Merck has announced the initiation of a pivotal phase-IIb/III trial evaluating MK-8748 (also known as Tiespectus, EYE201), a novel investigational bispecific antibody that directly activates Tie2 signaling and inhibits Vascular Endothelial Growth Factor (VEGF), for the treatment of NeoVascular (wet) Age-Related Macular Degeneration (NVAMD).

The study, known as MALBEC, is the first trial of a broader late-phase development programme for MK-8748, with a second study in NVAMD scheduled to begin this year (NCT07496567). The decision to advance into pivotal studies is based on results from the phase-I/IIa RIOJA trial (NCT06664502), a two-part study evaluating MK-8748 in patients with either NVAMD, macular edema secondary to Branch Retinal Vein Occlusion (BRVO) or Diabetic Macular Edema (DME).

“Despite available therapies, many patients with NeoVascular Age-Related Macular Degeneration remain at risk of further vision loss due to continued vascular leakage. With its differentiated dual mechanism directly agonising Tie2 and inhibiting VEGF, MK-8748 has the potential to offer a novel approach to maintain vascular stability for patients with serious retinal diseases,” said Dr David Guyer, Founder, Chief Executive Officer and President, EyeBio.

Merck is advancing an ophthalmology pipeline aimed at addressing certain retinal diseases associated with vascular leakage and neovascularisation, including NVAMD, DME and macular edema secondary to Retinal Vein Occlusion (RVO). In addition to MK-8748, the company is developing MK-3000 (also known as Restoret, EYE103), an investigational, potentially first-in-class tetravalent, tri-specific antibody that activates the Wingless-related integration site (Wnt) signaling pathway that is being studied in two fully enrolled, ongoing registrational phase-IIb/III studies for the treatment of DME.