On May 27, 2025 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and Alzheimer’s disease (AD) through the inhibition of Semaphorin 4D (SEMA4D), reported that it will present new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies in the neoadjuvant setting that are associated with improved pathologic response in patients with head and neck cancer (Press release, Vaccinex, MAY 27, 2025, View Source [SID1234653404]). Lead investigator and collaborator, Conor Steuer, MD from Winship Cancer Center at Emory University, will present results at the 2025 Annual Meeting of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in Chicago on June 1, 2025.
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ASCO Conference Information:
Date: Sunday, June 1, 2025
Presentation title: Neoadjuvant biomarker trial of pepinemab to enhance nivolumab or ipilimumab activity in resectable head and neck cancer. Abstract 103.
Time: 9:45-11:15 AM CST/10:45 AM – 12:15 PM EST.
Session Title: Clinical Science Symposium – Turning "Cold" Tumors "Hot"
Previously reported data from our collaboration with Emory University suggest a crucial role of pepinemab treatment in melanoma patients to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS. By blocking the SEMA4D inhibitory signal to Dendritic Cells (DC), pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses.
New data presented at ASCO (Free ASCO Whitepaper) will characterize the mechanisms of neoadjuvant treatment with pepinemab in patients with resectable head and neck cancer (HNSCC). Standard of care for these patients often involves toxic chemotherapy and/or radiotherapy, in addition to surgery, which can significantly impact their quality of life. Peri-operative treatment with immunotherapy has recently reported promising and potentially practice-changing results. Certain HNSCC with hot beds of immune cells organized into TLS have been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. However, many HNSCC are considered immunologically "cold" tumors, due to exclusion of immune cells from tumor and/or high levels of immune suppressor cells, making them resistant to immune checkpoint therapy.
Pepinemab has potential to be a major advance for HNSCC patients with cold and resistant disease, with capacity of a well-tolerated and effective treatment that can induce formation and harness the power of TLS to optimize the clinical benefit of immunotherapy. Our data demonstrate that the addition of pepinemab to neoadjuvant immune checkpoint treatments did not compound toxicities, yet it enhanced TLS maturity that correlated with improved pathologic response. Collectively, these results highlight the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative head and neck cancer, into hot immune centers by inducing robust and mature TLS.
About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton and lead to loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and other glial cells in the brain. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different cancer and neurological indications.