On October 31, 2023 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company, reported that it will present novel findings for its lead product, pepinemab, in two presentations at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), being held in San Diego, CA November 1-5, 2023 (Press release, Vaccinex, OCT 31, 2023, View Source [SID1234636558]). Vaccinex reports consistent findings from two independent studies demonstrating novel activity of pepinemab antibody to induce the formation of lymphoid structures in tumors that promote efficient immune responses and are known to be associated with improved outcomes to immune checkpoint inhibitors (ICI). In a pre-specified interim analysis of the Phase 2 KEYNOTE-B84 study (NCT04815720) evaluating pepinemab in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) for immunotherapy of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), these structures were associated with an approximate doubling of objective responses (ORR) and progression free survival (PFS) relative to historical results with checkpoint monotherapy in patients with hard-to-treat tumors that express low levels of PD-L1 (CPS<20). Similarly, findings will be reported from a separate study with collaborators at Emory University indicating that pepinemab in combination with nivolumab and/or ipilimumab (BMS), appeared to induce tertiary lymphoid structures in tumors. Remarkably, patients receiving neoadjuvant treatment with the triple combination have not experienced tumor recurrence for more than 2 years following treatment (ongoing response in 8/8 patients) (NCT03769155).
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The potential of immune checkpoint therapies to sustain cytotoxic T cells is limited by insufficient support from other immune cell interactions, including with myeloid cells and B cells. The tumor microenvironment creates barriers to efficient immune cell communication, including by expression of semaphorin 4D (SEMA4D), which binds receptors on myeloid cells to inhibit the migration and maturation of dendritic cells (DC) that are crucial for priming and expanding T cells in adaptive immune responses. Preclinical and clinical studies have previously demonstrated improved trafficking of DC and T cells and reduction of immature myeloid derived suppressor cells in tumor following treatment with pepinemab SEMA4D blocking antibody. Data from two independent studies to be presented at SITC (Free SITC Whitepaper) provide new evidence that pepinemab induces the formation of lymphoid structures within treated tumors and that this is associated with enhanced immune interactions and durable responses. These results highlight pepinemab’s novel mechanisms to overcome limitations of ICI.
"Neoadjuvant SEMA4D inhibitor pepinemab combination with nivolumab increases crosstalk between B cell and CD26hi T cell in patients with resectable stage III melanoma" will be presented by Dr. Ayana Ruffin of Emory University together with Vaccinex authors on Friday, November 3, 2023.
"Pepinemab, anti semaphorin 4D antibody, in combination with pembrolizumab induced formation of organized lymphoid aggregates and enhanced response to treatment in CPS<20 R/M HNSCC tumors (KEYNOTE-B84)" will be presented by Dr. Terrence Fisher together with Merck authors and study investigators on Saturday, November 4, 2023.
About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can trigger collapse of the actin cytoskeleton and loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and glial cells in the brain. Pepinemab has been administered to more than 400 patients and appears to be well-tolerated and to have a favorable safety profile.