Trials update: Geron Presents Early Clinical Trial Data for Its Telomerase Inhibitor Cancer Drug
MENLO PARK, Calif.--(Business Wire)--Geron Corporation (Nasdaq:GERN) today announced the presentation of the first clinical trial data for its telomerase inhibitor cancer drug, GRN163L, at the 18th EORTC-NCI-AACR International Conference on "Molecular Targets and Cancer Therapeutics" in Prague.
Presented by Laurence Elias, M.D., Geron's vice president, oncology clinical development, the data demonstrate the safety, tolerability and predicted pharmacokinetics in low-dose cohorts from a Phase I/II trial in patients with chronic lymphocytic leukemia (CLL) and a Phase I trial in patients with solid tumors.
"The early clinical data are very encouraging," said Alan Colowick, M.D., Geron's president, oncology. "This is the first time telomerase inhibition has been tested in cancer patients. The excellent tolerability and pharmacokinetics observed so far enable us to advance to the therapeutic dose cohorts, where we hope to demonstrate safe, sustained telomerase inhibition in the targeted tumor cells."
Safety and Tolerability
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 two dose cohorts of the CLL trial and the first three dose cohorts of the solid tumor trial were well tolerated with no dose-limiting toxicities (DLTs), and no reported serious adverse events (SAEs). Although patients in these early cohorts received doses predicted to be sub-therapeutic with respect to telomerase inhibition, these data support dose escalation to the therapeutic range, expected to occur by the end of 2006 for both trials.
Pharmacokinetics
Pharmacokinetic (PK) data for three subjects in the first cohort of the CLL trial who received approximately 0.5 mg/kg over six hours were similar between subjects and consistent with PK predictions made from preclinical studies in monkeys. Drug levels were measurable for eight to 12 hours after the start of infusion. The maximum plasma concentration (Cmax) during the six-hour infusion averaged 1.44 micro-g/ml, with an initial half-life (t 1/2(alpha)) of about four hours. PK data from one subject in the second dose cohort who received twice the dose (approximately 1.0 mg/kg over six hours) exhibited a Cmax of 2.7 micro-g/ml, suggesting dose-linearity over this range.
Initial PK data for one subject in the solid tumor trial showed a predicted higher Cmax (3.5 micro-g/ml) than the CLL subjects at a similar dose (0.4 mg/kg) and a similar t 1/2(alpha) of about four hours. These results are consistent with preclinical animal modeling experiments.
These early PK results are significant because they appear to confirm the expected relationships between dose, dosing interval and plasma levels that were predicted in preclinical studies in monkeys. Similar data collected in the higher dose cohorts should enable dose and dosing intervals to be optimized to achieve plasma levels consistently above the threshold thought to be necessary to achieve clinically relevant inhibition of the telomerase target in tumor cells, but well below the concentrations believed to trigger complement activation or coagulation prolongation side effects common to polyanionic oligonucleotides.
Pharmacodynamics
Data were presented on pre-treatment baseline telomere lengths from fractionated peripheral blood cells for five CLL patients and two solid tumor patients. Notably, telomere lengths in CLL mononuclear fractions (comprised largely of malignant lymphocytes) are significantly shorter than those in the polymorphonuclear (PMN) fractions (non-malignant white blood cells) from both CLL and solid tumor patients and also shorter than the mononuclear fraction from the solid tumor patients. These data support the concept that short telomeres in malignant cells will render them highly sensitive to telomerase inhibition.
Complete data on telomerase inhibition in CLL tumor cells in these early dose cohorts is not yet available due to the batching schedules of samples for analysis. Those data are expected shortly.
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 at low levels in most normal adult tissues.
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 a Menlo Park, Calif.-based biopharmaceutical company that is developing and intends to commercialize first-in-class therapeutic products for the treatment of cancer and degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. The products are based on Geron's 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 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 Sharon Weinstein, 212-845-4271 (Investors) sharon.weinstein@eurorscg.com
Copyright Business Wire 2006 10Nov06 12:30 GMT
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