Slide 1: Intravitreal aflibercept 8 mg in patients with PCV: PULSAR subgroup analysis
Intravitreal aflibercept 8 mg in patients with polypoidal choroidal vasculopathy (PCV): A subgroup analysis from the Phase 3 PULSAR trial Chui Ming Gemmy Cheung,’ Tien Y Wong,? Jeffery S Heier,? Xin Zhang,4 Tobias Machewitz,° Andrea Schulze,> Sergio Leal on behalf of the PULSAR study investigators ‘
Slide 2: Disclosures
Disclosures Gemmy Cheung has received consultant fees, speaker fees and grant funding from Bayer, Roche, Novartis, Boehringer Ingelheim, Topcon, Zeiss, Janssen, and Avirmax The PULSAR study was sponsored by Bayer AG (Leverkusen, Germany) and co- funded by Regeneron Pharmaceuticals, Inc. (Tarrytown,
Slide 3: Polypoidal choroidal vasculopathy
Polypoidal choroidal vasculopathy + PCV presents as serosanguinous exudative maculopathy characterized by retinal PED, serous exudation, and hemorrhage in multiple retinal layers!:2 + PCV is particularly prevalent among Asian populations (25-50% of Asian patients with nAMD have PCV)13 + The most rel
Slide 4: Aflibercept 8 mg: VEGF-A/PlGF binding and formulation
-1 binding > Novel intravitreal formulation delivers 8 mg in 70 uL injection (114.3 mg/mL) >» 4-times higher molar dose compared with aflibercept 2 mg is hypothesized to provide longer effective vitreal concentrations and enable a more sustained effect on VEGF signaling Here, we present the PCV subg
Slide 5: PULSAR study design
PULSAR study design Multicenter, randomized, double-masked study in patients with treatment-naive nAMD Randomized at baseline 1 (2q8) : 1 (8q12) : 1 (8q16) 2q8 Aflibercept 2 mg every 8 weeks after 3 initial monthly injections n=336 Primary endpoint at Week 48 Mean change in BCVA (non-inferiority) Ke
Slide 6: Key inclusion/exclusion criteria
Key inclusion/exclusion criteria Inclusion Criteria + Men or women 250 years of age with treatment-naive nAMD Active subfoveal CNV, with a total area >50% of the total lesion area in the study eye Presence of IRF and/or SRF fluid in the central subfield on OCT BCVA of 78-24 letters (Snellen equivale
Slide 7: PULSAR: Dosing Schedule and Regimen Modification in Year 1
PULSAR: Dosing Schedule and Regimen Modification in Year 1 DRM Criteria for Shortening Dosing Interval” DRM in Year 1 + >5-letter loss in BCVA due to persistent or Intervals can only be Week 16 and 20: Patients on 8q12 and worsening nAMD 8q16 meeting DRM criteria shortened to q8 AND Week 24: Patient
Slide 8: PCV in PULSAR
PCV in PULSAR + PULSAR is a global study conducted across 223 sites in 26 countries , « ICGA was optional and conducted in 297 patients in 12 countries* « 141 patients — PCV present * 153 patients — PCV absent * 3 patients — data missing Patients with PCV present (n=141) r Ethnicity of PCV subgroup*
Slide 9: PCV subgroup: Baseline demographics and disease characteristics
PCV subgroup: Baseline demographics and disease characteristics Age, years Female, % BCVA, EDTRS letters CRT, um CNV size, mm2 FAS, data are mean (SD) unless otherwise indicated. FAS, full analysis set. 2q8 n=54 72.6 (8.2) 31.5% 57.6 (15.5) 378 (163) 5.8 (4.7) PCV subgroup n=45 72.2 (8.0) 48.9% 56.7
Slide 10: PCV subgroup: Absolute and change from baseline in BCVA through Week 48
PCV subgroup: Absolute and change from baseline in BCVA through Week 48 PCV subgroup GB Overall population 70 Absolute 65 BCVA 69.1 8q16 66.9 8q12 66.6 2q8 60 66.5 2q8 64.9 8q12 66.3 8q16 55 + T T T T 1 0 4 8 12 16 20 24 28 32 36 40 44 48 0 4 8 12 16 20 24 28 32 36 40 44 48 15 n 7 a es oa aa n a a E
Slide 11: PCV subgroup: Proportions maintained on q12 and q16 intervals through Week 48
PCV subgroup: Proportions of patients maintained on q12- and qieaweek intervals through! Week 48 e912" PCV subgroup 86% of 8 mg patients maintained dosing intervals 212 weeks 8q16 n=38" All 8 mg _n=80" q8* q8* q8* population ike 83% of 8 mg patients maintained dosing intervals 212 weeks 8q12 n=316"
Slide 12: PCV subgroup: Proportions without retinal fluid at Week 16
PCV subgroup: Proportions of patients without retinal fluid in the center subfield at Week 16 79% 68% | 63% 58% = open 65% 63% j ; / i] ’ i 8q12 8qi6-—s All 8 mg : 8q12 8q16 All 8 mg PCV subgroup Overall population a £ io 2 = oO a - 3 < 2 £ ) a ) 2 a Without retinal fluid defined as absence of IRF a
Slide 13: PCV subgroup: Absolute and change from baseline in CRT through Week 48
PCV subgroup: Absolute and change from baseline in CRT through Week 48 PCV subgroup Change from baseline at Week 48 -146 8q16 -148 2q8 -171 8q12 Overall population 24 28 32 36 40 44 Week LOCF; FAS: PCV subgroup, 2q8 n=54; 8412 n=45; 8416 n=42; overall population, 2q8 n=336; 8q12 n=335; 8q16 n=338 (a
Slide 14: Ocular AEs through Week 48
Ocular AEs (%)° through Week 48 PCV subgroup Overall population n=338 | n=673 37.6% | 38.0% 3 (5.6%) 2 (4.4%) 0 PARI M 20 (6.0%) | 12 (3.6%) | 18 (5.3%) | 30 (4.5%) 2 cases of cataracts* 2 (3.7%) 3(6.7%) 1(2.4%) 4 (4.6%) Any ocular AE* Reduced visual acuity (n, %) Cataract 10 (3.0%) | 12 (3.6%) | 12
Slide 15: PCV subgroup: Safety summary
PCV subgroup 2q8 8q12 B8qIGVAIl8mg 2q8 n=54 n=45 n=42 n=87 Patients with = 1 TEAE (%) 44.4 53.5 57.1 55.2 Nesom N=meree 11.1% 11.1% 11.9% 11.5% Deaths (%) 0 0 0 0 SAF. No cases of APTC, hypertension events, and non-ocular SAEs were reported in the PCV subgroup SAF, safety analysis set; TEAE, treatme
Slide 16: Conclusions: Aflibercept 8 mg monotherapy in PCV
Aflibercept 8 mg monotherapy in PCV Aflibercept 8 mg monotherapy* showed robust efficacy benefits Extended durability Comparable safety profile with aflibercept 2 mg “without active rescue PDT. Conclusions — Robust increases in BCVA from baseline at Week 48 were observed in the 8q12, 8q16, and 2q8 g