Geron Reports Advances in Its Human Embryonic Stem Cell Programs.

Business Editors/Health/Medical Writers

BIOWIRE2K

MENLO PARK, Calif.--(BUSINESS WIRE)--April 3, 2003

Presentations Demonstrate Engraftment of Dopaminergic 

Neurons in a Model of Parkinson's Disease as Well as

Characterization and Long-Term Stability Data

Geron Corporation (Nasdaq:GERN) reported on multiple advances in its human embryonic stem cell (hESC) programs at the 2003 Keystone Symposium entitled "From Stem Cells to Therapy" held in Steamboat Springs, Colorado. Geron scientists presented data showing engraftment of hESC-derived dopaminergic neurons transplanted into the brains of a rat model of Parkinson's disease and the production of pure populations of hESC-derived cardiomyocytes. Also, in four separate presentations, Geron scientists described studies that defined the properties and biological stability of hESCs over long-term culture.

Neurons for Parkinson's Disease

Geron scientists demonstrated that hESCs can be differentiated into dopaminergic neurons, the therapeutic cell type for the potential treatment of Parkinson's disease. Using protocols developed at Geron, hESCs were differentiated first into neural progenitors and then into neurons expressing thyrosine hydroxylase - the rate-limiting enzyme for the production of dopamine. The differentiated cells formed robust, viable dopaminergic neural grafts after transplantation into the brains of an established rat model of Parkinson's disease.

"These results demonstrate that hESCs can be differentiated into target cells which have been difficult to scalably produce by other means," said Jane S. Lebkowski, Ph.D., Geron's vice president of regenerative medicine. "The survival of the human dopaminergic neurons in the brains of the rat model of Parkinson's disease shows that these cells can engraft in the adult brain micro-environment."

Cardiomyocytes for Heart Disease

Geron scientists presented new data showing that cardiomyocytes (heart muscle cells) can be derived from hESCs and enriched by a serum-free culture formulation that prevents the growth of unwanted cell populations. These hESC-derived cardiomyocytes displayed appropriate cardiomyocyte molecular markers and responded normally to cardiac drugs used clinically to treat heart disease. These results are important because they predict integration of the hESC-derived cardiomyocytes into damaged heart tissue when transplanted. Furthermore, the results predict that such newly regenerated heart muscle tissue will respond normally to cardioactive drugs.

hESC Stability

Recent Geron data demonstrate that the unique properties of undifferentiated hESCs are fully retained even after long-term continuous culture. Three different hESC lines were cultured long-term using feeder-free conditions (developed by Geron) and monitored for eight cell surface markers. All eight markers were continually expressed for over 70 culture passages (more than one year in continuous culture). This remarkable cellular stability was also reflected by the constant expression during the culture period of telomerase activity and multiple specific transcription factors known to regulate gene expression. Microarray analysis further demonstrated this stability: only 23 of 2,798 tested genes exhibited more than a three-fold change in expression after hESCs were cultured for 12 to 27 weeks. Approximately 80% of individual hESCs cultures maintained their normal complement of chromosomes, and those that developed karyotypic abnormalities could be identified, discarded and replenished from frozen hESC banks. Most importantly, the hESCs remained pluripotent -- capable of differentiating into cells of all major lineages of the body -- even after nearly one and one half years in continuous culture.

"These data show that hESCs have very stable properties when scalably propagated in feeder-free culture," stated Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "This important and unique feature of hESCs validates our product model for commercialization of hESC-based therapies. The therapeutic cells can be manufactured in large, multi-dose lots, shipped and stored frozen for 'off the shelf' use by healthcare providers."

hESC Qualification

Finally, Geron presented data on the qualification and culture of hESCs for human therapeutic use. Qualification of hESCs establishes safety and consistency criteria necessary for use in human testing.

Four hESC lines, originally derived at the University of Wisconsin-Madison, were tested for sterility and various human pathogens including HIV 1 & 2, human T-cell leukemia viruses 1 & 2, human cytomegalovirus, and hepatitis B & C viruses. All four hESC lines showed no evidence of infection with any of these human pathogens. In addition, the H1 cell line was extensively tested for infection by pathogens that could have contaminated the reagents used to derive or culture that particular hESC line. No evidence was found for H1 line infection by viruses of human, porcine, murine, or bovine origin. Other results presented by Geron at the meeting demonstrated that defined and highly purified reagents can be used to culture hESCs, enabling the development of manufacturing specifications for hESC-based products that will meet the high standards required for human therapeutic use.

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for applications in oncology and regenerative medicine, and research tools for drug discovery. Geron's product development programs are based upon three patented core technologies: telomerase, human embryonic stem cells and nuclear transfer.

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 future applications of Geron Corporation's technology constitute forward-looking statements involving risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, need for additional capital, need for regulatory approvals or clearances, and the 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 annual report on Form 10-K for the year ended on December 31, 2002.