On April 21, 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 exciting new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies, corresponding with improved survival benefit in patients with melanoma and head and neck cancer at the 2025 Annual Meeting of American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Chicago on April 29, 2025 (Press release, Vaccinex, APR 21, 2025, View Source [SID1234651995]). Elizabeth Evans, PhD, Senior VP Discovery and Translational Medicine, will present results of these studies in two presentations.
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AACR Conference Information:
Date: Tuesday, April 29, 2025
Presentation title: Regulating dendritic cells to promote mature tertiary lymphoid structures and enhance anti-tumor immunity. Presentation #3975
Time: 9-12 AM CDT/10 AM – 1 PM EDT.
Session Title: The Tumor Immune Interplay as a Driver of Progression
Presentation title: Neoadjuvant pepinemab enhances DC function associated with mature tertiary lymphoid structures and activity of immune checkpoint blockade in patients with metastatic melanoma. Presentation #6007
Time: 2-5 PM CDT/ 3-6 PM EDT.
Session Title: Therapeutic Antibodies, Including Engineered Antibodies 2
Access: Posters will be presented in-person on Tuesday, April 29 at McCormick Place Convention Center, Chicago, Illinois, and on AACR (Free AACR Whitepaper) 2025 virtual meeting platform at 1:00 PM ET on Friday, April 25, 2025.
Previously reported data from these two clinical studies suggest a crucial role of pepinemab 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 will characterize clinical outcomes, biomarkers, and mechanisms of these interactions in patients treated with pepinemab in combination with immune checkpoint therapy.
Boosting TLS within tumors is an area of growing excitement because the presence of TLS has been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. A limitation in the field has been identification of safe and effective therapies that can induce formation and harness the potential of TLS to enable durable benefit to patients. Pepinemab may represent a solution to this problem, as our data demonstrate the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative and PD-L1-low head and neck cancer, into hot immune centers by inducing robust and mature TLS.
Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various cancers, showing improved immune and clinical benefit in the preoperative setting compared to standard post surgery adjuvant treatments. Despite these advances, many patients who initially benefit from antibodies that block inhibitory checkpoint molecules (e.g. PD-1, CTLA 4) will progress. More effective combination therapies are needed. Neoadjuvant treatment with pepinemab enhanced TLS maturity and correlated with longer recurrence-free survival when combined with immune checkpoint inhibitors in patients with metastatic melanoma. Evaluation of pepinemab in the neoadjuvant setting for patients with head and neck cancer is ongoing and will be reported at upcoming scientific meeting this Spring.
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 in cells 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.