Product Technology

JENNEREX designs, creates and develops targeted, armed oncolytic virotherapy products. During the product design process, we initially select the optimal virus and strain based on the biology we want for specific large market tumor targets. We subsequently engineer the virus products to target genetic pathways that are critical in the vast majority of human cancers. This results in enhanced safety and a large "therapeutic index" (differential cell killing) between cancer tissue and normal tissues in the body. We refer to this method as targeting cancer's Achilles' Heel since these same genetic changes in cancer that support growth of our viruses are also critical to cancer progression itself. The primary mechanism-of-action for our products is virus replication-dependent oncolysis ("onco" cancer, "lysis" cell destruction). This is a novel and unique cancer-destruction mechanism that does not, in contrast to the majority of cancer treatments, rely on cancer cell "suicide" (apoptosis); cancer cell destruction is therefore not passive but active. Our products are then armed with therapeutic payloads (transgenes) that have additional, complementary mechanisms-of-action. The resulting products therefore wage a multi-pronged attack on cancer. Finally, imaging genes are added to allow assessments of virus replication and trafficking in the body. In summary, our products have excellent cancer selectivity, tolerability and can be effective against cancers that are resistant to killing by approved chemotherapies, antibodies or small molecule kinase inhibitors.

To understand how we achieve these results, we summarize the engineering approach below:

• Safety/Therapeutic Index: We engineer deletions within specific viral genes to enhance tumor cell targeting and therefore safety. The deleted genes are essential for virus replication in normal tissues, and their deletion "cripples" the virus in normal tissues making it safer. These same genes, however, are expendable in cancer cells because cancers have already activated the cellular targets or homologues of the viral gene (i.e. the cancer cell has done the job for the viral gene already). We refer to this as targeting Cancer's Achilles' Heel since these same genetic changes in cancer that support replication and targeting of our viruses are also critical to cancer progression itself.

• Efficacy: We seek to maximize cancer destruction by selecting the most potent viruses (species and strains) for oncolysis (see above). We subsequently arm these products with therapeutic "payloads" (transgenes for therapeutic peptides, proteins). These payloads are expressed under control of viral or synthetic promoters that ensure high-level expression in a cancer-selective fashion. The payloads we choose to insert have mechanisms-of-action that are complementary to viral oncolysis.

• Monitoring: The insertion of "imaging tags" (transgenes for marker genes) into our products allows us to track the replication, gene expression and trafficking of our products in the body. These "imaging tags" are expressed under control of viral or synthetic promoters that ensure high-level expression primarily in a cancer-selective fashion.



Normal cells depicted in light color, cancer cells depicted in dark color, dying cells in pebbled texture.