How does it work? What is the nature of your technology?

We engineer viruses to destroy cancer cells, but not normal cells. Our virus products target pathways that are commonly activated in most solid tumors including most lung, colon, breast and prostate cancers.

During a normal viral infection, a virus stimulates cellular activity so the virus can replicate itself. Our viruses are unable to do this in normal cells because we have deleted key viral genes. However, cancer cells are commonly activated in control pathways that can complement our viral gene deletions, so the Jennerex virus can still replicate in cancer cells and destroy them, even though they are attenuated in normal cells.

In addition, our viruses express additional genes that help destroy cancer cells by other means, such as stimulating the body�s immune system to rid itself of the cancer. So we attack the cancer in multiple ways, which is why it is less likely a cancer will become resistant to this treatment than to traditional therapies.

This "multi-pronged attack" also allows our products to be effective against cancers that have failed standard therapies such as small molecules kinase inhibitors and chemotherapies.

What virus are you using?

The virus we are using is Vaccinia Virus, the virus used safely in hundreds of millions of people as a live and active component of the vaccine against smallpox. Our virus has distinct competitive advantages as a cancer therapeutic. The original approach in the field used a weak cold virus called Adenovirus. The adeno work we did validated the approach, but in its current state it does not appear to be useful for cancer that has spread from a local region.

The Jennerex team instead surveyed the virology field (analogous to a �library of compounds") and identified a virus (our �pharmacophore�) that had the key features to make it an ideal oncolytic anti-cancer agent. Vaccinia�s advantages include a broad anti-cancer spectrum, rapid and robust replication and spread, a natural biology that evolved to allow it to travel through the bloodstream with preferential accumulation in tumors, and the ability to engineer deletions and make multiple therapeutic and monitoring gene additions.

In addition, vaccinia naturally targets the EGF-Receptor pathway, a "therapeutically-validated" and large market target in cancer including lung, colon, breast, and pancreas cancers.

The other viruses in development have limited engineering capacity, limited IV stability and delivery and/or have very narrow spectra of activity due to native tropism and limiting levels of the virus receptor in many cancer types. Therefore, our vaccinia virus platform has distinct competitive advantages over other viruses in clinical development currently.

How does your virus target cancer cells?

We have two targeting mechanisms in our initial products.

The first is via deleting the viral thymidine kinase (TK) gene. Without this enzyme, the virus cannot make the raw materials needed for DNA replication (nucleotides). However, human cells also have a TK gene, whose expression is driven by the transcriptional activator E2F. In normal cells the cellular TK levels are generally very low so the virus is severely "crippled". In contrast, mutations that are commonly found in tumors, such as loss of the tumor suppressor Rb or increase in cyclin activity, lead to E2F pathway activation and high levels of TK expression. Thus, cancer cells have high TK levels and the virus can replicate and spread efficiently.

The second mechanism of targeting is via deletion of the vaccinia growth factor (VGF) gene. VGF is a homolog of mammalian epidermal growth factor (EGF) and can bind and activate the EGF Receptor (EGFR). What the virus VGF normally does is �prime� the infected cell and neighboring cells for supporting vaccinia replication. Our products lack VGF, and therefore growth is restricted to cells with EGF pathways already activated, and this pathway is commonly mutated in cancers. The EGF pathway is a validated pathway, with marketed pharmaceuticals such as Erbitux and Iressa targeting the EGF pathway.

Is it a Vaccination? Cancer immunotherapy?

No. This approach is entirely novel and distinct from cancer vaccine or other immunotherapy approaches. While vaccinia has been used safely and effectively in hundreds of millions of people as the vaccine against smallpox, we have engineered it for a different purpose � to attack cancer cells directly. Some of our products express proteins that will stimulate the immune system, but this is meant to augment the primary machanism-of-action which is virus replication and direct cancer cell killing (oncolysis). We feel expressing proteins that stimulate the immune system will be particularly important in cases where there are micrometastases. The virus may not accumulate at these sites, and an additional mechanism, such as immune system stimulation will enhance overall efficacy.

Is this like Gene Therapy?

No, gene therapy is simply delivering a gene. This approach is likely to fail for a number of reasons. Our approach could not be more different. In contrast to gene therapy, our virus products amplify themselves in cancer cells, kill them and spread to neighboring cancer cells. One major advantage of our approach (targeted oncolytic virotherapy) is that in addition to the unique mechanism-of-action, our viruses CAN be engineered to express protein therapeutics to give them an extra boost.