Despite anti-VEGF advancements, durable therapies are needed to improve long-term outcomes.
Wet AMD and DME are complex diseases that may require more than VEGF suppression.
TKIs work intracellularly to inhibit the key receptors and pathways involved in wet AMD and DME pathogenesis.
EYP-1901 (vorolanib intravitreal insert) is a sustained release TKI in development. Based on pre-clinical data, it inhibits VEGF receptors 1, 2, and 3, PDGFR, and IL-6 pro-inflammatory signaling.
It is designed to deliver a continuous daily dose for at least 6 months.
EYP-1901 was well tolerated and met primary and key secondary endpoints in wet AMD/DME phase 2 trials.
It is currently in phase 3 for wet AMD and DME.
EYP-1901 combines vorolanib with the Durasert E technology to deliver a continuous daily dose for at least 6 months. It is currently being investigated in pivotal phase 3 trials for the treatment of wet AMD and DME.
To date, EYP-1901 has been studied in >190 patients across four phase 1 and 2 clinical trials, with a favorable safety profile. A recent independent review of the phase 3 LUGANO/LUCIA masked safety data showed that the observed safety profile is consistent with previous EYP-1901 clinical trials.
Blocks signaling from all VEGF isoforms and PDGF at the receptor level and inhibits IL-6 pro-inflammatory signaling
Therapeutic levels of vorolanib reached within hours*
Consistent daily dosing for ≥6 months*
No free-floating drug particles
Preloaded sterile IVT syringe injector; to be shipped and stored at an ambient temperature
*Data from preclinical studies. Following a single EYP-1901 900-µg dose in Dutch-Belted rabbits, vorolanib reached concentrations exceeding IC50 in the choroid and retina within hours of administration.
Vorolanib intracellularly binding to VEGFR
*Data from preclinical studies. Following a single EYP-1901 900-µg dose in Dutch-Belted rabbits, vorolanib reached concentrations exceeding IC50 in the choroid and retina within hours of administration.
Vorolanib, a small molecule TKI, works intracellularly, binding to key receptors involved in wet AMD and DME pathogenesis, while anti-VEGFs act extracellularly binding to select VEGF ligands.
Vorolanib is a TKI that binds to VEGFR-1/2/3, PDGFR, and JAK-1, to inhibit angiogenic and IL-6 pro-inflammatory signaling.
PDGF contributes to pathological fibrosis and pericyte recruitment, potentially leading to treatment resistance.
Based on pre-clinical data, vorolanib acts within endothelial cells to inhibit the downstream activation of VEGFR-1/2/3, PDGFR, and IL-6 pro-inflammatory signaling.
Vorolanib has been shown to:
Based on pre-clinical data, vorolanib acts within the endothelial cells to inhibit the downstream activation of VEGFR-1/2/3, PDGFR, and IL-6 pro-inflammatory signaling.
Site of Action
Intracellular
MOA
A small molecule that binds to receptor tyrosine kinases
Target Profile
Delivery and Durability
Sustained release: a continuous daily dose for at least 6 months
Site of Action
Extracellular
MOA
Biologics bind to VEGF ligands, thereby preventing the receptor from being activated
Target Profile
Primarily targeting VEGF-A†
Delivery and Durability
Rapid vitreous clearance limits durability and requires frequent injections, 4-16 weeks
†Anti-VEGFs with additional targets: aflibercept binds placental growth factor (PlGF); faricimab-svoa binds angiopoietin-2 (Ang2).
Durasert E™ is an investigational next-generation bioerodible intravitreal insert that delivers a continuous daily dose of vorolanib for at least 6 months. It is currently being studied in four phase 3 trials.
Durasert® technology has been proven safe following use in thousands of eyes across 4 FDA-approved products: Vitrasert®, Retisert®, ILUVIEN®, and YUTIQ®.
For illustrative purposes only. Insert not to scale.
Each insert is:
For illustrative purposes only.
EYP-1901 combines vorolanib with next-generation Durasert E technology to deliver a continuous daily dose for at least 6 months.
AMD, age-related macular degeneration; DME, diabetic macular edema; FDA, US Food & Drug Administration; IC, inhibitory concentration; IVT, intravitreal; MOA, mechanism of action; PDGFR, platelet-derived growth factor receptor; PEG, polyethylene glycol; PLGA, poly lactic-co-glycolic acid; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor.
EYP-1901 is an investigational product and the safety and efficacy of EYP-1901 has not been established. FDA has not approved EYP-1901 in the United States. The materials discussed on this site do not predict future FDA approval. Conclusive evidence of efficacy and safety of EYP-1901 will require further investigation in well-controlled Phase 3 clinical trials.
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