VIENNA, Va., Oct. 5 /PRNewswire-FirstCall/ -- The following letter is being released by CEL-SCI Corporation (NYSE AMEX: CVM) to its shareholders:
Dear Fellow Shareholders:
After FDA had communicated several weeks ago that we could proceed with our initial clinical trial with our proposed H1N1 treatment for hospitalized H1N1 patients, we have received many questions with regards to H1N1. With this in mind, we have asked one of our outside collaborators, Ken S. Rosenthal, Ph.D., Professor, Microbiology, Immunology and Biochemistry, Northeastern Ohio Universities Colleges of Medicine and Pharmacology, to help explain in layman's terms the course of the H1N1 disease and why it can be so dangerous. Dr. Rosenthal also has provided an explanation of how CEL-SCI's investigational H1N1 treatment may help in very sick hospitalized patients. Dr. Rosenthal explains:
Background information on influenza and H1N1 influenza:
Influenza infection could have very mild consequences or cause very severe disease. At the least, it may seem like a severe cold and at the worst, it can be life-threatening. Influenza is a respiratory virus spread in the tiny water droplets that we release every time we exhale and then are inhaled by another person. These droplets enter the mouth and nose and travel down the throat and into the lungs. When influenza infects a person's lungs, there are three destructive components working together to cause disease: the virus's ability to kill the lung cells; the immune system's inflammatory reactions that kill influenza infected cells; and bacterial infections that establish themselves in the diseased environment.
Influenza virus infects the ciliated epithelial cells of the respiratory tract that help keep foreign material out of the lungs. The virus attaches to these cells through specific sugar molecules, called sialic acids, on the proteins and lipids on the surface of the cell. Different influenza viruses bind to variations of these sialic acids. These sialic acids can be different in different parts of the lung and so some influenza viruses infect the upper respiratory tract, like H1N1, whereas others, like avian flu H5N1, infect cells in the lower lung. Avian flu also likes the warmer environment that is deeper in the lung. While avian flu has high mortality, it is not easily transmitted because it requires special receptors present on a cell to enter the cell and those receptors are only present in cells deep down in the lungs. Therefore large amounts of virus are required to infect a patient with avian flu H5N1. Swine flu, H1N1, on the other hand, is easily transmitted because it prefers other receptors to enter a cell and infects the upper respiratory tract.
After infection, the infected cell becomes a factory to make more viruses. Ultimately, when the virus reproduces in the cell, the cell will die. Before the cell dies, it sends out a molecular warning to other cells, a cytokine protein called interferon. Interferon is an early warning system that puts other cells on the alert to go on strike and not become a virus factory and also warns the body to activate immune protections. The immune protections cause the flu like symptoms that go with influenza disease.
As the infection progresses and spreads, white blood cells called dendritic cells that are in the lung detect the virus, become stimulated and release other cytokines to activate the body's defenses. These cytokines include tumor necrosis factor alpha, interleukin 1 and interleukin 6. These cytokines promote inflammation. Influenza is a very good inducer of these cytokines. The dendritic cells also activate another white blood cell called a T lymphocyte, or T cell. The T cell makes even more cytokines that activate protections, including the production of antibodies by another type of lymphocyte, called a B cell, as well as killer T cells that travel to the infection to kill the influenza infected cells. Although the T cells and antibody are very important to control and eliminate the virus infection, it takes a long time (up to about 8 days) before they are ready to do so. By this time, the virus has spread extensively and caused considerable damage. Even though these immune protections are important for controlling the spread of the virus, they are also very destructive. Like an ever expanding forest-fire or a growing war zone, the longer the virus has to reproduce and spread, the harder it is to control, the more damage it causes and the more damage the immune response causes to control the infection, peripheral damage to the lung and surrounding tissue.
The virus damaged tissue in the respiratory tract is now also more susceptible to the bacteria that normally reside in the nose, including Staphylococcus aureus. The virus kills the ciliated epithelium that pushes these bacteria out of the lungs and dissolves the mucous lining that protects the underlying cells. The infection also exposes cells that are more susceptible to the bacteria. As a result, many people who are infected with influenza end up with a bacterial pneumonia that can be life threatening.
The new H1N1 swine flu virus is a much more lethal virus than previous influenza viruses, including previous H1N1 influenzas. Unlike other influenzas, the new H1N1 virus is especially lethal in young adults. It appears that H1N1 may be able to bind to more cells in the lung, reproduce faster, and spread faster. The more cells that are infected, the more difficult it is for the immune system to eliminate the virus and the more damage the immune system causes by inflammation during the process. Also, H1N1 may cause even more cytokines to be produced which also make the inflammation much more severe. This is called a cytokine storm. Young adults, as they have a very strong immune system, have a very potent inflammatory response, seemingly more active than in young children or older adults. Although it seems illogical, their overactive inflammatory response may put these individuals at higher risk to serious disease due to the damage it causes in trying to eliminate the virus infection.
