Effects Seen in Melanoma, Breast, Prostate and Lung
Cancer
BERKELEY HEIGHTS, NJ - November 19, 2003
-Genta Incorporated (Nasdaq: GNTA) today announced the presentation
of preclinical data from three presentations showing the activity
of Genasense
TM
(oblimersen sodium), the Company's lead anticancer compound. These
results were presented at the "Molecular Targets and Cancer
Therapeutics" meeting that was sponsored jointly by the American
Association of Cancer Research (AACR), the European Organization
for Research and Treatment of Cancer (EORTC), and The National
Cancer Institute (NCI) in Boston, MA.
Genasense blocks the production of a key cancer protein called
Bcl-2 - a factor that is widely believed to contribute to the
inherent resistance of cancer cells to anticancer treatments. By
blocking production of Bcl-2, Genasense may enhance the
effectiveness of cancer therapy. High levels of Bcl-2 have also
been associated with a poor response to radiation therapy in
patients. However, unlike chemotherapy for which numerous studies
have documented high levels of synergy with Genasense, no prior
studies have examined the activity of Genasense combined with
radiation.
In the first study, investigators from the Fox Chase Cancer
Center, Philadelphia, PA, studied whether the response to radiation
was affected by Genasense-induced decrease in Bcl-2. Prostate
cancer cells (known as PC3 and LnCAP) that had been treated with
Genasense or control oligonucleotides were then exposed to
radiation. Genasense treatment caused a marked increase in
programmed cell death (apoptosis) and a significant reduction in
clonogenic survival compared with cells treated with control
oligonucleotides.
In a second study, investigators from The University of Texas
M.D. Anderson Cancer Center, Houston, TX, compared Bcl-2 expression
and sensitivity to radiation in various cell lines, including
melanoma (A375), lung cancer (H1299), and prostate cancer (LnCAP).
When compared with controls, cells treated with Genasense plus
radiation showed down-regulation of Bcl-2 and increased cell
death.
A final study tested the ability of various breast cancer cell
lines to incorporate Genasense and down-regulate Bcl-2. Results
showed uptake of Genasense at low concentration (500 nM), which
caused a significant decrease in Bcl-2 levels and increased cancer
cell death. The reduction in cell survival was observed in the
absence of chemotherapy, indicating a direct effect of Genasense
that was not seen with a control oligonucleotide. Finally, cells
that expressed lower levels of Bcl-2 were more sensitive to the
direct killing effect of Genasense compared with high-expressing
cells.
"Radiosensitization is a logical extension from prior
observations of synergy with chemotherapy, which points to a future
direction for our preclinical and clinical programs," commented Dr.
Bob Brown, Genta's Vice President, Research and Technology. "The
direct effects of Genasense on breast cancer cells has not been
previously reported, and it represents an important complement to
the clinical breast cancer program that is currently being run by
the investigators at M.D. Anderson."
About Genasense
Genasense is being broadly tested in more than 20 randomized and
non-randomized trials for its ability to increase the effectiveness
of current types of anticancer therapy for a number of diseases,
including acute and chronic leukemias, multiple myeloma,
non-Hodgkin's lymphoma, and cancers of the breast, colon, kidney,
lung, liver, pancreas, and prostate. Genasense is currently the
subject of a "rolling" New Drug Application (NDA) submission to the
Food and Drug Administration for the treatment of malignant
melanoma, based on positive data in the largest randomized trial
ever conducted for the treatment of advanced metastatic melanoma.
Genta has also completed enrollment in two additional randomized
trials (multiple myeloma and chronic lymphocytic leukemia) with
Genasense.
About Genta
Genta Incorporated is a biopharmaceutical company with a
diversified product portfolio that is focused on delivering
innovative products for the treatment of patients with cancer. The
Company's research platform is anchored by two major programs that
center on oligonucleotides (RNA and DNA-based medicines) and small
molecules. Genasense
TM
(oblimersen sodium), the Company"s lead compound from its
oligonucleotide program, is being developed with Aventis and is
currently undergoing late-stage, Phase 3 clinical testing. The
leading drug in Genta's small molecule program is Ganite
TM
(gallium nitrate injection), which the Company is exclusively
marketing in the U.S. for treatment of patients with cancer-related
hypercalcemia that is resistant to hydration. For more information
about Genta, please visit our website at:
http://www.genta.com/
.
This press release contains forward-looking statements with
respect to business conducted by Genta Incorporated. By their
nature, forward-looking statements and forecasts involve risks
and uncertainties because they relate to events and depend on
circumstances that will occur in the future. There are a number
of factors that could cause actual results and developments to
differ materially. For a discussion of those risks and
uncertainties, please see the Company"s Annual Report/Form 10-K
for 2002.
SOURCE: Genta Incorporated
