Slide 1: Impact of Baseline Central Retinal Thickness on Visual and Anatomic Outcomes in DME
Impact of Baseline Central Retinal Thickness on Visual and Anatomic Outcomes in Patients With Diabetic Macular Edema: Post Hoc Analysis of the Phase 2/3 PHOTON Trial Rahul N. Khurana, MD,’ on behalf of the PHOTON study investigators 1Northern California Retina Vitreous Associates, Mountain View, CA,
Slide 2: Disclosures
Disclosures DME Dr. Khurana serves on the Advisory Board to Arrowhead Pharmaceuticals, Bausch + Lomb, Genentech, Inc., NGM Biopharmaceuticals, Opthea and Regeneron; and has received research funding from Annexion, Apellis, Chengdu Kanghong, Clearside Biomedical, EyePoint, Genentech, NGM Biopharmaceu
Slide 3: Background
* photon Background ; ; : DME * Aflibercept is a fully human recombinant Dose-dependent Duration of Leakage Inhibition? fusion protein that binds VEGF-A, VEGF-B, and PIGF, thereby inhibiting the activation O Alfbercept (125 megleye; n=19) 1 Atibercept (500 mog/eye; n=10) of cognate VEGF receptors! S
Slide 4: PHOTON Study Design
PHOTON Study Design Multi-center, randomized, double-masked study in patients with DME? Randomized 1 (2q8) : 2 (8q12) : 1 (8q16) Note: 2 mg arm received 5 initial monthly injections versus 8 mg arms, which received only 3 initial monthly injections 2q8 Aflibercept 2 mg every 8 weeks after 5 initial
Slide 5: PHOTON: 48-Week BCVA Primary Endpoint Met in Both 8 mg Groups
PHOTON: 48-Week BCVA Primary Endpoint Met in Both 8 mg Groups BCVA Change from Baseline? a ° a & © D © ac ro) Ic G o = BCVA, ETDRS Letters Oo ° LS mean change from BL it in Lg means vs. 2q8 _2-sided 95% Cl at Week 48 (MMRM) 1-sided test for non-inferiority at 4-letter margin 2q8 8.7 8q12 8.1 -0.57 8
Slide 6: Mean CRT Through Week 48
Mean CRT Through Week 48 296 2q8 279 8q12 306 8q16 Mean CRT, pm This analysis evaluated the effect of aflibercept 8 mg versus 2 mg on clinical outcomes in patients with DME based on disease severity, as defined by baseline CRT Observed values (censoring data post-ICE); FAS: 248 n=167; 8q12n=328; 8q1
Slide 7: Analysis methods and key outcomes assessed
Mean CRT Through Week 48 296 2q8 279 8q12 306 8q16 Mean CRT, pm 24 Week + Analyses were descriptive and 1 patient was excluded due to missing baseline CRT + Key outcomes assessed include: — Mean change in BCVA through Week 48 — Mean change in CRT through Week 48 — Proportion of patients who maintain
Slide 8: Baseline Characteristics by Baseline CRT Quartiles
Baseline Characteristics by Baseline CRT Quartiles Q2: 2361-<430 pm Q3: 2431-<528 ym Q4: >528 pm (n=163) (n=163) (n=164) 2q8 (n=45) 612 | 608 | 614 Age, years (10.6) | (13.2) | (9.8) ; 29 55 30 Male, n (%) (64.4) | (76.4) | (63.8) 143 | 14.2 | 15.1 (8.8) | (9.7) | (10.7) 56.7 | 574 | 534 (12.8) | (1
Slide 9: Treatment Exposure to Week 48 by Baseline CRT Quartiles
Treatment Exposure to Week 48 by Baseline CRT Quartiles 7) ta ° S 2) © 2 c - i) i ® 2 & Ss c c G o = 2q8 8q12 84q16 2q8 8q12 8q16 2q8 8q12 8q16 2q8 8q12 8q16 (n=47) (n=85) (n=35) | —(n=39) (n=78) (n=46) | — (n=36) (n=92) (n=35) | — (n=45) (n=72) (n=47) a1 Q2 Q3 Q4 FAS, observed cases. Q1: <360 ym; Q
Slide 10: Mean BCVA and CRT Through Week 48 in Baseline CRT Q1 and Q2
