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2015 – The Year in Review
Emmett Cunningham M.D., Ph.D., M.P.H.
Partner, Clarus Ventures, LLC
OIS Attendance Over Time
0
100
200
300
400
500
600
700
800
900
1000
2009 2010 2011 2012 2013 2014 2015
> 900
> 400
OIS@AAO
OIS@ASCRS
OIS@AAO 2015
Perspectives May Differ
Drugs
Original NDA/BLA Approvals – 1988 to 2015
Center for Drug Evaluation and Research
Data provided by :
Wiley A. Chambers, MD
Supervisory Medical Officer
Division of Transplant and Ophthalmology Products
0
20
40
60
80
100
120
140
Total Ophthalmic Approvals Total Approvals
Linear (Total Ophthalmic Approvals) Linear (Total Approvals)
• Range: 0 – 9
• Mean: 4.4
• Median: 4
Ophthalmic / Year: Stable
Original NDA/BLA Approvals
Center for Drug Evaluation and Research - FY2015
Gary Novack, PhD
Pharma . Logic Consulting, Inc.
111
2
0
20
40
60
80
100
120
Ophthalmic
Non-Ophthalmic
October 1, 2014 thru September 30, 2015
• Olopatadine ophthalmic solution (PAZEO®), 0.7%, a mast cell stabilizer
indicated for the treatment of ocular itching associated with allergic conjunctivitis,
January 30, 2015 (NDA) – Alcon Res, LTD.
• Phenylephrine hydrochloride (Phenylephrine Hydrocloride), 2.5% &
10%, an alpha-1 adrenergic receptor agonist indicated to dilate the pupil, January 15,
2015 (NDA) – Akorn, Inc.
1.8% Ophthalmic
Data provided by :
Wiley A. Chambers, MD
Supervisory Medical Officer
Division of Transplant and Ophthalmology Products
Phase III Trials
Positive Phase 3 Trial of SPK-RPE65
for the treatment of RPE65-
mediated inherited retinal
dystrophies (IRDs).
BLA Submission 2016
*As measured by the change in bilateral mobility testing between baseline and one year. The multicenter, pivotal Phase 3 trial randomized 31
subjects with confirmed RPE65 gene mutations. The ITT population included 21 subjects in the intervention group and 10 in the control group.
Leo A. The Gene Therapy Renaissance. April 18, 2013.
http://hms.harvard.edu/news/gene-therapy-renaissance-4-18-13
0
1
2
3
4
5
6
BL D30 D90 D180 Y1
Luxscore,bilateral
Study visit
Intervention Control
Mean MT Lux Score/Level - Bilateral
(mITT/safety population, n=29)
Humira®
(Adalimumab)
Positive Phase 3 Studies in
Non-Infectious Intermediate,
Posterior, and Panuveitis /
Behcet’s Disease
IgG1 Fc
Fab
Anti - TNFa
Vision-1 & 2 Studies Met Primary Endpoint
Of Prolonging Time to Treatment Failure.
FDA Filing Submitted. Approval Anticipated
By 4Q2016
http://acrabstracts.org/abstract/adalimumab-in-patients-with-inactive-non-infectious-uveitis-requiring-systemic-treatment/
http://abbvie.mediaroom.com/2015-05-05-AbbVie-Announces-Pivotal-Phase-3-Data-Evaluating-Efficacy-and-Safety-
of-HUMIRA-adalimumab-in-Patients-with-Non-Infectious-Intermediate-Posterior-or-Panuveitis
Lifitegrast 5.0%
LFA Inhibitor
Dry Eye
Corneal Staining
OPUS-3 Phase 3 Trial Met Primary (12 wks) & Key Secondary
(2 & 6 wks) Endpoints - Improvement in Dry Eye Symptoms
Data to support FDA
resubmission 1Q2016
Phase 2 Dose Ranging
Latanoprostene bunod
ophthalmic solution 0.024%
NDA Submitted, July 24, 2015
Expected US Launch, 2H2016
July, 2016 PDUFA
http://ir.valeant.com/investor-relations/news-releases/news-release-details/2014/Bausch--Lomb-and-Nicoxs-
Glaucoma-Candidate-VESNEO-latanoprostene-bunod-Meets-Primary-Endpoint-in-Phase-3-Studies/default.aspx
Met Phase 3 Primary Endpoint
Non-Inferiority vs Timolol
Once Daily ROCK / NET Inhibitor
Lowers EVP
Preparing NDA Filing for
RhopressaTM in 3Q2016
Rocket 2
Rocket 1
Rocket 2 met
primary endpoint –
non-inferior to
Timolol
Rocket 1 met
secondary endpoint –
supportive
Upcoming
Milestones …
FovistaTM Phase 3 Trials
In Wet AMD
Combined Trial Data 4Q2016
Fovista 1.5mg + Lucentis (N=311) Consistent w/Lucentis dosing schedule
Q4W approved in EU*
Lucentis 0.5mg (N=311) Consistent w/Lucentis dosing schedule
Q4W approved in EU*
OPH1002
N = 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: Q8W
Avastin Q4W / Eylea Q4W for 3 months, then Q8W
Avastin 1.25mg / Eylea 2mg (N=311) Avastin Q4W / Eylea Q8W
Avastin Q4W / Eylea Q4W for 3 months, then Q8W
Year 2
OPH1003
N = 622
OPH1004
N = 622
Primary
Endpoint
• Positive Phase 2 results reported in
allergic conjunctivitis - October, 2014
• Phase 3 trial in moderate to severe
allergic conjunctivitis topline data
expected 1Q 16
• Potential BLA filing 2H 17
Phase 2 AC Data
Receptor
EBI-005
Treating late phase response as
shown by separation over 5 hours
Isunakinra (EBI-005):
Topically administered
IL-1 receptor blocker
p=0.033
p=0.046
Phase 2 Data
Anticipated 2016
X-linked retinoschisis (XLRS)
http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/XLRS.htm
https://clinicaltrials.gov/ct2/show/NCT02510794?term=ranibizumab+sustained&rank=2
Ranibizumab (RBZ) Port Delivery System (RPDS)
For Wet AMD – LADDER Trial
Phase 2 Data 1H2017
Global Ophthalmic Pharmaceutical Market
Revenues by Indication
Market Scope ®Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/
9.3
16.5
4.7
6.1
3.1
3.7
3.8
4.2
0
5
10
15
20
25
30
35
2015 2020
$20.9 Bn
$39.5 Bn
Anti-VEGF/Retina
Glaucoma
Dry Eye
All Other
IVT Injections….
Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz
Global IVT a – VEGF Injections
Source: Market Scope Estimates Market Scope ®
4.6M
Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/
0
5
10
15
20
25
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
United States Outside United States Global
(M)
17.6M
22.2M
Most Growth OUS
Anti-VEGF for nAMD, DME, RVO
Market Scope ®
US Retina Specialist Treatment for Wet AMD
Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/
0.0%
10.0%
20.0%
30.0%
40.0%
50.0%
60.0%
70.0%
Q3-2013 Q3-2014 Q3-2015
Lucentis Eylea Avastin Other
61%
23%
12%
4%
Avastin
Eylea
Lucentis
Other
How Would You Treat a
New wet AMD Patient?
