Geron Presentations at the ASCO 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.
GRN163L Exhibits Rapid and Selective Cytotoxicity in T-PLL Cells
T-cell prolymphocytic leukemia (T-PLL) is an aggressive lymphoproliferative disease characterized by resistance to chemotherapy, high telomerase activity and very short telomeres (Roth, et. al., Leukemia, 21:2456-2462, 2007). In a poster presentation authored by Geron scientists and collaborators from the University Hospital, Essen, Germany and the University Hospital, Bern, Switzerland, T-PLL cells from patients were selectively killed in dose-dependent fashion by seven-day incubations with GRN163L. Annexin staining confirmed a dose-dependent increase in apoptosis caused by exposure to GRN163L. Normal T-cells were unaffected by GRN163L, and a mismatch control oligonucleotide had no effect on the viability of the leukemic cells.
The results demonstrate selective cytotoxicity of GRN163L on T-PLL cells leading to rapid leukemic cell death and provide the rationale for clinical trials of GRN163L in patients with T-PLL.
Phase I Study of GRN163L in Refractory, Advanced Solid Tumors
Interim analysis of an ongoing Phase I study of GRN163L in refractory, advanced solid tumor patients was presented by Geron scientists and collaborating principal investigators from the University of Chicago and Wayne State University. Data were presented on 28 patients, each of whom had received at least one infusion of GRN163L at doses ranging from 0.4 - 4.8 mg/kg. A total of 175 doses were administered as of May 12, 2008. Patients had received up to nine prior therapies with more than half receiving four or more.
The plasma half-life was approximately three hours and Cmax appeared to be linear with dose. Dose-limiting toxicity (thrombocytopenia) was observed in one patient at the 3.2 mg/kg dose and in two patients out of 14 at the 4.8 mg/kg dose. No objective responses have been seen at these dose levels.
The maximum tolerated dose of GRN163L has not been established in this heavily pretreated patient population. Dose escalation will continue with evaluation of intermittent dosing schedules to minimize platelet effects. Measurement of hair follicle telomerase activity has been incorporated into the protocol as dose escalation continues in order to define the pharmacokinetic-pharmacodynamic relationship for GRN163L in this patient population.
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 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 March 31, 2008.
Posted: June 2008