Announcement • Jul 09
Vaccinex, Inc. Reports New Biomarker Data and Plans for Phase 2B Clinical Trial of Pepinemab in Alzheimer’s Disease Vaccinex, Inc. announced that it will present promising new biomarker data from its Phase 1b/2 trial to support plans for an enlarged randomized phase 2B SIGNAL-AD study of pepinemab for treatment for early Alzheimer’s disease at the Alzheimer’s Association International Conference in London, United Kingdom, on July 13, 2026. Elizabeth Evans, PhD, Chief Operating Officer and Senior VP Discovery and Translational Medicine, will chair the Featured Research Session and present novel results of the SIGNAL-AD phase 1/2 study and plans for continued investigation in the SIGNAL-AD2 study. Presentation title: Glial Biomarkers Associated With Disease Progression Are Regulated By SEMA4D Blocking Antibody Pepinemab in Patients with Early-stage AD. Pepinemab’s novel mechanism of action, a differentiated approach to treating neurodegenerative disease: Vaccinex scientists discovered that Semaphorin 4D (SEMA4D), a molecule that binds to plexin-B1 receptors expressed on astrocytes in the brain, is highly upregulated on stressed or damaged neurons during progression of Alzheimer’s Disease (AD). The Company’s hypothesis, which is being tested in the Phase 1b/2 SIGNAL-AD study, is that treating with pepinemab antibody can block SEMA4D signaling through astrocyte plexin-B1 receptors and slow or prevent the damaging consequences of astrocyte activation. An independent transcriptomic meta-analysis by a team of researchers led by Dr. Philip De Jager at Columbia University Medical Center, identified a unique reactive astrocyte subset that was strongly associated with cognitive impairment and Alzheimer’s Disease progression. Through a collaboration, scientists from Vaccinex and Dr. De Jager’s team discovered key biomarkers of reactive astrocytes and dynamic disease processes associated with synaptic loss, cognitive decline and neuroinflammation that appear to be regulated by pepinemab treatment. Evidence from these studies support and inform the design of an enlarged randomized Phase 2B trial “SIGNAL-AD2” for the treatment of people living with early Alzheimer's dementia. The SIGNAL-AD study was funded in part by a grant from the Alzheimer’s Association as well as by investments from the Alzheimer’s Drug Discovery Foundation (ADDF). 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 astrocytes and other glial cells in the brain and of dendritic cells in immune tissue. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different neurological and cancer indications. Announcement • May 27
Vaccinex to Report Promising New Clinical Results of Neoadjuvant Treatment with Pepinemab to Enhance Immunotherapy in Patients with Head and Neck Cancer At Asco Annual Meeting Vaccinex, Inc. announced 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. Lead investigator and collaboration, Conor Steuer, MD from Winship Cancer Center at Emory University, will present results at the 2025 Annual Meeting of Clinical Oncology (ASCO) in Chicago on June 1, 2025. 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 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. However, many HNSCC are considered immunologically " cold" tumors, due to exclusion of immune cells from tumor and/or high levels of immune inhibitor 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. The 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. Announcement • Apr 21
Vaccinex to Report Promising New Clinical Data Revealing Pepinemab's Unique Mechanism to Enhance Immunotherapy at Annual Meeting of American Association for Cancer Research (AACR) Vaccinex, Inc. announced that it will present exciting new data characterized 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) in Chicago on April 29, 2025. Elizabeth Evans, PhD, Senior VP Discovery and Translational Medicine, will present results of these studies in two presentations. 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. About Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind toplexin-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. 
