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HER2 homodimer and HER2 total protein assays validated.

Monogram Biosciences, Inc. (South San Francisco, CA) presented the results of a study detailing the HERmark Assay's ability to identify metastatic breast cancer patients who are most likely to respond to Herceptin. The study results were presented this week at the San Antonio Breast Cancer Symposium. Also this week, Monogram received confirmation from the College of Pathologists that the HERmark assays are approved for routine patient testing in Monogram's CLIA certified clinical reference laboratory.

"The results are an important step along the way to clinical validation of HERmark, the first product based on the VeraTag technology platform," said William Young, Monogram chief executive officer. "In addition to the presentation of important clinical data, I am pleased to report that the HERmark assays have completed their validation process in Monogram's CLIA-certified clinical reference laboratory. The establishment of solid technical validation data and the ability to perform the assays under high-throughput, well controlled conditions will provide a strong basis for commercialization of HERmark after completion of our ongoing clinical studies."

In the study, Monogram analyzed tissue samples from patients with metastatic breast cancer who were treated with Herceptin, having been selected for such treatment by centralized IHC testing. While current testing methods identified all these patients as being appropriate for Herceptin treatment, Monogram's HERmark Assay was able to distinguish separate sub-populations of patients with different clinical outcomes.

Patients with higher HER2 expression levels (i.e. in the upper half of the distribution for the study cohort) experienced a 59% objective response rate while those with lower levels of HER2 expression (i.e. in the lower half of the distribution) had a response rate of only 18%. Additional analyses revealed that patients with higher HER2 expression values had a median time-to-progression of 12.8 months while those in the lower half of the distribution had a median time-to-progression of only 4 months. This result was statistically significant (p = 0.01). Finally, multivariate Cox proportional hazards models identified HER2 expression (HR = 0.16, p < 0.001) and HER2:HER2 dimer levels (HR = 0.32, p < 0.001) as measured by HERmark as being statistically significant predictors of time-to-progression.

"Current testing technologies do not provide an accurate or precise view of HER2 biology in breast cancer, classifying patients as either HER2 'positive' or HER2 'negative'," continued Young. "At best, conventional technologies provide a semi-quantitative analysis. However, only about half of metastatic patients selected by current technologies for Herceptin treatment respond to the drug. Data are now emerging to suggest that patients who could benefit from Herceptin may be missed by currently used assays. Our HERmark studies have provided data which consistently indicate that HERmark can precisely measure HER2 expression and HER2:HER2 dimer levels in clinical FFPE samples, and that those patients with higher levels of expression have significantly better clinical outcomes than those with lower levels. These data strongly suggest that HERmark can identify patients who are likely to respond to Herceptin better than the assays currently in use." HERmark Assay in Metastatic Breast Cancer

At ASCO in June 2007, Monogram reported results of studies of HERmark in two patient cohorts. In the first of these studies, it was demonstrated that within a population of patients that were stringently selected by FISH testing, the HERmark assay was able to measure a gradient of HER2 expression and HER2 homodimer levels that was significantly correlated with time-to-progression and overall survival on Herceptin. In the second metastatic patient cohort presented at ASCO, selected by IHC in a clinic-based setting, the HERmark assay was also able to demonstrate that patients who were confirmed HER2 positive by IHC on repeat testing showed a gradient of response, and that those with higher levels of HER2 expression and HER2 homodimer levels as measured by HERmark lived longer than those who had lower levels. The results of these two previously reported cohorts, along with the third cohort presented, provide the basis for Monogram's ongoing work in metastatic breast cancer. There are approximately 60,000 women annually in the United States who are newly diagnosed with Stage IV breast cancer or who have progressed from earlier stages of disease. These are patients for whom the cancer has spread beyond the breast, and in many cases multiple treatments may have already been provided.

Monogram has initiated a study with one of the leading oncology clinical trial cooperative groups in the country. In this ongoing study, we are performing HERmark assays on tissue samples from up to 1,600 breast cancer patients treated with Herceptin in the adjuvant setting. The goal of the study is to clinically validate the ability of HERmark to predict clinical outcome in these Herceptin-treated patients. These patients are generally newly diagnosed with breast cancer, have had surgery and are now on a first course of treatment to supplement the surgical procedure. In the United States, there are approximately 200,000 new cases of breast cancer each year, most of whom are candidates for adjuvant treatment and therefore would be candidates for the HERmark adjuvant breast cancer assay.

HERmark is a proprietary diagnostic that accurately quantifies HER2 expression and dimerization in patients with breast cancer. Preliminary data from three cohorts of Herceptin-treated patients with metastatic breast cancer who were identified as "HER2 positive" by conventional assays suggest that HERmark can identify patients who are likely to respond to Herceptin with greater precision than currently available tests, permitting stratification of patients according to their degree of clinical benefit from the drug. Additional studies of HERmark for breast cancer in both the metastatic and adjuvant settings are in progress.

VeraTag is a proximity-based assay technology platform that accurately quantifies proteins and functional protein complexes. This platform provides a researcher or clinician a more thorough understanding of protein-protein interactions or signaling pathway activity allowing for disease characterization at the molecular level. VeraTag is designed to run on standard formalin-fixed paraffin embedded patient samples.

Monogram is advancing individualized medicine by discovering, developing and marketing innovative products to guide and improve treatment of serious infectious diseases and cancer. The company's products are designed to help doctors optimize treatment regimens for their patients that lead to better outcomes and reduced costs. The company's technology is also being used by numerous biopharmaceutical companies to develop new and improved anti-viral therapeutics and vaccines as well as targeted cancer therapeutics.

Monogram Biosciences, Inc.

+1-650-624-4576

www.monogrambio.com
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Publication:BIOTECH Patent News
Date:Dec 1, 2007
Words:1057
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