By Randall Osborne

With a non-invasive, DNA-based test for detecting colorectal cancer and its early lesions (polyps) nearly ready for clinical trials, Exact Laboratories Inc. is taking aim at the cancer that kills more people than almost any other in the U.S.

"The time is right," said Stanley Lapidus, founder and president of Maynard, Mass.-based Exact. "This disease is an absolute scourge." Only lung cancer surpasses colorectal cancer in mortality rates.

Half of newly diagnosed patients die from colorectal cancer within five years, but people with the disease have a better than 90 percent survival rate when diagnosed early, as Lapidus said the test will do.

Last month, Exact raised $10.6 million in its second round of venture financing. The first round, in December 1996, brought in $5 million. Founded in 1995, the company has 18 employees, 13 of whom are scientists.

Lapidus said the DNA-based test is expected to enter clinical trials late this summer or in early fall.

The test involves recovering DNA from the stool and examining it for genetic mutations. Although most DNA harvested this way is normal, about two to five percent may have show mutation, in as few as one base pair, Lapidus said.

"If you've got a mutation, you've got an abnormality in the colon that should be removed," Lapidus told BioWorld Today.

An available test evaluates stool for fecal occult blood.

"The idea is that, while it may be tough to detect a cancer, some of the cancers bleed some of the time," Lapidus said. "The problem is that there are many reasons why there is blood in the stool, such as hemorrhoids or taking an aspirin a day to prevent heart attacks."

Other tests are the sigmoidoscopy and colonoscopy, in which a fiber optic tube is inserted into the patient's rectum to examine the colon.

"The same instrument is used in both tests," Lapidus said. "The difference is in how far the physician pushes it, and most individuals can't tolerate that without sedation or anesthesia."

Remove The Polyps, Cure The Disease

Lapidus, with a family history of polyps — which is one of the risk factors for colorectal cancer — underwent the scope procedure himself.

"It was the single most uncomfortable encounter I've had with the healthcare system in my life," he said. "It's downright painful."

A sigmoidoscopy checks the lower third of the colon, but about half the cancers occur out of its range. The more expensive colonoscopy procedure is more thorough, but is often inflicted on patients who don't need it, Lapidus said.

The DNA-based test would ensure the appropriate patients undergo the expensive, sometimes humiliating test, he said. Patients would provide stool samples in a container supplied by the physician. A courier would pick up the sample and deliver it to Exact's lab, which would do the rest.

Lapidus said five percent or less of colorectal cancers are related to heredity, and these non-polyposis cases are characterized by early onset. Most colorectal cancers, called "sporadic," strike patients at a median age of 69.

"You normally would have another 10 to 15 years, if you'd lived to that age," Lapidus said. Removing precancerous polyps is a fairly simple procedure, he added, "and if you remove the polyps, you cure the disease."

The high mortality rate is blamed on late detection, Lapidus said.

"Almost all patients today are diagnosed because they present with symptoms — bleeding, pain, and occasionally intestinal blockage," he said.

The company's business model is that of a commercial testing laboratory.

"We're not unlike Myriad [Genetics Inc., of Salt Lake City] and OncorMed [Inc., of Gaithersburg, Md.], but we're extremely focused on this one disease," Lapidus said.

By the year 2001, Exact expects to offer limited testing through a partner yet to be signed.

Lapidus, an engineer, started Cytyc Corp., of Boxborough, Mass., in 1987. The medical devices company markets the ThinPrep System, designed for use in diagnosing cancers of the cervix, lung, bladder and gastrointestinal tract. Included in the system is the ThinPrep Pap Test.

"It's having quite a good run in the market now," said Lapidus, president of the company until 1994. Cytyc's revenues for the first quarter of this year were estimated at $8 million.

With Exact's DNA-based test for colorectal cancer, he hopes to duplicate the Cytyc success.

"As an epithelial cancer, it takes many years to develop," he said. "But this is a huge organ, very long and very difficult to get to. Our goal is no less than to eradicate the disease in a regularly screened population." *