Geron Announces New Data on GRN163L, a Telomerase Inhibitor Drug for Cancer Therapy
Geron Corporation (Nasdaq:GERN) announced the
presentation of additional data from preclinical studies of GRN163L, a
potent and specific telomerase inhibitor, at the American Association
for Cancer Research (AACR) Annual Meeting in Orlando, Florida. The
results presented confirm and extend the in vitro and in vivo efficacy
of GRN163L in solid tumors, specifically liver and ovarian cancer, and
report a sensitive, accurate, and reproducible assay for the detection
of the drug in human blood.
"We are pleased to be presenting data from these efficacy studies
and newly developed analytical methods at AACR," said Calvin B.
Harley, Ph.D., Geron's chief scientific officer. "We have now
collected efficacy data in two types of hematologic tumors (multiple
myeloma and lymphoma), and five solid tumors (glioblastoma, hepatoma,
and cancer of the cervix, prostate, and ovary). These studies,
together with our ongoing safety assessment and drug manufacturing
activities, mark our progress towards human clinical trials."
The first study, conducted by researchers at Memorial
Sloan-Kettering Cancer Center in New York in collaboration with Geron
scientists, examined the efficacy of GRN163L in human ovarian tumor
cell lines. In tissue culture, GRN163L inhibited telomerase in all
four tumor lines, and caused telomere loss and cell death in three of
the four. In addition, in a mouse model of human ovarian cancer, it
was demonstrated that GRN163L inhibited growth in a dose-dependent
manner when administered three times per week into the abdominal
cavity.
The second set of studies, conducted by researchers at Medical
School Hannover in Hannover, Germany in collaboration with Geron
scientists, focused on the effect of GRN163L and Geron's related
telomerase inhibitor, GRN163, on human liver cancer (hepatoma) cells.
They first reported on the potency of each compound against a panel of
tumor lines representing multiple different cancer types in culture.
GRN163L was on average about ten times more potent than GRN163 in
inhibiting telomerase activity in cultured tumor cells. For two
hepatoma lines in the panel, GRN163L was 7 and 18 times more potent.
One of the hepatoma tumor lines, Hep3B, was also studied in an in
vivo mouse model of human liver cancer. In the first set of
experiments, human hepatoma-bearing animals were dosed Monday-Friday
via intraperitoneal (systemic) injection for 4 weeks with control
vehicle, GRN163L, or GRN163. In a second set of experiments designed
in part to define the minimum effective dose of the drugs, both
compounds were administered at lower concentrations and 3-times per
week rather than 5-times per week. GRN163L was effective at reducing
tumor growth in both sets of experiments, while GRN163 was only
effective in the first model system. These experiments are consistent
with the earlier observations of increased potency of GRN163L over
GRN163 and are supportive of pharmacokinetic data that predicted a
more durable effect of GRN163L in tissue compared to GRN163.
The third presentation reported on Geron's development of a
sensitive and specific assay for the detection of GRN163L and GRN163
in human plasma and tissue samples. The assay can measure as low as
0.1 nanogram (less than 1 billionth of a gram) of the drug in a plasma
sample, and is suitable for parallel (multi-well, or high-throughput)
processing of material. The assay will be an important tool for
Geron's understanding of the relationship between drug levels in the
body and drug safety and efficacy in both animal studies and human
clinical trials.
Both GRN163L and GRN163 are oligonucleotide drugs that bind to
telomerase with high affinity and specificity, and potently inhibit
telomerase in cancer cells with little impact on normal cells. They
have the same nucleic acid sequence, but GRN163L contains a lipid to
enhance cellular uptake. The enhancement increases potency of the
drug, reducing the dose requirements to achieve efficacy. |
