Vaccinex to present SIGNAL-AD trial results for Pepinemab in Alzheimer's at AAIC, July 2024

Vaccinex, Inc., a clinical-stage biotechnology company specializing in treatments for Alzheimer’s disease (AD) and cancer by targeting Semaphorin 4D (SEMA4D), has announced the presentation of key data from its SIGNAL-AD study at the Alzheimer's Association International Conference in Philadelphia. The study, led by Principal Investigator Eric Siemers, MD, aims to evaluate the safety and efficacy of the SEMA4D blocking antibody, pepinemab, in individuals with mild cognitive impairment or early Alzheimer’s dementia. The presentation is scheduled for July 31, 2024.

SEMA4D plays a significant role in Alzheimer’s by binding to plexin-B1 receptors on astrocytes, leading to neurotoxic inflammatory activity. This activity is thought to worsen the progression of AD. The SIGNAL-AD study hypothesizes that pepinemab can block this signaling pathway, potentially preventing or slowing the harmful effects of astrocyte activation.

Previous studies have shown that blocking SEMA4D with pepinemab protects astrocyte functions and slows disease progression in Huntington’s disease. The current study aims to establish whether similar benefits can be observed in Alzheimer’s, specifically focusing on safety, tolerability, and the impact on brain metabolic activity and astrocyte reactivity, as measured by plasma levels of glial fibrillary acidic protein (GFAP). Additionally, the study seeks to understand if blocking astrocyte reactivity can also slow the progression of neurodegeneration, indicated by plasma levels of phosphorylated tau peptide (p-tau 217).

Astrocytes are crucial brain cells that, when functioning correctly, support neuron health. However, when SEMA4D binds to their receptors, they switch to a neurotoxic state, contributing to Alzheimer’s progression. Pepinemab is designed to inhibit this binding, maintaining astrocytes' supportive roles.

The importance of this study is underscored by the prevalence of Alzheimer’s, with six million diagnosed cases in the U.S. alone. Current treatments, like anti-Aβ amyloid antibodies, have limitations. If successful, pepinemab could serve as an alternative or complementary treatment, offering a different mechanism of action and possibly enhancing the effectiveness of existing therapies. Notably, pepinemab has shown good tolerance in over 600 patients across various trials.

The SIGNAL-AD study is partially funded by the Alzheimer’s Association and the Alzheimer’s Drug Discovery Foundation (ADDF).

Pepinemab, a humanized IgG4 monoclonal antibody, functions by blocking SEMA4D, preventing it from binding to plexin-B1 receptors. This action helps maintain the structural integrity and homeostatic functions of astrocytes and other glial cells, as well as dendritic cells in immune tissues. Pepinemab has demonstrated a favorable safety profile in multiple clinical trials for various neurological and cancer conditions.

Vaccinex, Inc. is dedicated to novel treatments for slow-progressing neurodegenerative diseases and cancer by inhibiting SEMA4D. The company’s lead drug candidate, pepinemab, is being investigated both as a monotherapy and in combination with other treatments such as KEYTRUDA® in head and neck cancer and BAVENCIO® in metastatic pancreatic adenocarcinoma. Several studies sponsored by investigators are also evaluating pepinemab in solid tumors, including breast cancer and melanoma.

Vaccinex holds global commercial and development rights to pepinemab and collaborates with Merck Sharp & Dohme Corp on the KEYNOTE-B84 study. Further details about these studies are available on clinical trial registries.