Slide 1: VEGF Trap-Eye for Central Retinal Vein Occlusion
VEGF Trap-Eye for Central Retinal Vein Occlusion A Randomized, Double Masked, Controlled Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated Intravitreal Administration of VEGF Trap- Eye in Subjects with Macular Edema Secondary to Central Retinal Vein Occlusion (CRVO)
Slide 2: Introduction
Introduction + CRVO is an obstruction of the retinal venous system due to thrombus formation + Prevalence currently of all RVO 0.7-1.6% and increases with age — BRVO 3 to 4 times greater incidence versus CRVO Nonischemic Up to 50% have visual acuity decrease to S$ 20/200 < 10% recover normal visual
Slide 3: CRVO Phase 3 Study Design
COPERNICUS CRVO Phase 3 Study Design Randomized, multicenter, double-masked trial in patients with macular edema secondary to CRVO with CRT > 250 pm and ETDRS BCVA of 20/40 to 20/320 N=189 Subjects randomized 3:2 ne ; Treatment to Week 24° seeonaary enaporne ronerien or Sie Gainers (primary endpoint
Slide 4: Key Exclusion Criteria
COPERNICUS Key Exclusion Criteria Treatment naive patients Previous use of intraocular or periocular corticosteroids in the study eye Previous treatment with anti-angiogenic drugs in the study eye (Pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc.) Prior panretinal laser photocoa
Slide 5: Patient Disposition
COPERNICUS Patient Disposition Sham Randomized 74 Received Study Medication 74 (100%) Completed Week 24 60 (81.1%) Discontinuation Before Wk 24 14 (18.9%) Withdrawal Of Consent 4 (1.4%) Protocol Deviation® 4 (1.4%) Adverse Event* 3 (4.1%) Death* 2 (2.7%) Lost To Follow-Up 2 (2.7%) Treatment Failure
Slide 6: Baseline Demographics
n (full analysis set) COPERNICUS Baseline Demographics 73 Age years (SD) 67.5 (14.29) Gender Women (%) 35 (48%) Men (%) 38 (52%) Race (%) White 59 (80.8%) Black 5 (6.8%) Asian 2 (2.7%) American Indian/Alaska Native 0 Native Hawaiian/Pacific Islander 1 (1.4%) Not Reported/Multi racial 6 (8.2%)
Slide 7: Baseline Disease Characteristics
COPERNICUS Baseline Disease Characteristics n (full analysis set) 73 ETDRS BCVA letter score (SD) 48.9 (14.4) Snellen Equivalent 20/126 BCVA > 20/200 (%) 55 (75.3) BCVA = 20/200 (%) 18 (24.7) Central Retinal Thickness um (SD) 672.4 (245.3) Baseline perfusion status n (%) Perfused* 50 ( 68.5%) Non-pe
Slide 8: Efficacy
Slide 9: % Patients Who Gain Letters at Week 24
COPERNICUS % Patients Who Gain 2 15 letters at Week 24 100% 80% 60% % Patients 40% 20% 0% 215 letter gain* = Sham =2q4 *P<0.0001 vs. Sham ‘Compared to baseline; LOCF; full analysis set; sham n=73; 2q4 n=114;
Slide 10: % Patients Who Gained Letters Over Time
COPERNICUS % Patients Who Gained 2 15 letters 56.1%" 2q4 % Patients 12.3% sham te) 4 8 12 16 20 24 “®Sham 204 *P<0.0001 vs. sham LOCF full analysis set; sham n=73; 294 n=114; “i
Slide 11: Mean Change in Visual Acuity
COPERNICUS Mean Change in Visual Acuity +17.3" 294 2 13 ary 21.3 letter ry difference G3 in = = = = = 24, -4.0 Sham Week “@Sham 204 LOGE full analysis set; sham n=73; 294 n=114; a
Slide 12: Proportion of Patients Who Gained Vision at Week 24
COPERNICUS Proportion of Patients Who Gained Vision at Week 24* % Patients 2O letter gain* 2410lettergain* 215 letter gain* 230 letter gain® *Compared to baseline; Full analysis set; sham n=73; 294 n=114; 2
Slide 13: Mean Change in Visual Acuity at Week 24
COPERNICUS Mean Change in Visual Acuity at Week 24
Slide 14: Mean Change in Central Retinal Thickness
COPERNICUS Mean Change in Central Retinal Thickness Week 0) 4 8 12 16 20 24 C) -100 144.8 Sham -200 Es Z 312.2 um ao difference -400 -457.8° 2q4 -500 sham 294 “P <0.001 vs. Sham LOGF; full analysis set; sham n=73; 2q4 n=114; 14
Slide 15: % with Anterior Segment Neovascularization by Week 24
COPERNICUS % with Anterior Segment Neovascularization by Week 24 20% % Patients g 6.8% 0% 0% % with anterior segment neovascularization by Week 24 = Sham = 2q4 Compared to baseline; full analysis set; sham n=73; 244 n=114; 15
Slide 16: Quality of Life at Week 24
COPERNICUS Quality of Life at 24 Weeks* Change in NEI-VFQ Score cS N=59 Total Scores “104 *P= 0.001 = Sham "294 vs. Sham “Compared to baseline; full analysis set; sham n=59; 244 n=104;
