October 15, 2008
Geron’s GRN163L Sensitizes Resistant Breast Cancer Cells to Trastuzumab in Preclinical Study
Geron Corporation (Nasdaq:GERN) today announced the publication of preclinical data demonstrating that its telomerase inhibitor drug, GRN163L, significantly boosts the effects of trastuzumab (Herceptin(TM)) against HER2-positive breast cancer cells and restores sensitivity to trastuzumab in trastuzumab resistant tumor cells.
The research published online yesterday in Breast Cancer Research and Treatment was conducted by Dr. Brittney-Shea Herbert and colleagues at Indiana University Melvin and Bren Simon Cancer Center in collaboration with scientists at Geron.
"The data show strong synergy of GRN163L with one of the best anti-breast cancer drugs available," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "These are important preclinical results that bear upon the development of our telomerase inhibitor drug, currently in five clinical trial programs, including one for the treatment of breast cancer."
HER2 amplification is associated with a more aggressive breast cancer and also with an increase in telomerase activity. The study assessed the viability and proliferation of tumor cells among a panel of HER2-positive breast tumor cell lines, including two trastuzumab resistant lines, when treated with GRN163L and trastuzumab, alone or in combination. The data showed that GRN163L acted synergistically with trastuzumab to inhibit growth of each tumor cell line at all combination doses tested. A mismatch control lipidated oligonucleotide did not enhance or alter the growth inhibition effects of trastuzumab. No effect on cell growth was seen in nontumorigenic breast epithelial cells, as further evidence of the specificity of GRN163L to cancer cells without limiting the proliferation and viability of normal cells.
"Amplification of HER2 in breast cancer is associated with a more aggressive disease and poorer prognosis than HER2-negative cancer. Herceptin is an important therapeutic option in HER2-positive breast cancer, but resistance to the treatment develops rapidly in a large number of patients," said Brittney-Shea Herbert, Ph.D. "GRN163L's ability to inhibit growth as a single agent, and importantly, to restore sensitivity to trastuzumab in resistant breast cancer cells, highlights a potential clinical role for GRN163L in the treatment of cancers that have acquired resistance to standard therapy."
About Telomerase and 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.
GRN163L 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.
GRN163L has demonstrated anti-tumor effects in a wide range of preclinical hematological and solid tumor models, including breast cancer.
Geron is a biopharmaceutical company that is developing first-in-class therapeutic products for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure and diabetes. The products are based on our core expertise in telomerase and human embryonic stem cells. 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 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 June 30, 2008.