Data Show Geron's Telomerase Inhibitor Cancer Drug is Active Against Cancer Stem Cells From Multiple Myeloma Patients
MENLO PARK, Calif.--(Business Wire)--Geron Corporation (Nasdaq:GERN) today announced that its telomerase inhibitor cancer drug, GRN163L, is active against cancer stem cells from multiple myeloma patients, according to data presented at the American Society of Hematology 48th Annual Meeting in Orlando, Fla.
Resulting from a collaboration between Geron and investigators with the department of oncology at the Johns Hopkins University School of Medicine, the data demonstrated activity in a model derived from multiple cell lines as well as cells from fresh specimens taken from the bone marrow of multiple myeloma patients. Cancer stem cells, which are often resistant to standard treatments, are believed to be critically important to cancer's ability to replicate and spread throughout the body. Johns Hopkins' William Matusi, M.D., was the lead author of the study, which Richard J. Jones, M.D., presented.
"I believe the activity of GRN163L against cancer stem cells in multiple myeloma is very intriguing," said Dr. Jones, who is the director of the bone marrow transplant program and co-director of hematologic malignancies at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center. "Our data suggest that cancer stem cells, which are resistant to most agents currently in use in multiple myeloma, are the cause of disease relapse in many patients. Therefore, the ability to target cancer stem cells holds considerable clinical promise."
Specifically, the data demonstrated that GRN163L inhibited telomerase activity and eliminated the colony forming potential of cancer stem cells from three independent multiple myeloma cell lines. GRN163L also inhibited the clonogenic potential of more mature myeloma cells. In separate experiments using primary clinical samples, cancer stem cells isolated from the bone marrow of three patients with multiple myeloma and then exposed to GRN163L also had a marked reduction in clonogenic growth. Previous data using these models for agents commonly used in the treatment of multiple myeloma did not demonstrate similar effects on myeloma cancer stem cells.
In another presentation (Tressler, et al., Abstract #2595), Geron showed that GRN163L continues to demonstrate excellent tolerability and predictable pharmacokinetics in a Phase I/II trial in patients with chronic lymphocytic leukemia (CLL) and a Phase I trial in patients with solid tumors.
Subjects with CLL received increasing doses of GRN163L intravenously over six hours, while subjects in the solid tumor trial were administered similar doses over two hours. To date, all infusions in the first three dose cohorts of both trials were well tolerated with no dose-limiting toxicities (DLTs). Pharmacokinetic analysis demonstrated dose-proportionality over the range of doses tested. Peak plasma concentrations achieved were 3 mcg/ml and 10 mcg/ml in these initial cohorts of the CLL and solid tumor studies, respectively. Pre-clinically, telomerase activity within cancer cells can typically be inhibited by concentrations of 5 to 10 mcg/ml. These data support escalation to higher doses which are predicted to result in sustained exposure levels that fall within the therapeutic range.
"The early clinical data continue to be encouraging," said Alan Colowick, M.D., Geron's president, oncology. "The excellent tolerability and pharmacokinetics observed in the early cohorts enable us to advance to the therapeutic dose cohorts. Additionally, based upon the data generated from our collaboration with the group from Johns Hopkins demonstrating important effects of GRN163L against myeloma cancer stem cells, we plan to initiate a clinical trial in patients with multiple myeloma in the first half of 2007."
Background
Telomerase is a broadly applicable and critical tumor target. It is expressed in a broad array of malignant tumors, essential for malignant cell growth and absent or expressed transiently, typically at low levels, in most normal adult tissues.
GRN163L is a short chain oligonucleotide that has high resistance to nuclease digestion in blood and tissues and very high affinity and specificity for telomerase. The molecule has superior cellular and tissue penetration properties due to its proprietary chemistry and its 5' lipid chain. The drug is a specific inhibitor of telomerase enzymatic activity. The mechanism of action involves direct binding to the template region of telomerase and is distinct from that of other oligonucleotide drugs with "antisense" activity.
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 degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. The company is advancing an anticancer 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 a product to treat spinal cord injury expected to enter clinical trials in late 2007. 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 the status of Geron's technology and clinical development and potential applications of Geron's technologies 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.
Geron David L. Greenwood, 650-473-7765 Chief Financial Officer info@geron.com or Noonan Russo David Schull, 858-546-4810 (Media) david.schull@eurorscg.com Matthew Haines, 212-845-4235 (Investors) matthew.haines@eurorscg.com
Copyright Business Wire 2006 11Dec06 12:30 GMT
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