Emmett T. Cunningham, Jr., M.D., PhD., M.P.H

Transcription

1 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

2 Financial Disclosures What Conflict of Interest? I work here in my spare time

3 Prognosticators

4 1 - Funding Largely / Increasingly Private (Private Equity / Corporate)

5 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

6 Total VC vs Biotech vs Device Investments ( ) $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

7 $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 ( ) $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% $ Source: PricewaterhouseCoopers, Silicon Valley Bank Courtesy Jon Norris

8 Ophthalmic Investments Over Time ( *) # Deals # Biotech Deals # Device Deals VC Investment ($USD, Millions) Ophthalmic VC Funding Stable Overall ~ $ M / year / 15 Device Funding Slow ($M) *2015 figures through October SOURCE: Strategic Transactions business intelligence

9 NEI Funding Comparable to VC, but Modest in Comparison to Industry at Large Alcon ~ $670M ~1Bn VC ~ $380M ~$500M NEI ~ $665M ~$676M + etc

10 Translational Research Early Stage VCs Late Stage VCs Laboratory Research Clinical Research Treatments SBIR Industry

11 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

12 Private Placements ($M) VC Investment By Ophthalmic Indication ( *) 1, ,100 1, Number of Deals 0 0 *2015 figures through October SOURCE: Strategic Transactions Dollars ($ Millions) Number of Deals

13 2 Retina Enhanced Efficacy Through Improved Compliance (Sustained Release & Gene Therapy)

14 Global Causes of Blindness World Health Organization 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%

15 Global Ophthalmic Procedures 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. Market Scope

16 35 30 Global Ophthalmic Pharmaceutical Market Revenues by Indication $30.5 Bn 4.2 All Other 25 $20.9 Bn 3.7 Dry Eye Glaucoma Anti-VEGF/Retina ~ 54% Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

17 Sustained-Release Corticosteroids

18 IVT a-vegf Injections. Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz

19 (M) Global IVT a VEGF Injections 22.2M Most Growth OUS 17.6M M United States Outside United States Global Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

20 Anti-VEGF for namd, DME, RVO

21 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% Q Q Q Lucentis Eylea Avastin Other 23% 12% 4% Eylea Lucentis Other Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

22 Bevacizumab Ranibizumab

23 Strong Correlation Between Injection Frequency and Vision Gain Am J Ophthalmol 2014, 157: Study-Enforced Compliance Results in 4-5 Letter Mean Gain As Much As Effective Add-On Therapy

24 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

25 Ranibizumab (RBZ) Port Delivery System (RPDS) For Wet AMD LADDER Trial Phase 2 Data 1H2017

26 Gene Therapy in Ophthalmology At the Tipping Point? Sisyphus Snowball Tipping Point

27 Lux score, bilateral Positive Phase 3 Trial of SPK-RPE65 for the treatment of RPE65- mediated inherited retinal dystrophies (IRDs). BLA Submission Mean MT Lux Score/Level - Bilateral Leo A. The Gene Therapy Renaissance. April 18, *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

28 Phase 2 Data Anticipated 2016 X-linked retinoschisis (XLRS)

29 3 Glaucoma Enhanced Efficacy Through Improved Compliance (Sustained Release & MIGS)

30 Global Causes of Blindness World Health Organization Undetermined Diabetic Retinopathy 1% Trachoma 3% 21% Glaucoma 8% Refractive Error Childhood 3% 4% Corneal Opacity AMD 4% 5% Cataract 51% Glaucoma 8%

31 Global Ophthalmic Procedures 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. Market Scope

32 35 30 Global Ophthalmic Pharmaceutical Market Revenues by Indication $30.5 Bn 4.2 All Other $20.9 Bn Dry Eye Glaucoma ~ 20% Anti-VEGF/Retina Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

33 Am J Ophthalmol 2005; 140: Adherence Poor (< 50% by 6 months for most gtts) 2x higher with once daily therapy (prostaglandins) still low

34 1234 Eligibile Beneficiaries A Minority had Good Adherence Over Time 20% at 1 year 15% at 4 years

35 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

36 Founded MIGS Space istent istent - Approved for Glaucoma Surgery June, 2012 istent inject (G2) istent SUPRA (G3)

37 CyPass Micro-Stent PMA Submission Accepted by FDA October, 2015 CyPass Micro-Stent Pivotal COMPASS Trial Results Positive through Two Years

38 A Number of Followers in Clinical Development MicroShunt XEN Glaucoma Implant Hydrus Microstent

39 US Glaucoma Surgical Procedures (000) > 450, All Growth in MIGS In US Filtration Tube Shunts MIGs-Other (Forecast) 2020 Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

40 Global Glaucoma Surgical Procedures (000) > 900, All Growth in MIGS Globally Filtration Tube Shunts MIGs-Other Source: Market Scope Estimates; Courtesy Dave Harmon. Market Scope

41 4 Cataract Pharaceutical Treatment

42 Global Causes of Blindness World Health Organization Undetermined 21% Diabetic Retinopathy 1% Trachoma 3% Refractive Error Childhood 3% 4% Corneal Opacity 4% AMD 5% 51% Cataract Glaucoma 8%

43 Global Ophthalmic Procedures 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. Market Scope

44 Sterol eye drops reverse cataracts in mice Nature Jul 30;523(7562):

45 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

46 5 India / China Centers of Innovation

47 An Eye on India and China 1.3 Bn 1.4 Bn

48 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

49 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

50 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Projected Relative Global Economies % 4% 3% 12% 18% 17% 6% 17% 11% 28% 23% 28% 12% 12% 15% 14% 12% 9% 18% 28% 16% Japan Other non-oecd Other OECD Euro Area India China USA

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52 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

53 Opinions May Vary

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