Redwood City, CA, January 24, 2011 – Pathwork Diagnostics, Inc., a privately held molecular
diagnostics company focused on oncology, announced today that results from a decision impact
study of its Tissue of Origin Test were presented this weekend at the ASCO 2011
Gastrointestinal Cancers Symposium in San Francisco. In the study of 111 cases derived from
more than 65 academic and community practices, after receiving the Tissue of Origin Test
results, the determination of the primary diagnosis site and treatment management was
changed in more than half of patients.

“This study confirms that in metastatic cancer patients, the test provides useful information that
influences the primary diagnosis site in more than 50% of patients and alters cancer-specific
management in even more patients,” commented John Hornberger, M.D., M.S., CEO/President
of Cedar Associates LLC and Principal Investigator of the study. “This rigorous study has
provided important data regarding the Tissue of Origin Test as used in routine clinical practice.”
The poster, “Effect of a gene expression-based tissue of origin test’s impact on patient
management for difficult-to-diagnose primary cancers,” was authored by Drs. John Hornberger,
Mahul Amin, Gauri Varadhachary, W. David Henner and J. Scott Nystrom (Poster Board #A104;
General Poster Session Saturday, January 22).

Registry Study
An important step for a novel test is assessing its clinical utility and real-world effect on
diagnosis and patient management. The study collected data from 66 participating physicians
who have ordered the Pathwork Tissue of Origin Test for 111 patients with difficult-to-diagnose
primary cancers. A detailed survey interview was conducted using both a web-based
questionnaire and a confirmatory telephone interview with the physicians, including questions
regarding their working diagnoses, diagnostic procedures ordered and treatment
recommendations prior to and after Tissue of Origin Test results.

Study results indicated that most patients had undergone extensive evaluation including multiple
imaging tests and average of 10 immunohistochemistry tests prior to gene expression analysis.
After receiving the Tissue of Origin Test results, determination of the primary diagnosis site was
changed in 54% of patients and a change in any aspect of cancer-specific management
resulted for 68% of patients. Two-thirds of physicians agreed that the test results were clinically
useful in their care of their patients.

Requiring very small amounts of FFPE tumor tissue, the Tissue of Origin Test measures the
gene expression levels in more than 2,000 genes and compares the gene expression pattern of
the specimen to that of 15 tissues in the test database, to indicate the most likely match.
A large validation and reproducibility study published in this month’s Journal of Molecular
Diagnostics (JMD) showed that the Tissue of Origin Test can assist in accurately and reliably
identifying the origin of metastatic or poorly differentiated tumors using FFPE tissue, which is
the most common clinical specimen type used in testing of cancer tumors.

The Pathwork Tissue of Origin Test is the only FDA-cleared molecular diagnostic test for tissue
of origin and the most rigorously validated test of its kind. The test is available through the
Pathwork Diagnostics Laboratory. To have a specimen processed by the Pathwork Diagnostics
Laboratory using the Tissue of Origin Test or to learn more about the service, call Pathwork
Diagnostics at (877) 808-0006 or visit www.pathworkdx.com.

About Pathwork Diagnostics
Pathwork Diagnostics, Inc. is a privately held company based in Redwood City, CA, that
develops and commercializes high-value molecular diagnostics for oncology. The company’s
flagship Pathwork Tissue of Origin Test is the only FDA-cleared molecular test of its kind. For
more information call toll-free (877) 808-0006 or visit www.pathworkdx.com.
# #

Molecular profiling test utilizes common clinical specimen type
to help identify cancers

REDWOOD CITY, Calif., June 15, 2010 – Pathwork Diagnostics Inc., a molecular diagnostics
company focused on oncology, today announced the U.S. Food and Drug Administration (FDA)
cleared the Pathwork® Tissue of Origin Test for formalin-fixed, paraffin-embedded (FFPE)
tissues. The FDA clearance allows the Tissue of Origin Test to be broadly utilized on common
clinical FFPE tumor specimens from both community and research hospitals and paves the way
for additional FFPE-based cancer tests on the Pathwork platform.

With some metastatic and poorly differentiated tumors, identifying the tumor’s origin is complex
and can make diagnosis and treatment difficult. The Pathwork Tissue of Origin Test uses
microarray-based RNA profiling to compare the patient’s specimen to a database of known
tumor types. The highly accurate and reproducible results are evaluated by the physician in the
context of the patient’s clinical history and complementary diagnostics, such as
immunohistochemistry. Pathwork has the only FDA-cleared molecular classification tests for
tissue of origin.

