Corporate Presentation August 2018

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1 Corporate Presentation August 218

2 Forward-Looking Statements This presentation contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. The words may, will, could, would, should, expect, plan, anticipate, intend, believe, estimate, predict, project, potential, continue, target and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Clearside Biomedical, Inc. s views as of the date of this presentation about future events and are subject to risks, uncertainties, assumptions, and changes in circumstances that may cause Clearside s actual results, performance, or achievements to differ significantly from those expressed or implied in any forward looking statement. Although Clearside believes that the expectations reflected in the forward looking statements are reasonable, Clearside cannot guarantee future events, results, performance, or achievements. Some of the key factors that could cause actual results to differ from Clearside s expectations include its plans to develop and potentially commercialize its product candidates; Clearside s planned clinical trials and preclinical studies for its product candidates; the timing of and Clearside s ability to obtain and maintain regulatory approvals for its product candidates; the extent of clinical trials potentially required for Clearside s product candidates; the clinical utility and market acceptance of Clearside s product candidates; Clearside s commercialization, marketing and manufacturing capabilities and strategy; Clearside s intellectual property position; and Clearside s ability to identify additional product candidates with significant commercial potential that are consistent with its commercial objectives. For further information regarding these risks, uncertainties and other factors you should read the Risk Factors section of Clearside s Annual Report on Form 1-K for the year ended December 31, 217, filed with the SEC on March 16, 218 and Clearside s other Periodic Reports filed with the SEC. Clearside expressly disclaims any obligation to update or revise the information herein, including the forward-looking statements, except as required by law. This presentation also contains estimates and other statistical data made by independent parties and by Clearside relating to market size and growth and other data about its industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of Clearside s future performance and the future performance of the markets in which Clearside operates are necessarily subject to a high degree of uncertainty and risk. 2

3 A World Without Blindness Dedicated to developing treatments that restore and preserve vision for people with serious eye diseases Proprietary suprachoroidal treatment approach offers unprecedented access to the back of the eye 3

Administration Include: Corticosteroids reach unintended tissues, causing cataracts and glaucoma Anterior Chamber Lens Posterior

4 Retinal Diseases ~5 M patients in the U.S. with target indications treated by approx. 1,9 uveitis and retinal specialists Privileged Organ Requiring Local Therapy Limitations of Current Approaches to Local Administration Include: Corticosteroids reach unintended tissues, causing cataracts and glaucoma Anterior Chamber Lens Posterior Chamber Multi-kinase inhibitors and gene therapies require precise placement at diseased tissue Certain drugs like complement inhibitors require improved exposure to the choroid Retina Choroid Macula 4

Exclusive and Proprietary Access to the Back of the Eye Through

injection site areas of the eye including the anterior chamber

into the eye Fluid flows instantaneously and posteriorly

5 Exclusive and Proprietary Access to the Back of the Eye Through the Suprachoroidal Space ( SCS ) Intravitreal & Periocular Suprachoroidal VS.5 ml bolus at.5 ml 1 ml injected Drug diffuses to all Highly variable drug injection site areas of the eye including the anterior chamber and lens 5 into periocular space diffusion across the sclera into the eye Fluid flows instantaneously and posteriorly Designed consistent suprachoroidal injection procedure Fluid with drug is absorbed into the choroid, RPE and retina

6 Suprachoroidal CLS-TA Designed to Improve Ocular Distribution of Triamcinolone Acetonide (TA) Concentration (ng/ml) 3,5, 3,, 2,5, 2,, 1,5, 1,, 5, Sclera-Choroid-Outer Retina SCS IVT Concentration (ng/ml) 6, 5, 4, 3, 2, 1, Aqueous Humor SCS IVT Concentration (ng/g) 1,2, 8, 4, Lens SCS IVT Time, days Over 1X the amount of TA remaining in the choroid and RPE following suprachoroidal administration compared to intravitreal injection Time, days Time, days The anterior segment is relatively spared following suprachoroidal dosing when compared to intravitreal dosing Potentially providing improved visual outcomes, increased durability, reduced treatment burden that can lead to improved benefit to risk 6 *Based on pre-clinical studies

