Research documents scalable production, survival following engraftment and positive impact on cardiac function in infarcted rats for geron's human embryonic stem cell-based therapeutic for heart failure

Company's Second Cell Type for Clinical Development - Cardiomyocytes for Treatment of Heart Failure - is Subject of Feature Presentation at ISSCR Annual Meeting

MENLO PARK, CA, USA | June 19, 2007 |
Geron Corporation (Nasdaq: GERN) today reported that research documenting the scalable production, survival following engraftment and positive impact on cardiac function in infarcted rats was presented today for GRNCM1, the company's human embryonic stem cell (hESC)-based therapeutic for heart failure, at the International Society for Stem Cell Research (ISSCR) Annual Meeting in Cairns, Australia.

The presentation was one of seven involving Geron scientists and collaborators that documented the company's progress in developing multiple therapeutic products from its hESC platform. Other presentations focused on the gene expression and neurotrophic protein secretion patterns of hESC-derived oligodendroglial progenitor cells for acute spinal cord injury, the functional characterization of hESC-derived islets for diabetes, and hESC-derived chondrocytes for arthritis and other orthopedic applications.

"We have made significant progress in the development of hESC-based therapeutics," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "GRNCM1 will be the second product we intend to develop clinically. Large animal proof of concept studies are imminent. With our most advanced cell type, GRNOPC1 for acute spinal cord injury, we remain on track for the filing of an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration later this year pending the outcome of our ongoing safety studies. Lastly, we recently published our scalable method to produce GRNIC1, hESC-derived islets for diabetes. We presented data at the ISSCR Annual Meeting on a procedure to enhance the insulin-secreting potency of the cells that are currently in animal studies in our collaborator's laboratories at the University of Alberta. Geron remains at the forefront of taking embryonic stem cell-derived products into clinical development."

Cardiomyocytes for the Treatment of Heart Failure
The results of work performed in collaboration with Drs. Charles Murry and Michael Laflamme at the University of Washington were presented by Dr. Joseph Gold, Geron's director of stem cell biology. The presentation described efficient differentiation of cardiomyocytes from hESCs and their effectiveness in preventing the onset of heart failure in rodent infarct models. In the differentiation procedure, cardiomyocytes were generated using non-conditioned, serum-free media and a directed differentiation protocol that produces cells with the phenotypic, electrophysiological and contractile properties of human immature cardiomyocytes. The new protocol produces cardiomyocytes with high efficiency, yielding 10-100 fold more cardiomyocytes per undifferentiated hESC than conventional "embryoid body-based" protocols. The differentiation protocol produced cardiomyocyte populations of up to 70% purity at scales sufficient to enable both preclinical and early clinical development. Moreover, the final cardiomyocyte product could be cryopreserved and thawed with high viability.

When transplanted together with survival enhancement factors directly into the myocardial infarct zone of rats, the GRNCM1 cells survived for at least four weeks and formed grafts expressing key markers of human cardiomyocytes, including beta myosin heavy chain. Echocardiographic and magnetic resonance imaging analysis showed that the animals transplanted with GRNCM1 cells had improved (smaller) end-left ventricular systolic and diastolic diameters, increased fractional shortening, improved infarct wall thickening and increased ejection fraction compared to control animals injected with factors alone or controls injected with non-cardiac cells derived from hESCs. These data show that engrafted GRNCM1 cells significantly improved heart function after myocardial infarction.

"This is animal proof of concept for our second therapeutic cell type," said Jane S. Lebkowski, Ph.D., Geron's senior vice president of regenerative medicine. "The fact that functional cardiomyocytes can be generated at a large scale and successfully cryopreserved provides another validation of our product-based business model. The model is for Geron to provide cell-based therapies as off-the-shelf products for the treatment of chronic degenerative diseases."

Oligodendroglial Progenitors for the Treatment of Spinal Cord Injury
The properties and functions of GRNOPC1, Geron's lead hESC product for the treatment of spinal cord injury, were discussed in four presentations at the ISSCR Annual Meeting. GRNOPC1 is a hESC-derived cell population containing oligodendroglial progenitor cells. Oligodendroglial cells are responsible for myelinating, or insulating, neurons, a critical function allowing unimpeded nerve impulse conduction.

