Geron Announces Publication of Data on GRN163, a Telomerase Inhibitor, in Animal Models of Human Brain Tumors
MENLO PARK, Calif.--(BUSINESS WIRE)--July 1, 2004--Geron
Corporation (Nasdaq:GERN) announced today the publication of
preclinical testing of GRN163, its first-generation telomerase
inhibitor drug, in models of human glioblastoma, one of the deadliest
forms of brain cancer. The results indicate that GRN163 can prevent or
suppress the growth of human glioblastoma tumor cells in mice and
rats. In addition, the data suggest that intracranial injection of
GRN163 achieves robust distribution of the compound in the brain. The
paper, authored by scientists at Geron and the Brain Tumor Research
Center and Department of Pathology, University of California, San
Francisco, appears in the July 2004 issue of the journal
Neuro-Oncology and is available online at
neuro-oncology.mc.duke.edu.
In three independent studies of athymic (immune-compromised) mice,
human malignant glioblastoma cells were implanted under the skin of
the flank, and allowed to grow to various sizes. The resulting tumors
were then treated with injections of GRN163 plus a lipid carrier. In
each study, after short-term treatment (7-19 days) with GRN163,
average tumor size was significantly reduced in the treated versus
control mice, and the survival of treated mice was significantly
increased (p less than 0.01). In some cases, tumor growth in the
treated mice was essentially blocked and in one case, the tumor
completely disappeared.
GRN163 was also tested in an intracranial model of human
glioblastoma in athymic rats. In these studies, GRN163 was tested
without the lipid carrier, as it was first established that GRN163
alone could penetrate brain cells and would widely distribute itself
within the hemisphere of the brain into which it was injected. In the
distribution study, GRN163 was labeled with a fluorescent tag, infused
by pump into the rat brain over a period of seven days and found to
persist without diminution for at least four days after infusion (the
longest time-point studied).
Two types of efficacy studies were then conducted in rats. In the
first study, designed to mimic a model of minimal residual disease or
tumor prevention, human glioblastoma tumor cells were injected into
the rat brain, and beginning 1-2 hours thereafter, GRN163 was infused
into the same site over a 7- or 14-day period. Five out of seven rats
treated with GRN163 showed no neurological signs of tumor progression
and were found to have no evidence of brain tumors at the end of the
study (day 103). They were considered cured. In contrast, all four
control rats required euthanasia between days 41 and 43, and were
found to have large brain tumors at the site of cell injection.
In the second intracranial (within the brain) rat model, designed
to mimic a typical therapeutic efficacy study, tumors were implanted
into 20 rats and allowed to become established for 14 days before
GRN163 or a control oligonucleotide was infused over a 7-day period
into the implantation site. The control animals had a median survival
of 37.5 days (range 37-43), while the low- and high-dose GRN163
animals had median survivals of 45 and 54 days, respectively, with two
of the eight animals (25%) in each of the GRN163 groups being cured --
i.e., they showed no signs of a tumor and no signs of any neurological
symptoms at day 94 when they were sacrificed. The increased survival
of GRN163-treated animals over the control group was statistically
significant at both doses.
"These rodent studies suggest that GRN163 might prove effective
for the treatment of human brain tumors, as well as the prevention of
relapse following surgical removal of tumors," stated Dennis Deen,
Ph.D., senior author of the paper and Professor of Neurological
Surgery in the Brain Cancer Research Center at UCSF.
"We believe that GRN163 or our improved second-generation
compound, GRN163L, will be useful in the treatment of brain cancer,"
stated Calvin Harley, Ph.D., Geron's chief scientific officer. "We are
currently focused on the development of GRN163L, our lipid-conjugated
analog of GRN163, for the systemic (whole body) treatment of
hematologic tumors in order to establish safety and pharmacological
activity. However, we are optimistic that we can move into multiple
solid tumor trials, including brain cancer, after demonstrating
positive clinical results with hematologic tumors."
Geron has broad proprietary rights covering GRN163, GRN163L and
the platform technologies underpinning this approach to treating
cancer through telomerase inhibition. For example, Geron holds issued
U.S. and overseas patents to the sequence of the hTR molecule and
oligonucleotides derived from hTR, including GRN163 and GRN163L, and
the uses of such oligonucleotides to inhibit telomerase. Geron also
owns patents and patent applications covering oligonucleotides with
phosphoramidate backbone linkages and methods of synthesizing such
oligonucleotides. More broadly, Geron has over 180 issued patents
worldwide on various aspects of telomere biology, telomerase and
telomerase inhibition and oligonucleotide chemistry, and more than 95
pending patent applications.
Geron is a biopharmaceutical company focused on developing and
commercializing therapeutic and diagnostic products for cancer based
on its telomerase technology, and cell-based therapeutics using its
human embryonic stem cell technology.
This news release may contain forward-looking statements made
pursuant to the "safe harbor" provisions of the Private Securities
Litigation Reform Act of 1995. Investors are cautioned that such
forward-looking statements in this press release regarding product
development and future applications of Geron's technology constitute
forward-looking statements that involve risks and uncertainties,
including, without limitation, risks inherent in the development and
commercialization of potential products, reliance on collaborators,
need for future capital, need for regulatory approvals or clearances,
and the maintenance of our intellectual property rights. Actual
results may differ materially from the results anticipated in these
forward-looking statements. Additional information on potential
factors that could affect our results and other risks and
uncertainties are detailed from time to time in Geron's periodic
reports, including the quarterly report on Form 10-Q for the quarter
ended March 31, 2004.
CONTACT: Geron Corporation
David L. Greenwood, 650-473-7765 |
