TECHNOLOGY OVERVIEW
Scientific
Rationale
The scientific foundation of Can-Fite is based on the
scientific achievements of the company’s founding scientist, Prof.
Pnina Fishman who developed a research program to understand the clinical
observation that cancer rarely metastasizes to skeletal muscle. Early
observations confirmed that skeletal muscle cells release small non-peptide
molecules with anti-cancer activity. Further investigations led to the
observation that these small molecules were agonists to the Gi protein
associated cell surface receptor (A3AR) and that
their anti-cancer activity could be simulated by synthetic A3AR
agonists such as Can-Fite’s lead compounds CF101 and CF102. Importantly,
experiments confirmed that the endogenous compound was not adenosine.
Subsequent research also demonstrated that A3AR
agonists also possess potent anti-inflammatory activity in many in
vitro and in vivo models. CF101 and CF102 and the company’s
other pipeline molecules are protected by composition of matter patents
licensed from leading medicinal chemistry laboratories in the US NIH and
the Leiden University in the Netherlands.
Mechanism
of Action
Activation of the A3AR with high
affinity agonists initiates de-regulation of the Wnt and the NF-kB pathways,
leading to modulation of key signaling proteins, including PI3K, PKA,
PKB/Akt, GSK-3ß, ß-catenin, IKK and TNF-a;
all of these proteins play critical roles in the modulation of cancer
and chronic inflammatory diseases. As a result, apoptosis of inflammatory
and tumor cells takes place. In addition, the A3AR
agonists mediate the anti-viral effect through the inhibition of the nonstructural
RNA-binding protein NS5A (interferon resisting protein).
Differential
Effect on Normal vs Diseased Cells
Can-Fite’s research further suggests that activation
of the A3AR yields a differential effect on diseased
cells versus normal cells. While specific A3AR
agonists like CF101 and CF102 induce apoptosis of cancer and inflammatory
cells, they do not appear to induce such effects in normal proliferating
cells such as white blood cells or fibroblasts. These observations are
supported by data demonstrating low A3AR
expression levels on normal cells when compared to high receptor expression
on abnormal cells.
Intellectual
Property
The Company enjoys a strong intellectual property position
with 20 families of patents totaling more than 100 individual cases. These
cases include composition-of-matter patents and patent applications exclusively
licensed for all fields from the National Institutes of Health in the
USA and Leiden University in the Netherlands covering the company’s
development compounds (CF101, CF102, CF502, CF602 and others); and method
of use, indication and mechanism of action claims residing in company-owned
intellectual properties. Through the combined portfolio of patents or
patent applications licensed to or owned by Can-Fite, patent exclusivity
for the company’s current development pipeline extends beyond 2021.
Can-Fite is not currently aware of any
issued or pending patents that may block the company’s freedom to
operate.
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The A3AR is highly expressed in the
pathological cells. The company drugs bind exclusively to the ‘sick’
cells thereby inducing a specific anti-inflammatory and anti-cancer
effect |
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