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

Pepinemab

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.

Immuno-oncology

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)

Learn more about Pepinemab for Immuno-oncology

Neurology

Neurodegenerative diseases, such as Huntington's disease (HD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and progressive multiple sclerosis (MS), are some of the world’s most complex and difficult-to-treat disorders. Very few impactful treatment options exist for these conditions, which affect an estimated 6.5 million Americans. As the world’s population ages, there is an urgent need for new therapeutic options.

Semaphorin 4D (SEMA4D) has been found to contribute to driving the neuroinflammation implicated in progression of these disorders, suggesting that blocking SEMA4D has promising potential as a new therapy for neurodegenerative diseases. Vaccinex is studying pepinemab in clinical trials of patients with Huntington’s and Alzheimer’s disease, and is exploring the potential to treat other neurological disorders.

In 2020/2021 Vaccinex reported results of the SIGNAL phase 2 study of pepinemab in subjects with early manifest or late prodromal Huntington’s disease randomized for 18-months, double-blind treatment with single agent pepinemab or placebo. Although the study did not meet the pre-specified primary endpoints, the results indicated significant benefit for patients with early manifest disease in terms of cognition as measured using the Huntington’s Disease Cognitive Assessment Battery, reduced apathy as measured by the Problem Behaviors Asssessment subscore, reduced caudate atrophy detected by MRI, and increased brain metabolic activity determined by FDG-PET. We believe this consistent pattern of benefit is strongly supportive of continued development in a larger phase 3 study for Huntington’s disease. Because of similarities in pathogenic activity in other slowly progressive neurological diseases, Vaccinex has also initiated a randomized study in patients with early stage Alzheimer’s disease, SIGNAL-AD.

Vaccinex has global commercial and development rights to pepinemab, and is sponsor of the SIGNAL and SIGNAL-AD studies in Huntington’s and Alzheimer’s disease.

Learn more about Pepinemab for Neurology

DISCOVERY SERVICES

Whether you need Antibody Discovery, Complex Membrane Antigens, Target Identification, or Protein Optimization, our ActivMAb® Discovery services offer unique solutions to assist in your Drug Discovery and Development projects.

Let us help you move faster from bench to clinic.

ActivMAb®

Vaccinex has developed a fusion protein technology to enable the direct incorporation of multipass membrane proteins such as GPCRs and ion channels into the membrane of a mammalian virus. This method recovers the protein of interest naturally expressed in the mammalian cell derived membrane, and does not require complex manipulations to generate properly folded protein. The technology can be applied using multiple different cell types in order to maximize protein expression and to provide for any necessary chaperones. Antigen expressing virus can be readily purified and used for antibody selection employing either in vitro display or in vivo immunization methods.

We use a similar fusion protein strategy with our antibody discovery platform that enables efficient mammalian cell based expression of a library of human antibodies in full length IgG format on the surface of both the mammalian virus and infected cell. The platform combines the advantages of virus panning and cell sorting into one seamless selection process. This technology enables the rapid selection of >1010 antibody combinations and thus selection of high affinity leads with varied frameworks that recognize multiple epitopes. The selected antibodies are ideally suited for development because they have already passed mammalian cell quality control during the selection process.

ActivMAb technology offers:

  • an innovative and efficient method for selecting antibodies against multi-pass membrane proteins, an important class of pharmacological targets.
  • rapid generation of high affinity, full-length, human monoclonal antibodies synthesized and naturally modified in mammalian cells,
  • evolution/optimization of protein expression by mutagenesis and selection for desired variants in a fully mammalian cell system.

Learn more about ActivMAb®