7 Focused Pipeline of SCS Treatments For Multiple Blinding Eye Diseases INDICATION STUDY DRUG CURRENT STATUS Uveitis (macular edema associated with non-infectious uveitis) RVO (retinal vein occlusion) DME (diabetic macular edema) Suprachoroidal CLS-TA (corticosteroid triamcinolone acetonide) Suprachoroidal CLS-TA with anti-vegf (Intravitreal Eylea, Lucentis or Avastin ) Suprachoroidal CLS-TA alone or with anti-vegf (Intravitreal Eylea) PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA Retinal Vascular Disease Proprietary Compound(s) PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA Orphan Diseases Gene Therapy PRECLINICAL PHASE 1 PHASE 2 PHASE 3 NDA 7

8 UVEITIS One of the World s Leading Causes of Blindness 8

9 Current Treatment Paradigm for Noninfectious Uveitis Corticosteroids = most common treatment for uveitis complications 35, patients US uveitis patients 115,5 patients 33% macular edema 21, eyes 82% disease in both eyes Topical steroid for anterior uveitis Periocular (Sub-tenon) 2 mg TA Sustained release dexamethasone implant (Ozurdex ) Intravitreal 4 mg TA Oral steroids 9 Note: TA = triamcinolone acetonide Current treatments 9

The Opportunity In Treating Macular Edema with Uveitis Primary Need 1) An approved therapy that targets vision impairment due to the underlying macular edema associated with all non-infectious

10 The Opportunity In Treating Macular Edema with Uveitis Primary Need 1) An approved therapy that targets vision impairment due to the underlying macular edema associated with all non-infectious uveitis The Problem 1) Inflammation creates sight threatening macular edema 2) No approved treatment for macular edema associated with uveitis 3) No new local treatments for uveitis since 29 4) Oral corticosteroids often prescribed when disease is local to the eye 1 1

11 PEACHTREE Design for Pivotal Phase 3 Clinical Trial Suprachoroidal CLS-TA Suprachoroidal CLS-TA Day Active Arm: Suprachoroidal injection of 4 mg CLS-TA -2 Day Enrollment Control Arm: Sham injection procedure Day SHAM SHAM Screening (2 weeks) Randomization Phase (6 months) Two-arm, randomized, controlled, double-masked, multi-center trial at ~6 clinical sites 3:2 randomization of suprachoroidal CLS-TA vs. sham injection; 16 patients total Primary endpoint at 6 months; superiority of best corrected visual acuity outcome from treatment 11 11

12 PEACHTREE Met Its Primary Endpoint ETDRS BCVA Proportion of patients in each arm gaining 15 ETDRS letters in BCVA from baseline at 24 % patients gaining 15 ETDRS letters in BCVA from baseline % (n=45) 46.9 p< % (n=1) 15.6 Active Control N=96 N=

13 PEACHTREE Met its Secondary Endpoint Mean Change from Baseline in CRT at 24 in Microns ITT N=96 N=64 Active Control Mean change from baseline at week 24 in central retinal thickness (microns) µm p< µm Baseline retinal thickness (microns) µm: active arm; 518. µm: control arm 13 Source: Table

14 Vision Gained Rapidly and Sustained Through 24 Mean Change in BCVA in ETDRS Letters by Visit Mean change at each visit from baseline in BCVA in ETDRS letters read Active Arm Control Arm Wk Wk 4 Wk 8 Wk 12 Wk 16 Wk 2 Wk Baseline ETDRS letters read 54.7: active arm; 53.6: control arm 14

15 % Subjects Reading 2/4 or Better Legal Driving Vision in Most States 6 5 Active 52 Control Percent patients Baseline 24 Baseline Starting at week 8, approximately 5% of the Active patients could read 7 or more ETDRS letters (2/4) This improvement was sustained through the 24 weeks of the trial 15 15

16 Clear Evidence Suprachoroidal CLS-TA Provides Resolution of Inflammation in Uveitis % subjects with scores of zero Anterior Chamber Cells Anterior Chamber Flare Vitreous Haze Active CLS-TA arm Control Arm Resolution of signs of uveitis is a clinically significant outcome Suprachoroidal CLS-TA provides clinically relevant outcomes in all anatomical locations 16 16

