Vaccinex, Inc. (Nasdaq: VCNX) is pioneering a differentiated approach to treating cancer and neurologic diseases through the inhibition of semaphorin 4D (SEMA4D). SEMA4D is a potent biological effector that is believed to prevent immune infiltration and induce myeloid suppressor cells in tumors and also triggers neuroinflammation through reactive gliosis in the brain. The company’s lead drug candidate, pepinemab, blocks SEMA4D and has potential to increase immune activity against tumors and to reprogram underlying pathogenic immune mechanisms that amplify damage in chronic neurological disorders such as Azheimer’s and Huntington’s disease.

The company additionally is leveraging its proprietary drug discovery platform, ActivMAb®, to create opportunities for future pipeline expansion and strategic collaborations.

CLINICAL PROGRAMS

VX15/2503 (USAN Council approved name "pepinemab") is a humanized monoclonal IgG4 antibody that binds and blocks the signaling activity of SEMA4D. SEMA4D is an extracellular signaling molecule that regulates the migration and activation of immune and inflammatory cells at sites of injury and cancer. In cancer, we discovered that tumors exploit expression of a high concentration of SEMA4D at their margins to block immune cell infiltration and suppress anti-tumor activity, contributing to mechanisms to evade immune protection against cancer.In chronic brain diseases, such as Huntington’s and Alzheimer’s disease, we have discovered that SEMA4D triggers neuroinflammation with an associated loss of normal brain functions that accelerates disease progression. Pepinemab’s mechanism of action is to block the SEMA4D signal so as to preserve normal functions and slow or prevent disease progression.

Note: Pepinemab (VX15/2503) is an investigational drug currently in clinical studies. It has not been demonstrated to be safe and effective for any disease indication. There is no guarantee that pepinemab (VX15/2503) will be approved for the treatment of any disease by the U.S. Food and Drug Administration or by any other health authority worldwide.

Pepinemab, in combination with a checkpoint inhibitor, has been found to significantly enhance T-cell infiltration and to simultaneously reduce immunosuppressive cells in tumors, a potentially powerful combination to increase anti-tumor activity. Data from a Phase 1b/2 clinical trial in non-small cell lung cancer shows that the combination of pepinemab with BAVENCIO® (avelumab), appears to increase the frequency of objective responses and extend progression-free survival relative to single agent avelumab.

More recently, we reported that two of the first three patients treated in the KEYNOTE-B84 study of pepinemab in combination with Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) experienced a complete response (CR). The study is planned to enroll up to an additional 62 patients and the company plans to report interim data at upcoming medical conferences.

Vaccinex has global commercial and development rights to pepinemab, and is sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Merck is known as MSD outside of the United States and Canada)