Geron Presents Interim Clinical Data on Its Telomerase Inhibitor Drug at AACR-NCI-EORTC

Dosing Schedule of Imetelstat Achieves Drug Exposure Consistent with In Vivo Inhibition of Tumor Growth

MENLO PARK, CA, USA | November 19, 2009 | Geron Corporation (Nasdaq:GERN - News) today announced the presentation of interim data from its ongoing trial of imetelstat (GRN163L), a telomerase inhibitor drug, in patients with refractory, advanced solid cancers at the 2009 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

This Phase I study of imetelstat as a single agent is one of six company-sponsored Phase I clinical trials designed to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination, in solid tumors, chronic lymphoproliferative disease, multiple myeloma, lung and breast cancers.

“I am pleased to report that we have met our Phase I objectives for imetelstat and can advance the program,” said Stephen M. Kelsey, M.D., F.R.C.P., F.R.C.Path., Geron’s executive vice president and chief medical officer, oncology. “As the data from the study in patients with solid tumors presented today illustrates, we are achieving exposures to imetelstat that exceed the levels that have been associated with efficacy in several models of human cancers and we are also observing telomerase inhibition in tissue samples from patients, while minimizing hematological toxicities through an alternative dosing schedule. In 2010 we plan to initiate four Phase II clinical trials of imetelstat in multiple cancers.”

An interim analysis of the ongoing Phase I study of imetelstat in patients with advanced solid tumor malignancies that do not respond to standard treatments was presented by Geron clinical scientists and collaborating principal investigators from the University of Chicago Medical Center and Barbara Ann Karmanos Cancer Center. Data were presented on 25 patients, with one currently on study. The patients were given imetelstat as a single agent by two hour intravenous infusions using an intermittent dosing schedule on days one and eight of 21-day cycles (two weeks on treatment, one week off). Dosing started at 4.8 mg/kg and escalation proceeded to 11.7 mg/kg. Prior to enrollment, 22 of 25 patients had received a mean of four prior cytotoxic treatment regimens and 15 had received prior irradiation.

Pharmacokinetic and Pharmacodynamic Results

Exposure to imetelstat during the treatment period was determined by measuring the concentrations of the drug in the plasma of patients prior to and following infusions and calculating the Area Under the Curve (AUC) for drug concentration against time. At doses of 7.5 mg/kg and above, the level of exposure to imetelstat was higher than the exposure that is associated with inhibition of telomerase and tumor growth in multiple xenograft animal models. Preliminary analysis of pre- and post-treatment hair follicle samples for pharmacodynamic activity shows a trend for telomerase inhibition.

Safety Results

An intermittent dosing schedule of imetelstat on days one and eight of a 21-day cycle was tested to increase drug exposure and tolerability because of dose limiting thrombocytopenia (low number of blood platelets) previously observed with weekly dosing at 4.8 mg/kg in this patient population. Intermittent dosing ameliorated the thrombocytopenia and was generally well tolerated; other toxicities were mild or infrequent. Dose escalation proceeded to 11.7 mg/kg; however, due to hematologic toxicities, this dose was considered to exceed the maximum tolerated dose (MTD). The 9.4 mg/kg dose given on days one and eight of a 21-day cycle is the recommended dose for single agent Phase II studies.

About Telomerase and Imetelstat (GRN163L)

Telomerase is a critical and potentially broadly applicable tumor target. The enzyme is expressed in a wide range of malignant tumors, and its activity is essential for the indefinite replicative capacity of cancer cells that enables their malignant cell growth. Telomerase is absent or expressed only transiently at low levels in most normal adult tissues.

Imetelstat is a short chain oligonucleotide that binds with high affinity and specificity to the catalytic site of telomerase, resulting in competitive inhibition of enzyme activity. Proprietary manufacturing chemistry and the addition of a 5' lipid chain have enabled the molecule to penetrate cells and tissues throughout the body.

Imetelstat has demonstrated anti-tumor effects in a wide range of preclinical hematological and solid tumor models.

Preclinical studies have also demonstrated that imetelstat can inhibit clonogenic growth of both primary patient samples and subpopulations from cell lines enriched for cancer stem cells from multiple tumor types. These subpopulations show resistance to several conventional chemotherapeutic agents. Cancer stem cells capable of clonogenic growth may play an important role in the rapid regrowth of tumors after initial reduction by standard treatments.

About Geron

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 in different cancers. For more information, visit www.geron.com.

SOURCE: Geron Corporation

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