17 AE: Elevated IOP IOP AE Rates Among All 16 Subjects IOP AE Rates Among 64 Control Subjects Percent Subjects Percent Subjects N=11/96 Active N=1/64 Control 5 No Rescue (N=18) Other Rescue (N=8) N=1/38 Local Corticosteroid Rescue** (N=38) 17 Elevated IOP includes (a) increased IOP, (b) ocular hypertension, and (c) glaucoma AE = adverse event; IOP, intraocular pressure. ** intravitreal OZURDEX (dexamethasone intravitreal implant) and subtenon and intravitreal triamcinolone acetonide 17

18 Cataracts in CLS-TA and Sham Arms % Cataract AEs in Each Arm 8 Percentage of cataract AEs % 6.3% Active Control No cataract surgeries in this trial 18 Mar-218 NIU program P3, PEACHTREE, trial Topline data 18

19 Patient Rescue: Kaplan-Meier Over 85% of subjects in the Active arm did not require rescue therapy, compared to 28% of subjects in the Control arm Proportion of Patients Not Rescued Time to Rescue (days) Active Control + Censored 19

Planned Transition from Clinical-Stage to Commercial-Stage Company Based on feedback from end-of-phase 2 meeting with the FDA, we believe PEACHTREE will be the only Phase 3 clinical trial required to

20 Planned Transition from Clinical-Stage to Commercial-Stage Company Based on feedback from end-of-phase 2 meeting with the FDA, we believe PEACHTREE will be the only Phase 3 clinical trial required to support the filing of a New Drug Application (NDA) Anticipating NDA submission by end of 218 Ramping up commercial capabilities: o o Building team with launch experience spanning all areas of commercial expertise, including marketing, access and reimbursement, sales and market analytics Strategizing as to how to efficiently reach the approximately 1,9 uveitis and retinal specialists in the U.S. Also intend to pursue marketing authorizations outside of the U.S. 2 2

21 RVO New Approach with CLS-TA + anti-vegf 21

22 Current Treatment Paradigm for RVO 16.4 M patients Global RVO patients 2.2 M patients US RVO patients Eylea, Lucentis, and off-label Avastin Sustained release dexamethasone implant (Ozurdex ) Intravitreal Triamcinolone Acetonide 1 st Line treatment 2 nd Line treatment 22

The Opportunity In Treating RVO Primary Need 1) More rapid and fuller resolution of macular edema to allow patients to recover as much vision as soon as possible The Problem 1) Compared to uveitis

23 The Opportunity In Treating RVO Primary Need 1) More rapid and fuller resolution of macular edema to allow patients to recover as much vision as soon as possible The Problem 1) Compared to uveitis and DME, macular edema following RVO is more severe, as is the attendant vision loss / potential vision gain 2) Multiple inflammatory cytokines are involved in addition to VEGF being upregulated 3) Chronic, monthly anti-vegf injections are necessary for many patients 23

24 SAPPHIRE Design for First Phase 3 RVO Clinical Trial Intravitreal Eylea Suprachoroidal CLS-TA + Intravitreal Eylea Combination arm: Suprachoroidal CLS-TA + Intravitreal Eylea; Q12Wk Day ww xx yy zz Enrollment 2 Month primary efficacy endpoint Submit with 6 months data PRN Continue to follow subjects out to 1 year Day ww xx yy zz Control arm; Intravitreal Eylea; Q4Wk 24 Two-arm, randomized, controlled, double-masked, multi-center trial at ~15 clinical sites 1:1 randomization of suprachoroidal CLS-TA + intravitreal Eylea vs. intravitreal Eylea alone Randomization across similar populations of BRVO and CRVO One year study with primary outcome at 2 months; superiority of best corrected visual acuity

25 TOPAZ Second Phase 3 Clinical Trial in RVO Designed to Support a Potential anti-vegf Class Label Combination arm; Suprachoroidal CLS-TA + Intravitreal anti-vegf 1 ; Q12Wk Intravitreal anti-vegf Suprachoroidal CLS-TA + Intravitreal anti-vegf Day ww xx yy zz Enrollment 2 Month primary efficacy endpoint Submit with 6 months data PRN Continue to follow subjects out to 1 year Day ww xx yy zz Control arm: Intravitreal anti-vegf 1 ; Q4Wk 1 Lucentis or Avastin Two-arm, randomized, controlled, double-masked, multi-center global trial; 46 patients 1:1 randomization of suprachoroidal CLS-TA + intravitreal anti-vegf 1 vs. intravitreal anti-vegf 1 alone Randomization across similar populations of BRVO and CRVO Primary outcome at 2 months; superiority of best corrected visual acuity 25

