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Oncolytic ("onco" meaning cancer, and "lytic" meaning "killing") viruses represent an innovative potential therapeutic class with many advantages over current cancer therapeutics: the ability to selectively destroy cancerous cells without affecting normal cells, greatly reduced levels of toxicity, and, rapid efficacy following a single, low-dose administration. Viruses have a natural propensity to selectively replicate in certain kinds of tissue, including tumor tissue (tropism). The tumor environment and numerous cellular pathways altered within cancer cells create an ideal environment for virus replication. For example, it is well know that tumors have multiple mechanisms which significantly down-regulate an immune response, thus enabling them to avoid normal immune surveillance. This provides for a protective environment for virus replication. Tumors are also rapidly dividing thus providing many key building blocks necessary for virus replication. Some cancer cells are also proficient at avoiding apoptosis, one of the primary mechanisms whereby virus replication in normal cells is limited. In addition, all oncolytic viruses, either naturally or via genetic engineering, target one or more specific pathways altered in cancer cells.

Despite this natural propensity, most oncolytic viruses tested to date have one or more inherent properties that prevent successful commercialization as cancer therapeutics. These include lack of systemic delivery, low tumor/normal cell selectivity, manufacturing challenges, and general safety issues. Neotropix has developed a proprietary rapid screening process, ViruScreen, which targets these areas of deficiency and isolates just those viruses that overcome them. Furthermore Neotropix has identified sources of existing viruses that have never been tested for oncolytic activity. This extremely rich source of naturally occurring, biologically relevant material was previously untapped and represents a unique opportunity for Neotropix.

Utilizing ViruScreen and these unique sources of material, the Company has already identified 19 unique viruses that demonstrate oncolytic activity. Of these 19, Seneca Valley Virus (SVV), re-named NTX-010, has been brought through an extensive development process including phylogenetic, sequence and serotype analysis, mechanism of action elucidation and full pre-clinical studies resulting in an IND and ongoing human clinical trials. The Company maintains full ownership rights to all 19 viruses discovered to date.

NTX-010 was originally discovered in fetal bovine serum by the founder and his team at Novartis Pharmaceuticals. The Company now holds an exclusive worldwide license to develop and commercialize NTX-010. NTX-010, offers several significant advantages over other oncolytic candidates. NTX-010 is the only oncolytic virus that is not inhibited by any component of human blood that would prevent the virus from circulating, reaching tumor masses, and infecting them at reasonable doses. Systemic delivery is the only route of administration to reach all metastases in the body. NTX-010 can be delivered systemically and does not require intratumoral delivery like most other oncolytic viruses in development. NTX-010 is also unique in that it can be produced to an extremely high level in cell lines that have already been approved by the FDA as suitable cell lines for manufacturing. Since it is a native, unaltered virus, there is no chance to generate recombinants as observed for other viruses. Finally, NTX-010 targets cells having altered pathways known to be critically involved in metastases and invasion.

The Company believes that NTX-010 is a paradigm for our strategy; seeking out new, naturally occurring oncolytic viruses that very specifically target tumor cells and are commercially viable. NTX-010 was previously undiscovered but nevertheless existed in swine (now known to be a natural host) and likely other farm animals for potentially centuries. The reason it was not previously discovered is because NTX-010, like many viruses, is asymptomatic in adult swine despite having some tropism toward normal cells; infection simply goes unnoticed. It also hasn’t been linked to any known human disease despite the fact that farmers are in close contact with the source. Neotropix believes that the normal animal host cells are limited, widely dispersed, and carry molecular features similar to human tumor cells that are susceptible to the virus. These same molecular features are believed to be expressed during early fetal development. This is consistent with the discovery of the virus as a contaminant of fetal bovine serum. Additionally, many tumors express embryonic antigens as they de-differentiate into more primitive cell types.

One of the company’s key competitive advantages is the ability to rapidly discern key components of viral selectivity (BioScreen), and to use these biomarkers early in drug development. The advantages of this approach include being able to: use the biomarker(s) to screen normal tissues for potential target organs of toxicity; screen a wide array of cancer indications to determine which cancers are best able to respond and at what probable response rates; and more efficiently, rapidly, and cost-effectively perform clinical trials with a high probability of FDA approval. In addition, some key reagents and molecules identified during tropism evaluation may be novel cancer targets or potential therapeutics, and, as such, may be candidates for out-licensing and/or partnering. NTX-010 serves as a paradigm for this strategy. We have identified key components of the mechanism of tropism (selectivity) and demonstrated that NTX-010 targets key pathways in cancer known to be involved in metastases and invasion, several of which are also present during early fetal development and on embryonic stem cells widely dispersed in normal tissues.

The Company believes that in addition to NTX-010 and the other 18 hits, there are many more naturally occurring viruses with oncolytic activity that remain undiscovered due to their lack of pathogenicity in humans or animals.

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