BUSINESS WIRE
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Today, PhiloGene will debut its revolutionary advances in understanding
the biology and the treatment of cancer and macular degeneration to a
group of eminent venture capitalists and executives from pharmaceutical
and biotechnology companies. PhiloGene, through collaboration with
Professor David Bates and Dr. Steve Harper at Bristol University in the
UK, have found that a novel form of the cytokine VEGF, VEGFb™,
is an extremely potent anti-angiogenic drug. VEGFb is
endogenously expressed and predominates in most normal tissues. Unlike
the conventional form of VEGF (VEGF), VEGFb does not promote
angiogenesis. Furthermore, VEGFb is anti-angiogenic in the
context of pathological neo-angiogenesis, but is essential to maintain
the physiological balance that permits re-vascularisation of ischemic
tissue by physiological angiogenesis. Hence, Professor Bates and Dr.
Harper have discovered that the body creates and maintains the health
and function of its vascular system, as well as the organ systems
perfused by this vascular system, by modulating the ratio of VEGF to VEGFb.
This new understanding of vascular biology is likely to have a
revolutionary impact on the biotechnology and pharmaceutical industry,
since VEGFb appears to be a much more potent and safer
anti-angiogenic drug, than the anti-angiogenic drugs on the market. This
breakthrough discovery also provides the mechanism to explain why
current anti-angiogenic drugs are significantly limited in both efficacy
and safety. This discovery, most importantly, offers an orthogonal
approach to developing anti-angiogenic drugs, which will be more
effective and safer than traditional approaches.
Current anti-angiogenic treatments are problematic, because they
indiscriminately reduce the level of not only VEGF, but also VEGFb. When
these drugs knock out all species of VEGF, including VEGFb, a
cytoprotective, survival cytokine that is essential for the proper
functioning of a variety of critical organ systems is eliminated.
Thereby, significant “black box”
side effects are seen, including death. When these drugs knock out both
VEGF and VEGFb the result is poor efficacy, due to dose limiting
side effects. Significantly greater and safer anti–angiogenic
effect can be obtained by adding back VEGFb to reach a
homeostatic and physiological ratio of VEGFb to VEGF. The
scientists at Bristol University found that tumors in different tissues
have greatly reduced levels of VEGFb, in the context of VEGF
levels that may be greatly or modestly increased. A pro-angiogenic
milieu predominates, because the VEGFb/VEGF balance is disturbed.
Currently used anti-angiogenic treatments have, at best, stabilized
tumor growth temporarily. In some cancers there is no increase in
patient lifespan and in others life can be prolonged for up to one year.
But in all cancers treated with approved anti-angiogenic drugs as the
sole agent, the cancers recur, leading to death. These efficacy and side
effect problems leave significant room for improvement in the field of
anti-angiogenesis.
PhiloGene has developed a revolutionary paradigm in anti-angiogenic
therapy to address the current shortcomings in the field. Their novel
approach is specific and targeted: not to reduce quantitative VEGF
expression per se in a tumor, but to re-establish the proper balance
between pro- and anti-angiogenic VEGF isoforms that exist in normal
non-angiogenic tissues. This method allows anti-angiogenesis to occur in
the context of cyto-protection of the resident normal epithelial and
neuronal cells.
Preclinical Anti-cancer Results:
PhiloGene, Professor Bates, and Dr. Harper treated an established colon
cancer tumor in a xenograft model with BiVastin™
(VEGFb), resulting in the tumor shrinking to a small fraction of
its initial size within 10 days. In contrast, Avastin®,
the leading anti-angiogenic drug caused the tumor to stop growing, but
with no reduction in size. BiVastin™ was
chosen as the name of PhiloGene’s cancer drug,
reflecting its dual functions; it is anti-angiogenic as well as a
cytoprotective/survival cytokine.
Pre-clinical Ophthalmic Results
VEGFb is shown to potently inhibit choroidal neovascularization
in a preclinical model. This efficacy model is acceptable for inclusion
in the preclinical efficacy section of an Investigational New Drug
Application, which will be submitted to the FDA, before beginning
studies in patients with wet macular degeneration. In this preclinical
model, BiCentis™ is 10 to 50 times more
potent than Lucentis®, an anti-angiogenic
drug approved for the treatment of macular degeneration. PhiloGene
expects BiCentis™ to be a significantly more
effective and safer drug for the treatment of patients with macular
degeneration, than other marketed drugs or drugs in development. BiCentis™
also has dual functions; it is an extremely potent anti-angiogenic
compound and it is cyto-protective for the retinal-pigmented epithelial
cells, the endothelial cells, and the neurons in the retina.
About PhiloGene
PhiloGene is now in a unique, proprietary, position to develop an
extremely potent class of anti-angiogenic drugs, based upon endogenous
VEGFb, which will potentially change the entire anti-angiogenic
sector of biomedicine. Mendi Ze'evi, President of PhiloGene commented, “I
have worked in drug development for more than twenty-five years and my
ideal and the ideal of all in the industry is to have a drug like VEGFb,
that is effective and safe, when used against a validated mechanism and
target in the body.”
PhiloGene is the first and only company known, that is developing a revolutionary
new class of dual action, remarkably more potent, more effective,
and safer anti-angiogenic drugs. PhiloGene achieved this by using a
completely orthogonal approach to that of all predecessors
in this field. The first results of this program are BiVastin™
and BiCentis™, which are dual
action drugs to treat cancer and proliferative and
hyper-permeability eye lesions respectively. Because angiogenesis is one
of the most validated and explored targets in medicine, the development
path for BiVastin™ and BiCentis™
will be accelerated. BiVastin™ and BiCentis™
are not only “first in class,”
they are in a revolutionary new class of dual action anti-angiogenic
drugs. Unlike other VEGF inhibitors, VEGFb is a survival
factor for many epithelial cells (kidney, colon, eye, etc.) as well as
for neurons.
http://www.philogene-inc.com/