Mean BCVA and CRT Through Week 48 in Baseline CRT Q1 and Q2 Q1: $360 um Q2: 2361-430 ym 0298 (n=47) 8+ 8q12 (n=85) =t-8q16 (n=35) 2 6 3 Mean BCVA, ETDRS letters a 3 Mean BCVA, 8 ETDRS letters a 3 ° 4 8 12 16 20 24 28 32 36 40 44 48 Week ~ ° | 3 0-298 (n=39) —l-8q12 (n=78) —a~8q16 (n=46) 8 12 16 20 2
Slide 11: Mean BCVA and CRT Through Week 48 in Baseline CRT Q3 and Q4
Mean BCVA and CRT Through Week 48 in Baseline CRT Q3 and Q4 Q3: 2431-528 ym Q4: >528 um ro) 6 Mean BCVA, ETDRS letters 3 #298 (n=36) --8q12 (n=92) —&-8q16 (n=35) ro) ° 4 8 12 16 20 24 28 32 36 40 44 48 Week Mean BCVA, ETDRS letters a 3 0298 (n=45) 8 8q12 (n=72) 2 6 = ) 3 —#-8q16 (n=47) 8 12 16 20 24
Slide 12: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 298 (n=45) -™@+8q12 (n=72) -*-8q16 (n=47) a tS) fo} £ = E ~ oO c o ® = 4 8 12 16 20 24 28 32 | a 8q12 and 8q16: 3 initial monthly doses ———————EEEEEEEE 2q8: 5 initial monthly doses Q4 baseline CRT: >528
Slide 13: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym +™-8q12 (n=72) —&-8q16 (n=47) 400 4 380 4 360 4 340 4 320 4 £ = E ~ oO c o ® = 300 4 280 Ee Cl 8q12 and 8q16: 3 initial monthly doses Q4 baseline CRT: >52
Slide 14: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym +™-8q12 (n=72) —&-8q16 (n=47) 400 4 380 4 360 4 340 4 320 4 £ = E ~ oO c o ® = 300 4 280 Ee Cl 8q12 and 8q16: 3 initial monthly doses Q4 baseline CRT: >52
Slide 15: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym +™-8q12 (n=72) —&-8q16 (n=47) 400 4 380 4 360 4 340 4 ACRT 8 weeks after last dose 300 4 8q12: +3.5 um 8q16: +5.7 um 320 4 £ = E ~ oO c o ® = 280 0 4 8 12
Slide 16: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym #298 (n=45) -™+-8q12 (n=72) -4-8q16 (n=47) 2q8: 644.2 ym 400 380 4 360 4 340 4 363} 351.3 £ = E a Oo e c Oo = 320 4 300 + Matched dosing period | 0 4 8 12
Slide 17: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym #298 (n=45) -™+-8q12 (n=72) -4-8q16 (n=47) 2q8: 644.2 ym 400 380 4 360 4 340 4 363} 351.3 £ = E ~ oO c o ® = 320 4 300 + Matched dosing period | 0 4 8 12
Slide 18: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym #298 (n=45) -™+-8q12 (n=72) -4-8q16 (n=47) 2q8: 644.2 ym 400 380 4 360 4 340 4 363} 351.3 320 4 335.1 331.3 332.1 328.1 £ = E ~ oO c o ® = 300 + Matched d
Slide 19: 8 mg vs 2 mg Among Eyes in Q4
Numerically Less Fluid Reaccumulation Was Observed With Aflibercept 8 mg vs 2 mg Among Eyes in Q4 Mean CRTat BL 8q12: 632.4 um 420 + aqi6.6109 ym #298 (n=45) -™+-8q12 (n=72) -4-8q16 (n=47) 2q8: 644.2 ym 400 380 ACRT 8 weeks after last cee monthly injection (um) 340 £ = E ~ oO c o ® = 320 300 4 Match
Slide 20: Majority of Aflibercept 8 mg Patients Maintained Randomized Dosing Intervals Through Week 48
Majority of Aflibercept 8 mg Patients Maintained ffeton Randomized Dosing Intervals Through Week 48 P DME @ Maintained i Shortened to Q12 or Q8 interval per DRM criteria? 100 | I xs | | | ; | | l Hn = 804 I | I s I I I S | | | | 76.2 33.2 fim &1 © | ! i= & 404 | | I = | | | 9 | | | s 2 I | | a 3.8 a
Slide 21: Conclusions
Conclusions ¢ Aflibercept 8 mg demonstrated meaningful visual and anatomic improvements in patients with DME at Week 48 across a wide range of baseline CRT values, with up to an average of 3 fewer injections compared with aflibercept 2 mg * In eyes with baseline CRT >528 um, fluid reaccumulation was