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Monograms eTag Diagnostic To Take on HER Receptors

Monogram will soon release data showing how its eTag test can gauge cancer patients’ responses to the Her family of receptors, a company official said last week at a life sciences conference.
Monogram is using its eTag dimerization assay to “go after the Her family of receptors,” William Welch, senior vice president, said last week at the Harvard-Partners Center for Genetics and Genomics conference on personalized medicine in Boston. “We’re coming out with data hopefully in breast cancer, lung cancer, and colon cancer.”
Monogram CFO Alf Merriweather previously said that the company was working on “a range of assays … for all the dimers of Her1, Her2, and Her3," and that it is involved in clinical studies to identify and validate correlations between those dimers and clinical response [see Pharmacogenomics Reporter 06-07-06].
At the HPCGG conference, Welch did not expound on the study details or say when the study results will be released. The company’s Her family eTag assays are not yet on the market.
In an interview with Pharmacogenomics Reporter this week, Monogram CEO William Young said the company “has identified correlations between clinical response and measurements of Her family receptors made with eTag assays.”
“These correlations have been consistent in two separate cohorts of clinical samples,” Young said. “We are currently in the process of obtaining access to additional cohorts of clinical breast cancer tissue samples to confirm the correlations. When completed, we will seek to publish the results of these studies.”
Formerly called ViroLogic, the company changed its name to Monogram to “take advantage of the fact that we were also working in oncology and other diseases [and not] be limited to just viral diseases,” Young said. The company gained the eTag platform as part of its 2004 acquisition of Aclara Biosciences.
“We are hard at work using that platform to develop products in oncology that would help decide what the right targeted drug would be for a given patient,” Young said.
Monogram claims its eTag assays quantitatively measure specific dimers and levels of protein expression in Formalin-Fixed, Paraffin-Embedded tissue. The assay is intended to measure the targets of drugs attacking the full ErbB family, including Herceptin, Tykerb, Omnitarg, and other compounds in development.
The eTag platform is different from the qRT-PCR tests being developed by Genentech and Roche in that it aims to detect dimerization directly rather than using qRT-PCR to infer it. Monogram has claimed that it has no direct competitors in the area and holds IP in this regard.
In the area of Her2 positive breast cancer, the eTag would be moving into a space currently occupied by Oncor’s Inform HER-2/neu Gene Detection System, PathVysion’s HER-2 DNA Probe Kits and Dako’s HercepTest. Oncor and PathVysion’s products are based on fluorescence in situ hybridization detection of the HER-2/neu gene.
When asked to differentiate Monogram’s test from HercepTest, Young maintained that the eTag is “a much more accurate way of measuring the protein target because what HercepTest does is measure qualitatively the amount of Her2 that’s there.”
HercepTest is a semi-quantitative immunohistochemical assay that determines Her2 protein overexpression in breast cancer tissues by using specific antibodies that recognize, bind to, and stain cell-surface receptors that are produced by HER-2/neu gene amplifications and overexpression. The slides are then evaluated by light microscopic examination as strongly positive (3+), weakly positive (2+), or negative (0-1+). Pathologists determine the results by the intensity of immunostaining.
Ultimately, the Her2 protein is not a target of Herceptin, Young said. “What really is a target of Herceptin is a dimerized version of Her2. If you could measure that you can theoretically have a more accurate assessment of the likelihood of the patient responding,” he explained.
“ETag has a very sophisticated method of measuring proteins and protein complexes,” Young continued.
He gave the example that there is still a large percentage of Her2 positive breast cancer patients who are eligible for Herceptin therapy but do not respond to therapy.

Monogram’s eTag is “a much more accurate way of measuring the protein target because what HercepTest does is measure qualitatively the amount of Her2 that’s there.”

Additionally, many patients form resistance to Herceptin. In such patients, “other hetero-dimers form that signal the cell and aren’t down-regulated by Herceptin,” Young said. “If you could measure those, you should be able to sort out what the appropriate therapy would be for a given patient, cancer being a very heterogeneous disease.”
“We hope to be able to use [the eTag] technology to sort out the responders from the non-responders in targeted drugs, such as Herceptin, Tarceva and Erbitux. We’re developing products for them,” he added.
Monogram has announced more than nine collaborations with major pharmaceutical and biotechnology companies to evaluate its eTag assay, including one with Merck KGaA for Erbitux [see Pharmacogenomics Reporter 10-27-05].
After Monogram makes headway in oncology, the company may pursue other disease areas such as immunology and cardiovascular disease with eTag. The company does not intend to seek FDA clearance for the CLIA-lab certified test.
From HIV to Cancer
Welch’s discussion of the eTag was part of a presentation on a Monogram/Pfizer collaboration to make available worldwide Monogram’s HIV tropism assay for Pfizer’s investigational drug Maraviroc (see related story).
According to Welch, Monogram is moving into oncology because the disease area is beginning to resemble the HIV market, an area in which the company has garnered extensive expertise.
“We view the oncology space much like HIV. We see resistance patterns. We see family class patterns,” Welch said. “Cancer is behind but coming up to HIV, where HIV has plenty of drugs and 60 in the clinic … [in oncology] the number of factors aren’t quite there but” increasingly the “question is 'Which drugs do you put the patients on?'”
Cancer drugs typically “cost $40,000 to $100,000 per year … [and] we feel the area is ripe for bringing more information to clinicians to help them make decisions,” he said.

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