Mr. Moore: The history of Advaxis in its current form begins in 2002, when the company licensed the technology for Listeria from the University of Pennsylvania. Prior to that, the company had existed as a shell company called Great Expectations. But the licensing in 2002, which was a competitive option, was what gave the company the technology needed to go forward. In 2004 the company went public through the shell and renamed itself Advaxis. That's really how the company got started.
I joined the company in 2006 as a board member and then was elected CEO in December of 2006. The company has devoted itself exclusively to the development of Listeria technology. Along the way, we have raised about 20 million in the public markets.
Listeria is the core of our technology. It's based on the work done by Dr. Yvonne Paterson. Dr. Paterson is a professor at the University of Pennsylvania in microbiology, and she is also an Associate Dean. She is also a fellow of the American Academy for the Advancement of Science. In the early 1990s, she had a brush with breast cancer and decided to devote her research efforts to use her knowledge of immunology to make cancer less of a threat to everybody else. She started with the insight that our immune system actually clears cancer out of our body several times during our lives, as our cells will misbehave from time to time. And the immune system picks it up and destroys those cells before they can turn into a tumor. But sometimes cancer develops and tumors develop for reasons we don't quite understand. The immune systems stops attacking cancer tissue and actually forms a cooperative arrangement with the tumor that provides it with protection from the immune system. Not only does the immune system agree not to attack it, but also to provide a number of protective cells inside the tumor called regulatory T cells, which neutralize the killer T cells that might come that way and possibly attack the tumor. So it's a two-fold kind of protection. Immunology for the last 20 years has been trying to undo that protective contract between the immune system and tumor by presenting the antigen, which is kind of a sample of the exterior of a tumor cell to the immune system in a way which will get the immune system to re-recognize the tumor and open an attack against it. These approaches haven't been as successful as people expected, and it probably reflects two problems. One is that you can get the immune system to recognize the new antigen by basically carrying it into the body through a vector like a virus. But that doesn't spark the kind of broad-scale immune response that's needed to defeat a tumor that's already there and present in the body. Secondly, until recently, people weren't aware that the exterior of the tumor have these protective regulatory T cells, which foiled any immune attack which the antigen that the immune therapies try to introduce might produce. A lot of researchers were frustrated because they will take blood samples from the arm, which should show a high-degree of immune activity, and conclude that they will make some real progress against the tumor. Then the actual results are much less than they expect or expected. That relates to the fact that these regulatory T cells were actually neutralizing the killer T cells that the immune system produces when it's exposed to antigens, and therefore no real attack was occurring inside the tumor. So Yvonne Paterson reasoned that we would get a much more effective immune attack if we could take advantage of that already existing immune response, which had developed over hundreds of thousands of years, and which would be very deep and very sophisticated at many arms or response to it. She chose the immune response that the body has to this bacteria called Listeria.
Listeria is a bacteria that is around us all the time. It's in the soil. It's in leafy vegetables. It's in dairy products. We eat it very frequently. Listeria, in fact, is a very dangerous bacteria because it infects cells and particularly the cells of the immune system. If our immune system wasn't working - and unfortunately some people eat a lot of Listeria and their immune systems are not operating properly, whether they be victim of immune deficiency or undergoing cancer treatment, or sometimes women in their final trimester of pregnancy - it can create a very dangerous disease, basically meningitis, and often leads to severe problems or sometimes death. But with our functioning immune systems, we don't even know we are eating it, and that's how dramatic that immune response really is.
She developed the way of taking that immune response and turning it against the cancer tumor. We've developed the technology further by incorporating the antigen that we want the immune system to attack and fusing it with a protein that's associated with Listeria, which also creates a very strong immune response. By fusing them together and putting them inside the Listeria, Listeria will actually secrete this material and create a continuous immune response that is quite dramatic and more effective than other immunotherapies have been. We do that by taking the bacteria and attenuating it, which means we'll make it weaker by a factor of about 10,000 times. We incorporate this protein ring or plasmid, which has the antigen that we want the immune system to attack, fuse this protein material that Listeria excretes that also creates immune response. We inject it into the patient. The patient's immune system absorbs bacteria very rapidly. In the interior of the immune cell, the bacteria action infects the cell and starts secreting this plasmid, which the cell then takes and presents to the rest of the immune system as a continuous reminder to attack the cancer represented by the antigen and to do so with the utmost urgency. The second part of this, which was kind of an accident but a happy one, is that this protein that's fused the antigen also reduces the number of regulatory T cells inside the tumor by 80%. We also sweep away the factor, which has foiled past immunotherapies and that allows us to get a full immune attack. The reaction of Listeria creates other things, which further undermine the tumor. But that gets a little bit long and windy. That's the principal way the technology works. What makes it distinct from other cancer immunologies? It's the bacterial nature of the therapy, which gives us this access to a far more sophisticated and strong immune response. This is what makes it work.
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