Geron Presentations at the AACR 2008 Annual Meeting
Geron is currently testing GRN163L in four clinical trials with 15 U.S. medical centers recruiting patients with solid tumors, chronic lymphoproliferative disease, multiple myeloma and non-small cell lung cancer. New combination trials in breast cancer and multiple myeloma at additional trial sites are scheduled to initiate in the coming months. Geron is also conducting a multi-center Phase II trial of GRNVAC1, a telomerase therapeutic vaccine, in high risk acute myelogenous leukemia (AML) patients. We expect Merck & Co., Inc., under license from Geron, to initiate a therapeutic vaccine trial targeting telomerase in patients with non-small cell lung and prostate cancers.
"These Geron presentations and the many others on telomerase and cancer continue to highlight the importance of telomerase-targeted therapeutics for the treatment of cancer," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "We are excited by the near-term prospects for our ongoing trials of GRN163L and GRNVAC1."
GRN163L Sensitizes Resistant HER2-Positive Breast Cancer Cells to Trastuzumab
Overexpression of HER2 in breast cancer is associated with more aggressive disease, high recurrence rates and decreased overall survival. Trastuzumab, a HER2 inhibitor, is an important therapeutic alternative for patients with HER2-positive breast cancer, although resistance develops rapidly in a large number of patients. HER2 overexpression is also associated with increased expression of telomerase, prompting the study of GRN163L in HER2-positive breast cancer cells.
Presented in a poster by Dr. Brittney-Shea Herbert and colleagues from Indiana University and Geron, their data show that GRN163L effectively inhibited telomerase in HER2-positive breast cancer cells, including breast cancer cells that had become resistant to trastuzumab and, that GRN163L acts synergistically on these cells in combination with trastuzumab. Moreover, their data also show that exposure of trastuzumab resistant cells to GRN163L restored the cells' sensitivity to trastuzumab. These two findings provide the rationale for testing GRN163L in combination with trastuzumab in breast cancer patients who have developed resistance to standard cancer therapy.
GRN163L Increases Sensitivity of Non-Small Cell Lung Cancer Cells to Paclitaxel and Carboplatin
Presented in a mini-symposium lecture by Robin Frink and colleagues from the University of Texas Southwestern Medical Center, their data show that GRN163L effectively inhibited telomerase in three different non-small cell lung cancer (NSCLC) lines and caused shortening of their telomeres. Additionally, their data show that treatment of NSCLC cells with GRN163L increases their sensitivity to paclitaxel and carboplatin. These two findings provide the rationale for using GRN163L in combination with paclitaxel and carboplatin in NSCLC cancer patients, and a clinical trial with this combination is currently ongoing in this indication.
GRN163L Inhibits Telomerase in Human Hair Follicles, Allowing Simple Monitoring of Pharmacodynamic Effects in Patients
Rational optimization of dosing regimens in targeted cancer therapies requires an understanding of pharmacokinetic-pharmacodynamic relationships - what exposure of drug is required to inhibit its target. Because it is not always possible to repeatedly sample the tumor mass in treated patients, the availability of accessible surrogate tissue that contains the drug target is highly desirable. In two posters presented by Ekaterina Bassett and colleagues at Geron, data were presented that showed GRN163L reproducibly inhibits telomerase from hair follicles in a dose dependent manner, at the same concentrations that inhibit telomerase in tumor cells and reduce their proliferation. Tumor-bearing rodents treated with standard doses of GRN163L exhibited equivalent degrees of telomerase inhibition in their tumors as in their whiskers, and those doses of GRN163L also resulted in the expected reduction in the animals' tumor volume. When applied in vitro to human scalp hair follicles, similar dose-dependent inhibition of follicle telomerase by GRN163L was observed. These results suggest that measuring telomerase inhibition in hair follicles is a suitable surrogate pharmacodynamic assay to allow the optimization of dosing regimens of GRN163L in man. This assay is now being implemented in the ongoing GRN163L solid tumor trial.
GRN163L and Multiple Myeloma Stem Cells
Cancer stem cells (CSCs) are a rare sub-population of self-renewing, immortal tumor cells capable of differentiating into the various types of cells seen within a bulk tumor. They are now widely believed to be distinct from bulk tumor cells and to be responsible for many cases of drug resistance and cancer recurrence.
GRN163L has been shown to inhibit the proliferation of CSCs in multiple myeloma, as well as causing cell death in mature bulk myeloma cells (Matsui, ASH 2006), providing the rationale for the ongoing trial that tests GRN163L as a single agent in multiple myeloma and a new study testing GRN163L in combination with bortezomib. These data on GRN163L were reviewed in the broad context of myeloma CSCs in an Educational Session by Dr. William Matsui of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who co-chaired the two hour session entitled, "The Cancer Stem Cell Hypothesis: Biological and Clinical Implications."
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. Geron is also the world leader in the development of human embryonic stem cell-based therapeutics, with its spinal cord injury treatment anticipated 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 statements in this press release regarding ongoing and future clinical trials and 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 annual report on Form 10-K for the year ended December 31, 2007.
David L. Greenwood, 650-473-7765
Chief Financial Officer
Russo Partners, LLC
Media and Investors:
David Schull, 858-717-2310
Tracey Milani, 619-814-3511
Posted: April 2008