LONDON, July 13, 2026. Vaccinex Inc. presented new biomarker data from its Phase 1b/2 SIGNAL-AD trial of pepinemab in early Alzheimer’s disease at the Alzheimer’s Association International Conference on Monday, outlining plans for an enlarged, randomized Phase 2b study the company is calling SIGNAL-AD2.

Elizabeth Evans, PhD, Vaccinex’s chief operating officer and senior vice president of discovery and translational medicine, chaired a Featured Research Session at the conference and presented findings showing that blockade of SEMA4D, the target of pepinemab, regulates a set of glial biomarkers associated with disease progression in people with mild Alzheimer’s dementia.

Pepinemab takes a mechanistically distinct approach to Alzheimer’s compared with the amyloid- and tau-targeted antibodies that have dominated the field’s recent approvals. The antibody is designed to block SEMA4D signaling through the plexin-B1 receptor on astrocytes, the brain’s most abundant glial cell type, which become abnormally activated early in Alzheimer’s disease and are increasingly understood to drive downstream synaptic loss, cognitive decline and neuroinflammation. Rather than clearing existing amyloid deposits, pepinemab is intended to interrupt that reactive astrocyte cascade before it compounds.

The data presented Monday build on results from the original SIGNAL-AD Phase 1b/2 trial, which evaluated safety and efficacy of pepinemab in people with mild Alzheimer’s dementia and identified biomarkers of reactive astrocyte activity that the company says correlate with the dynamic disease processes underlying synaptic loss and cognitive decline. Vaccinex is using that biomarker work to justify a larger, randomized SIGNAL-AD2 study intended to more definitively test whether reducing reactive astrocyte activity translates into a clinical benefit.

As Vaccinex scopes site networks for the expanded trial, it will be competing with a rapidly growing field of concurrent CNS and Alzheimer’s studies for enrollment capacity, a dynamic playing out across the sector this week in London. That competition has pushed a growing number of sponsors to diversify their site footprint beyond the traditional US and Western European base, with jurisdictions offering faster study start-up, such as Australia’s Clinical Trial Notification pathway, drawing increased interest from mid-sized biotechs looking to activate expanded studies without multi-year enrollment queues.

Vaccinex’s approach places it among a broader cohort of developers now pursuing neuroinflammation and glial biology as a distinct therapeutic axis in Alzheimer’s disease, running parallel to, rather than in competition with, the amyloid-clearing antibodies already on the market. Whether that axis produces a clinically meaningful result remains an open question the company hopes SIGNAL-AD2 will help answer.