New target antigen for prostate cancer therapies
STEAP Antigen a Promising Route for New Therapies, PNAS Reports
Santa Monica, CA, December 7, 1999 - UroGenesys, Inc. today reported the discovery of a novel gene that provides a promising route for developing new therapies to treat prostate cancer. The studies, published today in the journal Proceedings of the National Academy of Sciences (PNAS), describe a novel cell-surface antigen called STEAP which is expressed at high levels on prostate cancers, but is rarely produced in non-prostate tissues. These results indicate that the STEAP molecule maybe useful as a target for new prostate cancer therapies, as well as for improved diagnostic tools to help monitor progression of the disease.

"STEAP possesses several features that make it a promising target for new cancer treatments," said Aya Jakobovits, Ph.D., Vice President of Research and Chief Scientific Officer at UroGenesys and an author on the paper. "The antigen is expressed at high levels on prostate tumors throughout all stages of the disease, including metastatic tumors. Its prostate-specific expression suggests that drugs targeted to STEAP may have a favorable safety profile."

Dr. Jakobovits continued, "STEAP is also expressed in androgen-independent tumors, providing an avenue for treatment of cancers that have become resistant to conventional hormone ablation therapies. Its presence on the surface of prostate cancer cells makes the molecule suitable for a wide variety of therapeutic approaches, including antibodies, small molecules and vaccines."

"STEAP is the first antigen to emerge from UroGenesys' in-house discovery program," said Donald B. Rice, Ph.D., President and Chief Executive Officer of UroGenesys. "The discovery illustrates how our disease-focused genomics program positions UroGenesys to identify and advance the development of products that may lead to improved treatments for prostate and other cancers."

Dr. Rice says that UroGenesys plans to speed up development of new therapeutic and diagnostic products based on antigens they ghave developed and own. They plan to work with pharmaceutical and biotechnology companies, while pursuing selected clinical developments separately.

Researchers at UroGenesys identified the STEAP gene by comparing RNA sequences isolated from patient-derived specimens of prostate cancer to sequences isolated from benign prostatic tissues. Once they had successfully cloned STEAP (named for Six-Transmembrane Epithelial Antigen of the Prostate), the UroGenesys team looked for its presence in a wide variety of normal and diseased tissues. They found high cell-surface expression of STEAP in all human prostate cancer samples tested, and showed that expression of the protein was almost entirelt restricted to the prostate among normal body tissues. Studies of STEAP¹s structure and localization to the cell surface imply its function as an ion channel or transport protein.

Key to the STEAP gene discovery was UroGenesys' use of its proprietary xenograft mouse models that mimic the progression of advanced prostate cancer in humans, including the development of metastatic and hormone refractory disease. By implanting patient-derived tumor samples into immune-deficient mice, the Company is also able to generate a renewable supply of primary and metastatic tissues that are otherwise difficult to obtain. UroGenesys utilizes these tissues in its gene discovery and validation programs.

"Use of these xenografts is critical to the discovery of clinically-relevant targets that are uniquely expressed in prostate tumors and other cancers," noted Dr. Jakobovits. "Applying this tool together with our target validation expertise has already led to the discovery of over 30 additional new antigens implicated in prostate cancer."

Prostate cancer, which accounts for about 40 percent of all male cancers, is currently the most common type of cancer in American men and the second leading cause of cancer-related death in this population. An estimated 180,000 new cases of prostate cancer are diagnosed each year in the United States, and approximately 40,000 American men die of the disease annually. These numbers are expected to rise as the U.S. population experiences an increasing number of men entering their senior years, when most prostate cancers are diagnosed.

These figures underscore the need for new therapeutic approaches, particularly for metastatic and androgen-independent disease. As yet, few targets that are specific to prostate cancer and are cell surface antigens have been discovered.