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PhiloGene's most advanced program is based on naturally occurring antagonists of vascular endothelial growth factor acting on VEGF Receptors 1 and 2.
Traditionally, VEGF isoforms have been universally described as pro-angiogenic cytokines. Recently, an entire family of sister molecules of VEGF variants with anti-angiogenic activity was identified and characterized. Under physiological conditions the balance between the pro-angiogenic and anti-angiogenic forms of VEGF is about 1:1. In pathological conditions (cancer, diabetic retinopathy) the balance between the pro- and anti-angiogenic forms of VEGF is disturbed (see Figure).
Extensive efficacy animal data suggest that PhiloGene’s leads PLG101 and PLG201 are potent and specific anti-angiogenic factors that inhibit tumor growth and retinal neovascularization.
The VEGF Receptor family is clinically validated that continue to be an attractive objective for drug development. The discovery of the native antagonists of VEGFR and the elucidation of the control mechanism that regulates the balance between the pro- and anti-angiogenic forms of VEGF is a paradigm shift from current therapeutic approach. While the current therapeutic approach relies on the removal of the pan VEGF forms, PhiloGene’s new approach is to restores the balance between the pro-angiogenic and anti-angiogenic forms of VEGF and thus presenting a more effective and safe strategy in treating both ophthalmology disease and cancer.
Figure: Pro and anti angiogenic VEGF levels in normal human tissues (left) and in prostate tumor vs. benign prostate tissue (right). Left panel: anti-angiogenic isoforms, denoted as VEGFxxxb, make up half or more of the total VEGF found in most normal human tissues. Right panel: in malignant human prostate tissue, production of anti-angiogenic VEGF165b isofrom falls in comparison with benign prostate tissue.
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