“When there is uncertainty about the identity of the tumor, we are challenged to provide the best
treatment,” said Gauri Varadhachary, M.D., associate professor, Department of Gastrointestinal
Oncology, M.D. Anderson Cancer Center. “With the molecular information provided by the
Pathwork Tissue of Origin Test, we have the opportunity to be better equipped to define
preferred therapeutic approaches for our patients.”

“Pathologists can consider using molecular profiling to help classify the cancer when existing
methodologies may not be sufficient to provide a definitive diagnosis,” said Marina Nikiforova,
M.D., director, Molecular Anatomic Pathology Laboratory, University of Pittsburgh. “Since the
performance of the Pathwork Tissue of Origin Test is cleared by the FDA, we can use this test
and resulting information with more confidence.”

“Over the past two years, we have seen significant adoption for our Tissue of Origin Test from
leading oncologists and pathologists at major academic medical centers and top cancer clinics
across the country,” said Deborah J. Neff, CEO, Pathwork Diagnostics. “The FDA clearance
demonstrates our ability to develop and commercialize robust FFPE diagnostics, and opens the
door for future tests to be offered on the Pathwork platform.”

The Pathwork Tissue of Origin Test measures the degree of similarity between the RNA
expression patterns in a patient’s tumor and the RNA expression patterns in a database of 15
tumor types (metastatic, poorly differentiated and undifferentiated cases) that were diagnosed
according to then current clinical and pathological practice. The test uses microarray technology
from Affymetrix Inc. (Nasdaq: AFFX) to measure the expression levels of more than 2,000
genes.

Pathwork will transition its Tissue of Origin Test for FFPE offered through its CLIA-certified
laboratory from a Laboratory Developed Test (LDT) to an in vitro diagnostic (IVD). The
company also plans on making an IVD kit available to customers who want to run the test in
their own clinical laboratory. For more information on how to order the Tissue of Origin Test,
please visit: http://www.pathworkdx.com/OrderOrigin.

About Pathwork Diagnostics
Pathwork Diagnostics Inc. is a privately held company based in Redwood City, Calif., that
develops and commercializes high-value molecular diagnostics for oncology. The company’s
flagship Tissue of Origin Test is the only FDA-cleared molecular test of its kind. For more
information, please call toll-free 1.877.808.0006 or visit www.pathworkdx.com.

When Jo Symons was found to have cancer, there was an extra complication: doctors could not tell what type of cancer she had.

Tumors were found in her neck, chest and lymph nodes. But those tumors had spread there from someplace else, and her doctors could not determine whether the original site was the breast, the colon, the ovary or some other organ. Without that knowledge, they could not offer optimal treatment.

Such mystery tumors are estimated to account for 2 percent to 5 percent of all cancer, or at least 30,000 new cases a year in the United States, making them more common than brain, liver or stomach cancers. For patients, such a diagnosis can amount to a double agony — not only do they have cancer, but doctors cannot treat it properly.

”You don’t believe that in the 21st century it is possible for the medical profession not to know where the cancer is coming from,” said Ms. Symons’s husband, John.

But now 21st-century medicine may help. New genetic tests may pinpoint the origin of the mystery tumors. The tests, which cost more than $3,000 each, still need to prove their worth better, experts say, though some of them are hopeful.

”I can tell you there have been several patients I’ve had where their therapy was altered” based on the test results, said Dr. F. Anthony Greco, director of the Sarah Cannon Cancer Center in Nashville and a leading expert on cancer of unknown primary, or CUP, as the mysterious disease is formally known.

Dr. Greco said it appeared that in many cases the primary tumor was too small to be detected, and in other cases it may have disappeared. ”Why the primary tumor didn’t grow and get bigger we have no idea,” he said.

Such tumors are typically found in the liver, the lymph nodes or the bones, but can be in other places as well. But when tumor samples, taken either from a biopsy or from surgical removal, are examined under a microscope, they do not resemble cancers that would originate in the places they are found. Nor do the cells clearly resemble those from breast, colon or other types of cancer.

The problem is that cancers are treated based on their origin. If a cancer that originated in the breast is found in the liver, it is still classified as breast cancer and treated with breast cancer drugs.

Lacking such a classification, doctors can use drugs that work for a variety of cancers. But such treatment presumably is less effective than one using drugs matched to the type of cancer.

So the discovery of an unclassified cancer often sets off a frantic search for the original tumor.

”I had every test out there — PET scan, M.R.I., colonoscopy, mammogram — I even swallowed a pill with a camera on it” to take pictures of the digestive tract, Lori Young of Huntsville, Ala., wrote on a Web site for people with cancer of unknown primary. But her original tumor could not be found.

Ms. Young, 39 and a mother of two, was found to have tumors that had spread to her liver in October 2007. She is being treated with drugs typically used for lung cancer.

Patients say the inability to find the original tumor adds to their anxiety.

