Geron Corporation (NASDAQ:GERN) today announced enrollment of the first patient in a Phase 2 clinical trial to evaluate the activity of the company’s telomerase inhibitor drug, imetelstat (GRN163L), in patients with essential thrombocythemia (ET). ET is a chronic disorder that arises in the hematopoietic (blood) stem cells in the bone marrow. The leukemic stem cells produce aberrant clones of platelet-forming cells (megakaryocytes), which results in increased numbers of circulating platelets.

“Our Phase 2 clinical trials of imetelstat are focused on malignancies in which cancer stem cells are thought to play an important role in disease progression, including breast and lung cancers, multiple myeloma and myeloproliferative neoplasms, such as essential thrombocythemia,” said Stephen M. Kelsey, M.D., Geron’s executive vice president and chief medical officer, oncology. “In ET, we think that targeting the leukemic stem cell with imetelstat might impact the biology of the disease, which is not possible with current standard treatments.”

Rationale for the Clinical Trial

Data from Phase 1 clinical trials and preclinical studies of imetelstat provide the rationale for evaluating the effect of the telomerase inhibitor drug in patients with ET.

Preclinical studies have demonstrated imetelstat’s activity against a broad range of cancer stem cells from both solid and hematological tumor types. In addition, leukocytes from patients with ET have notably high telomerase activity and short telomeres, providing further rationale for evaluating the effects of inhibiting telomerase with imetelstat in these patients.

Phase 2 Trial Design

The clinical trial is a Phase 2, open-label study of imetelstat as a single agent in patients with ET who have failed or are intolerant to at least one prior therapy or who refuse standard therapy, such as hydroxyurea, anagrelide or interferon-alpha.

The primary efficacy endpoint is best overall hematologic response rate, determined by a normalization or reduction in platelet counts. Approximately half of patients with ET have a molecular mutation in the JAK2 or MPL genes. The rate of molecular response is a secondary endpoint in patients who have one or both of these mutations at baseline. A molecular response is determined by a reduction in the percentage of mutant JAK2 or MPL alleles detected in patients’ granulocytes. Safety and tolerability will also be assessed.

Patients in the trial will be stratified based on the presence or absence of mutations in the JAK2 and MPL genes. Imetelstat is administered at an initial dose of 7.5 mg/kg weekly in a 28 day treatment cycle. The dose may be escalated to 9.4 mg/kg and up to a maximum of 11.7 mg/kg weekly, depending on hematologic response and tolerability. Dose and dosing schedule will be titrated based on platelet counts. Phase 1 clinical trials of imetelstat have demonstrated that doses of 7.5 mg/kg and higher allow exposure to imetelstat that exceed the levels associated with efficacy in xenograft models of human cancers and telomerase inhibition in tissue samples from patients.

The trial will be conducted at clinical sites in the U.S. and EU. The lead principal investigator is Srdan Verstovsek, M.D., Ph.D., at The University of Texas MD Anderson Cancer Center in Houston, Texas. For further information about this clinical trial, please visit www.clinicaltrials.gov/ct2/show/NCT01243073.

About Essential Thrombocythemia

Essential thrombocythemia (ET, also known as essential thrombocytosis) is a chronic blood disorder characterized by increased numbers of platelets in the blood. These platelets may have abnormal function, which can lead to an increased risk of thrombotic or hemorrhagic complications. Patients with ET may also develop myelofibrosis or acute myeloid leukemia.

The precise cause of ET is not known, though approximately half of patients have mutations in the genes for Janus kinase 2 (JAK2) or, less frequently, myeloproliferative leukemia (MPL). These gene mutations result in stable activation of the JAK-STAT signaling pathway and lead to megakaryocytic hyperplasia and thrombocytosis.

In the United States, there are approximately 7,200 new cases of ET annually. Life expectancy may be normal in the majority of patients with ET in the first decade after diagnosis, but subsequently survival is reduced approximately two-fold compared with the general population. Currently used treatments (such as hydroxyurea, anagrelide or interferon-alpha) can be effective in reducing platelet counts in patients with ET, but do not alter the biology or eliminate the disease. Moreover, clinical resistance or intolerance to these standard agents occurs in a proportion of patients.

About Telomerase

Telomerase is a critical and 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 that enables malignant cell growth. Telomerase is absent or expressed only transiently at low levels in most normal adult tissues. Telomerase has now also been shown to be a target for cancer stem cells. Cancer stem cells are rare populations of malignant cells with the capacity for endless self-renewal found in many types of cancer and are believed to be responsible for the growth, recurrence and metastasis of tumors. Their resistance to chemotherapy and conventional anti-cancer agents make them important targets for novel therapies.

About Imetelstat (GRN163L)

Imetelstat is a lipidated 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 xenograft models of human solid and hematological tumors, and potent activity against cancer stem cells derived from primary patient samples or cancer cell lines from multiple tumor types.

Imetelstat has been tested in six Geron-sponsored Phase 1 clinical trials at 22 U.S. medical centers treating over 180 patients examining the safety, tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in combination with other standard therapies, in patients with different hematological and solid tumors.

Two randomized Phase 2 clinical trials of imetelstat have been initiated - the first in non-small cell lung cancer and a second was recently initiated in breast cancer. A single arm Phase 2 clinical trial in multiple myeloma is open to enrollment. All the trials focus on malignancies in which cancer stem cells are believed to play an important role in disease progression and relapse after standard therapy. For further information about clinical trials using imetelstat, please visit http://clinicaltrials.gov/ct2/results?term=imetelstat.

About Geron

Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases. The company is advancing anti-cancer therapies through multiple Phase 2 clinical trials in different cancers by targeting the enzyme telomerase and with a compound designed to penetrate the blood-brain barrier (BBB). The company is developing cell therapy products from differentiated human embryonic stem cells for multiple indications, including central nervous system (CNS) disorders, heart failure, diabetes and osteoarthritis, and has initiated a Phase 1 clinical trial in spinal cord injury. 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 and oncology 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 protection 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, 2010 and annual report on Form 10-K for the year ended December 31, 2009.