26 TANZANITE Design for Phase 2 TANZANITE Trial Day Month Month Month 1 * 2 * 3 * Combination Arm: Intravitreal Eylea + Suprachoroidal CLS-TA Enrollment * As needed Eylea Control Arm: Intravitreal Eylea only Day Month Month Month 1 * 2 * 3 * Evaluation period 3 months Controlled, masked, randomized (1:1) study Patients RVO; Treatment naïve - BCVA worse than 7 letters read; macular edema >31 µm on SD-OCT Single treatment at Baseline - Subjects were observed for 3 months post treatment; 46 patients enrolled: 23 per arm 26

27 Number of Patients Requiring Additional Injections Additional Intravitreal Eylea Injections Control p=.13 9 Combination Number of patients who received additional Intravitreal Eylea Control p= Combination Intent-to-treat (ITT) population: N = 46 (23:23) 6% fewer additional intravitreal Eylea injections in the suprachoroidal CLS-TA + intravitreal Eylea arm versus control over 3 months Intent-to-treat (ITT) population: N = 46 (23:23) 69% fewer patients required additional Eylea treatments 27 1) Based on post-hoc analysis

28 Improved Visual Acuity Suprachoroidal CLS-TA + Intravitreal Eylea resulted in more improved visual acuity at months 1, 2, 3 vs. intravitreal Eylea alone 25 ITT population N = 46 (23:23) BCVA ETDRS letters read: change from baseline M1 Control +4.6 M1 Combination M2 Control +8.5 M2 Combination M3 Control M3 Combination 15 letters gained (2) 39% 52% 15 letters gained (1) 39% 61% 15 letters gained (2) 43% 52% 28 M1 = month 1; M2 = month 2; M3 = month 3 (1) p=.4 (2) although numerically this shows more improved visual acuity at M1 and M2, this difference does not achieve statistical significance

29 Retinal Thickness Reductions Suprachoroidal CLS-TA + intravitreal Eylea resulted in sustained retinal thickness reductions at months 1, 2, 3 vs. intravitreal Eylea alone 1 Control Arm; N=23 Intravitreal aflibercept + Sham CST (microns) µm 731 Combination Arm; N=23 Intravitreal aflibercept + CLS-TA 4. mg Baseline 1 Month 1 2 Month 2 3 Month 3 Baseline 728 µm and 731 µm in the Control and Combination arms 29 Note: Bars are one-sided standard deviations

TANZANITE Safety Summary All patients completed the TANZANITE trial There were no serious adverse events AEs 5% in any arm were: conjunctival haemorrhage (2/23; 1/23); IOP increased (/23; 2/23); eye

30 TANZANITE Safety Summary All patients completed the TANZANITE trial There were no serious adverse events AEs 5% in any arm were: conjunctival haemorrhage (2/23; 1/23); IOP increased (/23; 2/23); eye pain (2/23; 7/23), ocular hypertension (/23; 2/23); and visual acuity reduced (2/23; /23) in the Elyea alone and combination arms respectively Suprachoroidal CLS-TA and intravitreal Eylea used together in the combination arm was generally well tolerated and there were no unique safety events 3

31 Post-TANZANITE Evaluation 74% of patients who received combination therapy did not receive additional treatment through a minimum 9 months Monotherapy (n=11) 6 (55%) re-treated Combination (n=2) 3 (15%) including Month 3 patients re-treated Control arm: 17% (n=4/23) Combination arm: 74% (n=17/23) 31

32 DME Suprachoroidal CLS-TA Alone or in Combination with an Anti-VEGF Agent 32

33 Current Treatment Paradigm for DME 8.3 M patients Diabetic Retinopathy patients in U.S. 1.1 M patients Diabetic Macular Edema (DME) patients Eylea, Lucentis, and off-label Avastin Sustained release steroid (Ozurdex ) Intravitreal Triamcinolone Acetonide 1 st Line treatment 2 nd Line treatment 33 33

