Favorable Pharmacokinetics; Pharmacodynamics Consistent with Expectations
A pharmacokinetic analysis of three patients in the highest dose cohort (cohort 4, 160 mg/m2 IV/week) has shown transient peak plasma concentrations of GRN163L of approximately 10 ug/ml. This and other data indicate that the drug continues to exhibit favorable pharmacokinetic properties that are linear with respect to the doses tested so far.
Up to the current dose levels, no significant changes in telomerase activity or telomere length in the bulk circulating CLL cells of treated patients have been observed. These pharmacodynamic results are consistent with expectations because of the relatively short exposure of CLL cells in patients' blood to concentrations of drug capable of inhibiting telomerase.
Good Tolerability Profile
With dosing and accrual to cohort 4 continuing, patients treated at the current dose levels have tolerated the drug well, and the maximum tolerated dose has not yet been identified. Grade 1-2 partial thromboplastin time (aPTT) prolongation has been observed, and one patient each has experienced Grade 3 and Grade 4 thrombocytopenia.
One patient in cohort 4 has completed two cycles of treatment, and stable disease has been observed. A second patient has had clinical findings consistent with tumor lysis syndrome, a transient metabolic abnormality resulting from the rapid destruction of malignant cells. This patient experienced a transie nt reduction in absolute lymphocyte count of 48% that persisted for approximately two weeks. The etiology of this finding is uncertain at this time given the lack of measured telomerase inhibition in this patient.
"We are encouraged by the results," said Dr. Colowick. "The first and only telomerase inhibitor in clinical trials continues to demonstrate predictable pharmacokinetics over the range investigated and appears to be well tolerated. We will apply what we are learning to the continued dose escalation as we move further into the predicted therapeutic dose cohorts for both the CLL and solid tumor trials. Furthermore, we are adding two additional sites for the CLL trial to accelerate patient enrollment."
"Based on preclinical data demonstrating the effects of GRN163L on both mature and cancer stem cells in multiple myeloma, Geron will initiate a clinical trial involving multiple myeloma patients," continued Dr. Colowick. "In addition, the company will begin a fourth trial of GRN163L in combination with carboplatin and paclitaxel in patients with non-small cell lung cancer. The basis for this trial is the result of promising preclinical animal data demonstrating the drug's activity in this tumor type as well. Geron expects to initiate both trials in the coming months."
Geron's ongoing Phase I/II trial is a sequential cohort, dose escalation study to determine the safety and tolerability of GRN163L administered intravenously on a weekly basis to patients with refractory or relapsed CLL. Patients interested in enrollment into the trial should visit the Patient Information page of Geron's website at www.geron.com.
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 developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. 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 such forward-looking statements in this press release regarding potential applications of GRN163L and 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 deta iled from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended March 31, 2007.
David L. Greenwood, 650-473-7765
Chief Financial Officer
Russo Partners, LLC
David Schull, 858-717-2310 (Media)
Matthew Haines, 212-845-4235 (Investors)