| Anti-angiogenesis Program |
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| Xcovery is developing a next-generation small-molecule
anti-angiogenesis therapy targeting multiple receptor tyrosine
kinases. This program is designed to succeed therapeutics
such as Sutent ®, Nexavar®, or Avastin®. |
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| The Xcovery program is built upon the experience of Dr.
Chris Liang in developing therapeutic inhibitors of tyrosine
kinase signaling. The program's design objectives are to
surpass existing therapies in efficacy and toxicity, driven
by increased selectivity and better target and off-target
knowledge. |
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| The anti-angiogenesis program is unique in that it targets
all isoforms of the vascular
endothelial growth factor receptor (VEGFR 1, 2, and 3 -
also sometimes referred to as FLT1,
KDR/Flk1, and FLT4 and all isoforms
of the platelet derived growth factor receptor (PDGFR alpha
and beta). It is expected
that specifically inhibiting
all five of these kinases will produce a more significant
and efficacious therapeutic effect. |
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| The anti-angiogenesis program also includes Xcovery innovations
to reduce toxicity, which is a problem of current VEGFR-targeting
therapies, as well as improvements in other drug properties. |
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| An emerging and accepted therapeutic approach to cancer,
anti-angiogenesis is the treatment of cancer by restricting
the growth of blood vessels essential to the survival and
growth of the cancer tumor. Anti-angiogenic therapeutics
fights cancer by restricting the growth of blood vessels
through the inhibition of the targets and signals essentials
to vascular growth. In 2006, sales of anti-angiogenic therapies
(Sutent®, Nexavar®, Avastin®, Erbitux®,
and others) exceeded $4.6B worldwide. |
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| Anti-angiogenesis Program |
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Objective
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To improve the selectivity of multi-targe
ted kinase inhibitors to reduce toxicity while maintaining
efficacy. |
Background
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Avastin validated the anti-angiogenesis strategy for
cancer treatment and its market potential. By targeting
both VEGFR and PDGFR, Sutent (SU11248) proves to be
more effective as single agent. But Sutent is not as
well tolerated as Avastin. |
Hypothesis
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We hypothesized that the major toxicities of Sutent
arise from its activity against a kinase that is not
relevant to angiogenesis. By designing compounds with
less activity against the identified kinase and with
optimized drug properties, the toxicity of Sutent can
be reduced while maintaining its anti-angiogenesis activities. |
Status
(April 2007)
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Similar in vitro potency to Sutent® |
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Reduced activity against the kinase causing toxicity |
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>10x more potent than sorafenib and vandetanib |
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Less toxic in cells than Sutent®, Ssrafenib
Sorafenib , and vandetanib |
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Desirable PK properties in rat |
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Provisional patent application filed in July 2006 |
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| Next Milestone |
In vivo efficacy by early summer, 2007 |
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