0.9%
13.7%
21.1%
64.3%
1.9%
34.5%
24.5%
39.4%
0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00%
Other
Lucentis
Eylea
Avastin
Ex-USA USA
2015 Membership Survey
Bevacizumab Ranibizumab
Am J Ophthalmol 2014, 157:825-833.
Study-Enforced
Compliance
Results in
4-5 Letter
Increased
Mean Gain –
As Much
As Effective
Add-On Therapy
Strong Correlation Between
Injection Frequency and Vision Gain
Scientific
Breakthrough …
Nature. 2015 Jul 30;523(7562):607-11.
“Sterol eye drops reverse
cataracts in mice”
51%
8%
5%
4%
4%
3%
3%
1%
21%
Cataract
Glaucoma
AMD
Corneal Opacity
Childhood
Refractive Error
Trachoma
Diabetic Retinopathy
Undetermined
Global Causes of Blindness
World Health Organization - 2010
http://www.who.int/blindness/data_maps/en/
Global Ophthalmic Procedures - 2015
Vitrectomies
Laser
Photocoagulation
IVT Injections
Cataract, RLE,
Phakic IOLs
Laser Refractive
Glaucoma Filtering, Shunts, MIGs
Glaucoma Laser
All Other
22.2M
Market Scope ®Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/
Sterols target crystallin to restore lens
transparency in mouse models of cataracts
Slit lamp biomicroscopy photographs from R120G
cryAB mice dosed topically with c29 eyedrops
c29Vehicle
Lens
Opacity
(Cataract)
Transparency
Recovered
c29 binds and stabilizes the dimer
of cryAB to reverse aggregation
www.viewpointtherapeutics.com
Devices
3007
73
0
500
1000
1500
2000
2500
3000
3500
Ophthalmic
Non-Ophthalmic
2.4% of Total
510(k) Clearances
Division of Ophthalmic and Ear, Nose and Throat Devices - FY2015
Data provided by :
Malvina B. Eydelman, MD
Director
Division of Ophthalmic, and
Ear, Nose and Throat Devices, FDA
Lee Kramm, MD, MSE & Judy Gordon, DVM
ClinReg Consulting Services, Inc.
0
10
20
30
40
50
60
70
80
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
PMA 510(k)
PMA Approvals & 510(k) Clearances – 2004 to 2015
Division of Ophthalmic and Ear, Nose and Throat Devices
73
4
Data provided by :
Malvina B. Eydelman, MD
Director
Division of Ophthalmic, and
Ear, Nose and Throat Devices, FDA
Lee Kramm, MD, MSE & Judy Gordon, DVM
ClinReg Consulting Services, Inc.
PMA Approvals
Division of Ophthalmic and Ear, Nose and Throat Devices- FY2015
53
4
0
10
20
30
40
50
60
Ophthalmic
Non-Ophthalmic
7.0% of Total
October 1, 2014 thru September 30, 2015
• Kamra® Inlay
• AcrySof® IQ ReSTOR® +2.5 D Intraocular Lens (IOL)
• TECNIS® MULTIFOCAL IOL,+2.75 D and +3.25 D
• STAR S4 IR Excimer Laser System and iDesign Advanced
WaveScan Studio System
Data provided by :
Malvina B. Eydelman, MD
Director
Division of Ophthalmic, and
Ear, Nose and Throat Devices, FDA
Lee Kramm, MD, MSE & Judy Gordon, DVM
ClinReg Consulting Services, Inc.
Noteworthy Approvals …
FDA Approved*
April 17, 2015
*For intrastromal corneal implantation to improve near vision by extending the depth of focus in the non-dominant eye of phakic,
presbyopic patients between the ages of 45 and 60 years old who have cycloplegic refractive spherical equivalent of +0.50 D to -0.75 D
with less than or equal to 0.75 D of refractive cylinder, who do not require glasses or contact lenses for clear distance vision, and who
require near correction of +1.00 D to +2.50 D of reading add.
US Commercial Lauch May, 2015.
Over 1000 KAMRA inlay surgeries completed to date.
FDA Approved*
De Novo Classification
June 18, 2015
*The BrainPort V100 is an oral electronic vision aid that provides electro-tactile stimulation to aid profoundly blind patients in
orientation, mobility, and object recognition as an adjunctive device to other assistive methods such as the white cane or a guide dog.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451779.htm
De Novo Approvals – 2004 to 2015
Center for Devices and Radiological Health
0
5
10
15
20
25
30
2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
de novo 510(k)
Increasing Number of De Novo Approvals
“A regulatory pathway for some low- to moderate-risk medical devices that are not
substantially equivalent to an already legally-marketed device.”
LipiFlow®
Thermal Pulsation System
TearScience® , Inc.; June, 2011
BrainPort® V100
Oral Visual Aid Device
Wicab, Inc.; June, 2015
Data provided by :
Malvina B. Eydelman, MD
Director
Division of Ophthalmic, and
Ear, Nose and Throat Devices, FDA
Lee Kramm, MD, MSE & Judy Gordon, DVM
ClinReg Consulting Services, Inc.
Upcoming
Milestones …
Raindrop ® Near Vision Inlay
PMA Submission Accepted by FDA
November 10, 2015
CyPass® Micro-Stent
CyPass® Micro-Stent
PMA Submission
Accepted by FDA
October, 2015
“Pivotal COMPASS
Trial Results
Positive through
Two Years”
http://transcendmedical.com/intent-to-file-premarket-approval-application-with-fda/
Handheld
Unit
Disposable Tip
with Hydrogel
Lacrimal Gland
Pivotol Study Ongoing
De Novo Classification
FDA Filling Anticipated 3Q2016
Funding
NEI Funding Flat, but …
At 1999 Level After Adjusting for Inflation
Data provided by :
Mala Dutta, Ph.D.
