SBIR-STTR Award

For bladder cancer, we seek to improve patient outcomes and reduce healthcare costs by delivering to the urological market an assay with enhanced ability to predict disease progression to an invasive or metastatic phenotype. Specifically, we will strive to validate and improve on an assay with potential to detect mutations in the p53 gene of bladder cancer cells that are exfoliated into the lumen of the bladder and collectable in either voided urines or bladder irrigations (washes). The assay to be examined is NIRCA(TM) (Non-Isotopic RNase Cleavage Assay) and was developed at Ambion, Inc. UroCor, Inc., this nation's largest provider of diagnostic services to the urology market, will determine the sensitivity and specificity of the NIRCA assay for p53 mutations in bladder cancer specimens. UroCor will also determine the frequency of heterozygosity of neutral alleles of the p53 gene in healthy individuals. In phase II, the expected clinical utility of p53 mutational analysis for predicting bladder cancer progression will be tested in the appropriate retrospective and prospective trials. This work will involve Ambion in a collaborative, consultative and contractual basis. Ambion will help train UroCor staff and assist in meeting Phase l goals. PROPOSED COMMERCIAL APPLICATIONS: The nationwide market for bladder cancer evaluations is about 750,000 tests per year. Analysis of p53 mutations would likely improve the prognostic value of these evaluations significantly. At about $100 per assay, this market has a potential value of $75MM. UroCor could expect to command a large portion of this market.

The p53 tumor suppressor gene regulates many physiologic pathways that are important in the development of cancer and is the gene most frequently observed to be mutated in metastatic cancers. As a result, p53 mutations in cancer cells indicate that the tumor containing such p53 mutated cells is at high risk for disease progression to a higher clinical stage and/or grade. P53 mutated cancers are also more likely to recur after initial treatment than p53 wild type cancers and respond differently to some therapies. This project consists of a combination of clinical trials and programs of incremental improvement that seek to further develop and validate a robust commercially viable clinical assay to detect p53 gene mutations in bladder cancers cells that are exfoliated into the lumen of the bladder and collected in bladder cytology specimens. The successful completion of this phase II SBIR will change the way bladder cancer patients with stage T1 or greater disease are managed. The improvements in technology delivery and the expanded prospective and retrospective clinical trials will validate both the technology and its clinical utility to assess patient prognosis. These achievements will, in turn, direct patients to their most effective primary and adjuvant therapies. PROPOSED COMMERCIAL APPLICATION: The work proposed in this phase II SBIR grant application will further facilitate the acceptance and adoption of this test by urologists as a tool to be used in managing bladder cancer patients. Thus, the work proposed is also essential for the commercial success of this project at UroCor. The total p53 mutation detection market for bladder cancer prognosis is roughly 60,000 specimens/ year with a market approaching $15 million. Cost savings to the medical community due to more effective treatment of bladder cancer is significantly greater.