Slide 1: Dr. Jason Slakter
Dr. Jason Slakter Clinical Professor of Ophthalmology NYU School of Medicine Chairman of the Anecortave Acetate Clinical Study Group
Slide 2: RETAANE 15mg (anecortave acetate for depot suspension)
RETAANE® 15mg (anecortave acetate for depot suspension)
Slide 3: Overview
Overview ®@ Development Strategy @ RETAANE® Depot Overview @ Study Design C-01-99 ® Study Results C-01-99 @ Next Steps
Slide 4: RETAANE Depot Development Strategy
RETAANE® Depot Development Strategy Goal: To deliver a superior physician and patient experience. @ Mechanism of Action: Addresses multiple factors, including VEGF plus angiogenic cell division, migration and tissue changes. ® Molecule: Developed to be devoid of the negative side effects of steroids
Slide 5: RETAANE (anecortave acetate for depot suspension)
RETAANE® 15 mg mY (anecortave acetate for depot suspension) i @ Devoid of glucocorticoid activity @ Novel angiostatic Cortisene Addition of 21-Acetate Introduction) of C9-11~ Double Bond Removal of 11b-Hydroxyl
Slide 6: PJD Administration
PJD Administration ®@ Administration outside the eye by posterior juxtascleral delivery (PJD) for transcleral delivery to the macula with a curved, blunt-tipped cannula ® Single PJD administration every 6 months
Slide 7: RETAANE Depot vs VISUDYNE PDT
RETAANE® Depot vs VISUDYNE® PDT C-01-99 Study 12 Month Results
Slide 8: RETAANE Depot - Phase III Non-Inferiority Study Design
RETAANE® Depot - Phase III Non-Inferiority Study Design Per Protocol RETAANE® VISUDYNE® Depot PDT (N=255 Enrolled) (N=256 Enrolled) (N=214 at 12 Months) (N=220 at 12 months) Patients randomized 1:1
Slide 9: C-01-99 Study Design
C-01-99 Study Design @ 12 month primary efficacy readout with follow-up to 24 months @ RETAANE® Depot vs VISUDYNE® PDT = Masked by double sham (PJD or PDT sham) = Inclusion criteria « Age 250 years + Subfoveal CNV + Predominantly classic with GLD 5400yu « Vision: 20/40 - 20/400 (logMar 0.3 to 1.3)
Slide 10: C-01-99 Study Design
C-01-99 Study Design @ RETAANE® Depot vs VISUDYNE® PDT = Re-treat every 6 months for RETAANE® Depot and every 3 months with VISUDYNE® PDT if leakage (per PDT guidelines) along with appropriate sham @ Endpoint: The % patients maintaining vision at 12 months (<3 lines loss of VA)
Slide 11: C-01-99 Statistical Design
C-01-99 Statistical Design Goal: To demonstrate non-inferiority of RETAANE® Depot relative to VISUDYNE® PDT at Month 12 ®@ Primary analysis is based on the per protocol data set without LOCF ® Non-inferiority is demonstrated based on a confidence interval around the observed difference between the 2
Slide 12: Patient Data Sets
Patient Data Sets eS RETAANE® Depot Enrolled Discontinued and Excluded from Intent to Treat Intent to Treat Patients Not Evaluable Per Protocol Per Protocol Overall Per Protocol at Month 12: Discontinued Prior to Month 12 Missed Visit / Protocol Violation Net Per Protocol Data at Month 12 * One ITT
Slide 13: Reasons for Discontinuation Prior to Month 12
Reasons for Discontinuation Prior to Month — 12 for All Patients oA ®@ 53/530 (10%) patients discontinued prior to Month 12 visit RETAANE® Visudyne® Reason Depot Adverse Event 18 Disease Progression Inclusion/Exclusion Lost to follow-up Packaging Error Patient Decision Transportation Total
Slide 14: C-01-99 Study Demographics
C-01-99 Study Demographics wt (Per Protocol) RETAANE® | Visudyne® Depot PDT % Caucasian 99.2% 96.5% % Females 56.5% 48.4% Mean VA at 0.74 (log baseline MAR) 0.71 (log MAR) Mean age 76.4 years Teayears 76.8 years
Slide 15: C-01-99 Baseline Lesion Characteristics
C-01-99 Baseline Lesion Characteristics Total Lesion Size CNV Classic Component Lesion Age (From Diagnosis) (Per Protocol) Retaane® 15 3.7 mm? Mean 2.9 mm? Median 3.3 mm? Mean 2.6 mm? Median 3.0 mm? Mean 2.3 mm? Median 36 Days Median | Visudyne® PDT 3.7 mm? Mean 2.7 mm? Median 2.4 mm? Median 3.0 mm?
