Geron Announces Presentations on GRN163L and Its Telomerase Vaccine at the AACR Special Conference on the Role of Telomerase in Cancer
MENLO PARK, Calif. -- (Business Wire) -- Nov. 8, 2004
Geron Corporation (Nasdaq:GERN) announced presentations
of new data from clinical and preclinical studies of its
telomerase-based cancer therapeutics at the American Association for
Cancer Research (AACR) Special Conference on the Role of Telomeres and
Telomerase in Cancer, in San Francisco, California. Reported were
updates on results from the Phase I/II study of Geron's telomerase
vaccine at Duke University and IND-enabling studies of its telomerase
inhibitor, GRN163L.
¶ Geron co-sponsored this international AACR Special Conference on
telomeres and telomerase in cancer. The meeting included over 150 oral
and poster presentations focused on understanding telomere and
telomerase biology for the development of cancer therapeutics. The
meeting chairpersons were Dr. Jerry W. Shay, University of Texas
Southwestern Medical Center, Dallas, Dr. Elizabeth H. Blackburn,
University of San Francisco, California, and Dr. Maria A. Blasco,
Spanish National Cancer Center, Madrid, Spain.
¶ GRN163L Reduces Metastatic Potential of Tumor Cells
¶ In the opening session of the meeting, Dr. Shay provided an
overview of the importance of telomerase as a universal and highly
specific target for the development of novel cancer therapies, and
reviewed the breadth of approaches to kill telomerase-positive tumor
cells while sparing normal tissue. Dr. Shay also presented new data
from his laboratory indicating that Geron's novel oligonucleotide
telomerase inhibitor, GRN163L, can have a relatively rapid effect on
tumor cells in culture, making them less able to grow at low density
(reduced clonogenicity), as well as inhibiting tumor cell invasion and
migration through an extracellular matrix. These drug effects may be
important to reduce the metastatic potential of cancer cells.
¶ The short-term effects of GRN163L were seen before cell growth was
affected (i.e. before telomeres become critically short due to
telomerase inhibition) and were seen even when telomeres were
lengthened by pretreatment with Adeno-hTERT, a virus that transiently
expresses high levels of telomerase. A mis-match control
oligonucleotide with the same chemistry as GRN163L, but with a
different nucleotide sequence, had no apparent effect, suggesting that
the observed anti-clonogenicity and inhibition of migration/invasion
were dependent upon telomerase inhibition. These observations, seen
with breast and lung cancer cell lines, are consistent with previously
reported data indicating that tumor cells may rely upon telomerase for
more than just telomere maintenance. Dr. Shay then presented data
showing that GRN163L, given systemically in a mouse model of human
metastatic lung cancer, significantly inhibited the number of tumors
that arose in the lungs after intravenous injection of tumor cells.
¶ "We are excited about the potential of GRN163L as an anti-cancer
agent, and our new data help explain why we sometimes see relatively
rapid effects of telomerase inhibition on tumor cells in vivo," said
Dr. Shay. "Although we don't yet know why telomerase inhibition
impacts clonogenicity and migration/invasion of tumor cells, it is an
encouraging observation for the development of this drug."
¶ Progress on GRN163L IND-Enabling Studies
¶ The drug development status of GRN163L was presented by Calvin B.
Harley, Ph.D., Geron's chief scientific officer. Dr. Harley indicated
that scaled-up production of GRN163L using GLP (good laboratory
practices) standards has been achieved at the multi-hundred gram
scale, enabling the ongoing preclinical studies in support of an IND
application to the FDA. In addition, similar quantities of GRN163L
have been made at higher purity under GMP (good manufacturing
practices), and the first lot of Phase I clinical trial drug product
has been successfully manufactured. Dr. Harley reviewed the safety,
toxicology, pharmacokinetic, biodistribution, and pharmacodynamic
studies that have been conducted in multiple animal species. These
studies, together with the growing body of human xenograft efficacy
data in rodents, suggest that intermittent intravenouse dosing of
GRN163L should achieve therapeutic tissue levels of the drug in cancer
patients, while maintaining an acceptable safety profile.
¶ "One problem with oligonucleotide drugs is that it has been
difficult to deliver effective, safe concentrations of the drug
throughout the body," stated Dr. Harley. "We believe our molecule has
unique advantages in this regard. The novel backbone chemistry of
GRN163L provides greatly enhanced stability and extremely specific and
high affinity binding to telomerase, while the lipid modification on
GRN163L significantly improves its potency and biodistribution. These
properties increase the chances of effectively inhibiting telomerase
in cancer cells throughout the body with relatively low doses of the
drug."