Office of Translational Research, NEI
$676K
$411K
10.4%10.5%
9.0%
7.2%
3.8% 4.1%
8.7%
15.0%
19.1%19.2%
17.3%
18.1%
18.7%
17.1%
19.3%
16.9%
15.8%15.5%15.3%
12.5%12.4%
0.0%
5.0%
10.0%
15.0%
20.0%
25.0%
Percent of Total Venture Capital Invested in Biotech
Relative Biotech
Investing Down
0
5
10
15
20
25
30
Billions($)
Venture Capital Investments Over Time
Biotech Software
Absolute Biotech
Investing Up at ~ $5.6 Bn
0
100
200
300
400
500
600
700
800
900
1000
Number of "First Financings" of New Startups
Biotech Software
Absolute Biotech
Deals Stable ~ 100 Deals/Year
Source: PricewaterhouseCoopers, Silicon Valley Bank
Total VC vs Biotech vs Device
Investments (2001-2015)
Courtesy Jon Norris
$0
$5
$10
$15
$20
$25
$30
$35
$40
$45
$50
Total VC Dollars ($Bn) Biotech ($Bn) Device ($Bn)
$1.9Bn
$5.6Bn
$47Bn
Biotech + Device Venture Capital
Invested vs Raised
Source: PricewaterhouseCoopers, Silicon Valley Bank
$6.0
$7.3
$9.1
$8.6
$6.6
$6.3
$7.7
$6.7
$6.7
$8.6
$3.4
$6.6
$7.9
$6.1
$5.2
$1.8
$3.7 $3.6
$3.9
$6.1
$0.0
$1.0
$2.0
$3.0
$4.0
$5.0
$6.0
$7.0
$8.0
$9.0
$10.0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
Invested ($Bn)
Fundraised ($Bn)
Courtesy Jon Norris
Amounts Up Significantly ~28%
Gap Narrowing
business intelligence
Ophthalmic Investments Over Time (1999 – 2015*)
1 2 2
5 5
8
10
3
10
5
11
7
13
11
9
5
2
1 5
2 3
9 5
7
14
9
10
6
11
8
1
0
100
200
300
400
500
600
0
5
10
15
20
25
30
# Biotech Deals # Device Deals VC Investment ($USD, Millions)
*2015 figures through October
SOURCE: Strategic Transactions
Ophthalmic
VC Funding Stable
~ $400 - 500M / year
Fewer Device Deals
($M)# Deals
77
30
22 22 21 19
16
11 9 9
0
10
20
30
40
50
60
70
80
90
Courtesy Jon Norris
US Biotech Series A
Investments* By Indications – 2009 to 3Q2015
* > $2M
Courtesy Jon Norris
US Device Series A
Investments* By Indications – 2009 to 3Q2015
* > $2M
46 45
42
29
26
14
11 10
5 5
0
5
10
15
20
25
30
35
40
45
50
VC Investment By Ophthalmic Indication (1999-2015*)
*2015 figures through October
SOURCE: Strategic Transactions
49
37
21
19
12
14
10 7
14
10
3
4
0
10
20
30
40
50
60
0
100
200
300
400
500
600
700
800
900
1,000
1,100
1,200
NumberofDeals
PrivatePlacements($M)
Dollars ($ Millions)
Number of Deals
Biotech Stock Index (NBI) Continues Upward
Despite Corrections . . .
2008
Courtesy David Nierengarten, Wedbush
(M)
IPOs Completed in the USA by Sector
1995 to 2015
One in Six IPOs in Healthcare
Courtesy David Nierengarten, Wedbush
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Percent of All VC-Backed IPOs by Sector
Biotech Software Other
50% of Recent
VC-Backed IPOs Biotech
0
20
40
60
80
100
120
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Ophtho
Medtech
Biotech
Recession
- 398
- 312
- 27
Healthcare IPOs by Year - Cyclic
Courtesy David Nierengarten, Wedbush
?
?
Ophthalmology IPOs by Year - Cyclic
1
2
4
1 1
3
1 1 1
2
6
4
0
1
2
3
4
5
6
7
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Recession
Courtesy David Nierengarten, Wedbush
Positives
• Unemployment, low
• Inflation, low
• Interest rates, low
• Consumer spending, continues
Negatives
• GDP, modest
• Business spending, low
Economic
Indicators
Mostly Positive
Courtesy David Nierengarten, Wedbush
Yield Curve Spread Over 20 Years
(Treasury Interest Rates - 10 year - 2 year Spread)
Yield Curve Spread
Inversion
Pre-dates Recession Recession
Inversion Inversion
Yield Curve Spread Suggests Further Growth
Yield Curve Spread
Still Positive ~ + 1.5
Courtesy David Nierengarten, Wedbush
“The four most expensive words in
the English language are…”
‘This time is different.’
Sir John Templeton
(November 29, 1912 – July 8, 2008)
Mergers &
Acquisitions
Biotech & Medtech M&A Activity
2005 to 3Q2015
Courtesy Joe Gilliam
42
49 51
32
36
53 52
45 46
50
46
9
34
27 27
23 25
28
17
21
18
36
0
10
20
30
40
50
60
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Medtech Biotech
Private Company Acquisitions
Possible Trend Toward Fewer Structured Deals
~ 40% Structured ~ 65% Structured
Courtesy Jon Norris
0%
20%
40%
60%
80%
100%
Biopharma
Non-Structured Structured
0%
20%
40%
60%
80%
100%
Device
Non-Structured Structured
$300M
$125M + Undisc CVP
$66Bn
$50M + Undisc CVP
$300M + Undisc CVP
$124M + $1.1Bn CVP
$51M + $291M CVP
$20M $379M
An Eye on India and China
1.3 Bn 1.4 Bn
“Necessity may be the mother in invention”*
BUT
“Prosperity is the father of innovation…..”
*“...let us begin and create in idea a State; and yet a true creator is necessity, which is the mother of our invention.”
The Republic, Book II, 369c, Plato
Plato
A strong and sustained culture of innovation is predicated upon a
strong economy with real or perceived discretionary spending…
Global Contribution to World's GDP by
Major Economies from 1 AD to 2003 AD
Maddison A (2007), Contours of the World Economy I-2030AD,
Oxford University Press, ISBN 978-0199227204
Projected Relative Global Economies
2011 – 2030 - 2060
23% 28%
16%
17%
28%
28%
6%
11%
18%17%
12% 9%
18%
15% 14%
12%
12% 12%
7% 4% 3%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2011 2030 2060
USA
China
India
Euro Area
Other OECD
Other non-OECD
Japan
An Eye on India and China
Intas Pharmaceuticals
Launches Razumab
‘Similar’ to Ranabizumab
Kanghong Biotech
Launches Combercept
‘Similar’ to Afilbercept
Sun Pharma
Acquires Insight - $48M
Emerging Centers of Innovation
http://ois.net/category/podcast/ 64 Episodes
with Over
14,000 Plays
To Date …
Tom Salemi
tom@healthegy.com
Save the Dates
5th Annual OIS@ASCRS
New Orleans, LA
May 5th, 2016
8th Annual OIS@AAO
Chicago, Illinois
October 13th, 2016
HASHTAG: #OISAAO
ecunningham@clarusventures.com
Jonathan Piazza
Director
jonathan.piazza@barclays.com
650-289-6046
Will Han
Analyst
william.han@barclays.com
650-289-6147
1
(SkQ1)
/
(KPI-121 – Cataract surgery
inflammation)
Ophthalmic Opportunity Roadmap
Glaucoma Dry Eye AMD Other
(IBI-10090 – Cataract surgery
inflammation)
_________________________
Source: Company information.
