Geron Announces Publication of Data on Its Telomerase Inhibitor in Glioblastoma

Posted : Tue, 05 Jan 2010 12:30:40 GMT

Author : Geron Corporation

MENLO PARK, Calif. - (Business Wire) Geron Corporation (Nasdaq:GERN) today announced the publication of preclinical data demonstrating that its telomerase inhibitor drug, imetelstat (GRN163L), inhibited telomerase activity and reduced tumor size in xenograft models of glioblastoma, and inhibited the activity of glioblastoma stem cells in culture.

The data, authored by Geron collaborators at the University of Texas Southwestern Medical Center at Dallas, were published in the January 1, 2010 issue of Clinical Cancer Research. The abstract of the publication is available on the journal’s website at http://clincancerres.aacrjournals.org/content/16/1/154.abstract.

“We are excited by the telomerase inhibition observed in the glioblastoma model. The blood-brain tumor barrier limits the delivery of most therapeutic drugs to brain tumors, but these data show that imetelstat penetrates that barrier,” said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. “Cancer stem cells pose an additional therapeutic challenge. These data add to the growing list of cancer types where the inhibition of cancer stem cells by imetelstat has been shown preclinically. We will further investigate imetelstat’s anti-cancer stem cell potential clinically in our Phase II trials in breast and lung cancers, multiple myeloma and chronic leukemias that will begin later this year.”

Recent evidence suggests that glioblastomas contain rare populations of cells with a capacity for endless self-renewal, known as cancer stem cells or tumor initiating cells, and may be responsible for tumor growth and recurrence. Cancer stem cells also show resistance to many conventional anti-cancer agents and are therefore important targets for novel therapies.

Glioblastoma tumor initiating cells isolated from patient samples can be propagated indefinitely in vitro, maintaining the molecular properties of the original tumor. The current data show that the clonogenic and proliferative capacity of primary human glioblastoma tumor initiating cells is vastly decreased by exposure to imetelstat in vitro, compared to controls. Telomerase activity and telomere length were reduced, ultimately leading to cell death. In addition, temozolomide and ionizing radiation, standard treatment regimens for glioblastoma after surgical resection, boost the effects of imetelstat, further decreasing the viability of cultured glioblastoma tumor initiating cells.

Orthotopic tumors were established by implanting glioblastoma tumor initiating cells into the brains of mice. Telomerase was inhibited by 60-70% in these tumors within 3-5 days after administering imetelstat intraperitoneally (into the body cavity). This is an important observation demonstrating that imetelstat can penetrate the blood-brain tumor barrier, unlike many chemotherapeutic agents. Further in vivo animal data using a subcutaneous tumor model showed that imetelstat treatment led to a significant decrease in tumor growth rate and a 10-fold decrease in tumor size after 53 days of treatment compared to the vehicle control treated group.

About Telomerase and Imetelstat (GRN163L)

Telomerase is a critical and potentially broadly applicable tumor target. The enzyme is expressed in a wide range of malignant tumors, and its activity is essential for the indefinite replicative capacity of cancer cells that enables their malignant cell growth. Telomerase is absent or expressed only transiently at low levels in most normal adult tissues.

Imetelstat is a short chain oligonucleotide that binds with high affinity and specificity to the catalytic site of telomerase, resulting in competitive inhibition of enzyme activity. Proprietary manufacturing chemistry and the addition of a 5' lipid chain have enabled the molecule to penetrate cells and tissues throughout the body.

Imetelstat has demonstrated anti-tumor effects in a wide range of preclinical models of hematological and solid tumors and is currently being tested in six Phase I clinical trials in patients with solid tumors, chronic lymphoproliferative disease, multiple myeloma, lung and breast cancers, as a single agent or in combination with standard treatments.

About Geron

Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure and diabetes. The company is advancing an anti-cancer drug and a cancer vaccine that target the enzyme telomerase through multiple clinical trials in different cancers. For more information, visit www.geron.com.

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 statements in this press release regarding potential applications of Geron’s telomerase technology and imetelstat constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and 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, 2009.

Geron Corporation
Anna Krassowska, Ph.D., 650-473-7765
Investor and Media Relations
info@geron.com