Slide 17: Quality of Life Subscales at Week 24
COPERNICUS Quality of Life Subscales at 24 Weeks* 0 Total * Near « Distance* Dependence + °" Ba a 8.25 g 56 g c- Pa Fa 1.84 0 *P=0.001 2 *P=0.071 = Sham "2q4 Pp = 0.032 4P =0.083 vs. Sham ‘Compared to baseline; full analysis set; sham n=59; 294 n=104;
Slide 18: Safety
SAFETY
Slide 19: % Patients with Study Eye Ocular SAEs at Week 24
COPERNICUS % Patients with Study Eye Ocular SAEs at Week 24 Sham n (Safety analysis set) 74 # subjects with at least 1 AE 40 (13.5%) Vitreous Hemorrhage 4 (5.4%) Neovascular Glaucoma 2 (2.7%) Iris Neovascularization 2 (2.7%) Retinal hemorrhage 2 (2.7%) Visual acuity reduced 4 (1.4%) Retinal Artery O
Slide 20: Deaths through Week 24
COPERNICUS Deaths through Week 24 Day Day em ltaeerese eee from Last Preferred Term Injection to with Fatal Outcome to Death Death Arrhythmia Acute myocardial infarction
Slide 21: % Patients with APTC Events through Week 24
COPERNICUS % Patients with APTC Events through Week 24 N (Safety analysis set) 2@r%) Vascular Deaths 2 (2.7%) 0 o 0 21
Slide 22: Conclusions
COPERNICUS Conclusions Safety: + VEGF Trap Eye was tolerated without evidence of negative ocular or systemic effects Efficacy: + Statistically significant difference in proportion of patients who have gained = 3 lines (56.1% vs 12.3%) * Statistically significant difference in mean BCVA by 21 letters
Slide 23: One Year Analysis
COPERNICUS One Year Analysis « After the primary endpoint at Week 24, all patients were eligible to receive VEGF Trap-Eye on a PRN basis Sham > VTE PRN VTE 2q4 >» VTE PRN « Therefore, all but 3 patients in the sham arm who continued into the 2"¢ 6 months of the study received at least one dose of VE
Slide 24: Study Schedule
COPERNICUS Study Schedule Week 0 4 8 12 16 2 24 28 32 36 40 44 48 2q4 open MEE EE Sham >PRN Box = Injection [il Solid = VTE active Primary Outline = sham Endpoint Hatched = VTE PRN
Slide 25: % Patients Who Gain Letters at Week 52
COPERNICUS % Patients Who Gain 2 15 letters *P<0.01 I vs. Sham 100% | I 80% I I g 60% | 2 ! 56.1%" £ 40% I = i] aK 30.1% | I 0% 1 Sham Sham> VTE2q4. 9 VTE2q4> VTE PRN VTE PRN Week 24 Week 52 Week 24 Week 52 ‘Compared to baseline; LOCF; full analysis set; sham n=73; 2q4 n=114;
Slide 26: Mean Change in Visual Acuity
COPERNICUS Mean Change in Visual Acuity e 473" +162" g 2q4PRN 13 Ss 2 MD 8 a 38 = 3 Ee Sham PRN 24Ng 8 12 16 20 24/28 32 36 40 44 48 52 4 4.0 Week *P< 0.001 vs. Sham LOCF; full analysis set; sham n=73; 24 n=114;
Slide 27: Retreatment Criteria
COPERNICUS Retreatment Criteria + > 50um increase in CRT on OCT compared to lowest previous measurement + New or persistent cystic retinal changes or sub-retinal fluid on OCT or persistent diffuse edema = 250 ym in the central subfield on OCT + Loss of 25 letters from the best previous measurement i
Slide 28: Treatment Summary
COPERNICUS Treatment Summary Total PRN Injections (Week 24 to Week 52) Median time mean Min:Max* | Median | to first PRN (SD) injection 2q4 > VTE PRN (n= 110) Sham > VTE PRN* (n = 60) 201-7) || Or. 3.9(2.0) 0:7 *Maximum of 7 injections possible +3 Patients in the sham arm did not get treated with VT
Slide 29: % Patients with Study Eye Ocular SAEs (Safety analysis set)
COPERNICUS % Patients with Study Eye Ocular SAEs 1 (Safety analysis set) Ht subjects w/ 2 1 AE Cataract Retinal Hemorthage Visual Acuity Reduced Vitreous haemorrhage Cystoid macular edema Glaucoma Iris Neovascularization Retinal tear Retinal vein occlusion Retinal Artery occlusion Endophthalmitis Co
Slide 30: % Patients with APTC Events
COPERNICUS % Patients with APTC Events N (safety analysis set) 2 (2.7%) Vascular Deaths 2 (2.7%) 1 0 Arrhythmia 4 Non Fatal MI C) Non Fatal Stroke (ischemic) oO
Slide 31: One-Year Conclusions
COPERNICUS One-Year Conclusions * Efficacy maintained to Week 52 with less frequent dosing — 55% of 3 line gainers for VTE/PRN vs. 30% for Sham/PRN — Mean change of BCVA at week 52 within 1 letter of week 24 outcome in the original 2q4 group * Safety — VTE was generally well tolerated — Most common