The Opportunity In Treating DME Primary Need 1) Improved resolution of edema and lower burden of care for diabetic patients The Problem 1) DME course and response to anti-vegf injection is largely

34 The Opportunity In Treating DME Primary Need 1) Improved resolution of edema and lower burden of care for diabetic patients The Problem 1) DME course and response to anti-vegf injection is largely variable 2) 4% and 55% of subjects have continued macular edema in years 2 and 3, respectively, even after monthly intravitreal anti-vegf injections 3) Need for ongoing monthly intravitreal anti-vegf therapy results in high burden for DME patients 34 34

35 TYBEE Design for Phase 2 DME Clinical Trial Combination arm: Intravitreal Eylea + Suprachoroidal CLS-TA (n=36) Intravitreal Eylea Suprachoroidal CLS-TA + Intravitreal Eylea Day As needed Eylea Enrollment Evaluate at 6 months As needed Eylea Day Control arm: Intravitreal Eylea only (n=35) Any additional treatment based on as needed criteria at 16 and 2 will be intravitreal Eylea 35 Controlled, masked, randomized study of combination CLS-TA + intravitreal Eylea vs. intravitreal Eylea alone Evaluation at Month 6; treatment is based on PRN criteria from Month 3 Primary outcome measure is comparison of mean change from baseline in BCVA at 24 weeks between the combination arm and the control arm. The study was powered and designed to show that the mean change in BCVA is not different between the two arms. 35

36 TYBEE Met Its Primary Endpoint Mean Change in BCVA from baseline at 24; the data 1 are tested for equivalence by comparing the 9% confidence intervals Mean change from baseline in BCVA (ETDRS letters) read (1) 13.5* 12.3* Control Combination Baseline BCVA in ETDRS letters: 58: control arm; 57: active arm At 24 each arm shows a statistically improvement in BCVA from baseline (*p<.1) Data at each visit starting 4 show similar outcomes with no statistically or clinically meaningful difference when comparing data from each arm 36 (1) p=.664; p>.5 implies equivalence Table ; Listing Data without major deviations; data with major deviations shows similar result 36

37 Combination Arm Achieved Equivalent Vision with Fewer Treatments Number of additional Eylea Injections in the PRN stage Control (1) 1 Combination ~5% fewer treatments through week 12 ~57% fewer treatments in the PRN period (p=.3) 37 (1) p=.3 37

38 Central Retinal Thickness (CST) Mean Change from Baseline in CST by Visit Each arm shows a statistically significant improvement in CST from baseline at week 24 (*p<.1) Mean change from baseline in CST (microns) Day Wk4 Wk8 Wk12 Wk16 Wk2 Wk Control Combination 38 38

39 Resolution* of CST By Visit Control Combination Percent subjects with CST <3 microns Wk4 Wk8 Wk12 Wk16 Wk2 Wk24 A significantly greater percentage of patients in the Combination arm showed resolution* in their CST at the week 4 visit (p<.1) compared to those in the Control arm The greater resolution in CST appeared to be sustained through each visit through week 24 in the trial 39 *Defined as CST <3 microns CST: central subfield thickness 39

40 Efficacy TYBEE Trial High Level Summary This Phase 2 trial met its primary endpoint at week 24 Each arm showed a statistically significant improvement in BCVA from baseline (p<.1) Both arms were statistically equivalent at every time point A consistent trend in reduction of CST was observed in the Combination arm Safety Adverse events in the trial were generally consistent with other trials involving CLS-TA and Eylea Elevated IOP 8.3% (3/36) in the Combination arm and 2.9% (1/35) in the Control arm Cataracts 5.6% (2/36) in the Combination arm and 2.9% (1/35) in the Control am Elevated IOP events were consistent with previous trials with CLS-TA and resolved with eye drops 4 ETDRS: early treatment of diabetic retinopathy study; BCVA: best corrected visual acuity; CST: central subfield thickness 4