(IVT & Oral Kallikrein Inhibitor Program – DME)
(Eylea – Wet AMD, DME)
/
(Pan-90806 topical – Wet AMD)
(Jetrea – VMA)
Marketed
Phase III
Phase II
Phase I
Pre-
Clinical
(AKB-9778 – DME)
(Lifitegrast)
(GS010 – Gene
therapy for LHON)
(RST-001 – Gene therapy
for RP & Dry AMD)
(Gene therapy for wet AMD and XLRP)
(ACU-4429 – Dry AMD)
/
(BOL-303259-X)
/
(INO-8875)
(ALK-001 – Stargardt disease)
(SPK-RPE65 – Gene therapy for
inherited retinal dystrophies)
(Gene therapy for
Glaucoma-GT)
/
(Gene therapies for multiple indications)
/
(Anti-VEGF +
Anti-PDGF)
/
(AAV.REP1 for choroidemia)
(RetinoStat – Gene therapy for Wet AMD)
(hI-con1 – Wet AMD)
(KPI-121)
(ENV515)
(ENV905 – Cataract
surgery inflammation)
(AVA-101 – Gene therapy for Wet AMD)
/
(PF582 – Wet AMD)
(Fovista – Wet AMD)
/
(X-82 oral anti-VEGF + anti-
PDGF – Wet AMD)
(QLT091001 –
LCA and RP)
(Ocuvia – DME)
/
(ALG-1001 – DME)
/
(NS2 – SLS, Non-infectious uveitis)
(HuCNS-SC – Geographic Atrophy AMD)
(OpRegen – Dry AMD)
(hPRC Therapy for Retinitis Pigmentosa)
(EBI-005 – Allergic Conjunctivitis)
(RG7716 combo anti-VEGF/Ang2)
(Rhopressa & Roclatan)
(DARPin, Anti-VEGF / MP0112 – Wet AMD & DME)
/
(OTX-DP)
(OTX-TP)
(OTX-MP Moxifloxacin for bacterial conjunctivitis)
(OTX-DP for
allergy)
(Helios insert)
Presbyopia
Therapies
(Liquid Vision – Presbyopia)
(RGN-259/GBT-201)
(OPT-302 – Wet AMD)
(rAAV-hRS1 – Gene therapy for XLRS)
/
(MIM-D3)
/
(L-PDDS)
(Eye-D Insert)
(EGP-437)
(Cis-UCA)
(Cross-linked hyaluronic
acid)
(CycloASol)
(NT-503 – Wet AMD)
(TT-211/TT-231)
(RhoNova – Gene
therapy for RP
(PRO-001 for RP)
(FB-08I8 for RP)
(RPE – Stargardt & Dry AMD)
/
Ophthalmology M&A Activity
___________________________
Source: Company information, ThompsonSDC.
Therapeutics
($ in millions)
Devices
Date Target Acquiror Size Upfront Milestone Description
9/29/2015 Chauvin Opsia Cutting Edge Undisc. Undisc. Undisc.
Manufacturer and developer of intraocular implants designed to
perform cataract surgeries
9/3/2015 AqueSys Allergan $300 $300 $0
XEN45 soft ocular shunt for treatment of glaucoma-related
intraocular pressure
9/2/2015 Synergetics Valeant Pharmaceuticals 192 166 26 Vitreoretinal surgical devices
7/13/2015 Unilens Vision Valeant Pharmaceuticals 28 28 0
Develops and sells specialty contact lenses under the C-Vue,
Unilens, Sof-Form, Lombart and LifeStyle brands
7/6/2015 Oculeve Allergan Undisc. 125 Undisc.
OD-01 nasal neurostimulation device that increases tear
production in patients with dry eye disease
6/18/2015 Lumenis XIO Group 510 510 0 Ophthalmic surgical devices
5/8/2015 Paragon Vision Sciences Valeant Pharmaceuticals Undisc. Undisc. Undisc. Manufacturer of specialty contact lenses
5/4/2015 Improved Vision Systems OphthaliX 3 3 0
Medical devices for diagnosis and treatment of a variety of
ophthalmic diseases
Date Target Acquiror Size Upfront Milestone Disease Area
11/9/2015 Ocata Astellas $379 $379 $0 Stargardt's Disease, Dry AMD, Myopic Macular Degeneration
9/15/2015 InSite Vision Sun Pharmaceutical 48 48 0 Bacterial Infection, Surgical Inflammation
8/26/2015 R-Tech Ueno (Remaining Stake) Sucampo Pharmaceuticals 278 278 0 Glaucoma
8/3/2015 Foresight Biotherapeutics Shire 300 300 0 Pink Eye
11/20/2014 Potentia Pharmaceuticals Apellis Pharmaceuticals Undisc. Undisc. Undisc. Age-Related Macular Degeneration
11/17/2014 Allergan Actavis 66,000 66,000 0 Multiple
Ophthalmology Licensing Activity($ in millions)
___________________________
Source: Company information, RecapIQ.
1. Total includes upfront and potential milestone payments.
Date Licensor/Seller Licensee/Buyer Upfront Milestone Total(1)
Subject
11/2015 Mimetogen Allergan $50 Undisc. Undisc. Exclusive licensing agreement to develop and commercialize MIM-D3 against dry eye
10/2015 Atheln Nemus Bioscience Atheln to collaborate on development of Nemus' NB-1111 against open angle glaucoma
10/2015 Novaliq Ursapharm Arzneimittel Ursapharm to commerclialize Novaliq's EvoTears against dry eye disease in Europe
9/2015 Ramot Aerie Pharmaceuticals Collaboration on Tel Aviv University's anti-beta amyloid for ocular diseases
9/2015 Mannin Research Q BioMed Q BioMed to inlicense and acquire Glaucoma assets of Mannin Research
9/2015 Alcon Recipharm Recipharm to acquire Alcon's manufacturing facility for ophthalmology products
8/2015 Repugen Hanmi Pharmaceutical Repebody antibody platform collaboration for eye and systemic diseases
8/2015 Midatech Pharma Ophthotech Midatech's Q Sphera sustained delivery of wet AMD and other ocular indications products
8/2015 ADF, Inc. Imprimis Non-exclusive rights to ophthalmic injectable and topical formulations in Canada
8/2015 Alimera Sciences SIFI SIFI to commercialize ILUVIEN for DME in Italy, San Marino and Vatican City
8/2015 GrayBug Aerie Pharmaceuticals Option to polymer-based sustained-release versions of Aerie's ophthalmic products
7/2015 River Vision CMC Biologics Agreement for cGMP production of teprotumumab for Grave's Orbitopathy
7/2015 EyeGate Pharma Valeant 1 33 34 EGP-437, dexamethasone phosphate delivered using EyeGate II for uveitis, WW ex-U.S.
7/2015 Mablife Elsalys Biotech Anti-CD160 antibody against cancer and eye diseases
7/2015 AIST Astellas Pharma Drug discovery using IT Drug-Discovery Technologies for ocular and nephrology diseases
7/2015 AGTC Biogen 124 1,065 1,189 Option to develop gene therapies for ophthalmic diseases
6/2015 Gensight Biologics Novasep CMO agreement for cGMP manufacturing of GS010 for Leber Hereditary Optic Neuropathy
6/2015 Broda Technologies Redwood Pharma IntelliGel supramolecular hydrogel slow-release for use in Dry Eye therapeutic RP101
6/2015 XL-protein DNX PASylation half-life extension for therapeutics in indications including ophthalmology
5/2015 EyeCRO NeuMedics NM108, delivered based on MiDROPS formulation platform, for ophthalmic disorders
5/2015 Portola Pharma Ora Syk inhibitor, PRT2761 for ophthalmic diseases
4/2015 Eyenovia Senju Pharmaceutical Microdosed therapeutics in Japan and the rest of Asia
4/2015 Clearside Biomedical Spark Therapeutics Option to microinjector technology to deliver gene therapies to the back of the eye
4/2015 4D Molecular AGTC Directed Vector Evolution platform for AAV vectors for ophthalmic disease indications
4/2015 Santen R-Tech Ueno Purchased DE-105, a neurotrophic factor peptide, for persistent corneal epithelial defects
2/2015 AERI AyoxxA Biosystems Multiplexing technology for protein biomarker detection in the treatment of AMD
2/2015 Insite Vision NicOx 3 14 17 AzaSite and BromSite drug duration extension in the eye, in Europe and Africa
2/2015 Pfenex Hospira/Pfizer 51 291 342 PF582, a biosimilar version of LUCENTIS (ranibizumab injection) for retinal conditions
2/2015 Insite Vision NicOx 3 14 17 AzaSite, BromSite and AzaSite Xtra in Europe, Middle East and Africa
1/2015 Allegro Ophthalmics Hanmi Pharmaceutical 20 0 20 Luminate (ALG-1001), intraocular injection for vascular eye diseases in China and Korea
12/2014 Durect Santen Pharmaceutical 2 76 78 SABER technology to develop a sustained release product to deliver ophth drugs
11/2014 AVEO Oncology Ophthotech 3 103 106 Option to AV-951 (tivozanib), a VEGF inhibitor for ocular diseases worldwide ex-Asia

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OIS@AAO 2015 Year In Review

  • 1. 2015 – The Year in Review Emmett Cunningham M.D., Ph.D., M.P.H. Partner, Clarus Ventures, LLC
  • 2.
