Geron Provides Update on Human Embryonic Stem Cell Programs at International Society for Stem Cell Research Annual Meeting.

MENLO PARK, Calif. -- Geron Corporation (Nasdaq:GERN) announced today the presentation of studies which demonstrate significant advancement of Geron's programs to develop human embryonic stem cell (hESC) based products for drug development and therapeutic applications. In 12 presentations from Geron scientists and collaborators at the International Society for Stem Cell Research (ISSCR) annual meeting in San Francisco, progress on the derivation of new hESC lines, along with the differentiation, characterization, transplantation, and manufacture of cells relevant for drug development and therapeutic applications will be reported.

Functional Characterization of Oligodendroglial Progenitor Cells

In recent published studies, Geron's collaborator, Hans Keirstead, Ph.D. and his colleagues from the University of California, Irvine have shown that oligodendroglial progenitor cells derived from hESCs and transplanted into rodents with spinal cord injuries produced locomotor recovery and axonal remyelination. In these studies, the oligodendroglial progenitor cells enabled replacement of myelin sheaths that are lost after spinal cord injury. These myelin sheaths function to insulate neurons and promote efficient conduction of electrical pulses.

In new studies being presented by Geron scientists at the ISSCR meeting, the hESC-derived oligodendroglial progenitors are shown to produce neurotrophic factors which can induce growth of axons, the portion of the neuron that acts as a conduit for impulse conduction. This study shows that exposure of rat sensory neurons to medium conditioned by the hESC-derived oligodendroglial progenitors increased the length of both small and large neurons. "These data suggest that the oligodendroglial progenitor cells derived from human embryonic stem cells induce axonal regeneration in sensory neurons," stated R. Scott Thies, Ph.D. Geron's associate director of neurobiology and lead author on the study. "These factors may contribute to the reparative function of these cells when transplanted into the injured spinal cord."

Production of hESC Master Cell Bank

To enable production of hESC-derived therapeutic cell types for clinical use, Geron will report at the meeting that it has now produced a Master Cell Bank of the H1 hESC line. The master cell bank was produced in Geron's cGMP production facility using serum-free defined media with no direct contact with animal products. The master cell bank possesses the same properties as the originally isolated hESCs and has a normal karyotype. "This bank is undergoing extensive release and stability testing and will be used as the starting material for the production of oligodendroglial progenitor cells, Geron's lead product candidate for therapeutic testing," stated Ram Mandalam, Ph.D., Geron's executive director of product development.

Derivation of New Human Embryonic Stem Cell Lines

The first derivation of an hESC line without direct exposure to animal-sourced products will be described by the team led by Paul DeSousa at the Roslin Institute in Edinburgh, Scotland. Only reagents of recombinant or human origin were used during derivation of the RH3 hESC line. The resulting hESC line expressed markers characteristic of undifferentiated cells, yet also differentiated to form representatives of the major lineages of cells in tissues. This accomplishment builds upon recently published work by Geron scientists which demonstrated the propagation of hESC lines in a new culture system containing exclusively, a single growth factor, a human extracellular matrix protein, and a defined cGMP medium containing no animal-derived materials. Elimination of animal-derived products substantially reduces the theoretical risk of zoonosis from the hESC lines. The work was sponsored by Geron Bio-Med in the United Kingdom, a subsidiary of Geron Corporation.

Improved Production of Cardiomyocytes and Neural Progenitors

In presentations by lead scientist, Joseph Gold, Ph.D., Geron will describe an efficient method to differentiate cardiomyocytes from hESCs. This newly described method does not rely upon formation of aggregates of undifferentiated hESCs, known as "embryoid bodies" and is performed with defined growth factors in the absence of animal-derived serum. The cardiomyocytes differentiated using this method contract spontaneously and contain proteins specific to the structural, mechanical and functional properties of human cardiomyocytes.

Similar improvements in the differentiation procedures for hESC-derived neural progenitors have been reported by Wei Cui, Ph.D. from the Roslin Institute in additional studies sponsored by Geron Bio-Med. These neural progenitors led to the production of glial cells and neurons, the latter of which could be used for the treatment of neurodegenerative disorders such as multiple sclerosis and Parkinson's disease. In the current presentation, Dr. Cui will describe a new procedure to produce neural progenitors from hESCs which utilizes defined growth factors and requires neither multicellular aggregate formation nor accessory cells.

"These new processes significantly improve both the yield, scalability, and control of the production of cardiomyocytes and neural progenitor cells from human embryonic stem cells," stated Jane S. Lebkowski, Geron's senior vice president of regenerative medicine. "We are actively transplanting cardiomyocytes and neural cells derived from human embryonic stem cells into animals models of myocardial infarction and neurodegenerative disease to optimize in vivo tissue repair and restoration of function."

Production of Hepatocytes

Two presentations of Geron Bio-Med studies at the Roslin Institute will reaffirm that cells with properties of hepatocytes can be derived from hESCs. In the studies to be reported by Dr. Cui and her colleagues, hepatocyte-like cells (HLCs) were derived from hESCs using serum-free medium without the use of multicellular aggregates. The HLCs expressed several genes characteristic of hepatocytes and showed functional clearing of indocyanine green (ICG), a compound used to evaluate liver function. Further studies showed that the starting hESCs could be genetically modified with reporter constructs which were activated when the cells reached a specific stage of hepatocyte differentiation. "These studies confirm that cells having the functionality of hepatocytes can be derived from human embryonic stem cells," stated Dr. Mandalam. "We are utilizing the developments reported here to build cell-based tools for drug discovery and development applications."

Production of Insulin Secreting Clusters

In another report, Dr. Anish Majumdar, Geron's senior director of immunology, will describe the differentiation of hESCs to insulin secreting aggregates for the potential use in the treatment of diabetes. Cells in these clusters express both insulin and glucagon, characteristic hormones found in pancreatic islets, and produce more insulin in response to increased concentrations of glucose. Study animals survived longer and human insulin and glucagon producing cells were found in the grafts. Moreover, human insulin, as measured by human c-peptide, was also found in the sera of these animals upon administration of high glucose. "This work represents a major step forward in the development of alternative sources of cells for the treatment of diabetes," stated Dr. Majumdar. "Our current efforts will focus on improving both the yields and purities of these clusters to normalize glucose levels in these animals." This work was performed in collaboration with Dr. Ray Rajotte and Dr. Greg Korbutt at the University of Alberta, Edmonton, Canada.

"The work described here represents a large directed effort by Geron and our collaborators to develop human embryonic stem cell technology to a stage where high quality cell types can be economically produced for both drug discovery and therapeutic use," stated Thomas B. Okarma Ph.D., M.D., Geron's president and chief executive officer. "The progress reported here illustrates the versatility of the technology platform and Geron's commitment to actualize its development into multiple products for clinical testing."

Geron is a biopharmaceutical company developing and commercializing three groups of products: i) therapeutic products for oncology that target telomerase; ii) pharmaceuticals that activate telomerase in tissues impacted by senescence, injury or degenerative disease; and iii) cell-based therapies derived from its human embryonic stem cell platform for applications in multiple chronic diseases.

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, dependence on 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 March 31, 2005.