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Data Show Geron's Telomerase Inhibitor Cancer Drug is Active Against Cancer Stem Cells From Multiple Myeloma Patients.


Other Presentation at ASH Annual Meeting Demonstrates Drug's Excellent Tolerability and Predictable Pharmacokinetics in Ongoing Clinical Trials

MENLO PARK, Calif. -- Geron Corporation (Nasdaq:GERN v. t. 1. To grin or yawn. ) today announced that its telomerase telomerase /telo·mer·ase/ (te-lo´mer-as) a DNA polymerase involved in the formation of telomeres and the maintenance of telomere sequences during replication.

te·lom·er·ase
n.
 inhibitor cancer drug, GRN GRN Green
GRN Green (Political) Party
GRN Global Recycling Network
GRN Gulf Restoration Network (New Orleans, LA)
GRN Goods Received Note
GRN Global Reference Network (GPS) 
163L, is active against cancer stem cells from multiple myeloma multiple myeloma

A malignant proliferation of abnormal plasma cells that populate the marrow-containing bones of the body. The affected plasma cells produce myeloma protein, a monoclonal antibody that replaces normal antibodies in the blood, thereby increasing susceptibility
 patients, according to data presented at the American Society of Hematology 48th Annual Meeting in Orlando, Fla.

Resulting from a collaboration between Geron and investigators with the department of oncology at the Johns Hopkins University School of Medicine The Johns Hopkins University School of Medicine, located in Baltimore, Maryland, USA, is a highly regarded medical school and biomedical research institute in the United States. , the data demonstrated activity in a model derived from multiple cell lines as well as cells from fresh specimens taken from the bone marrow of multiple myeloma patients. Cancer stem cells, which are often resistant to standard treatments, are believed to be critically important to cancer's ability to replicate and spread throughout the body. Johns Hopkins' William Matusi, M.D., was the lead author of the study, which Richard J. Jones, M.D., presented.

"I believe the activity of GRN163L against cancer stem cells in multiple myeloma is very intriguing," said Dr. Jones, who is the director of the bone marrow transplant bone marrow transplant: see bone marrow.  program and co-director of hematologic malignancies at Johns Hopkins' Sidney Kimmel Comprehensive Cancer Center. "Our data suggest that cancer stem cells, which are resistant to most agents currently in use in multiple myeloma, are the cause of disease relapse in many patients. Therefore, the ability to target cancer stem cells holds considerable clinical promise."

Specifically, the data demonstrated that GRN163L inhibited telomerase activity and eliminated the colony forming potential of cancer stem cells from three independent multiple myeloma cell lines. GRN163L also inhibited the clonogenic potential of more mature myeloma myeloma /my·elo·ma/ (mi?e-lo´mah) a tumor composed of cells of the type normally found in the bone marrow.

giant cell myeloma  see under tumor (1).
 cells. In separate experiments using primary clinical samples, cancer stem cells isolated from the bone marrow of three patients with multiple myeloma and then exposed to GRN163L also had a marked reduction in clonogenic growth. Previous data using these models for agents commonly used in the treatment of multiple myeloma did not demonstrate similar effects on myeloma cancer stem cells.

In another presentation (Tressler, et al., Abstract #2595), Geron showed that GRN163L continues to demonstrate excellent tolerability and predictable pharmacokinetics in a Phase I/II trial in patients with chronic lymphocytic leukemia chronic lymphocytic leukemia
n. Abbr. CLL
Lymphocytic leukemia occurring mainly in older adults, characterized by slow onset and gradual progression of symptoms.
 (CLL CLL
abbr.
chronic lymphocytic leukemia


CLL,
n.pr See leukemia, chronic lymphocytic.

CLL 1. Chronic lymphocytic leukemia 2. Cholesterol-lowering lipid
) and a Phase I trial in patients with solid tumors.

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 three dose cohorts of both trials were well tolerated with no dose-limiting toxicities (DLTs). Pharmacokinetic analysis demonstrated dose-proportionality over the range of doses tested. Peak plasma concentrations achieved were 3 mcg/ml and 10 mcg/ml in these initial cohorts of the CLL and solid tumor studies, respectively. Pre-clinically, telomerase activity within cancer cells can typically be inhibited by concentrations of 5 to 10 mcg/ml. These data support escalation to higher doses which are predicted to result in sustained exposure levels that fall within the therapeutic range.

"The early clinical data continue to be encouraging," said Alan Colowick, M.D., Geron's president, oncology. "The excellent tolerability and pharmacokinetics observed in the early cohorts enable us to advance to the therapeutic dose cohorts. Additionally, based upon the data generated from our collaboration with the group from Johns Hopkins demonstrating important effects of GRN163L against myeloma cancer stem cells, we plan to initiate a clinical trial in patients with multiple myeloma in the first half of 2007."

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, typically at low levels, in most normal adult tissues.

GRN163L is a short chain oligonucleotide that has high resistance to nuclease nuclease /nu·cle·ase/ (noo´kle-as) any of a group of enzymes that split nucleic acids into nucleotides and other products.

nu·cle·ase
n.
 digestion in blood and tissues and very high affinity and specificity for telomerase. The molecule has superior cellular and tissue penetration properties due to its proprietary chemistry and its 5' lipid chain. The drug is a specific inhibitor of telomerase enzymatic activity. The mechanism of action involves direct binding to the template region of telomerase and is distinct from that of other oligonucleotide drugs with "antisense antisense, DNA or RNA manipulated in a laboratory so that its components (nucleotides) form a complementary copy of normal, or "sense," messenger RNA (mRNA; see nucleic acid). " activity.

GRN163L has been demonstrated to have anti-tumor effects in a wide range of hematological hematological, hematologic

pertaining to or emanating from blood cells.


hematological tests
total and differential white cell counts, hematocrit estimation, erythrocyte count.
 and solid tumor models and appears to be unique in its observed effects on tumor stem cells stem cells, unspecialized human or animal cells that can produce mature specialized body cells and at the same time replicate themselves. Embryonic stem cells are derived from a blastocyst (the blastula typical of placental mammals; see embryo), which is very young : the rare, chemotherapy-resistant cancer cells that cause cancer recurrence.

Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and degenerative diseases, including spinal cord injury Spinal Cord Injury Definition

Spinal cord injury is damage to the spinal cord that causes loss of sensation and motor control.
Description

Approximately 10,000 new spinal cord injuries (SCIs) occur each year in the United States.
, heart failure, diabetes and HIV/AIDS HIV/AIDS Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome . The company is advancing an anticancer 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 a product to treat spinal cord injury expected to enter clinical trials in late 2007. 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 The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and  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.
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Date:Dec 11, 2006
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