Influenza vaccines activate immune responses in people that can last for a long time. For a vaccinated individual the vaccine induced immune response can act quickly to stop the reproduction of the virus, limit the spread of the virus and quickly prevent significant virus damage. Currently there are two types of influenza vaccines, a live vaccine and a killed vaccine. A person receiving the Flumist live vaccine is infected with a weakened mixture of influenza viruses that cannot cause serious disease but they activate the immune response to produce T cells that make cytokines to activate T cells and other white blood cells that will kill influenza infected cells and stimulate antibody production. Other influenza vaccines use inactivated virus or the H1 and N1 proteins of the virus to immunize a person and produce only antibodies against the virus. These vaccines take approximately 10 days to produce a protective immune response.
CEL-SCI's DENDRITIC H1N1 TREATMENT
CEL-SCI's dendritic H1N1 treatment, being developed as a treatment for H1N1 hospitalized patients, utilizes the unique LEAPS vaccine technology to convert an individual's white blood cells into cells targeted to killing influenza. The treatment is based on CEL-SCI's L.E.A.P.S. technology. LEAPS vaccines are small proteins that combine a piece of an influenza protein with a small activator protein. The combined protein activates the dendritic cell, a white blood - cell, which presents the influenza protein to the T cell and then tells that T cell with a focused, controlled amount of cytokine, to grow and make the cytokines necessary to activate protective T cell immune responses including killer T cells. This unique action promotes the production of inducer cytokines without the tissue damage and flu-symptom promoting cytokines (pro-inflammatory cytokines), tumor necrosis factor alpha or interleukin 1. This helps prevent or get around the issue of cytokine storm in which the production of too many pro-inflammatory cytokines contributes to the clinical decline and death of the patient. The activated dendritic cells seek out T cells that are specific for H1N1 influenza, present the influenza protein to them with the appropriate cytokines to get them excited, increase their numbers so that they can attack the infected cells with minimal peripheral damage.
The dendritic H1N1 treatment customizes the anti- influenza power of the LEAPS influenza technology. In short, the dendritic H1N1 treatment causes the maturation of monocyte white blood cells into dendritic cells that can direct and activate the subsequent immune response against H1N1 infected cells with minimal peripheral damage.
End of Dr. Rosenthal's explanation.
We are currently moving forward as fast as is possible with our proposed dendritic H1N1 treatment for hospitalized H1N1 patients, while proceeding with due caution and taking all necessary steps to meet regulatory requirements. The virus was only discovered 6 months ago and already we are embarking upon our initial clinical trial.
With regard to our investigational cancer medicine Multikine, we are preparing to commence the global Phase III clinical trial designed to support marketing approval. The validation of our new manufacturing facility for contract manufacturing operations is nearing completion, and we have expanded that validation to cover the manufacturing of Multikine in the new manufacturing facility as well.
From my perspective, we are in the best condition ever. We finally have the financial resources to move forward on our programs. Our manufacturing facility is coming online, the global Phase III cancer trial for Multikine is being launched together with Teva Pharmaceuticals and Orient EuroPharma as two of our main partners, and we are racing to develop what we hope to be the first effective treatment for hospitalized H1N1 patients. We will continue to keep you up-to-date with any further material developments.
We thank you for your support as we move forward in several key areas. Sincerely, Geert Kersten Chief Executive Officer For more information, please visit http://www.cel-sci.com/.
When used in this report, the words "intends," "believes," "anticipated" and "expects" and similar expressions are intended to identify forward-looking statements. Such statements are subject to risks and uncertainties which could cause actual results to differ materially from those projected. Factors that could cause or contribute to such differences include, lack of regulatory clearance to proceed with clinical trials, an inability to duplicate the clinical results demonstrated in clinical studies that have been completed or that are initiated in the future, timely development of any potential products that can be shown to be safe and effective, unwillingness of regulatory authorities to engage in further regulatory dialogue, receiving necessary regulatory approvals, difficulties in manufacturing any of the Company's potential products, inability to raise the necessary capital, and the risk factors set forth from time to time in CEL-SCI Corporation's SEC filings, including but not limited to its report on Form 10- K/A for the year ended September 30, 2008. The Company undertakes no obligation to publicly release the result of any revision to these forward-looking statements which may be made to reflect the events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.
CEL-SCI Corporation
CONTACT: Gavin de Windt of CEL-SCI Corporation, +1-703-506-9460
Web Site: http://www.cel-sci.com/