¶ GRN163L in Combination with Chemotherapy
¶ Dr. Harley also presented new results from animal models using
GRN163L in combination with other approved cancer drugs. The first
study, conducted at Geron, used melphalan (an alkylating agent) in a
mouse model of minimal residual disease with human SK-Mel-2 melanoma
cells implanted subcutaneously. In this model, five doses of melphalan
alone given over a two week period had an immediate, dramatic impact
on tumor growth, but the effect was not durable -- large tumors
eventually appeared in most mice by the end of the study. However, in
mice treated systemically with GRN163L in addition to the melphalan
injections, tumor growth was significantly delayed, and in mice that
had tumors, the tumor size was much smaller than those in the
melphalan alone group. In the second model, conducted in Dr. M.A.S.
Moore's laboratory at Memorial Sloan Kettering Cancer Center, New
York, and separately presented in a poster at the meeting, human
Ovcar-3 ovarian carcinoma cells were implanted in the intraperitoneal
cavity of mice. Treatment by intraperitoneal injection began three
days post tumor implantation with vehicle control, GRN163L, and/or the
microtubule inhibitor taxol. In this experiment, both GRN163L and
taxol given alone prevented tumor growth, but neither drug decreased
tumor burden relative to the initial mass. However, the combination of
both agents resulted in a progressive decrease in tumor burden with
two of nine mice in the combination group showing essentially no
detectable tumor at the end of the study.
¶ "This type of effect is what we hope to achieve in later clinic
trials in which GRN163L will be tested in combination with approved
chemotherapy regimens," concluded Dr. Harley. "We hope to convert
partial or even complete responses that are often transient with
current therapies into durable responses and increased patient
survival."
¶ Dr. Harley indicated that the initial Phase I study is being
planned in a hematologic cancer to enable easy monitoring of safety,
pharmacokinetic and pharmacodynamic effects of GRN163L as a single
agent. Beyond the first Phase I trial, however, clinical studies would
likely involve both hematologic and solid malignancies with GRN163L in
combination with other drugs.
¶ Update on Geron's Telomerase Vaccine Phase I/II Trial
¶ Thomas B. Okarma, Geron's president and CEO, presented an in-depth
update of the completed Phase I/II trial of Geron's telomerase vaccine
in prostate cancer patients conducted at Duke University Medical
Center by Dr. Johannes Vieweg and colleagues. The talk emphasized the
improved cellular immune response seen in the study subjects who
received a modified version of the hTERT antigen that enabled the
generation of anti-telomerase CD4+ helper T-cells, as well as
telomerase-specific CD8+ killer T-cells. Ongoing new clinical studies
testing other modifications of the vaccine protocol were described
along with progress in automating the vaccine production process.
¶ Oncolytic Virus Update
¶ Throughout the meeting there were multiple additional
presentations and posters on telomerase- and telomere-based cancer
diagnostic and therapeutic opportunities, attesting to the importance
of telomere biology in cancer. In addition to direct enzyme inhibition
and telomerase immunotherapy for cancer treatment, approaches included
methods to block telomerase production, disrupt telomere function, and
use genes or viruses to trigger suicide or cell death in
telomerase-positive cells. In one talk, Dr. D.C. Yu, Director of
Oncolytic Virus Research and Principal Scientist at Cell Genesys,
presented data demonstrating the high degree of specificity and
effectiveness of one of their preclinical therapeutic product
candidates, the oncolytic virus, CG5757. Cell Genesys has a
non-exclusive license from Geron to use the hTERT promoter, the
genetic region regulating the expression of telomerase in tumor cells,
for the production of an oncolytic virus that specifically replicates
in and lyses tumor cells. CG5757 uses the promoters from hTERT and E2F
(another tumor associated gene) to control adenoviral genes necessary
for the replication of the virus. Studies preformed by Dr. Yu and his
colleagues at Cell Genesys showed that CG5757 was very efficient at
lysing multiple different tumor cell types in culture compared to
normal cells. Dr. Yu also presented data demonstrating anti-tumor
efficacy in rodent models of human lung, bladder, liver and prostate
tumors.
¶ 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 future
applications or development of Geron's technology for telomerase
inhibitors, telomerase cancer vaccines or oncolytic viruses constitute
forward-looking statements involving risks and uncertainties,
including, without limitation, risks inherent in the development and
commercialization of potential products, reliance on collaborators,
need for additional 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 September 30, 2004.
Contacts:
Geron Corporation
David L. Greenwood, 650-473-7765 |
