Our science - SENECA VALLEY VIRUS

Seneca Valley Virus

Seneca’s lead asset is SVV-001 (SVV), an oncolytic virus of the genus Seneca in the Picornaviridae family.  SVV-001 is characterized by its ability to selectively replicate and kill certain human tumor cells (“SVV-permissive cells”), namely those that express TEM8, the receptor of SVV.  SVV has over 60 binding sites for TEM8 that lead to high apparent affinity and specificity.

SVV-001 and the Seneca genus was originally discovered in 2002 at Novartis Pharmaceuticals by Dr. Paul Hallenbeck.  SVV-001 was further developed as a novel cancer therapeutic at Neotropix, Inc. and has been extensively tested in over 30 non-clinical cancer models, including immunotherapeutic settings, and in three clinical trials for various solid cancers namely neuroendocrine tumors such as carcinoid, small cell lung cancer, and a variety of pediatric cancers.  These trials confirmed the safety of intravenous dosing of SVV and safety along with significant clinical benefit that correlated with SVV replication. SVV-001 does not infect humans and is nonpathogenic in swine.

Combining these data and the inherent properties of this viral agent, the product/platform can be utilized as an intravenously or intratumorally administered oncolytic virus to treat SVV permissive cancers. SVV kills tumor cells through replication in such cells, resulting in apoptosis and cell lysis that in turn, releases single and double-stranded RNA and tumor antigens that together activate the DAMP and PAMP pathways, resulting in a strong anti-tumor systemic immune response. SVV- 001 is a powerful T-Cell recruiter and immune modulator that turn “cold” tumors into “hot” tumors. These key features of SVV-001 were demonstrated in vivo and published. All these features make SVV a multifaceted therapeutic agent against cancer.

Armed SVV viruses

Multiple animal studies have shown synergistic anti-tumor activity when SVV is combined with immune modulators, cytokines and checkpoint inhibitors. At Seneca we have a program specifically to develop armed SVVs, whereby we are inserting therapeutic transgenes within SVV that will be as tumor specific expressed as is SVV replication itself leading to enhanced efficacy from high localized expression in the tumor and lower toxicity as not expressed in any normal cell type. Some examples are check point inhibitor sand other immunomodulators such as cytokines and chemokines.

Targeting Tumor Endothelial Marker 8 (TEM8) in cancer

Large-scale testing of cancer cell lines and FFPE tumor blocks estimate that over 60 percent of all solid cancers express TEM8 on the surface of tumor cells. High expression of TEM8 has been found in different types of cancer such as lung cancer (small cell lung cancer), gastric cancer, and colorectal cancer. High TEM8 expression has been correlated with poor survival, invasion, metastases, and drug resistance. TEM8 is also necessary for tumor growth as described in a recent publication as critical to utilizing collagen to support tumor growth.

Moreover, it has been demonstrated that TEM8 is expressed not only in tumor cells, but in the stroma surrounding cancer cells like angiogenic malignant cells, cancer stem cells, angiogenic endothelial cells, pericytes, invasive cancer cells, cancer-associated fibroblasts (CAFs), and macrophages.

Recently we have also discovered through a bioinformatic approach that ANTRX1 high-expressing patients fared poorly having much worse survival and enhanced resistance to numerous therapies. Altogether, this makes TEM8 an excellent cancer target because it not only is involved in metastasis but also, can possibly modulate the tumor microenvironment potentially making the cancer to become visible for the immune system (“hot tumor”).