GERON INITIATES CLINICAL TRIAL OF TELOMERASE CANCER VACCINE IN PATIENTS WITH ACUTE MYELOGENOUS LEUKEMIA
Study Builds on Positive Data Previously Generated in Metastatic Prostate Cancer Patients
Protocol Under Geron’s IND is First to Employ Prime-Boost Regimen to Extend Duration of Telomerase Immunity
MENLO PARK, Calif., July 11, 2007 – Geron Corporation (Nasdaq: GERN) announced today the initiation of a clinical trial of its telomerase cancer vaccine, GRNVAC1, in patients with acute myelogenous leukemia (AML) in complete remission.
The vaccine is produced from a patient’s blood using a unique process that generates highly activated dendritic cells (DC) that contain RNA coding for the protein component of telomerase. This new approach to cancer immunotherapy has been clinically shown to safely generate high levels of cytotoxic lymphocytes that kill telomerase positive cancer cells after as few as six weekly injections into the skin.
The primary objective of this new Phase I/II study is to evaluate the safety and feasibility of a prime-boost vaccination regimen that extends the duration of telomerase immunity. Secondary objectives are to evaluate the immune response to GRNVAC1 and to explore the effects of vaccination on minimal residual disease and relapse rates. A total of six sites in the United States are planned to participate in this multi-center trial.
“AML is an appropriate indication for investigating a cancer immunotherapy that targets telomerase because of high telomerase expression in AML cells, the great unmet clinical need, especially in older patients who frequently relapse after chemotherapy, and the low tumor burden after consolidation chemotherapy,” said John DiPersio, M.D., Ph.D., chief of the Division of Oncology and deputy director of the Siteman Cancer Center at Washington University School of Medicine, St. Louis, who is the study’s lead investigator. “Patients at high risk of relapse are in need of additional therapies that are well tolerated. This study is an important step in understanding the role that immunotherapy directed against telomerase might play in cancer treatment.”
Alan Colowick, M.D., Geron’s president, oncology, said, “We are excited to begin this multi-center study in AML patients who have a high risk for relapse. A great deal of work has enabled us to apply and extend the initial clinical findings for GRNVAC1 in prostate cancer to AML patients. We have scaled and modified the manufacturing of the vaccine to enable a multi-site design with central manufacturing. In addition, we have optimized the prime-boost regimen to enhance the duration of immunity to telomerase in previous clinical studies, and we have demonstrated successful ex vivo DC activation and loading with telomerase antigen in samples taken from patients with AML. We look forward to investigating the tolerability and potential clinical utility of GRNVAC1 in patients with AML.”
AML is the most common form of acute leukemia in adults. Although present in all age groups, AML is most often diagnosed in adults over the age of 60. The American Cancer Society estimates that there were more than 11,900 new cases of AML in 2006 in the United States. With current standard chemotherapy regimens, estimates of five-year survival are 25% to 30% for adults younger than 60. Fewer than 10% of older patients with AML attain long-term survival.
GRNVAC1 is an immunotherapeutic product made from autologous dendritic cells transfected with mRNA encoding telomerase protein and the lysosomal targeting signal, lysosome-associated membrane protein (LAMP). This autologous product is designed to induce cellular immune responses to telomerase, an antigen highly expressed in the nucleus of cancer cells and found on their surface but not expressed in most normal cells. Unlike other tumor targets, hTERT, the protein component of telomerase, is essential for maintaining the proliferative capacity and survival of the majority of tumor cell types.
Researchers at Duke University, in collaboration with Geron, have conducted both preclinical and clinical studies using a vaccine product comparable to GRNVAC1.
In Vitro Studies
In vitro studies have demonstrated that autologous dendritic cells transfected with hTERT mRNA stimulate hTERT-specific cytotoxic T-cells (CTL) from the peripheral blood of patients with cancer. These studies have also shown that DC transfected with hTERT mRNA containing the sequence for LAMP may further enhance the efficacy of this approach by optimally stimulating CD8+ and CD4+ T-cell responses (Nair et al, Nat. Med. 2000;6(9):1011-1017) (Su et al, Cancer Res. 2002;62(17):5041-5048).
Clinical Studies
The results of the first study testing hTERT-LAMP mRNA-transfected DC in metastatic prostate cancer patients were published in the Journal of Immunology (Su et al, J. Immunol. 2005;174(6):3798-807). In this study, 20 patients were enrolled and randomized to receive either hTERT mRNA-transfected DC (11 patients) or hTERT-LAMP mRNA-transfected DC (9 patients). Treatment was well tolerated. In 19 of 20 patients, expansion of hTERT-specific T-cells in the peripheral blood of patients was measured after vaccination, with 0.9% to 1.8% of circulating T-cells exhibiting anti-telomerase activity. Patients immunized with the chimeric hTERT-LAMP vaccine exhibited slightly stronger T-cell, and particularly CD4+ T-cell, immune responses to telomerase compared to patients immunized with the unmodified hTERT mRNA-transfected DC vaccine. Moreover, hTERT-specific T-cell killing was enhanced in subjects receiving hTERT-LAMP, suggesting that the improved CD4+ response can augment a CTL response.
Three other Phase I optimization studies of hTERT-LAMP mRNA-transfected DC were conducted at Duke University in patients with metastatic prostate cancer, renal cell carcinoma and hematologic malignancies. Approximately 45 cancer subjects have been treated to date under the Duke protocols. Vaccine-related toxicities were primarily Grade 1-2. Overall, the adverse event pattern in these studies included non-specific, disease-related effects and skin reactions consistent with delayed type hypersensitivity (DTH).
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 www.geron.com.
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 GRNVAC1 and Geron’s telomerase 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
