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Presentations on the Mechanism of Action of VEGFb, the World's only

SUMMIT, N.J.--(BUSINESS WIRE)--Sep 2, 2008 - Increasingly, VEGFb is becoming recognized as a unique endogenous drug, with a revolutionary mechanism of action. VEGFb is the world's only "triple action angiogenesis modulator;" a drug that regresses pathological blood vessels (such as those in solid tumors, wet macular degeneration, and other disorders), promotes the formation of normal blood vessels, while also acting as an essential survival factor for endothelial cells, neurons, and other cells and tissues.

The European Congress on Microcirculation, held in Budapest, Hungary, featured a symposium focused on VEGFb on Aug 26th 2OO8. The results presented at this symposium, showcased the breakthrough aspects of VEGFb's activities and its promise as a more effective and safer anti-angiogenic drug. Presenting, were Professor David Bates and Dr. Jeanette Woolard from the University of Bristol, Dr. Kurt Ballmer Hofer from the Paul Scherer Institute, Zurich, and Dr. Andrea Cupp from the University of Nebraska.

Professor Bates reviewed recent data showing that VEGFb prevents the formation of new blood vessels in response to injury in the retina (a model of choroidal neovascularization, the clinical problem in wet age related macular degeneration). Dr. Bates also presented a preclinical study demonstrating that VEGFb is remarkably effective in preventing the formation and growth of metastases, following surgical removal of primary human melanoma tumors in mice.

If caught early, a number of cancers can be treated by surgically removing the tumor. As we know from the deaths of friends and family, cancer often reoccurs and spreads to sites distant from the original tumor (metastases). Metastases are usually the cause of death from solid tumors. For instance, in early stage colon cancer, after surgical removal of the primary colon tumor, metastases form and grow in various organs within a year in half the patients. Patients with widespread colon cancer metastases are often untreatable, as is the case of metastases in a number of cancer types.

VEGFb has been shown to be a non-toxic and effective drug in animal models, and promises to play a critical role in preventing the postsurgical reoccurrence of cancer; that is metastatic colon, melanoma, renal, and breast cancer. VEGFb's safety profile may make it possible to treat all colon cancer patients undergoing surgery to prevent metastatic reoccurrence. Other cancer drugs are too toxic to be ethically used in the prevention of metastases. Preclinical models have also demonstrated that VEGFb, as a sole agent, causes the regression of a variety of primary tumors, hence, VEGFb also promises to be a safer and more effective first-line treatment for a variety of solid tumors.

At the meeting in Budapest, specific efficacy and mechanism data was presented from a variety of labs. Dr. Woolard presented recent work from her lab, which advances our understanding of how VEGFb expression is regulated by growth factors and splice factors. Dr. Cupp showed that VEGFb is involved in the development of reproductive organs in mice; inhibiting endogenous VEGFb resulted in increased angiogenesis in the testis and increased maturity of antral follicles in the developing ovary. Dr. Ballmer Hofer showed that VEGFb acts by partially activating the VEGFR2 resulting in signaling that prevents angiogenesis, and he provided evidence that this partial activation is due to VEGFb's inability to bind neuropilin. The mechanisms of VEGFb's receptor binding was elucidated, explaining the mechanism for the anti-angiogenic effect of VEGFb.

Further work at the conference presented from Dr. Leach's laboratory at Nottingham University showed that VEGFb is down regulated in diabetic placenta, and could be switched off by excess insulin perfusion.

This meeting, with presentations from a number of independent laboratories, further elucidates and validates the scientific community's understanding of the mechanism of VEGFb's actions and is expected to expedite the process of obtaining regulatory approval for this breakthrough drug.

About VEGFb

PhiloGene's most advanced program is VEGFb (Vascular Endothelial Growth Factor "b"). VEGFb is a naturally occurring anti-angiogenic (angiogenesis- growth of new blood vessels) factor. VEGFb causes regression of pathological blood vessels, such as those that are essential for the growth and survival of tumors. VEGFb also regresses (eliminates) abnormal new blood vessels generated in eye diseases, such as wet macular degeneration and diabetic retinopathy. Extensive efficacy animal data indicate that VEGFb is safe, potent, and a specific anti-angiogenic factor that inhibits tumor growth, causes tumor regression (renal, colon, and other cancers), and regresses pathological vascularization in the eye. VEGFb is also a survival factor that is essential for many tissue types in the body such as endothelial cells (cells that line the inside of blood vessels), kidney tissue, neurons in the eye and other cell types. VEGFb promotes normal vascularization, while reversing pathological vascularization. Preclinical data indicates that VEGFb's survival effects will prevent most of the side effects seen with the current generation of anti-angiogenic drugs.

The discovery of VEGFb, the native anti-angiogenic form of VEGF, and the elucidation of the mechanisms that control the balance between the pro- and anti-angiogenic forms of VEGF is a paradigm shift from current therapeutic approaches. Current therapeutic approaches are non-specific and remove both, the pro- and anti-angiogenic forms of VEGF. PhiloGene's completely novel approach is more selective and specific. To treat cancer, VEGFb is administered to patients to create a therapeutic ratio of the pro- and anti-angiogenic forms of VEGF. As a result, the tumor's blood vessels and the tumor fed by these blood vessels both regress. The elegance of PhiloGene's approach is that it utilizes the body's endogenous, natural, homeostatic system, which controls the creation and/or regression of blood vessels. In animal models of human cancer, the administration of VEGFb has led to the complete disappearance of a variety of established human tumors.

About PhiloGene

PhiloGene Inc. is a biopharmaceutical company focused on developing and commercializing novel protein therapeutics for unmet medical and patient needs. PhiloGene exploits the therapeutic potential of native growth and differentiation factors. The first drug in PhiloGene's pipeline is VEGFb, which is a triple action drug to treat cancer and other diseases with pathological angiogenesis. Because the anti-angiogenesis pathway is one of the most validated and explored in medicine, the development path of VEGFb will be accelerated. VEGFb is not only "first in class," but also in a class by itself, the only triple action "angiogenesis modulator" in development in the pharmaceutical industry. PhiloGene has a worldwide, exclusive, license for the anti-angiogenic family of VEGFb proteins from Bristol University, UK.

Posted: September 2008

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