AAIC 2025 Preclinical Results of Anti-Tau Antibody MK-2214 in Alzheimer Disease: Jonathan Sugam, PhD

WATCH TIME: 6 minutes

"The main findings, and the main excitement we have around this antibody, are that it uniquely targets a specific type of tau we believe is critical in driving the pathological progression of the disease, and that this species of tau is highly expressed in patients with Alzheimer disease. More importantly, the antibody itself has unique properties that we believe make it an optimal candidate for treating the disease."

The accumulation of misfolded, hyperphosphorylated tau in the brain is a hallmark of Alzheimer disease (AD), driving neurodegeneration and cognitive decline. Prior research has indicated that this pathology spreads through the brain via neuron-to-neuron transfer of extracellular tau, which seeds new pathology in healthy cells. Targeting extracellular tau with antibodies has emerged as a promising approach to limit its propagation in AD. Merck’s MK-2214 is a novel, highly potent, half-life extended antibody in designed to selectively bind phosphorylated serine 413 (pS413) tau species implicated.

A series of preclinical studies assessed MK-2214’s specificity, potency, and pharmacokinetic profile. Binding assays confirmed strong selectivity for pS413 tau, whereas immunoassays demonstrated potent binding to tau species in AD patient brain and cerebrospinal fluid. In vitro cell-based seeding models, findings showed that MK-2214 immunodepleted pathological tau seeds, reducing downstream pathology in human iPSC-derived neurons. In vivo studies in mice and nonhuman primates evaluated both efficacy and pharmacokinetics, which confirmed an extended half-life and target engagement.

There results were recently presented at the2025 Alzheimer’s Association International Conference, held July 27-30, in Toronto, Canada, by lead author Jonathan Sugam, PhD, principal scientist of neuroscience discovery at Merck. In an interview with NeurologyLive^® at the conference, Sugam discussed how MK-2214 bound extracellular tau with subnanomolar potency, significantly reducing tau pathology in both in vitro and in vivo seeding models. He also noted that the extended half-life supports less frequent dosing and that the therapy’s characteristics allow for potential subcutaneous administration, which could lower patient burden.

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REFERENCES
1. Sugam JA, Robey S, Suon S, et al. Preclinical development of MK-2214 a novel antibody targeting pS413 tau for the treatment of Alzheimer’s Disease. Presented at: 2025 Alzheimer’s Association International Conference; July 27-31; Toronto, Canada. Abstract 102913.