Progenics and Cytogen Report Positive Preclinical Results for Experimental Prostate Cancer Drug
In Laboratory Studies, Human Monoclonal Antibody Killed Prostate Cancer Cells While Leaving Normal Cells Unharmed
Monday September 23, 5:00 am ET
WASHINGTON--(BUSINESS WIRE)--Sept. 23, 2002-- The PSMA Development Company LLC, a joint venture of Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX - News) and Cytogen Corporation (Nasdaq: CYTO - News), today announced encouraging preclinical results with its prostate cancer immunotherapeutic agent.
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The experimental drug is a human monoclonal antibody that targets prostate-specific membrane antigen (PSMA), a biological marker abundantly found on the surface of prostate cancer cells. In new laboratory studies, the monoclonal antibody killed PSMA-expressing cells, while sparing normal cells. The scientific findings were presented this past weekend at the Ninth Annual CaPCURE Scientific Retreat in Washington, DC.
"This monoclonal antibody has demonstrated an impressive ability to selectively deliver a lethal payload to PSMA expressing tumor cells," said William C. Olson, Ph.D., Progenics' vice president of research and development. "Our next steps include selecting the optimal toxin and radioactive payloads in parallel with producing clinical-grade antibody."
Fully human high-affinity monoclonal antibodies to PSMA were originally developed in a collaboration with Abgenix, Inc. (Nasdaq: ABGX - News), using Abgenix' XenoMouse® technology. To increase their killing capacity, Progenics and Cytogen linked the antibody to a toxin molecule or a radioactive isotope. In both cases, the modified antibodies not only retained the ability to efficiently bind to the cell surface of PSMA-expressing cells, but were also internalized, thereby directing its lethal payloads within individual malignant cells. The joint venture intends to file an Investigational New Drug application (IND) next year.
"PSMA targeted therapies hold great promise for the treatment of prostate cancer, especially for patients in the advanced stages of the disease," said H. Joseph Reiser, Ph.D., president and CEO of Cytogen Corporation. "These early results indicate that the PSMA antibody has the potential to destroy prostate cancer cells without affecting normal cells in the body."
In these and prior studies, the antibody has exhibited an encouraging set of therapeutic properties. The fully human monoclonal antibody reacts specifically with the three-dimensional structure of PSMA as it appears on the exterior of prostate cancer cells. It also retains the ability to bind to PSMA with high affinity when linked to toxins or radioisotopes. Very low concentrations of the toxin-linked antibody (LD50 = 10 picomolar) kill PSMA-expressing cells, but not normal cells, and antibodies linked to either toxin or radioisotopes were rapidly internalized by target cells.
Human monoclonal antibodies are laboratory-produced "clones" of antibodies that are formed by the body in response to specific antigens or "foreign" invaders. Antigens are found on the surface of infectious agents, tumor cells, or foreign tissue cells. PSMA is a cell-surface protein that is abundantly expressed on prostate cancer cells at all stages of disease, including advanced or metastatic disease. The PSMA gene was first discovered by scientists at Memorial Sloan-Kettering Cancer Center and is exclusively licensed to Cytogen Corporation, which has sublicensed it to the PSMA Development Company for in vivo immunotherapy. PSMA is also present at high levels on the newly formed blood vessels (neovasculature) needed for the growth and survival of many types of solid tumors. If PSMA-targeted therapies can destroy or prevent formation of these new blood vessels, the therapies may prove valuable in treating a broad range of cancers.
In addition to fully human monoclonal antibodies, the PSMA Development Company expects to initiate clinical studies of a therapeutic prostate cancer vaccine, pending acceptance of an investigational new drug (IND) application by the Food and Drug Administration (FDA). The vaccine is comprised of a recombinant PSMA protein and an immune stimulant or adjuvant.
Company Profiles
Progenics Pharmaceuticals, Inc. of Tarrytown, NY, is a diversified biopharmaceutical company focusing on the development and commercialization of innovative therapeutic products to treat the unmet medical needs of patients with debilitating conditions and life-threatening diseases. The Company applies its expertise in immunology and molecular biology to develop biopharmaceuticals to fight viral diseases, such as human immunodeficiency virus (HIV) infection, and cancers, including malignant melanoma and prostate cancer. In supportive care, therapies are being developed to provide patients with an improved quality of life. The Company is conducting Phase II clinical studies with methylnaltrexone, a compound designed to block the debilitating side effects of opioid analgesics without interfering with pain palliation. The Company has initiated Phase II clinical trials with its lead HIV product, PRO 542, a viral-entry inhibitor and is in preclinical development with PRO 140 and other follow-on product candidates in HIV infection. Progenics' most clinically advanced product, GMK, is a cancer vaccine in Phase III clinical trials for the treatment of malignant melanoma. The Company is developing cancer immunotherapies based on PSMA (prostate specific membrane antigen) technology. Dehydroascorbic acid (DHA), a novel small-molecule antioxidant, is the subject of preclinical studies to treat stroke.
Cytogen Corporation, of Princeton, NJ, is a biopharmaceutical company with an established and growing product line in prostate cancer and other areas of oncology. Currently marketed products include ProstaScint® (a monoclonal antibody-based imaging agent used to image the extent and spread of prostate cancer); BrachySeed(TM) I-125 and Pd-103 (two uniquely designed next-generation radioactive seed implants for the treatment of localized prostate cancer), and Quadramet® (a skeletal targeting therapeutic radiopharmaceutical marketed for the relief of bone pain in prostate and other types of cancer). Cytogen is evolving a pipeline of oncology product candidates by developing its prostate specific membrane antigen, or PSMA, technologies, which are exclusively licensed from Memorial Sloan-Kettering Cancer Center. AxCell Biosciences of Newtown, PA, a subsidiary of Cytogen Corporation, is engaged in the research and development of novel biopharmaceutical products using its portfolio of functional proteomics solutions and collection of proprietary signal transduction pathway information. |
