Boston, MA and Cambridge, MA, May 11, 2000 - Dana-Farber Cancer Institute (DFCI), the National Cancer Institute (NCI) and Therion Biologics today reported in Clinical Cancer Research promising early clinical results for PROSTVAC, Therion's lead therapeutic vaccine for prostate cancer. In a Phase I study, 33 men with advanced cancer of the prostate were treated with three consecutive monthly doses of PROSTVAC. Data from the trial indicated that vaccination with PROSTVAC was well-tolerated in all patients. In addition, stabilization of PSA levels was observed for at least 6 months in 14 of 33 patients, and 9 patients remained stable for 11 to 25 months. Therion's PROSTVAC vaccine is comprised of a recombinant vaccinia virus, commonly known for its use in the smallpox vaccine, engineered to express human prostate specific antigen (PSA). The vaccine was designed and developed as part of a Collaborative Research and Development Agreement (CRADA) between The Laboratory of Tumor Immunology and Biology (Dr. Jeffrey Schlom, Chief) of the NCI and Therion.

"Although prostate cancer is currently the second leading cause of death in American men, there remains a lack of effective treatments for recurrent disease," said Joseph Paul Eder, Jr., M.D., of the Dana-Farber Cancer Institute and principal investigator for the study. "Patients with recurrent prostate cancer and rising PSA levels are currently treated by hormonal therapies associated with significant side effects or by a 'watch-and-wait' protocol. By incorporating the PSA antigen, which is expressed only by prostate cells, PROSTVAC is designed to stimulate the body's immune response against tumor cells. For patients with recurrent prostate cancer, PROSTVAC may offer a safe, alternative method to stabilize disease progression."

Study Design

Patients enrolled in the Phase I study were previously diagnosed with rising PSA levels after undergoing radical prostatectomy, radiation therapy or both for treatment of prostate cancer. Patients were divided into 3 cohorts and received 3 escalating dose levels of PROSTVAC. Ten of 21 patients who received the highest dose level of PROSTVAC also received granulocyte-macrophage colony-stimulating factor (GM-CSF) as an immunostimulatory adjuvant. Cells from 7 of these patients were assayed for development of a PSA-specific cellular immune response.

Trial Results

Results of the study showed that no vaccine-related toxicity was observed in any patient beyond a low-grade reaction at the site of inoculation. In the 10 patients treated with GM-CSF, only one patient developed fever and rapid heartbeat after the first dose of GM-CSF, but tolerated subsequent GM-CSF doses. PSA levels remained stable for at least 6 months in 14 of 33 men treated with PROSTVAC, with or without the addition of GM-CSF. In addition, 9 patients remained stable for 11 to 25 months. Of the 7 patients evaluated for PSA-specific immune responses, 5 demonstrated at least a two-fold increase of precursor T-cells specific for PSA after vaccination.

The stabilization of PSA levels in these patients correlated with the absence of any other indications of disease progression. However, the eventual rise in PSA levels over time suggests that boosting at periodic intervals may be required for sustained stabilization. Subsequent protocols may benefit by utilizing a diversified "prime-boost" protocol, which refers to an immune-conditioning regimen in which a PSA-expressing pox virus vector is first used to prime the immune system and a different, immunologically unrelated pox virus vector incorporating the same PSA antigen is subsequently administered to boost the immune response.

"This preliminary trial showed no significant disease progression for at least six months in over 40% of study subjects, demonstrating for the first time in human cancer patients that a recombinant vector expressing PSA may be useful for developing a cell-mediated immunotherapy approach to treat prostate cancer," said Dennis L. Panicali, Ph.D., President and Chief Executive Officer of Therion. "Because we observed that the patients' immune responses were generated primarily through the initial dose of PROSTVAC, we believe a prime-boost protocol may help increase the activity of our vaccine. Based on data from this trial and other studies, we are currently evaluating a prime-boost approach for PROSTVAC in two Phase II trials in collaboration with Dana-Farber and the Eastern Cooperative Oncology Group."

Dana-Farber Cancer Institute is among the leading cancer research and treatment centers in the United States, and is the only center in New England to be both a federally-designated Comprehensive Cancer Center and Center for AIDS Research. Visit www.dana-farber.net for more information.

Therion Biologics Corporation is engaged in the development of therapeutic vaccines for cancer and preventive vaccines for AIDS. Currently, Therion has nine products in Phase I and Phase II clinical development for the treatment of major cancers, including prostate, colorectal and breast cancer and melanoma. The Company also has a major corporate alliance with Aventis Pasteur for the development of therapeutic vaccines for colorectal and lung cancers and melanoma. Therion is headquartered in Cambridge, Massachusetts.