Table 1.

Clinical trial data on EYP-1901 (Vorolanib implant).

	wet AMD	wet AMD	Non-proliferative diabetic retinopathy (NPDR)
Phase	I (DAVIO) NCT04747197	II (DAVIO 2) NCT05381948	II (PAVIA) NCT05383209
Geography	US	US	US
Status	Completed	Ongoing	Ongoing
No. of Participants	17	150	105
Design	Non-randomized, Sequential Assignment, Multicenter, Prospective, Open-Label, Dose Escalation	Randomized, Multi-centre, Prospective, Randomized, Double-blind, Parallel Assignment	Multi-centre, Prospective, Double-blind, Parallel
Inclusion criteria	• Diagnosed with wet AMD in the study eye within 18 months before the screening visit. • ≥ 3 prior injections of any anti-VEGF • Response to anti-VEGF in the study eye • BCVA using ETDRS charts of 25 to 75 letters	• Diagnosed within the past 9 months • History of response to anti-VEGF • History of at least 2 injections in the last 6 months • BCVA ETDRS letter score: 35 letters (20/200 Snellen equivalent) - 80 letters (20/25 Snellen equivalent) in the study eye at the screening visit and on Day 1	• Moderately severe to severe NPDR (DRSS 47 or 53) • BCVA: ETDRS letter score ≥69 letters ( ~ 20/40 or better) • HbA1c%: ≤12% • No anti-VEGF injections in the past 12 months
Dose & Frequency	• EYP-1901: 440 μg, low dose (n = 3) • EYP-1901: 1030 μg, low mid-dose (n = 1) • EYP-1901: 2060 μg, mid dose (n = 8) • EYP-1901 3090 μg, high dose (n = 5)	• EYP-1901: 2 mg low dose (n = 48) • EYP-1901: 3 mg high dose (n = 48) • Aflibercept: 2 mg (0.05 mL) Q8W (n = 48)	• EYP-1901: 2 mg low dose (n = 35) • EYP-1901: 3 mg high dose (n = 35) • Day 1 single injection sham comparator (n = 35)
Primary endpoint	Incidence of ocular (study eye) and systemic treatment-emergent adverse events (TEAEs) – week 48	Change in (BCVA) – week 28 and week 32	% of subjects improving ≥2 steps in the DRSS score each EYP-1901 dose level versus the sham group.
Secondary endpoints	• Mean change in central retinal thickness on OCT (week 48) • Mean change in BCVA (week 48)	• Change in BCVA (week 56) • Mean change in CRT on OCT (week 56) • Number of rescue injections (week 56)	• % of subjects improving ≥2 steps in the DRSS score in each dose level vs. sham (at weeks 48 & 96) • % of subjects who developed a vision-threatening complication due to DR (at weeks 48 & 96) • Rates of ocular (study eye & fellow eye) and non-ocular TEAEs (at weeks 24, 48, & 96)
Results Efficacy	6- & 12-month data: • Significant reduction in the treatment burden of 75% at 6 months supporting treatment to maintain positioning & 73% reduction at 12 months • 53% supplemental anti-VEGF supplement injection free for up to 6 months Supplemental anti-VEGF therapy through 6 months: • Met all objectives (positive efficacy & durability) • Stabilization of mean BCVA and OCT throughout 6 months was achieved • 79% reduction in the treatment burden at 6 months Subjects 9/17 (53%) with no “excess fluid” at screening: • Mean change in BCVA from screening visit (n = 9)  ○ +1.2 letters at 5 months  ○ -0.4 letters at 6 months • Mean change in CST from screening visit (n = 9)  ○ +20.8 microns at 5 months  ○ -1.0 microns at 6 months • 92% reduction in treatment burden at 6 months among subjects with no “excess fluid” at screening (n = 9)	NA	NA
Safety	12-month data: • Phase 1 DAVIO clinical trial demonstrated favourable overall safety data at 12 months meeting the primary endpoint: No ocular SAEs, drug-related systemic SAEs, Durasert-related toxicity or tolerance issues & dose-limiting toxicity. • Supplemental anti-VEGF therapy through 6 months: • Met all objectives • No ocular SAEs, or drug-related systemic SAEs • Ocular AEs – the majority were mild and expected	NA	NA

AE adverse event, anti-VEGF anti-vascular endothelial growth factor, BCVA best corrected visual acuity, CRT central retinal thickness, CST central subfield thickness, DR Diabetic retinopathy, DRSS Diabetic Retinopathy Severity Score, ETDRS Early treatment diabetic retinopathy study, NPDR Non-proliferative diabetic retinopathy, OCT optical coherence tomography, SAE serious adverse event, TEAE treatment emergent adverse event, wet AMD wet age-related macular degeneration.