ICO World Ophthalmology Roundtable on Leadership Development (WORLD) Five Trends in Ophthalmic Innovation Poised to Impact Global Eye Health Emmett T. Cunningham, Jr., M.D., PhD., M.P.H Department of Ophthalmology, California Pacific Medical Center Department of Ophthalmology, Stanford University School of Medicine Francis I. Proctor Foundation, UCSF School of Medicine West Coast Retina Medical Group Clarus Ventures, LLC
Financial Disclosures What Conflict of Interest? I work here in my spare time
Prognosticators
1 - Funding Largely / Increasingly Private (Private Equity / Corporate)
NEI Funding Flat, but At 1999 Level After Adjusting for Inflation $676K $411K Data provided by : Mala Dutta, Ph.D. Office of Translational Research, NEI
Total VC vs Biotech vs Device Investments (2001-2015) $50 $45 $40 $35 $30 $25 $20 $15 $10 $5 $0 $47Bn Most Dramatic Increases NOT Biotech or Devices $5.6Bn $1.9Bn Total VC Dollars ($Bn) Biotech ($Bn) Device ($Bn) Source: PricewaterhouseCoopers, Silicon Valley Bank Courtesy Jon Norris
$10.0 $9.0 $8.0 $7.0 $6.0 $5.0 $4.0 $3.0 $2.0 $1.0 $6.0 Lifescience Venture Capital $7.3 Invested (2005 2014) $9.1 $8.6 Invested ($Bn) Invested ($Bn) $6.6 $6.3 $7.7 $6.7 $6.7 $8.6 But, Biotech and Devices Also up ~ 30% $0.0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 Source: PricewaterhouseCoopers, Silicon Valley Bank Courtesy Jon Norris
Ophthalmic Investments Over Time (1999 2015*) # Deals 30 25 20 15 10 # Biotech Deals # Device Deals VC Investment ($USD, Millions) Ophthalmic VC Funding Stable Overall ~ $400-500M / year 9 5 14 9 2014 / 15 Device Funding Slow 10 6 11 8 1 ($M) 600 500 400 300 200 5 0 5 1 5 1 2 2 2 2 3 5 5 8 10 7 3 10 5 11 7 13 11 9 100 0 *2015 figures through October SOURCE: Strategic Transactions business intelligence
NEI Funding Comparable to VC, but Modest in Comparison to Industry at Large Alcon ~ $670M 2009 2015 ~1Bn VC ~ $380M ~$500M NEI ~ $665M ~$676M + etc
Translational Research Early Stage VCs Late Stage VCs Laboratory Research Clinical Research Treatments SBIR Industry
Understand Funding Sources / Risks Stage Source Of Funds NEI Pre-Seed Seed / Startup Early Late Founders Friends Family SBIR / Foundations Angels / Incubators VCs Institutional Investors (VC) Industry Funds Required Availability Of Funds $50K $100K $1M $100M Innovation Gap Risk High Risk Not drawn to scale! Low Modified after: Center for Venture Research University of New Hampshire
Private Placements ($M) VC Investment By Ophthalmic Indication (1999-2015*) 1,200 60 1,100 1,000 900 49 50 800 700 600 500 400 300 200 100 37 21 19 12 14 10 7 14 10 3 4 40 30 20 10 Number of Deals 0 0 *2015 figures through October SOURCE: Strategic Transactions Dollars ($ Millions) Number of Deals
2 Retina Enhanced Efficacy Through Improved Compliance (Sustained Release & Gene Therapy)
Global Causes of Blindness World Health Organization - 2010 Undetermined Diabetic Retinopathy 1% Trachoma 3% 21% Retina 6% and growing Refractive Error Childhood 3% 4% Corneal Opacity 4% 51% Cataract AMD 5% Glaucoma 8% http://www.who.int/blindness/data_maps/en/
Global Ophthalmic Procedures - 2015 Glaucoma Filtering, Shunts, MIGs Laser Refractive Glaucoma Laser All Other Vitrectomies Laser Photocoagulation Retina 25.7M Cataract, RLE, Phakic IOLs 24.2M IVT Injections Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
35 30 Global Ophthalmic Pharmaceutical Market Revenues by Indication $30.5 Bn 4.2 All Other 25 $20.9 Bn 3.7 Dry Eye 20 3.8 6.1 Glaucoma 15 3.1 10 5 4.7 9.3 16.5 Anti-VEGF/Retina ~ 54% 0 2015 2020 Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Sustained-Release Corticosteroids
IVT a-vegf Injections. Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz
(M) 25 20 15 Global IVT a VEGF Injections 22.2M Most Growth OUS 17.6M 10 5 4.6M 0 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 United States Outside United States Global Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Anti-VEGF for namd, DME, RVO
US Retina Specialist Treatment for Wet AMD 70.0% 60.0% 50.0% 61% Avastin 40.0% 30.0% 20.0% 10.0% 0.0% Q3-2013 Q3-2014 Q3-2015 Lucentis Eylea Avastin Other 23% 12% 4% Eylea Lucentis Other Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Bevacizumab Ranibizumab
Strong Correlation Between Injection Frequency and Vision Gain Am J Ophthalmol 2014, 157:825-833. Study-Enforced Compliance Results in 4-5 Letter Mean Gain As Much As Effective Add-On Therapy
Sustained Release For Posterior Segment Phase 2b Ongoing Phase 2b 2Q2015 Simultaneous Detection of Chemokines, Cytokines, Growth Factors (eg, VEGF) Free Drug Release As Particles Erode Pre-IND Pre-IND Replenish Micropump TM
Ranibizumab (RBZ) Port Delivery System (RPDS) For Wet AMD LADDER Trial Phase 2 Data 1H2017 https://clinicaltrials.gov/ct2/show/nct02510794?term=ranibizumab+sustained&rank=2
