Geron Corporation Reports Publication of Research Validating Telomerase Cancer Immunotherapy.

Business Editors & Health/Medical Writers

MENLO PARK, Calif.--(BUSINESS WIRE)--Sept. 12, 2002

Geron Corporation (Nasdaq:GERN) announced today that researchers at Duke University Medical Center have published data providing additional validation for the use of telomerase as an antigen for cancer immunotherapy.

The research, published in the September 1, 2002 issue of Cancer Research, shows that RNA encoding the protein component of telomerase (TERT RNA), when introduced into dendritic cells (DCs), is effective in priming telomerase-specific cytotoxic T-lymphocytes (CTLs) to target and destroy malignant tumors. The TERT RNA-modified DCs also induced a significant "helper" T cell response, which is considered a critical component for potent and durable cellular immune responses. Importantly, the in vitro studies also suggest only a "minimal risk" that telomerase immunotherapy will target the rare normal cells that transiently express telomerase.

Telomerase is abnormally activated in all human cancer types, including breast, lung, colon, prostate and hematologic tumors. That makes telomerase an attractive candidate for use in a therapeutic cancer vaccine. A Phase 1 study of Geron's ex vivo telomerase vaccine is currently underway in patients with metastatic prostate cancer at Duke University Medical Center.

The newly published research, performed by Drs. Johannes Vieweg, Zhen Su, Eli Gilboa and their colleagues at Duke, builds on the earlier work by Duke and Geron researchers, published in the September 2000 issue of Nature Medicine, which demonstrated that TERT RNA-modified DCs generated an in vivo immune response in mice that inhibited the growth of all malignant tumors tested, including breast, melanoma, and bladder cancer. As announced on August 27, 2002, Geron has received U.S. Patent No. 6,440,735 which covers the application and commercialization of this novel approach to cancer therapy.

"These experimental results are very important," commented Calvin B. Harley, Ph.D., Geron's chief scientific officer. "It is widely recognized that telomerase is universally present in cancer cells, and that an effective TERT-based cancer vaccine could be used against a broad range of tumor types. These results demonstrate again that TERT RNA should function as an effective immunogen in cancer patients, stimulating telomerase-specific immune cells that can destroy cancer cells. They also suggest that the broad immune response stimulated by TERT RNA should lead to tumor cell death without damaging the normal cells that express lower levels of telomerase."

Study Results

The published paper notes the findings of other research that, to be effective, a cancer vaccine should produce both CD8+ T cells (such as CTLs) that bind to antigenic peptides in association with MHC Class I molecules, and CD4+ "helper" T cells that bind to antigens in the context of MHC Class II molecules. The TERT-modified DC vaccine did both.

The Duke scientists transfected DCs from human cancer patients with either TERT RNA or TERT RNA modified to include the sequence encoding LAMP (lysosome-associated membrane protein), which when coupled with an antigen has been shown to boost "helper" T cell response to that antigen. They demonstrated that both forms of TERT were equally effective at stimulating a telomerase-specific CTL response. As expected, the TERT RNA modified with LAMP demonstrated enhanced enlistment of CD4 "helper" T cells, which is hypothesized to result in a more robust anti-tumor immune response. Somewhat surprisingly, the unmodified TERT RNA also showed a significant CD4 response.

The investigators used TERT RNA-transfected DCs from a cancer patient to stimulate autologous CTLs from blood cells. The resulting CTLs were very effective at recognizing and destroying a number of telomerase-positive human targets, including prostate cancer cells, colon cancer cells, liver cancer cells and breast cancer cells, while not targeting control cells.

Although these telomerase-specific CTLs effectively lysed (destroyed) DCs that had been transfected with either TERT RNA or RNA from renal cancer cells, they did not lyse DCs transfected with RNA from several normal tissues that express telomerase transiently or at low levels, including bone marrow, normal renal epithelium, normal skin, or adrenal gland. As reported in the paper, these and other results suggest that the telomerase expression levels in the few non-malignant tissues that express the enzyme are "below the necessary threshold level to be targeted by telomerase immunotherapy." The authors concluded that "vaccine-induced autoimmunity may not be a serious issue with this approach."

"These preclinical results suggest that the ex vivo telomerase vaccine should be safe," said David B. Karpf, M.D., Geron's executive medical director. "The approach described in this paper is currently being explored in the Phase 1 trial of the ex vivo telomerase vaccine underway in patients with metastatic prostate cancer at Duke University Medical Center. The paper shows the potential of this approach for treating prostate cancer and other cancers as well."

Physicians or patients who would like more information on the Duke telomerase vaccine trial may contact the clinical trial coordinator at 919/668-3457.

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 statements involving risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, regulatory approvals and clearances, dependence on collaborative partners, 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 quarterly report on Form 10-Q for the quarter ended June 30, 2002.

Additional information about the company can be obtained at http://www.geron.com.

Note: In "CD8+" and "CD4+," the "+" should read superscript.