Geron Announces Presentations Showing Progress in Development of Human Embryonic Stem Cell-Based Therapies.

Business Editors/Health/Medical Writers

International Society for Stem Cell Research

MENLO PARK, Calif.--(BUSINESS WIRE)--June 14, 2004

Geron Corporation (Nasdaq:GERN) announced today the presentation of results demonstrating significant progress in its development of cell therapies based on human embryonic stem cells (hESCs). In nine presentations at the annual meeting of the International Society for Stem Cell Research (ISSCR) in Boston, Geron and its collaborators reported advancements in the differentiation of hESCs to therapeutic cell types, the engraftment of these differentiated cells in animal models, and the production of cells for eventual clinical testing.

Islet Cells for Treatment of Diabetes

Adding to the list of prospective therapeutic cells already produced from hESCs, Geron scientists demonstrated the differentiation of hESCs into islet-like cells similar to those found in the endocrine pancreas, which could potentially be used for the treatment of Type 1 Diabetes. The differentiated cells express the key islet hormones, insulin, glucagon, and somatostatin, as detected by both gene and protein expression analysis. The insulin-producing cells also secreted C-peptide, a cleavage product generated in islet cells during the secretion of insulin. Moreover, these differentiated cells increased their production of insulin in vitro in response to increasing concentrations of glucose, much like normal adult beta cells in pancreatic islets. "Geron is now focusing its activities on improving the purity and yields of islet cells in these differentiated hESC preparations and in transplanting these cells into animal models of Type I Diabetes," stated Greg Fisk, Ph.D. of Geron, the lead author of the presentation.

Cardiomyocytes, Oligodendrocytes and Hematopoietic Cells

Geron and its collaborators also presented data showing that cells differentiated from hESCs engraft in animal models and are functional in vivo without signs of inappropriate growth.

-- In studies performed by Dr. Charles Murry at the University of

Washington in collaboration with Geron scientists, hESCs were

differentiated into cell populations enriched in

cardiomyocytes which were injected into the left ventricular

wall of rats with a normal myocardium. Using probes specific

for human cells, the cardiomyocytes were observed to engraft

and expand during the first four weeks after transplantation,

in contrast to results previously seen with primary adult

rodent cardiomyocytes. At one week and four weeks after

transplant, 24% and 14.4% of the cardiomyocytes, respectively,

expressed Ki67, a marker of proliferating cells.

Non-cardiomyocyte cells present in the original cardiomyocyte

population,such as epithelial and endodermal cells, were lost

over the same 4-week time period, so that at the end of the

period the graft consisted entirely of cardiomyocytes. The

successful engraftment of the cells, which expressed several

markers of normal cardiomyocytes, provides evidence of the

feasibility of using hESC derivatives in myocardial repair.

Geron is currently testing these cells for their effect on

cardiac function in acute and chronic infarct animal models.

-- An update of data from Dr. Hans Keirstead's laboratory at the

University of California at Irvine showed that

oligodendroglial progenitors derived from hESCs can mediate

remyelination, neural sprouting and improvements in locomotor 

activity in rats with acute spinal cord injuries.

-- Dr. Mick Bhatia of the Krembil Centre for Stem Cell Biology at

Robarts Research Institute in London, Ontario showed that

hematopoietic progenitor cells derived from hESCs could

reconstitute the hematopoietic system of immunocompromised

mice. In these studies the hematopoietic progenitor cells,

which expressed the surface antigens CD45 and CD34

characteristic of hematopoietic progenitor cells, were

transplanted directly into the bone marrow cavity in the mouse

femur. Eight weeks after transplantation, the human cells had

engrafted and formed multi-lineage components of the

hematopoietic system including cells of the myeloid, erythroid 

and lymphoid lineages.

"These studies show again that cells differentiated from hESCs can form normal human tissues in vivo," stated Jane Lebkowski, Ph.D., Geron's senior vice president of regenerative medicine. "In none of the presented studies was there evidence of uncontrolled cell growth. The studies performed in Dr. Bhatia's laboratory also support the idea that hESC-derived hematopoietic cells can establish a chimeric state in a transplant recipient that could allow acceptance of an hESC-derived therapeutic cell graft without the need for long term immunosuppression."

Derivation of New hESC Lines

Further presentations at the meeting detailed Geron's advancements in producing hESCs and their derivatives with the high standards required for therapeutic biologic products. A presentation of studies performed in collaboration with Dr. Susan Fisher of the University of California at San Francisco described two new hESC lines which were derived without exposure to mouse cells or mouse products. These new hESC lines, derived from embryos left over following fertility treatment and donated for research, were grown on human placental fibroblast feeders that were fully qualified through extensive pathogen testing, and have the same properties as the original hESC lines. Unlike the hESC lines included in the NIH Stem Cell Registry, which will be treated as "xenografts" and for which the FDA will require testing to ensure that they are free of nonhuman pathogens, these new lines have never been exposed to cells of nonhuman origin. As a result, the chance of zoonosis of murine pathogens is essentially eliminated with these new lines.

Growth of hESCs in Defined Media

In another study presented at the meeting, Geron scientists demonstrated that hESCs could be grown using serum-free medium conditioned by placental fibroblasts or other human cell strains. With adjustment of the media supplements, current and newly derived hESC lines could be grown in unconditioned serum-free medium containing only specific growth factors on purified human extracellular matrix proteins. "This defined culture system provides a much simpler system to reproducibly and more economically grow hESCs with the high quality standards required by the FDA for biologic products," stated Ram Mandalam Ph.D., Geron's senior director of product development.

"Geron is committed to developing 'off-the-shelf' hESC-based therapeutic products," stated Thomas B. Okarma Ph.D., M.D., Geron's president and chief executive officer. "The studies presented at ISSCR show that we are making substantial progress toward that goal."

Geron is a biopharmaceutical company focused on developing and commercializing therapeutic and diagnostic products for cancer based on its telomerase technology, and cell-based therapeutics using its human embryonic stem cell technology.

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 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, need for future capital 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 March 31, 2004.