  • 3.
  • 4.
  • 5. OIS Attendance Over Time 0 100 200 300 400 500 600 700 800 900 1000 2009 2010 2011 2012 2013 2014 2015 > 900 > 400 OIS@AAO OIS@ASCRS OIS@AAO 2015
  • 8. Original NDA/BLA Approvals – 1988 to 2015 Center for Drug Evaluation and Research Data provided by : Wiley A. Chambers, MD Supervisory Medical Officer Division of Transplant and Ophthalmology Products 0 20 40 60 80 100 120 140 Total Ophthalmic Approvals Total Approvals Linear (Total Ophthalmic Approvals) Linear (Total Approvals) • Range: 0 – 9 • Mean: 4.4 • Median: 4 Ophthalmic / Year: Stable
  • 9. Original NDA/BLA Approvals Center for Drug Evaluation and Research - FY2015 Gary Novack, PhD Pharma . Logic Consulting, Inc. 111 2 0 20 40 60 80 100 120 Ophthalmic Non-Ophthalmic October 1, 2014 thru September 30, 2015 • Olopatadine ophthalmic solution (PAZEO®), 0.7%, a mast cell stabilizer indicated for the treatment of ocular itching associated with allergic conjunctivitis, January 30, 2015 (NDA) – Alcon Res, LTD. • Phenylephrine hydrochloride (Phenylephrine Hydrocloride), 2.5% & 10%, an alpha-1 adrenergic receptor agonist indicated to dilate the pupil, January 15, 2015 (NDA) – Akorn, Inc. 1.8% Ophthalmic Data provided by : Wiley A. Chambers, MD Supervisory Medical Officer Division of Transplant and Ophthalmology Products
  • 11. Positive Phase 3 Trial of SPK-RPE65 for the treatment of RPE65- mediated inherited retinal dystrophies (IRDs). BLA Submission 2016 *As measured by the change in bilateral mobility testing between baseline and one year. The multicenter, pivotal Phase 3 trial randomized 31 subjects with confirmed RPE65 gene mutations. The ITT population included 21 subjects in the intervention group and 10 in the control group. Leo A. The Gene Therapy Renaissance. April 18, 2013. http://hms.harvard.edu/news/gene-therapy-renaissance-4-18-13 0 1 2 3 4 5 6 BL D30 D90 D180 Y1 Luxscore,bilateral Study visit Intervention Control Mean MT Lux Score/Level - Bilateral (mITT/safety population, n=29)
  • 12. Humira® (Adalimumab) Positive Phase 3 Studies in Non-Infectious Intermediate, Posterior, and Panuveitis / Behcet’s Disease IgG1 Fc Fab Anti - TNFa Vision-1 & 2 Studies Met Primary Endpoint Of Prolonging Time to Treatment Failure. FDA Filing Submitted. Approval Anticipated By 4Q2016 http://acrabstracts.org/abstract/adalimumab-in-patients-with-inactive-non-infectious-uveitis-requiring-systemic-treatment/ http://abbvie.mediaroom.com/2015-05-05-AbbVie-Announces-Pivotal-Phase-3-Data-Evaluating-Efficacy-and-Safety- of-HUMIRA-adalimumab-in-Patients-with-Non-Infectious-Intermediate-Posterior-or-Panuveitis
  • 13. Lifitegrast 5.0% LFA Inhibitor Dry Eye Corneal Staining OPUS-3 Phase 3 Trial Met Primary (12 wks) & Key Secondary (2 & 6 wks) Endpoints - Improvement in Dry Eye Symptoms Data to support FDA resubmission 1Q2016
  • 14. Phase 2 Dose Ranging Latanoprostene bunod ophthalmic solution 0.024% NDA Submitted, July 24, 2015 Expected US Launch, 2H2016 July, 2016 PDUFA http://ir.valeant.com/investor-relations/news-releases/news-release-details/2014/Bausch--Lomb-and-Nicoxs- Glaucoma-Candidate-VESNEO-latanoprostene-bunod-Meets-Primary-Endpoint-in-Phase-3-Studies/default.aspx Met Phase 3 Primary Endpoint Non-Inferiority vs Timolol
  • 15. Once Daily ROCK / NET Inhibitor Lowers EVP Preparing NDA Filing for RhopressaTM in 3Q2016 Rocket 2 Rocket 1 Rocket 2 met primary endpoint – non-inferior to Timolol Rocket 1 met secondary endpoint – supportive
  • 17. FovistaTM Phase 3 Trials In Wet AMD Combined Trial Data 4Q2016 Fovista 1.5mg + Lucentis (N=311) Consistent w/Lucentis dosing schedule Q4W approved in EU* Lucentis 0.5mg (N=311) Consistent w/Lucentis dosing schedule Q4W approved in EU* OPH1002 N = 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: Q8W Avastin Q4W / Eylea Q4W for 3 months, then Q8W Avastin 1.25mg / Eylea 2mg (N=311) Avastin Q4W / Eylea Q8W Avastin Q4W / Eylea Q4W for 3 months, then Q8W Year 2 OPH1003 N = 622 OPH1004 N = 622 Primary Endpoint
  • 18. • Positive Phase 2 results reported in allergic conjunctivitis - October, 2014 • Phase 3 trial in moderate to severe allergic conjunctivitis topline data expected 1Q 16 • Potential BLA filing 2H 17 Phase 2 AC Data Receptor EBI-005 Treating late phase response as shown by separation over 5 hours Isunakinra (EBI-005): Topically administered IL-1 receptor blocker p=0.033 p=0.046
  • 19. Phase 2 Data Anticipated 2016 X-linked retinoschisis (XLRS) http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/XLRS.htm
  • 20. https://clinicaltrials.gov/ct2/show/NCT02510794?term=ranibizumab+sustained&rank=2 Ranibizumab (RBZ) Port Delivery System (RPDS) For Wet AMD – LADDER Trial Phase 2 Data 1H2017
  • 21. Global Ophthalmic Pharmaceutical Market Revenues by Indication Market Scope ®Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ 9.3 16.5 4.7 6.1 3.1 3.7 3.8 4.2 0 5 10 15 20 25 30 35 2015 2020 $20.9 Bn $39.5 Bn Anti-VEGF/Retina Glaucoma Dry Eye All Other
  • 22. IVT Injections…. Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz
  • 23. Global IVT a – VEGF Injections Source: Market Scope Estimates Market Scope ® 4.6M Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ 0 5 10 15 20 25 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 United States Outside United States Global (M) 17.6M 22.2M Most Growth OUS
  • 25. Market Scope ® US Retina Specialist Treatment for Wet AMD Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% Q3-2013 Q3-2014 Q3-2015 Lucentis Eylea Avastin Other 61% 23% 12% 4% Avastin Eylea Lucentis Other
  • 26. How Would You Treat a New wet AMD Patient? 0.9% 13.7% 21.1% 64.3% 1.9% 34.5% 24.5% 39.4% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% Other Lucentis Eylea Avastin Ex-USA USA 2015 Membership Survey
  • 28. Am J Ophthalmol 2014, 157:825-833. Study-Enforced Compliance Results in 4-5 Letter Increased Mean Gain – As Much As Effective Add-On Therapy Strong Correlation Between Injection Frequency and Vision Gain
  • 30. Nature. 2015 Jul 30;523(7562):607-11. “Sterol eye drops reverse cataracts in mice”
  • 31. 51% 8% 5% 4% 4% 3% 3% 1% 21% Cataract Glaucoma AMD Corneal Opacity Childhood Refractive Error Trachoma Diabetic Retinopathy Undetermined Global Causes of Blindness World Health Organization - 2010 http://www.who.int/blindness/data_maps/en/