41 A WORLD WITHOUT BLINDNESS In Summary 41

42 Patent No. Significance Expiration U.S. 7,918,814 U.S. 8,197,435 U.S. 8,636,713 Opportunity is Well Protected Provides exclusivity for the administration of any drug to the eye by inserting a microinjector into the sclera or corneal stroma of a patient s eye, and infusing the drug into the sclera or cornea Provides exclusivity for administration of any drug to the suprachoroidal space, when the drug is administered through a microinjector that is inserted into the patient s sclera Provides exclusivity for all hollow microinjector ocular delivery methods of anti-inflammatory drugs, so long as the anti-inflammatory drug is infused into the suprachoroidal space U.S. 8,88,225 Provides exclusivity for all hollow microinjector ocular delivery methods of drug, so long as the drug is infused into the suprachoroidal space U.S. 9,788,995 Provides exclusivity for all microinjector ocular delivery methods of drug at any ocular insertion site for controlled release 227 U.S. 9,18,47 Provides exclusivity for methods for delivering a substance to a region of the eye (e.g., SCS, sclera, choroid) via loss of resistance injection technology 234 U.S. 9,539,139 Provides exclusivity for apparatus with actuation rod configured to operate via loss of resistance injection technology 234 U.S. 9,636,253 Provides exclusivity for methods for delivery a substance to a region of the eye (e.g., SCS, sclera, choroid) via an adjustable needle and loss of resistance injection technology 234 U.S. 9,77,361 Provides exclusivity for apparatus with adjustable needle configured to operate via loss of resistance injection technology 234 U.S. 9,572,8 Provides exclusivity for methods of treating a posterior ocular disorder in a human via non-surgical administration of axitinib to the SCS 233 U.S. 9,636,332 U.S. Appl. No. 15/673,73 (allowed) U.S. Appl. No. 15/714,441 (allowed) U.S. Appl. No. 15/383,582 (allowed) Provides exclusivity for methods of treating a posterior ocular disorder in a human via non-surgical administration of triamcinolone to the SCS Provides exclusivity for methods of treating macular edema (e.g., secondary to RVO) in a human via non-surgical administration of an antiinflammatory drug to the SCS and non-surgical administration of a VEGF antagonist to the eye Provides exclusivity for apparatus with an adjustable needle configured to operate via loss of resistance injection technology and a medicament container containing triamcinolone Provides exclusivity for methods of delivering a substance to a target tissue using loss of resistance injection technology

43 Leadership Accomplished Team with Deep Ophthalmic Experience DANIEL WHITE President, CEO and Director CHARLES DEIGNAN Chief Financial Officer GLENN NORONHA, Ph.D. Chief Scientific Officer BRION RAYMOND Chief Commercial Officer Experience Years GSK, Stiefel, CIBA Vision, Alimera 25 AtheroGenics, AAIPharma, Schering-Plough 27 Alcon, Sucampo, TargeGen 19 Genentech, Carl Zeiss Meditec, Xoma 14 Ophthalmic Experience RAFAEL ANDINO VP, Engineering & Manufacturing CAROL HOANG, Pharm.D. VP, Medical Affairs JENNIFER KISSNER, Ph.D. VP, Clinical Development RICK MCELHENY VP, Business Development CR Bard, CIBA Vision, Dupont, GE, IBM 26 DigiSight, Novartis, Genentech, BMS 17 Alcon, Acucela, Vanderbilt 17 Sanofi, MEDA, Vidara 18 43

44 Major Near-Term Anticipated Milestones Provide Multiple Potential Value-Inflection Points Uveitis Publications P3 Data (PEACHTREE) NDA Submission NDA Review RVO Phase 3 (SAPPHIRE) Topline P3 Data Phase 3 (TOPAZ) DME Analysis & Presentation P2 Data (TYBEE) 44

45 THANK YOU! We see a world without blindness; relentlessly pursuing transformative, elegant, precise solutions to restore and preserve vision.

Charles C. Wykoff MD PhD Rahul N. Khurana MD

Charles C. Wykoff MD PhD Rahul N. Khurana MD HDWallpapers Suprachoroidal Triamcinolone Acetonide with & without Intravitreal Aflibercept for DME: Results of the 6 Month Prospective Phase 1/2 Hulk trial Blanton Eye Institute Charles C. Wykoff MD PhD