Slide 16: Baseline Ocular Characteristics
Baseline Ocular Characteristics C-01-99 Population: Predominantly Classic + 54% of lesions were 100% Classic C-98-03 C-01-99 Baseline VA (Looa.R) Total Lesion Size 0.73(~20/100) 8.0 mm? Mean 5.7 mm? Median 0.72(~20/100) 3.7 mm? Mean 2.8 mm? Median CNV Component 7.0mm? Mean 4.9 mm? Median 3.3 mm? Mea
Slide 17: Percent <3-Line Loss
Percent <3-Line Loss C-01-99 Study Results 4 Percent of Patients with <3-Line Loss in VA_ Per Protocol Intent To Treat 100% 100% 30% 11] " Fy 90% Praca No Stati al Difference BEng 10% p=04s fy 70% 60% E 60% 50% as 3 80% 0%. = 40% 0% 8 30% 20% jE 20% 10% 10% 0% 0% - RETAANE® VISUDYNE® RETAANE® VISUDY
Slide 18: Controllable Factors
Controllable Factors
Slide 19: Controllable Factors
Controllable Factors @ Drug Reflux ® Treatment Interval
Slide 20: Controllable Factors: Drug Reflux
Controllable Factors @ Drug Reflux = Occurs when a portion of the drug leaks out through the small incision in the conjunctiva during or immediately after application of the drug
Slide 21: Visual Outcome Without Reflux
Percent <3-Line Los: Visual Outcome Without Reflux — 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Li (Per Protocol Data) p=0.756 50% 49% RETAANE® Visudyne® No reflux at 6 months
Slide 22: Controllable Factors: Treatment Interval
Controllable Factors @ Drug Reflux ® Treatment Interval = Treatment interval refers to the timeframe during which re-administration of the drug should occur
Slide 23: Effect of PJD Dosing Interval
Effect of PUD Dosing Interval _ On Month 12 VA Outcome ~~ 2 -®- All Patients| a a Q 8 w 3 | N=200 = & Month 12 Outcome: Percent With <3-Line VA Lo: wn a & & 175 177 179 181 183 185 187 189 195 197 19 2M 23 25 terval (Days) fromihiéial PID to Month 6 Visit Cumulative
Slide 24: RETAANE Depot Visual Outcome Based on Treatment Interval
Percent <3-Line Los RETAANE® Depot Visual Outcome 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Based on Treatment Interval (Per Protocol Data) *p = 0.021 50% Within 6 months > 6 months
Slide 25: Effect of PJD Dosing Interval and Reflux
Effect of PJD Dosing Interval and Reflux OnMonth12VA Outcome |. a ~- No Month 6 Reflux] -®- All Patients 4 6s is 2 60 £8 dG a NE1OS a a + Fs g 3 50 me NET 4 £ 4s — -_—— 40 15 177 179 IL 183 195 187 189 191199 195 197 199 201 209. 205 Interval (Days) from Initial PJD ta Month 6 Visit Cumulative
Slide 26: Visual Outcome Without Reflux and Treatment within 6 Months
Percent <3-Line Los Visual Outcome Without Reflux aS and Treatment within 6 Months ~ (Per Protocol Data) 100% 90% p= O195 80% 70% 60% pee 49% 50% 40% 30% 20% 10% 0% RETAANE® Visudyne®
Slide 27: PJD: Critical Steps in Managing Reflux
PJD: Critical Steps in Managing Reflux ®@ Patient Body Position: Supine or reclined in an exam chair ® Patient Eye Position: Looking down and nasally ®@ Incision Location: 8 mm from Limbus ®@ Incision Size: 1.0 to 1.5 mm to minimize space between cannula and incision ®@ Incision Depth: Incision dept
Slide 28: PJD: Critical Steps in Managing Reflux
PJD: Critical Steps in Managing Reflux ® Syringe Size: The 1-cc syringe provides a more controlled rate of administration than the 3-cc syringe used in trials ®@ Administration: Slowly (at least 10 seconds) administer to allow for orbital fat delamination and formation of depot pocket
Slide 29: Enhanced PJD Procedure with Counter Pressure Device
Enhanced PJD Procedure with wet % Counter Pressure Device (CPD) —_ + CPD is effective at preventing reflux in pre-clinical evaluations. * Clinical PK study initiated
Slide 30: Posterior Juxtascleral Depot
Posterior Juxtascleral Depot ™
Slide 31: PJD: Critical Steps in Managing Reflux
PJD: Critical Steps in Managing Reflux ® Counter Pressure Device: Use CPD as far posterior as is feasible and perpendicular to globe straddling cannula. Hold in place 5 seconds after removal of PJD cannula @ Post Administration: = Tobradex® Ointment over incision site = Pressure Patch while patient
Slide 32: PJD: Critical Steps in Managing Reflux
PJD: Critical Steps in Managing Reflux ® Counter Pressure Device: = Will immediately be employed in all Anecortave Acetate clinical trials = Study to evaluate PK and reflux with CPD underway
Slide 33: C-01-99 Safety
C-01-99 Safety
Slide 34: RETAANE | Visudyne adverse events
RETAANE® | Visudyne® Visual Acuity Decrease Cataract Eye Pain ‘Vitreous Detachment IOP Decrease
Slide 35: RETAANE | Visudyne adverse events
RETAANE® | Visudyne® ‘Macular Degeneration (non-study eye) Vitreous Disorder IOP Increase Hyperel
Slide 36: RETAANE Depot Safety Data
RETAANE® Depot Safety Data xt Non-Ocular Fx) Visudyne® % Hypertension’ |. 6.7 Infection (Non-Ocular) 2 ir 2.6 Arthritis’ 5 4.9 | Hypercholesterolemia 2.6 Hyperlipemia 0.7 |Back Pa 9.0 2.6 Emphysema i 3.0 All events not related, with the exception of 1 report each of back pain and nausea for the Visu
Slide 37: C-01-99 Conclusions
C-01-99 Conclusions @ RETAANE® Depot is a potentially effective treatment for wet AMD. = Must further analyze and manage reflux and treatment interval. @ RETAANE® Depot maintains its remarkable safety profile. ®@ RETAANE® administration by PUD is a safe and convenient procedure.
Slide 38: Current RETAANE Activities
Current RETAANE® Activities — @ A two week PK study in >30 pts has been initiated to demonstrate control of reflux with the Counter Pressure Device, and enrollment is ongoing. = This study completion is not a prerequisite to final FDA (NDA) module submission. @ The NDA is planned for submission by y
Slide 39: Question and Answer
Question & Answer