  • 32. Global Ophthalmic Procedures - 2015 Vitrectomies Laser Photocoagulation IVT Injections Cataract, RLE, Phakic IOLs Laser Refractive Glaucoma Filtering, Shunts, MIGs Glaucoma Laser All Other 22.2M Market Scope ®Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/
  • 33. Sterols target crystallin to restore lens transparency in mouse models of cataracts Slit lamp biomicroscopy photographs from R120G cryAB mice dosed topically with c29 eyedrops c29Vehicle Lens Opacity (Cataract) Transparency Recovered c29 binds and stabilizes the dimer of cryAB to reverse aggregation www.viewpointtherapeutics.com
  • 35. 3007 73 0 500 1000 1500 2000 2500 3000 3500 Ophthalmic Non-Ophthalmic 2.4% of Total 510(k) Clearances Division of Ophthalmic and Ear, Nose and Throat Devices - FY2015 Data provided by : Malvina B. Eydelman, MD Director Division of Ophthalmic, and Ear, Nose and Throat Devices, FDA Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc.
  • 36. 0 10 20 30 40 50 60 70 80 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 PMA 510(k) PMA Approvals & 510(k) Clearances – 2004 to 2015 Division of Ophthalmic and Ear, Nose and Throat Devices 73 4 Data provided by : Malvina B. Eydelman, MD Director Division of Ophthalmic, and Ear, Nose and Throat Devices, FDA Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc.
  • 37. PMA Approvals Division of Ophthalmic and Ear, Nose and Throat Devices- FY2015 53 4 0 10 20 30 40 50 60 Ophthalmic Non-Ophthalmic 7.0% of Total October 1, 2014 thru September 30, 2015 • Kamra® Inlay • AcrySof® IQ ReSTOR® +2.5 D Intraocular Lens (IOL) • TECNIS® MULTIFOCAL IOL,+2.75 D and +3.25 D • STAR S4 IR Excimer Laser System and iDesign Advanced WaveScan Studio System Data provided by : Malvina B. Eydelman, MD Director Division of Ophthalmic, and Ear, Nose and Throat Devices, FDA Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc.
  • 39. FDA Approved* April 17, 2015 *For intrastromal corneal implantation to improve near vision by extending the depth of focus in the non-dominant eye of phakic, presbyopic patients between the ages of 45 and 60 years old who have cycloplegic refractive spherical equivalent of +0.50 D to -0.75 D with less than or equal to 0.75 D of refractive cylinder, who do not require glasses or contact lenses for clear distance vision, and who require near correction of +1.00 D to +2.50 D of reading add. US Commercial Lauch May, 2015. Over 1000 KAMRA inlay surgeries completed to date.
  • 40. FDA Approved* De Novo Classification June 18, 2015 *The BrainPort V100 is an oral electronic vision aid that provides electro-tactile stimulation to aid profoundly blind patients in orientation, mobility, and object recognition as an adjunctive device to other assistive methods such as the white cane or a guide dog. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm451779.htm
  • 41. De Novo Approvals – 2004 to 2015 Center for Devices and Radiological Health 0 5 10 15 20 25 30 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 de novo 510(k) Increasing Number of De Novo Approvals “A regulatory pathway for some low- to moderate-risk medical devices that are not substantially equivalent to an already legally-marketed device.” LipiFlow® Thermal Pulsation System TearScience® , Inc.; June, 2011 BrainPort® V100 Oral Visual Aid Device Wicab, Inc.; June, 2015 Data provided by : Malvina B. Eydelman, MD Director Division of Ophthalmic, and Ear, Nose and Throat Devices, FDA Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc.
  • 43. Raindrop ® Near Vision Inlay PMA Submission Accepted by FDA November 10, 2015
  • 44. CyPass® Micro-Stent CyPass® Micro-Stent PMA Submission Accepted by FDA October, 2015 “Pivotal COMPASS Trial Results Positive through Two Years” http://transcendmedical.com/intent-to-file-premarket-approval-application-with-fda/
  • 45. Handheld Unit Disposable Tip with Hydrogel Lacrimal Gland Pivotol Study Ongoing De Novo Classification FDA Filling Anticipated 3Q2016
  • 47. NEI Funding Flat, but … At 1999 Level After Adjusting for Inflation Data provided by : Mala Dutta, Ph.D. Office of Translational Research, NEI $676K $411K
  • 49. 0 5 10 15 20 25 30 Billions($) Venture Capital Investments Over Time Biotech Software Absolute Biotech Investing Up at ~ $5.6 Bn
  • 50. 0 100 200 300 400 500 600 700 800 900 1000 Number of "First Financings" of New Startups Biotech Software Absolute Biotech Deals Stable ~ 100 Deals/Year
  • 51. Source: PricewaterhouseCoopers, Silicon Valley Bank Total VC vs Biotech vs Device Investments (2001-2015) Courtesy Jon Norris $0 $5 $10 $15 $20 $25 $30 $35 $40 $45 $50 Total VC Dollars ($Bn) Biotech ($Bn) Device ($Bn) $1.9Bn $5.6Bn $47Bn
  • 52. Biotech + Device Venture Capital Invested vs Raised Source: PricewaterhouseCoopers, Silicon Valley Bank $6.0 $7.3 $9.1 $8.6 $6.6 $6.3 $7.7 $6.7 $6.7 $8.6 $3.4 $6.6 $7.9 $6.1 $5.2 $1.8 $3.7 $3.6 $3.9 $6.1 $0.0 $1.0 $2.0 $3.0 $4.0 $5.0 $6.0 $7.0 $8.0 $9.0 $10.0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Invested ($Bn) Fundraised ($Bn) Courtesy Jon Norris Amounts Up Significantly ~28% Gap Narrowing
  • 53. business intelligence Ophthalmic Investments Over Time (1999 – 2015*) 1 2 2 5 5 8 10 3 10 5 11 7 13 11 9 5 2 1 5 2 3 9 5 7 14 9 10 6 11 8 1 0 100 200 300 400 500 600 0 5 10 15 20 25 30 # Biotech Deals # Device Deals VC Investment ($USD, Millions) *2015 figures through October SOURCE: Strategic Transactions Ophthalmic VC Funding Stable ~ $400 - 500M / year Fewer Device Deals ($M)# Deals
  • 54. 77 30 22 22 21 19 16 11 9 9 0 10 20 30 40 50 60 70 80 90 Courtesy Jon Norris US Biotech Series A Investments* By Indications – 2009 to 3Q2015 * > $2M
  • 55. Courtesy Jon Norris US Device Series A Investments* By Indications – 2009 to 3Q2015 * > $2M 46 45 42 29 26 14 11 10 5 5 0 5 10 15 20 25 30 35 40 45 50
  • 56. VC Investment By Ophthalmic Indication (1999-2015*) *2015 figures through October SOURCE: Strategic Transactions 49 37 21 19 12 14 10 7 14 10 3 4 0 10 20 30 40 50 60 0 100 200 300 400 500 600 700 800 900 1,000 1,100 1,200 NumberofDeals PrivatePlacements($M) Dollars ($ Millions) Number of Deals
  • 57.
