(Copyright (c) 2002, Business Wire)
MENLO PARK, Calif.--(BUSINESS WIRE)--Dec. 11, 2002--Geron Corporation (Nasdaq:GERN) reported positive data from its telomerase-based cancer treatment programs at three scientific meetings in early December. The key developments presented at the meetings show progress on the development of GRN163, a potent and specific telomerase inhibitor, and on Geron's in vivo therapeutic vaccine and oncolytic virus. The data was presented at the University of California-San Francisco (UCSF) "War on Cancer" symposium in San Francisco, CA, December 7; the American Society of Hematology (ASH) 44th Annual Meeting in Philadelphia, PA, December 9; and the American Association for Cancer Research (AACR) Special Conference in Cancer Research in San Francisco, CA, December 10.
Geron also reported separately on preliminary observations from the Phase 1 clinical trial of an ex vivo telomerase-based cancer vaccine at Duke University Medical Center.
Geron's telomerase inhibitor, GRN163, continues to show efficacy without toxicity in multiple cancer animal models.
New work by Dennis Deen, Ph.D., Professor of Neurological Surgery at UCSF, and colleagues at the UCSF Brain Tumor Research Center presented at the UCSF and AACR meetings showed that GRN163 significantly inhibited tumor growth and increased survival in an intracranial glioblastoma rat model. In this study, GRN163 or a control solution was delivered to the human tumor cells shortly after orthotopic implantation (i.e., implantation in the brain rather than the flank) over a 7- or 14-day period. All of the control treated rats developed symptoms of excessive tumor growth by day 36 and required sacrifice by day 43, whereas 70% of the GRN163 treated rats were still alive, active, in good health and tumor-free on day 116. No side effects were noted following intracranial delivery of GRN163.
The efficacy and apparent safety of GRN163 was further demonstrated in new lymphoma and myeloma studies from the laboratory of Malcolm A.S. Moore, M.D., at Memorial Sloan Kettering Cancer Center (MSKCC), reported at the ASH and AACR meetings. GRN163 injected either intra-tumorally or intraperitoneally into immune-compromised mice with human subcutaneous tumors was as effective as or more effective than highly toxic cytotoxic agents, such as methotrexate and doxorubicin currently used as therapy, in slowing tumor growth by inducing tumor cell death. In contrast to the cytotoxic agents, each of which was administered at its maximum tolerated dose, no adverse side effects of GRN163 were noted.
A more formal analysis of the safety and stability of GRN163 was presented for the first time at the AACR meeting by David B. Karpf, M.D., Geron's executive medical director. Dr. Karpf reviewed the lack of non-specific toxicity for GRN163 observed during the treatment of 11 separate human tumor xenograft models in rodents following intra-tumoral, intracranial, intraperitoneal or intravenous injection. He also presented new data on ascending-dose acute toxicity studies and a 4-week chronic-dose GLP toxicity study in rats treated with intracranial and intravenous doses. These formal studies indicated no gross toxicity at concentrations expected to be efficacious against tumors in humans. In stability studies, Dr. Karpf reported that in a 24-week accelerated stability study of GRN163 there was good physical, chemical and biochemical stability following storage for up to 12 weeks at temperatures ranging from 4(degree) to 37(degree) C. He indicated these data will be used to support an IND filing with the FDA for the use of GRN163 in the treatment of glioblastoma.
Additional data also presented by Geron scientists demonstrated that GRN163 acts by competing in a highly potent and specific manner with binding of the natural telomere substrate to telomerase. This enzymatic-inhibition mechanism is totally different from antisense oligonucleotide mechanisms, and should confer an additional level of safety for the use of GRN163.
"These study results continue the progress of GRN163 towards the clinic," said Thomas B. Okarma, Ph.D., M.D., Geron's president and chief executive officer. "The efficacy of GRN163 in animal models of brain cancer appears unaccompanied by toxicity and confers significant survival benefit to the treated animals. In lymphoma and myeloma models, GRN163 was as effective or better than currently utilized highly toxic chemotherapeutic agents, again showing efficacy without apparent toxicity. GLP safety studies have now validated the safety profile of GRN163 in chronic dosing regimens. The observed safety profile of GRN163 is supported by the work showing that its mechanism of action is by inhibiting telomerase at the active site of the enzyme, not by a less specific antisense mechanism. These reports add to the growing body of evidence that the inhibition of telomerase by GRN163 will result in a non-toxic and efficacious new treatment modality for a broad range of human cancers."
Direct in vivo vaccination with telomerase slows tumor growth in animals, and human ex vivo trial progresses.
Choy-Pik Chiu, Ph.D., Geron's senior director of cell biology and pharmacology, presented data illustrating the potential of in vivo telomerase vaccines against human tumors at the AACR meeting. The antigen for this therapeutic cancer vaccine is the key telomerase protein component, hTERT. Geron had previously shown in collaboration with researchers at Duke University that RNA encoding hTERT could be used to prime antigen presenting cells (DCs) ex vivo, and that these cells in turn could stimulate a potent, telomerase-specific cytotoxic T-lymphocyte (CTL) response. That work led to a Phase 1 clinical study of the ex vivo therapeutic vaccine approach in prostate cancer which is currently ongoing under the direction of Johannes Vieweg, M.D., at Duke University.
In the current studies, Geron and collaborators examined the potential of direct in vivo vaccination using hTERT plasmid DNA or an adenovirus vector carrying the hTERT gene. The investigators found that in vivo vaccination elicited a telomerase-specific CTL response which correlated with increased levels of interferon-positive T cells in the spleens of the vaccinated mice, and a slowing of melanoma tumor growth compared to unvaccinated mice or mice vaccinated with the adenovirus vector lacking hTERT DNA.
"The data showing that direct immunization with telomerase can illicit a strong immune response that slows tumor growth is very exciting," said Dr. Karpf. "Our ongoing Phase 1 trial of a telomerase-based cancer vaccine with Dr. Vieweg at Duke is progressing very well. This trial in patients with metastatic prostate cancer uses an ex vivo immunization strategy, where the patient's dendritic cells are collected and transfected with the telomerase antigen, and then used to vaccinate the patient. We have seen a significant and substantial induction of telomerase-specific CTLs and T-helper cells in all patients in the trial, and thus far no safety problems have been noted even after 6 vaccinations. The vaccine appears to be very well tolerated. An analysis of the clinical response, including PSA, is currently under review and should be reported in the near future. The data reported at the AACR meeting suggests that direct vaccination with telomerase -- which is even easier to administer -- may also be effective."
Telomerase promoter-driven oncolytic virus induced tumor regression correlates with reduced markers of tumor growth.
Also at the AACR meeting, John Irving, Ph.D., Geron's director of molecular biology, presented new data on oncolytic viruses driven by the telomerase promoter. Dr. Irving reviewed earlier data showing that the hTERT promoter, placed ahead of the E1a gene in the adenovirus genome, causes the virus to replicate and kill telomerase-positive tumor cells, but not telomerase-negative normal cells. This conditionally lethal adenovirus selectively killed 12 different tumor lines in culture including prostate, liver, lung, pancreatic, colorectal, breast and ovarian cancers, while not impacting normal cells.
In the studies presented by Dr. Irving, reduction in the surrogate markers of tumor growth, AFP (for liver tumors) and PSA (for prostate tumors), strongly correlated with the regression and elimination of these tumors in the mice treated with the conditional oncolytic virus.
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 September 30, 2002.