Unique Structure of Geron's Telomerase Inhibitor Drug Promotes Anti-Tumor, Anti-Metastatic Activity in Lung Cancer Cells
Published in Cancer Research (2007; 67: 1121-29), the studies conducted by Dr. Jerry Shay and collaborators at the University of Texas Southwestern Medical School demonstrated that GRN163L induces altered tumor cell adhesion in animal models of lung cancer and that it may have additional benefit in the prevention of metastasis.
"These data contribute to the growing body of evidence regarding the anti-tumor effects of GRN163L," noted Alan Colowick, M.D., M.P.H., Geron's president, oncology. "Based on these and other data, Geron intends to initiate a clinical trial this year in patients with lung cancer to determine if these results translate into clinically important anti-tumor activity."
Previous studies from the Shay laboratory demonstrated that GRN163L reduces the tumorigenic potential of a human lung cancer cell line (A549-luc) both in vitro and in vivo (Cancer Research, 2005; 65(17):7866-73) and that the cells were morphologically and functionally altered in vitro by GRN163L. Further, GRN163L exposure for one week to five weeks reduced colony formation and other signs of malignant transformation, while cells treated with a mismatched control drug were unaffected. The altered morphology occurred within 24 hours of treatment with GRN163L and was independent of telomerase inhibition or telomere length. In an in vivo model of lung cancer metastasis in which tumor cells from an intravenous injection migrate to, attach and grow in lung tissue, multiple doses of GRN163L over a three-week period from the time of animal inoculation with A549-luc tumor cells resulted in significant reduction in tumor progression.
Data in the present publication demonstrate that these effects are due to specific structural elements of GRN163L. In a series of studies, analogues to GRN163L that differed in the lipid moiety component and the thio-phosphoramidate backbone, or lacked a G-triplet within its sequence, did not elicit similar morphological changes or anti-adhesive properties. This study also demonstrated that administration of a single dose of GRN163L at the time of animal inoculation in the in vivo model of lung cancer metastasis resulted in decreased tumor burden at days 13, 20 and 27. These data support the importance of the unique structure of GRN163L to its ability to exert the anti-tumor effects.
GRN163L is a short chain oligonucleotide that is unique in its resistance to nuclease digestion in blood and tissues and its very high affinity and specificity for telomerase. The molecule has superior cellular and tissue penetration properties due to its proprietary manufacturing chemistry and its 5' lipid chain.
GRN163L has been demonstrated to have anti-tumor effects in a wide range of hematological and solid tumor models and appears to be unique in its observed effects on tumor stem cells: the rare, chemotherapy-resistant cancer cells that cause cancer recurrence.
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. The company is advancing an anti-cancer drug and a cancer vaccine that target the enzyme telomerase through multiple clinical trials. Geron is also the world leader in the development of human embryonic stem cell-based therapeutics, with its spinal cord injury treatment poised to be the first product to enter clinical development. 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 such forward-looking statements in this press release regarding potential applications of Geron's telomerase technology and GRN163L 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, 2006.
David L. Greenwood, Chief Financial Officer, 650-473-7765
David Schull, 858-717-2310 (Media)
Matthew Haines, 212-845-4235 (Investors)
Posted: February 2007