  • 58. Biotech Stock Index (NBI) Continues Upward Despite Corrections . . . 2008 Courtesy David Nierengarten, Wedbush
  • 59. (M) IPOs Completed in the USA by Sector 1995 to 2015 One in Six IPOs in Healthcare Courtesy David Nierengarten, Wedbush
  • 60. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Percent of All VC-Backed IPOs by Sector Biotech Software Other 50% of Recent VC-Backed IPOs Biotech
  • 61.
  • 62. 0 20 40 60 80 100 120 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Ophtho Medtech Biotech Recession - 398 - 312 - 27 Healthcare IPOs by Year - Cyclic Courtesy David Nierengarten, Wedbush ?
  • 63. ? Ophthalmology IPOs by Year - Cyclic 1 2 4 1 1 3 1 1 1 2 6 4 0 1 2 3 4 5 6 7 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Recession Courtesy David Nierengarten, Wedbush
  • 64. Positives • Unemployment, low • Inflation, low • Interest rates, low • Consumer spending, continues Negatives • GDP, modest • Business spending, low Economic Indicators Mostly Positive Courtesy David Nierengarten, Wedbush
  • 65. Yield Curve Spread Over 20 Years (Treasury Interest Rates - 10 year - 2 year Spread) Yield Curve Spread Inversion Pre-dates Recession Recession Inversion Inversion Yield Curve Spread Suggests Further Growth Yield Curve Spread Still Positive ~ + 1.5 Courtesy David Nierengarten, Wedbush
  • 66. “The four most expensive words in the English language are…” ‘This time is different.’ Sir John Templeton (November 29, 1912 – July 8, 2008)
  • 68. Biotech & Medtech M&A Activity 2005 to 3Q2015 Courtesy Joe Gilliam 42 49 51 32 36 53 52 45 46 50 46 9 34 27 27 23 25 28 17 21 18 36 0 10 20 30 40 50 60 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Medtech Biotech
  • 69. Private Company Acquisitions Possible Trend Toward Fewer Structured Deals ~ 40% Structured ~ 65% Structured Courtesy Jon Norris 0% 20% 40% 60% 80% 100% Biopharma Non-Structured Structured 0% 20% 40% 60% 80% 100% Device Non-Structured Structured
  • 70. $300M $125M + Undisc CVP $66Bn $50M + Undisc CVP $300M + Undisc CVP $124M + $1.1Bn CVP $51M + $291M CVP $20M $379M
  • 71. An Eye on India and China 1.3 Bn 1.4 Bn
  • 72. “Necessity may be the mother in invention”* BUT “Prosperity is the father of innovation…..” *“...let us begin and create in idea a State; and yet a true creator is necessity, which is the mother of our invention.” The Republic, Book II, 369c, Plato Plato A strong and sustained culture of innovation is predicated upon a strong economy with real or perceived discretionary spending…
  • 73. Global Contribution to World's GDP by Major Economies from 1 AD to 2003 AD Maddison A (2007), Contours of the World Economy I-2030AD, Oxford University Press, ISBN 978-0199227204
  • 74. Projected Relative Global Economies 2011 – 2030 - 2060 23% 28% 16% 17% 28% 28% 6% 11% 18%17% 12% 9% 18% 15% 14% 12% 12% 12% 7% 4% 3% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 2011 2030 2060 USA China India Euro Area Other OECD Other non-OECD Japan
  • 75.
  • 76. An Eye on India and China Intas Pharmaceuticals Launches Razumab ‘Similar’ to Ranabizumab Kanghong Biotech Launches Combercept ‘Similar’ to Afilbercept Sun Pharma Acquires Insight - $48M Emerging Centers of Innovation
  • 77. http://ois.net/category/podcast/ 64 Episodes with Over 14,000 Plays To Date … Tom Salemi tom@healthegy.com
  • 78. Save the Dates 5th Annual OIS@ASCRS New Orleans, LA May 5th, 2016 8th Annual OIS@AAO Chicago, Illinois October 13th, 2016 HASHTAG: #OISAAO
  • 79.
