ROCHESTER, N.Y., July 8, 2026
Vaccinex announced that it will present new biomarker findings from its Phase 1b/2 SIGNAL-AD clinical trial evaluating pepinemab in patients with early Alzheimer’s disease (AD) during the Alzheimer’s Association International Conference (AAIC) 2026 in London on July 13, 2026. The company said the newly generated translational data will support the design of an expanded randomized Phase 2B SIGNAL-AD2 clinical trial, which aims to further evaluate pepinemab as a novel treatment for early Alzheimer’s dementia. The presentation will be delivered by Elizabeth Evans, Ph.D., Chief Operating Officer and Senior Vice President of Discovery and Translational Medicine, during a featured scientific session focused on Alzheimer’s therapies beyond amyloid, highlighting the growing interest in alternative biological pathways for treating neurodegenerative disease.
Novel Biomarker Data Strengthen Scientific Rationale for Pepinemab
The upcoming presentation will highlight new glial biomarker analyses showing that pepinemab regulates biological pathways associated with disease progression in early Alzheimer’s disease. According to Vaccinex, the Phase 1b/2 SIGNAL-AD study identified biomarkers linked to reactive astrocytes, a specialized population of brain support cells increasingly recognized as important contributors to neuroinflammation, synaptic loss, cognitive decline, and disease progression. Through a scientific collaboration with researchers led by Dr. Philip De Jager at Columbia University Medical Center, the company identified a unique reactive astrocyte subtype strongly associated with Alzheimer’s progression. The new findings indicate that treatment with pepinemab may regulate these disease-related biomarkers, providing additional evidence that the investigational therapy is engaging its intended biological target and supporting continued clinical development.
Pepinemab Targets SEMA4D to Reduce Neuroinflammation
Unlike therapies designed to remove amyloid plaques, pepinemab utilizes a first-in-class mechanism of action by selectively blocking Semaphorin 4D (SEMA4D), a signaling molecule that becomes highly expressed on stressed or damaged neurons during Alzheimer’s disease progression. Vaccinex researchers discovered that excessive SEMA4D signaling activates plexin-B1 receptors located on astrocytes, triggering inflammatory responses and disrupting the normal supportive functions of these brain cells. By inhibiting this signaling pathway, pepinemab, a humanized IgG4 monoclonal antibody, is designed to preserve astrocyte function, reduce harmful neuroinflammation, and potentially slow neurodegeneration. The company believes this differentiated therapeutic strategy could complement existing Alzheimer’s treatment approaches by targeting mechanisms that contribute directly to neuronal dysfunction and cognitive decline rather than focusing solely on amyloid pathology.
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SIGNAL-AD2 Will Build on Phase 1b/2 Findings in Early Alzheimer’s Disease
The encouraging biomarker observations generated from the SIGNAL-AD Phase 1b/2 study are expected to guide the design of the planned SIGNAL-AD2 Phase 2B randomized clinical trial, which will further evaluate pepinemab in patients with early Alzheimer’s dementia. Vaccinex noted that the Phase 1b/2 study received support from both the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation (ADDF). Beyond Alzheimer’s disease, pepinemab has demonstrated a favorable safety profile across multiple neurological and oncology clinical trials, including previously reported Phase 2 studies in Huntington’s disease and ongoing combination immunotherapy studies in several cancers. By advancing a therapeutic strategy centered on SEMA4D inhibition, Vaccinex continues to expand its clinical program targeting chronic neurodegenerative disorders, with the upcoming AAIC presentation representing an important milestone in the continued development of pepinemab as a potential disease-modifying therapy for Alzheimer’s disease.
Source: Vaccinex, Pepinemab press release
