Breakthrough in understanding vascular biology may lead to safer and more effective anti-angiogenics

VEGFb, an extremely potent anti-angiogenic which is cytoprotective for retinal cells, can inhibit choroidal neovascularization much more effectively than current anti-VEGF agents, according to preclinical results presented at this year's BIO National Venture Conference, held April 22–23 in Cambridge, US.

Professor David Bates and Dr Steve Harper of Bristol University, UK, in collaboration with PhiloGene Inc, treated an established tumour with VEGFb, which is endogenously expressed and predominates in most normal tissues.

The tumour, a colon cancer, shrank within 10 days of injection with VEGFb; conversely, a bevacizumab (Avastin) injection caused the tumour to stop growing but did not reduce its size. VEGFb was found to be anti-angiogenic in the context of pathological neo-angiogenesis; the body maintains vascular health by modulating the VEGF:VEGFb ratio, which is why anti-VEGF treatments that also eliminate VEGFb demonstrate poor efficacy. In this preclinical model, VEGFb was found to be "10 to 50 times more potent" than ranibizumab (Lucentis).

Unlike the conventional form of VEGF, VEGFb does not promote angiogenesis. This new understanding of vascular biology offers an orthogonal approach to developing safer and more effective anti-angiogenics, which work not simply to reduce VEGF levels but to restore a healthy VEGF/VEGFb balance.

PhiloGene now plans to submit an Investigational New Drug (IND) Application to the FDA and will then begin studies in patients with wet macular degeneration.