  • 82. (SkQ1) / (KPI-121 – Cataract surgery inflammation) Ophthalmic Opportunity Roadmap Glaucoma Dry Eye AMD Other (IBI-10090 – Cataract surgery inflammation) _________________________ Source: Company information. (IVT & Oral Kallikrein Inhibitor Program – DME) (Eylea – Wet AMD, DME) / (Pan-90806 topical – Wet AMD) (Jetrea – VMA) Marketed Phase III Phase II Phase I Pre- Clinical (AKB-9778 – DME) (Lifitegrast) (GS010 – Gene therapy for LHON) (RST-001 – Gene therapy for RP & Dry AMD) (Gene therapy for wet AMD and XLRP) (ACU-4429 – Dry AMD) / (BOL-303259-X) / (INO-8875) (ALK-001 – Stargardt disease) (SPK-RPE65 – Gene therapy for inherited retinal dystrophies) (Gene therapy for Glaucoma-GT) / (Gene therapies for multiple indications) / (Anti-VEGF + Anti-PDGF) / (AAV.REP1 for choroidemia) (RetinoStat – Gene therapy for Wet AMD) (hI-con1 – Wet AMD) (KPI-121) (ENV515) (ENV905 – Cataract surgery inflammation) (AVA-101 – Gene therapy for Wet AMD) / (PF582 – Wet AMD) (Fovista – Wet AMD) / (X-82 oral anti-VEGF + anti- PDGF – Wet AMD) (QLT091001 – LCA and RP) (Ocuvia – DME) / (ALG-1001 – DME) / (NS2 – SLS, Non-infectious uveitis) (HuCNS-SC – Geographic Atrophy AMD) (OpRegen – Dry AMD) (hPRC Therapy for Retinitis Pigmentosa) (EBI-005 – Allergic Conjunctivitis) (RG7716 combo anti-VEGF/Ang2) (Rhopressa & Roclatan) (DARPin, Anti-VEGF / MP0112 – Wet AMD & DME) / (OTX-DP) (OTX-TP) (OTX-MP Moxifloxacin for bacterial conjunctivitis) (OTX-DP for allergy) (Helios insert) Presbyopia Therapies (Liquid Vision – Presbyopia) (RGN-259/GBT-201) (OPT-302 – Wet AMD) (rAAV-hRS1 – Gene therapy for XLRS) / (MIM-D3) / (L-PDDS) (Eye-D Insert) (EGP-437) (Cis-UCA) (Cross-linked hyaluronic acid) (CycloASol) (NT-503 – Wet AMD) (TT-211/TT-231) (RhoNova – Gene therapy for RP (PRO-001 for RP) (FB-08I8 for RP) (RPE – Stargardt & Dry AMD) /
  • 83. Ophthalmology M&A Activity ___________________________ Source: Company information, ThompsonSDC. Therapeutics ($ in millions) Devices Date Target Acquiror Size Upfront Milestone Description 9/29/2015 Chauvin Opsia Cutting Edge Undisc. Undisc. Undisc. Manufacturer and developer of intraocular implants designed to perform cataract surgeries 9/3/2015 AqueSys Allergan $300 $300 $0 XEN45 soft ocular shunt for treatment of glaucoma-related intraocular pressure 9/2/2015 Synergetics Valeant Pharmaceuticals 192 166 26 Vitreoretinal surgical devices 7/13/2015 Unilens Vision Valeant Pharmaceuticals 28 28 0 Develops and sells specialty contact lenses under the C-Vue, Unilens, Sof-Form, Lombart and LifeStyle brands 7/6/2015 Oculeve Allergan Undisc. 125 Undisc. OD-01 nasal neurostimulation device that increases tear production in patients with dry eye disease 6/18/2015 Lumenis XIO Group 510 510 0 Ophthalmic surgical devices 5/8/2015 Paragon Vision Sciences Valeant Pharmaceuticals Undisc. Undisc. Undisc. Manufacturer of specialty contact lenses 5/4/2015 Improved Vision Systems OphthaliX 3 3 0 Medical devices for diagnosis and treatment of a variety of ophthalmic diseases Date Target Acquiror Size Upfront Milestone Disease Area 11/9/2015 Ocata Astellas $379 $379 $0 Stargardt's Disease, Dry AMD, Myopic Macular Degeneration 9/15/2015 InSite Vision Sun Pharmaceutical 48 48 0 Bacterial Infection, Surgical Inflammation 8/26/2015 R-Tech Ueno (Remaining Stake) Sucampo Pharmaceuticals 278 278 0 Glaucoma 8/3/2015 Foresight Biotherapeutics Shire 300 300 0 Pink Eye 11/20/2014 Potentia Pharmaceuticals Apellis Pharmaceuticals Undisc. Undisc. Undisc. Age-Related Macular Degeneration 11/17/2014 Allergan Actavis 66,000 66,000 0 Multiple
  • 84. Ophthalmology Licensing Activity($ in millions) ___________________________ Source: Company information, RecapIQ. 1. Total includes upfront and potential milestone payments. Date Licensor/Seller Licensee/Buyer Upfront Milestone Total(1) Subject 11/2015 Mimetogen Allergan $50 Undisc. Undisc. Exclusive licensing agreement to develop and commercialize MIM-D3 against dry eye 10/2015 Atheln Nemus Bioscience Atheln to collaborate on development of Nemus' NB-1111 against open angle glaucoma 10/2015 Novaliq Ursapharm Arzneimittel Ursapharm to commerclialize Novaliq's EvoTears against dry eye disease in Europe 9/2015 Ramot Aerie Pharmaceuticals Collaboration on Tel Aviv University's anti-beta amyloid for ocular diseases 9/2015 Mannin Research Q BioMed Q BioMed to inlicense and acquire Glaucoma assets of Mannin Research 9/2015 Alcon Recipharm Recipharm to acquire Alcon's manufacturing facility for ophthalmology products 8/2015 Repugen Hanmi Pharmaceutical Repebody antibody platform collaboration for eye and systemic diseases 8/2015 Midatech Pharma Ophthotech Midatech's Q Sphera sustained delivery of wet AMD and other ocular indications products 8/2015 ADF, Inc. Imprimis Non-exclusive rights to ophthalmic injectable and topical formulations in Canada 8/2015 Alimera Sciences SIFI SIFI to commercialize ILUVIEN for DME in Italy, San Marino and Vatican City 8/2015 GrayBug Aerie Pharmaceuticals Option to polymer-based sustained-release versions of Aerie's ophthalmic products 7/2015 River Vision CMC Biologics Agreement for cGMP production of teprotumumab for Grave's Orbitopathy 7/2015 EyeGate Pharma Valeant 1 33 34 EGP-437, dexamethasone phosphate delivered using EyeGate II for uveitis, WW ex-U.S. 7/2015 Mablife Elsalys Biotech Anti-CD160 antibody against cancer and eye diseases 7/2015 AIST Astellas Pharma Drug discovery using IT Drug-Discovery Technologies for ocular and nephrology diseases 7/2015 AGTC Biogen 124 1,065 1,189 Option to develop gene therapies for ophthalmic diseases 6/2015 Gensight Biologics Novasep CMO agreement for cGMP manufacturing of GS010 for Leber Hereditary Optic Neuropathy 6/2015 Broda Technologies Redwood Pharma IntelliGel supramolecular hydrogel slow-release for use in Dry Eye therapeutic RP101 6/2015 XL-protein DNX PASylation half-life extension for therapeutics in indications including ophthalmology 5/2015 EyeCRO NeuMedics NM108, delivered based on MiDROPS formulation platform, for ophthalmic disorders 5/2015 Portola Pharma Ora Syk inhibitor, PRT2761 for ophthalmic diseases 4/2015 Eyenovia Senju Pharmaceutical Microdosed therapeutics in Japan and the rest of Asia 4/2015 Clearside Biomedical Spark Therapeutics Option to microinjector technology to deliver gene therapies to the back of the eye 4/2015 4D Molecular AGTC Directed Vector Evolution platform for AAV vectors for ophthalmic disease indications 4/2015 Santen R-Tech Ueno Purchased DE-105, a neurotrophic factor peptide, for persistent corneal epithelial defects 2/2015 AERI AyoxxA Biosystems Multiplexing technology for protein biomarker detection in the treatment of AMD 2/2015 Insite Vision NicOx 3 14 17 AzaSite and BromSite drug duration extension in the eye, in Europe and Africa 2/2015 Pfenex Hospira/Pfizer 51 291 342 PF582, a biosimilar version of LUCENTIS (ranibizumab injection) for retinal conditions 2/2015 Insite Vision NicOx 3 14 17 AzaSite, BromSite and AzaSite Xtra in Europe, Middle East and Africa 1/2015 Allegro Ophthalmics Hanmi Pharmaceutical 20 0 20 Luminate (ALG-1001), intraocular injection for vascular eye diseases in China and Korea 12/2014 Durect Santen Pharmaceutical 2 76 78 SABER technology to develop a sustained release product to deliver ophth drugs 11/2014 AVEO Oncology Ophthotech 3 103 106 Option to AV-951 (tivozanib), a VEGF inhibitor for ocular diseases worldwide ex-Asia