Gene Therapy in Ophthalmology At the Tipping Point? Sisyphus Snowball Tipping Point
Lux score, bilateral Positive Phase 3 Trial of SPK-RPE65 for the treatment of RPE65- mediated inherited retinal dystrophies (IRDs). BLA Submission 2016 6 Mean MT Lux Score/Level - Bilateral 5 4 3 2 Leo A. The Gene Therapy Renaissance. April 18, 2013. http://hms.harvard.edu/news/gene-therapy-renaissance-4-18-13 *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. 1 0 Intervention BL D30 D90 D180 Y1 Study visit (mitt/safety population, n=29) Control
Phase 2 Data Anticipated 2016 X-linked retinoschisis (XLRS) http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/xlrs.htm
3 Glaucoma Enhanced Efficacy Through Improved Compliance (Sustained Release & MIGS)
Global Causes of Blindness World Health Organization - 2010 Undetermined Diabetic Retinopathy 1% Trachoma 3% 21% Glaucoma 8% Refractive Error Childhood 3% 4% Corneal Opacity AMD 4% 5% Cataract 51% Glaucoma 8% http://www.who.int/blindness/data_maps/en/
Global Ophthalmic Procedures - 2015 Laser Refractive 2.8M Glaucoma Filtering, Shunts, MIGs Glaucoma Laser All Other Vitrectomies Laser Photocoagulation Cataract, RLE, Phakic IOLs IVT Injections Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
35 30 Global Ophthalmic Pharmaceutical Market Revenues by Indication $30.5 Bn 4.2 All Other 25 20 $20.9 Bn 3.8 3.7 6.1 Dry Eye Glaucoma ~ 20% 15 3.1 10 4.7 16.5 Anti-VEGF/Retina 5 9.3 0 2015 2020 Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Am J Ophthalmol 2005; 140:598-606 Adherence Poor (< 50% by 6 months for most gtts) 2x higher with once daily therapy (prostaglandins) still low
1234 Eligibile Beneficiaries A Minority had Good Adherence Over Time 20% at 1 year 15% at 4 years
Sustained Release Drugs for Glaucoma Intracameral Bimatoprost SR P3 Intracameral Travoprost P2 Punctal Plug Latanaprost P2 Helios TM Insert Travoprost P2 Punctal Plug Travoprost P2
Founded MIGS Space istent istent - Approved for Glaucoma Surgery June, 2012 istent inject (G2) istent SUPRA (G3)
CyPass Micro-Stent PMA Submission Accepted by FDA October, 2015 CyPass Micro-Stent Pivotal COMPASS Trial Results Positive through Two Years http://transcendmedical.com/intent-to-file-premarket-approval-application-with-fda/
A Number of Followers in Clinical Development MicroShunt XEN Glaucoma Implant Hydrus Microstent
US Glaucoma Surgical Procedures (000) 500 450 > 450,000 400 350 300 250 All Growth in MIGS In US 200 150 100 50 0 Filtration Tube Shunts MIGs-Other 2014 2015 (Forecast) 2020 Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Global Glaucoma Surgical Procedures (000) 1000 900 800 > 900,000 700 600 500 All Growth in MIGS Globally 400 300 200 100 0 Filtration Tube Shunts MIGs-Other 2015 2020 Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
4 Cataract Pharaceutical Treatment
Global Causes of Blindness World Health Organization - 2010 Undetermined 21% Diabetic Retinopathy 1% Trachoma 3% Refractive Error Childhood 3% 4% Corneal Opacity 4% AMD 5% 51% Cataract Glaucoma 8% http://www.who.int/blindness/data_maps/en/
Global Ophthalmic Procedures - 2015 Glaucoma Filtering, Shunts, MIGs Laser Refractive Glaucoma Laser All Other Vitrectomies Laser Photocoagulation Cataract, RLE, Phakic IOLs 22.2M IVT Injections Source: Market Scope Estimates; Courtesy Dave Harmon. http://market-scope.com/ Market Scope
Sterol eye drops reverse cataracts in mice Nature. 2015 Jul 30;523(7562):607-11.
Sterols target crystallin to restore lens transparency in mouse models of cataracts Vehicle c29 c29 binds and stabilizes the dimer of cryab to reverse aggregation Lens Opacity (Cataract) Transparency Recovered Slit lamp biomicroscopy photographs from R120G cryab mice dosed topically with c29 eyedrops www.viewpointtherapeutics.com
5 India / China Centers of Innovation
An Eye on India and China 1.3 Bn 1.4 Bn
Necessity may be the mother in invention * BUT Plato Prosperity is the father of innovation.. A strong and sustained culture of innovation is predicated upon a strong economy with real or perceived discretionary spending *...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
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
100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Projected Relative Global Economies 2011 2030-2060 7% 4% 3% 12% 18% 17% 6% 17% 11% 28% 23% 28% 12% 12% 15% 14% 12% 9% 18% 28% 16% 2011 2030 2060 Japan Other non-oecd Other OECD Euro Area India China USA
An Eye on India and China Emerging as Centers of Innovation Sun Pharma Acquires Insight - $48M Intas Pharmaceuticals Launches Razumab Similar to Ranabizumab Kanghong Biotech Launches Combercept Similar to Afilbercept
Opinions May Vary
ecunningham@clarusventures.com