

mb

er of D

eals

Pri

vate

Pla

cem

ents

($

M)

Dollars ($ Millions) Number of deals

“One final question…Are we merging or are they?”

$600M

Undisclosed

$160M

$8M upfrontUp to $640M

0%

20%

40%

60%

80%

100%

120%

2006 2007 2008 2009 2010 2011 2012 2013

Biopharma

Non-Structured Structured

0%

20%

40%

60%

80%

100%

120%

2005 2006 2007 2008 2009 2010 2011 2012 2013

Device

Non-Structured Structured

Staged Buy-Outs Continue to beCommon for Private Companies

Courtesy Jon Norris, SVB

~50% ~80%

50%

100%

150%

200%

250%

300%

350%

400%

450%

2004 2006 2008 2010 2012 2014

10-year Stock Price Performance

53%

292%

Source: FactSet as of 09/16/141 Medtech index consists of medical technology companies traded on North American exchanges with market capitalizations over $1bn

78%

Returns summary

10 yr 5 yr YTD

Medtech1

63%

Biotech235%

S&P 50087%

16%

19%

9%

Best Three Years for Biotech in a Decade

Ophthalmology IPO MarketMost Active in 15 Years

2

0 0 0

4

1 1

2

0 0

2

9

0

100

200

300

400

500

600

700

0

1

2

3

4

5

6

7

8

9

10

2000 2001 2002 2003 2004 2005 2006 2010 2011 2012 2013 2014

Total Raised ($M) # of deals

# $M

Courtesy Tom SalemiExcludes 2002 Alcon IPO

IPOs In Ophthalmology –The Class Of 2014 & Beyond

Susan WasherPresident & CEO

AGTC

Vicente Anido, Jr., PhD CEO

Aerie Pharmaceuticals

Amarpreet Sawhney, PhD President and CEO Ocular Therapeutix

Brian Johnson Partner

WilmerHale

Thomas W. Chalberg, PhD Founder & CEO

Avalanche Biotechnologies

Michael Gaito Managing Director,

Head of West Coast Life Sciences J.P. Morgan

David R. Guyer, MDCEO

Ophthotech

MODERATOR

Industry Consolidation: The Good, The Bad & The Unknown

Jeff George President & Global Head

Alcon

William J. Link, PhD Managing Director Versant Ventures

David E.I. PyottCEO

Allergan

Murthy V. Simhambhatla, PhD President

Abbott Medical Optics

Ashley McEvoyCompany Group Chairman

Johnson & Johnson Vision Care

James Mazzo Chairman & CEO

AcuFocus

MODERATOR

Please Watch the Clock . . . .

[email protected]

ADDITIONAL SLIDES

Cataract, RLE, Phakic IOLs-23.4M

44%

Laser Refractive 3.3M6%

IVT Injections 16.5M31%

Laser Photocoagulation 1.9M

4%

Vitrectomies 1.4M3%

Glaucoma Laser 2.1M

4%

Glaucoma Filtering, Shunts, etc. 0.6M

1%

All Other 3.7M7%

Global Ophthalmic Procedures2014 (53.0 M)



0

5,000

10,000

15,000

20,000

25,000

30,000

2013 2019

Tho

usa

nd

s o

f P

roce

du

res

(ey

es)

Conventional Phaco Femto Laser Plus Phaco (FLCS) ECCE & Other

FLCS (2.0%)

FCLS (8.4%)

Total Phaco 66.4%

Total Phaco 70.1%

ECCE / OTHER 21.5%

ECCE / OTHER 31.6%

Global Cataract/RLE Procedures by Equipment Technology



0

500

1,000

1,500

2,000

2,500

2014 2019

Tho

usa

nd

s o

f P

roce

du

res

(ey

es)

Femto Laser PlusPhaco (FLCS)

Forecast 2014-2019 CAGR 36.5%

Expected 2013-2014 Growth 50.8%

Global Femtosecond Cataract Surgery Procedures


450K

2.1M


64 64 62

44 4654

20

42

255

0

50

100

150

200

250

300

2013 2014 (Forecast) 2019 (Forecast)

US

Gla

uco

ma

Su

rger

ies

(00

0)

Filtration Tube Shunts MIGS

US Glaucoma Surgical Procedures



0

200

400

600

800

1,000

1,200

1,400

2013 2014 2015 2016 2017 2018 2019

Tho

usa

nd

s o

f P

roce

du

res

(ey

es)

ATGS Procedures

Shunts

Filtering Surgery

Global Glaucoma Procedures(Excluding Laser Procedures)


690K

114K

341K


Biotech IPO Window Open, but Average Return Dropping

14

41

79

0

10

20

30

40

50

60

70

80

90

$0

$1,000

$2,000

$3,000

$4,000

$5,000

$6,000

2012 2013 2014

Total Cumulative $s Raised

# of Offerings

$M

Avg. Raise• 2012: $65.7M• 2013: $75.3M• 2014YTD: $65.9M

Avg. Mkt Cap• 2012: $341.9M• 2013: $374.7M• 2014YTD: $263.1M

Avg. Return: 45%* 49% 2%*Excluding extreme outliers:Puma Biotechnology (1331%) and Intercept Pharmaceuticals (1418%)

As of 10/9/2014Courtesy Doug Fisher

Phase III Trials

Date post:	14-Apr-2017
Category:	Healthcare
Upload:	healthegy
View:	355 times
Download:	0 times