Dr. Hans Keirstead with the University of California, Irvine, presented data showing that demyelination is a common finding in animal models of spinal cord contusion injury, the most common type of spinal cord injury occurring in humans, and that progressive demyelination continues even months after injury. Dr. Keirstead further described the differentiation of GRNOPC1 from hESCs and demonstrated that upon transplantation into rats with acute spinal cord injuries, GRNOPC1 stimulated extensive remyelination of neurons, improved neuronal survival and increased neurite outgrowth in damaged areas of the cord. This resulted in improved hind-limb locomotor activity.

Geron scientists presented additional studies showing that the production process for GRNOPC1 recapitulated the stages of oligodendroglial progenitor growth during human spinal cord development. By monitoring expression of specific genes during the production of GRNOPC1, researchers were able to document the emergence and specific identity of spinal cord oligodendroglial progenitors. Moreover, studies showed that GRNOPC1 secretes specific neurotrophic factors, including midkine, hepatocyte growth factor, activin A, transforming growth factor beta and brain-derived neurotrophic factor. These factors induce growth of neurons and are likely to contribute to the therapeutic effects of GRNOPC1 after transplantation in the injured spinal cord.

"These studies document some of the multiple mechanisms by which GRNOPC1 may potentiate spinal cord repair," said R. Scott Thies, Ph.D., Geron's director of cell technologies. "Furthermore the results provide specific markers to monitor and control the quality of the production of GRNOPC1, a critical element in the development of therapeutic cell products."

Islet Cells for the Treatment of Diabetes
In another presentation, Geron scientists described procedures to produce islet-like clusters from hESCs, a potential treatment for diabetes. In the work recently published online in Stem Cells Express and in an upcoming issue of Stem Cells, Geron scientists described a multistage protocol to differentiate hESCs into key cell types of the pancreas, including ductal, exocrine and endocrine cells. The endocrine cells appeared as bud-like clusters resembling the islets of Langerhans and included the major islet cell types that produce the hormones insulin, glucagon and somatostatin. Upon exposure to increased concentrations of glucose, the islet-like clusters secreted insulin. When transplanted into diabetic mice, the hESC-derived pancreatic cell population prolonged animal survival and produced human c-peptide in the serum of transplanted animals upon challenge with glucose. Neither prolonged survival nor C-peptide production was observed when the diabetic animals were transplanted with either human foreskin fibroblasts or undifferentiated hESCs. In new updates at the ISSCR Annual Meeting, procedures were described to physically enrich the bud-like clusters to produce cell populations containing as high as 10% insulin positive cells.

¡§We are currently focusing our efforts on improving both the yields and purities of these islet-like clusters to normalize glucose levels in animal models of diabetes,¡¨ said Anish Majumdar, Ph.D., Geron¡¦s senior director of cell therapy research. This work was performed in collaboration with Dr. Ray Rajotte and Dr. Greg Korbutt at the University of Alberta.

Chondrocytes for Orthopedic Applications
Finally, Geron collaborators at the University of Edinburgh reported the differentiation of chondrocytes from hESCs for use in the repair of diseased or injured articular cartilage. In these studies presented by Dr. Brendon Noble of the University of Edinburgh, hESCs were differentiated into chondrocytes and expressed type II collagen, one of the hallmarks of precursor cells that form cartilage. When the chondrocytes were seeded onto a scaffold matrix and implanted into osteochondral defects in the rat knee, evidence of human cell survival was noted up to 21 days. Animals receiving the hESC-derived chondrocytes showed formation of cartilaginous tissue near the subchondral bone, while control, untransplanted animals showed less cartilaginous tissue.

"These preliminary studies indicate that the implanted hESC-derived chondrocytes can function to produce cartilage," said Dr. Lebkowski. "We now have a renewable source of chondrocytes to enable the development of robust methods to produce articular cartilage of sufficient quality to repair cartilage defects, a major component of multiple forms of arthritis."

Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure, diabetes and HIV/AIDS. The company is advancing an anti-cancer 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 its spinal cord injury treatment anticipated to be the first product to enter clinical development. For more information, visit

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 human embryonic stem cell 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 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, 2007.


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