Molecular Cancer Profiling Study

[RandyW]

AviaraDx, Inc. and Massachusetts General Hospital Collaborate in Molecular Cancer Profiling Study

Wednesday May 17, 11:00 am ET

Collaboration Seeks to Develop and Commercialize Tumor Biomarkers for Improved Drug Response Prediction in Cancer Therapy

CARLSBAD, Calif., May 17 /PRNewswire/ -- AviaraDx, Inc., a leader in molecular cancer profiling and formerly known as Arcturus Bioscience, Inc., announced today that it has entered into a major research collaboration with the Massachusetts General Hospital (MGH) Cancer Center to identify molecular profiles of multiple types of cancer for the development of diagnostic technologies and tests in the field of cancer drug response prediction.

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Over the next two years, teams at MGH and AviaraDx will conduct a broad molecular profiling program to determine genes, gene signatures and polymorphisms that correlate with response to specific therapeutic agents in a wide range of different cancers. The initiative aims to identify and commercialize tumor biomarkers that predict which patients may respond to targeted drugs. MGH and AviaraDx will perform gene sequencing and gene expression analysis in a large number of cancers. The project results will not only provide valuable information to help identify patients likely to respond to a certain cancer drug, but also provide guidance with regard to a broader range of cancer types likely responding to an established drug.

Daniel A. Haber, MD, PhD, and Jeff Settleman, PhD, of MGH have extensive experience in the identification of genetic markers associated with drug response. Most recently, they reported the identification of a gene mutation that appears to identify those lung cancer patients who will likely respond to the cancer drug Iressa®. (1)

Mark Erlander, Ph.D. and Xiao-Jun Ma, Ph.D., of AviaraDx have developed the company's Molecular Cancer Identification (MCID) technology, which has been licensed to clinical laboratory partners in the US and Europe.

"The MGH Cancer Center is a world leading medical research center, and we are pleased to be collaborating with them in a program that may result in the development of molecular diagnostic tests for drug response prediction in cancer," said Antonius Schuh, Ph.D., Chief Executive Officer of AviaraDx, Inc. "Transforming the molecular basis of cancer into diagnostic technologies with proven clinical utility is the core focus for AviaraDx. Our molecular cancer identification (MCID) and breast cancer profiling (BCP) technologies are impressive achievements in this space.

"Our goal is the development of a rational basis for the selection of a specific drug regimen in a given patient," said Dr. Haber, who is the director of the MGH Cancer Center. "We are hopeful that this collaboration will generate technologies of relevant molecular diagnostic tests for predicting what therapy is best suited for specific patients."

About AviaraDx, Inc.

AviaraDx, Inc., formerly Arcturus Bioscience, Inc., is focused on developing and commercializing diagnostic technologies for molecular cancer profiling. AviaraDx leverages its technological leadership position in the analysis of cancer biopsies and proprietary bioinformatic methodologies to discover and commercialize molecular diagnostic products. The molecular diagnostic market segment of the diagnostic market is projected to grow at a compound annual growth rate of greater than 25% over the next decade and AviaraDx is targeting this market opportunity with three first-in-class molecular cancer diagnostic technologies: Molecular Cancer Identification (MCID), Breast Cancer Profiling (BCP) and Drug Response Profiling (DRP). AviaraDx estimates that the addressable U.S. market for its products and services is approximately $3 billion and has already licensed its MCID and BCP technologies for specific clinical indications and for defined detection platforms to diagnostic laboratories in the U.S. and Europe in order drive early market penetration and acceptance. AviaraDx has recently relocated its headquarters from Mountain View, California to Carlsbad, California. Please visit the AviaraDx website at http://www.aviaradx.com for more information.

About Massachusetts General Hospital

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. Its dedication to the treatment of cancer dates back to 1925, when the MGH opened the nation's first tumor clinic. Over the decades, the hospital has become widely known for its leadership in cancer surgery and radiation therapy. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare, an integrated health care delivery system.

(1) IRESSA® is a trademark of the AstraZeneca group of companies.

CONTACT:

Steve Zaniboni

Chief Financial Officer

+1-760-579-0514

[gpawelski]

The Microarray (gene chips) is a device that measures differences in gene sequence, gene expression or protein expression in biological samples. Microarrays may be used to compare gene or protein expression under different conditions, such as cells found in cancer.

Hence the headlong rush to develop tests to identify molecular predisposing mechansims whose presence still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class.

Genetic profiles are able to help doctors determine which patients will probably develop cancer, and those who will most likely relapse. However, it cannot be suitable for specific treatments for individual patients.

In the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies, the pressure is so great that the companion diagnostics they’ve approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies.

Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeting one pathway may not be as effective as targeting multiple pathways in a cancer cell.

Another challenge is to identify for which patients the targeted treatment will be effective. Tumors can become resistant to a targeted treatment, or the drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone. Understanding “targeted” treatments begins with understanding the cancer cell.

If you find one or more implicated genes in a patient's tumor cells, how do you know if they are functional (is the encoded protein actually produced)? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?

All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene won't tell you anything about protein interactions. Are you sure that you've identified every single gene that might influence sensitivity or resistance to a certain class of drug?

Assuming you resolve all of the preceeding issues, you'll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations. And what about external facts such as drug uptake into the cell?

Gene profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, are still years away from working successfully in predicting treatment response for individual patients. Perhaps this is because they are performed on dead, preserved cells that were never actually exposed to the drugs whose activity they are trying to assess.

It will never be as effective as the cell culture method, which exists today and is not hampered by the problems associated with gene expression tests. That is because they measure the net effect of all processes within the cancer, acting with and against each other in real time, and it tests living cells actually exposed to drugs and drug combinations of interest.

It would be more advantageous to sort out what's the best "profile" in terms of which patients benefit from this drug or that drug. Can they be combined? What's the proper way to work with all the new drugs? If a drug works extremely well for a certain percentage of cancer patients, identify which ones and "personalize" their treatment. If one drug or another is working for some patients then obviously there are others who would also benefit. But, what's good for the group (population studies) may not be good for the individual.

Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival above that achieved with "best guess" empiric chemotherapy through clinical trials.

It may be very important to zero in on different genes and proteins. However, when actually taking the "targeted" drugs, do the drugs even enter the cancer cell? Once entered, does it immediately get metabolized or pumped out, or does it accumulate? In other words, will it work for every patient?

All the validations of this gene or that protein provides us with a variety of sophisticated techniques to provide new insights into the tumorigenic process, but if the "targeted" drug either won't "get in" in the first place or if it gets pumped out/extruded or if it gets immediately metabolized inside the cell, it just isn't going to work.

To overcome the problems of heterogeneity in cancer and prevent rapid cellular adaptation, oncologists are able to tailor chemotherapy in individual patients. This can be done by testing "live" tumor cells to see if they are susceptible to particular drugs, before giving them to the patient. DNA microarray work will prove to be highly complementary to the parellel breakthrough efforts in targeted therapy through cell function analysis.

As we enter the era of "personalized" medicine, it is time to take a fresh look at how we evaluate new medicines and treatments for cancer. More emphasis should be put on matching treatment to the patient, through the use of individualized pre-testing.

Upgrading clinical therapy by using drug sensitivity assays measuring "cell death" of three dimensional microclusters of "live" fresh tumor cell, can improve the situation by allowing more drugs to be considered. The more drug types there are in the selective arsenal, the more likely the system is to prove beneficial.