Key Takeaways Merck has initiated the pivotal phase 2b/3 MALBEC trial to evaluate MK-8748, a dual-action bispecific antibody targeting Tie2 activation and VEGF inhibition, for wet AMD The late-stage program builds on positive phase 1/2a RIOJA results MK-8748 is part of Merck’s broader ophthalmology pipeline focused on retinal diseases driven by vascular leakage Merck announced the initiation of a pivotal phase 2b/3 clinical trial evaluating its investigational therapy MK-8748 (also referred to as Tiespectus, EYE201) for the treatment of wet age-related macular degeneration (AMD). The study, named MALBEC, marks the first trial in a broader late-stage development program for MK-8748. A second wet AMD study is expected to begin later this year under the identifier NCT07496567. The advancement into pivotal trials follows encouraging findings from the earlier phase 1/2a RIOJA trial (NCT06664502), which evaluated MK-8748 in patients with wet AMD, diabetic macular edema (DME), and macular edema secondary to branch retinal vein occlusion (BRVO). MK-8748 is a novel bispecific antibody designed with a dual mechanism of action: it directly activates the Tie2 signaling pathway while inhibiting vascular endothelial growth factor (VEGF). This approach aims to improve vascular stability and reduce leakage. “Despite available therapies, many patients with neovascular age-related macular degeneration remain at risk of further vision loss due to continued vascular leakage,” said David Guyer, MD, founder, CEO, and president of EyeBio, a wholly owned subsidiary of Merck. “With its differentiated dual mechanism directly agonizing Tie2 and inhibiting VEGF, MK-8748 has the potential to offer a novel approach to maintain vascular stability for patients with serious retinal diseases.” The MALBEC trial (NCT07440225) is a randomized, double-masked study assessing the safety and efficacy of two dose levels of intravitreal MK-8748 compared to aflibercept 2 mg, a current standard-of-care anti-VEGF therapy. Participants will be randomized in a 1:1:1 ratio to receive either one of two MK-8748 dosing regimens or aflibercept. All groups will initially receive 3 monthly (every 4 weeks) injections, followed by treatments every 8 weeks through week 48. After that, treatment intervals will be personalized based on patient response, with follow-up continuing through week 96. The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to one year, measured using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria. The MALBEC trial reflects Merck’s broader push into ophthalmology, targeting diseases characterized by vascular leakage and abnormal blood vessel growth, including wet AMD, DME, and RVO. In addition to MK-8748, the company is developing MK-3000 (Restoret, EYE103), a potentially first-in-class tetravalent, tri-specific antibody designed to activate the Wnt signaling pathway. MK-3000 is currently being evaluated in two fully enrolled, ongoing phase 2b/3 registrational studies for DME.