Merck has initiated the MALBEC Phase 2b/3 trial evaluating MK-8748, a bispecific Tie2 agonist and VEGF inhibitor, in patients with neovascular age-related macular degeneration, advancing its late-stage ophthalmology pipeline.
Written By: Dr. Anuja Badgujar, BDS
Reviewed By: Pharmacally Editorial Team
Merck known as MSD outside of the United States and Canada, has announced the initiation of a pivotal Phase 2b/3 trial evaluating MK-8748 (also known as Tiespectus, EYE201), an investigational bispecific antibody designed to directly activate Tie2 signaling and inhibit vascular endothelial growth factor (VEGF), for the treatment of neovascular (wet) age-related macular degeneration (NVAMD).
The study, known as MALBEC (NCT07440225), represents the first trial in a broader late-stage development program for MK-8748. A second Phase 2b/3 study in NVAMD (NCT07496567) is expected to begin later this year. The advancement into pivotal-stage development is supported by findings from the Phase 1/2a RIOJA trial (NCT06664502), which evaluated MK-8748 in patients with NVAMD, diabetic macular edema (DME), and macular edema secondary to branch retinal vein occlusion (BRVO).
Dr. David Guyer, founder, chief executive officer and president, EyeBio highlighted the ongoing unmet need in NVAMD, noting that despite existing therapies, many patients continue to experience vision loss due to persistent vascular leakage. The dual mechanism of MK-8748, combining Tie2 activation with VEGF inhibition, is intended to improve vascular stability and support long-term disease control.
Trial Design and Endpoints
MALBEC is a randomized, double-masked, pivotal Phase 2b/3 trial designed to evaluate the safety and efficacy of two dose levels of intravitreal MK-8748 compared with aflibercept 2 mg. Patients will be randomized in a 1:1:1 ratio to receive one of two MK-8748 dosing regimens or aflibercept.
Participants will initially receive three monthly (every 4 weeks) intravitreal injections, followed by dosing every 8 weeks through week 48. Beyond week 48, treatment intervals will be individualized based on patient response, with the final study visit scheduled at week 96.
The primary endpoint is the mean change in best-corrected visual acuity (BCVA) from baseline to Year 1, assessed using standardized Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria.
Mechanism and Clinical Rationale
MK-8748 is a bispecific antibody that targets two key pathways involved in retinal vascular disease. By activating the Tie2 pathway and inhibiting VEGF, the therapy aims to stabilize retinal and choroidal blood vessels, reduce vascular leakage, and limit fluid accumulation in the macula.
Preclinical and early clinical data suggest that this dual-pathway approach may enhance vascular stability and support vision preservation in patients with retinal diseases characterized by neovascularization and leakage.
Pipeline Context
Merck continues to expand its ophthalmology pipeline targeting diseases associated with vascular dysfunction, including NVAMD, DME, and retinal vein occlusion (RVO). In addition to MK-8748, the company is developing MK-3000 (Restoret, EYE103), a tri-specific antibody designed to activate the Wnt signaling pathway. MK-3000 is currently being evaluated in two fully enrolled registrational Phase 2b/3 trials in DME.
Disease Background
Neovascular (wet) age-related macular degeneration is a leading cause of vision loss in older adults. The condition is characterized by the growth of abnormal blood vessels beneath the retina, resulting in leakage, retinal damage, and progressive vision impairment. In the United States, approximately 1.5 million individuals are estimated to be living with late-stage AMD, including NVAMD.
Reference
Merck Announces Initiation of Pivotal Phase 2b/3 Trial Evaluating MK-8748 (Tiespectus), an Investigational Bispecific Tie2 Agonist/VEGF Inhibitor, for the Treatment of Neovascular Age-Related Macular Degeneration, 02 April 2026, Merck Announces Initiation of Pivotal Phase 2b/3 Trial Evaluating MK-8748 (Tiespectus), an Investigational Bispecific Tie2 Agonist/VEGF Inhibitor, for the Treatment of Neovascular Age-Related Macular Degeneration – Merck.com
A Clinical Trial of EYE201/MK-8748 in People with Macular Degeneration (MK-8748-002), ClinicalTrials.gov ID NCT07440225, https://clinicaltrials.gov/study/NCT07440225
Dr. Anuja Badgujar, BDS, is a dentist with expertise in US healthcare data and medical data annotation. With four years of experience handling US healthcare datasets, she brings strong domain knowledge and precision to her work. She is also deeply passionate about medical writing, with a focus on translating complex medical information into clear and structured content.