”You’re always in limbo,” said Susan Droman of Akron, Ohio, who discovered she had cancer of unknown primary after it had spread to her vertebrae a year ago, causing excruciating pain. ”We would have been happier if it had been an actual tumor you see so they could get it out of there.”

Mark Kargul, a former airline pilot from San Clemente, Calif., who has mystery tumors in his liver, likened the experience to being unable to find the source of a leak in one’s home. ”You can mop up the floor,” Mr. Kargul said, ”but the next day the flood will be back.”

It is even hard for patients to explain their situation to friends and family, or to get advice from them. The new tests may solve some mysteries. Already there are four such tests on the market, and at least one other is being developed.

Generally the tests analyze which genes are active or inactive in a tumor sample. They compare that genetic fingerprint with the fingerprints from known tumor types, trying to come up with the best match.

The Tissue of Origin test from Pathwork Diagnostics of Sunnyvale, Calif., measures the activity of 1,500 genes. The CancerType ID, from BioTheranostics, based in San Diego, looks at 92 genes. The CupPrint test from Agendia, which is based in the Netherlands, looks at about 500 genes. That test is not available yet in the United States.

The MiRview Mets test from Israel-based Rosetta Genomics takes a different approach, analyzing microRNAs, which are tiny snippets of genetic material that help control the activity of genes.

Only the Pathwork test has been approved by the Food and Drug Administration, although the approved version has been superseded by a more practical version that is not approved. Tests can be offered by laboratories without F.D.A. permission, even as they are still being validated.

The tests are generally 80 to 90 percent accurate, according to published studies.

But that is when they are used on tumors whose origin is known. In practice, the tests would be used on tumors whose origin is unknown. And those may by their very nature be harder to classify, said Dr. Lawrence Weiss, chief of pathology at the City of Hope cancer center in Duarte, Calif.

A study published last September in The Journal of Clinical Oncology reported that the Agendia test correctly classified 83 percent of known tumor samples. But the test could classify only 64 percent of unknown tumors.

And of course, if the tumor origins are truly unknown, how does one even know if the genetic test is coming up with the correct answer?

One way, Dr. Greco said, is that there are rare cases in which the primary site becomes known months later, like when a patient suddenly starts feeling pain at that site.

Dr. Greco collected the original biopsy samples from some of these patients and found the BioTheranostics test to be about 70 percent accurate in classifying the tumors, compared with only 10 percent to 20 percent for the most advanced pathology techniques.

How valuable the tests will be still remains to be seen. Some biopsies do not provide enough genetic material for analysis. Ms. Droman, for instance, could not get any answer from the Rosetta test, and Mr. Kargul could not get one from the BioTheranostics test.

Dr. Weiss of City of Hope said that pathologists now used antibodies that can latch onto telltale proteins in the tumor. That technique, called immunostaining, can classify about two-thirds of tumors that would have been considered unknown primaries about 30 years ago, Dr. Weiss said. That leaves only one-third, or about 1 percent of all cancers, that might benefit from the newer genetic tests.

Still, for those patients, however many there are, any clue could be helpful. Dr. Martin A. Martino, a gynecologic oncologist at Lehigh Valley Health Network in Allentown, Pa., said he recently used the Pathwork test to classify a patient’s tumor as ovarian. That allowed her to enroll in a clinical trial testing a new drug for ovarian cancer.

The real proof of the value of the tests would be to show that patients live longer after undergoing the tests, presumably because they would then receive treatment better matched to their tumors.

”That’s really the major question now,” said Dr. James Abbruzzese, chairman of gastrointestinal oncology at the University of Texas M.D. Anderson Cancer Center in Houston. ”Do patients have better outcomes from having a hopefully better handle on where the cancer came from?”

M.D. Anderson treats 250 to 350 patients a year with cancer of unknown primary. It is using the genetic tests in selected circumstances. ”We try to ask ourselves, ‘Is this information going to change the treatment we recommend for the patient?’ ” Dr. Abbruzzese said.

Jo Symons took the Agendia test, but not before being treated with two different chemotherapy regimes, both unsuccessful. The test showed that she had pancreatic cancer, so she was given chemotherapy for that cancer.

But pancreatic cancer is notoriously difficult to treat, and she died in September 2006, only seven months after her initial diagnosis. To help other patients, Mr. Symons set up the Cancer of Unknown Primary Foundation, also known as Jo’s Friends, after his late wife (www.cupfoundjo.org).

”It may have made more a difference psychologically than it did in terms of time,” Mr. Symons, who lives near Oxford, England, said of the genetic test. ”It gave us comfort to identify where the cancer had come from. It’s very uncomfortable not knowing where a problem has arisen in your body.”