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Exact Sciences Preparing to Launch Improved Cologuard, Liver Cancer Test

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NEW YORK – Exact Sciences released data on Tuesday for a new version of its Cologuard colorectal cancer test, showing that it can detect colorectal cancer and advanced adenomas with higher sensitivity than the current version of the test.

The company has been aiming to make improvements to the test, and in February, Exact Chairman and CEO Kevin Conroy said the company was working with investigators at the Mayo Clinic and had found promising biomarkers that could improve Cologuard's performance. He called the program Cologuard 2.0.

During the company's first quarter earnings call in May, Conroy provided an update, saying that a head-to-head comparison of the Cologuard 2.0 markers in stool with the current Cologuard test gave the company "confidence to continue moving forward with the program and to sit down with the [US Food and Drug Administration], and then thereafter begin a prospective study."

Now, the company has released data that it said proves its assertions about Cologuard 2.0. Alongside its third quarter earnings release on Tuesday, the company announced that new research from its collaboration with the Mayo Clinic showed that the new methylation and protein biomarkers they found enabled the detection of colorectal cancer and advanced adenomas with high accuracy.

The new markers were tested alongside the current Cologuard markers on 725 stool samples, including 117 colorectal cancers, 120 advanced adenomas, 161 non-advanced adenomas, and 327 controls. The results showed that the new markers were able to identify colorectal cancers with 92 percent sensitivity compared to 88 percent sensitivity for the current markers, and were able to identify advanced adenomas with 65 percent sensitivity, compared to the current 53 percent sensitivity. The new markers also maintained Cologuard's 92 percent specificity, the company said.

Exact also said it has initiated a 10,000-patient prospective study to validate the performance of the enhanced test.

On a conference call with analysts following the release of the earnings, Conroy said that the enhancement of Cologuard is a priority for Exact. One component of that strategy involved expanding the test's label to include people of average risk aged 45 to 49 — the FDA approved the label expansion in September.

"Expanding Cologuard's label is an important opportunity for growth and for detecting colorectal cancer earlier," Conroy said on the analyst call. "Last month, the FDA approved our label expansion providing access to Cologuard for the 19 million average risk unscreened Americans ages 45 to 49, and increasing its total addressable market by $3 billion to $18 billion."

The other component of the strategy is Cologuard 2.0, which presents an even greater opportunity to lift the test's "clinical and economic value proposition," and differentiate it as a frontline screening test, Conroy added. The new version's primary goal is to increase Cologuard's specificity, while maintaining a high level of sensitivity, which the data seems to show has been achieved.

However, Conroy also noted that the precancerous polyps tested in this study were typically larger in size than what Exact saw in its large prospective trial for Cologuard, making them easier to detect. "We may see some pre-cancer sensitivity improvement with Cologuard 2.0 from the current markers. However, the size of the pre-cancer polyps, stage of the cancer, timing of sample collection relative to colonoscopy, and many other factors can enhance performance in case-control studies," he added.

Ultimately, the company does not expect Cologuard 2.0 to detect advanced adenomas with 65 percent sensitivity, Conroy said.

Based on the data, the company is initiating the BLUE-C prospective trial to validate the performance of Cologuard 2.0 and prepare for an FDA submission. The first patients will be enrolled next month.

Conroy said that Exact has set the lower age limit for BLUE-C at 40 years old in order to make sure that the researchers generate data that could be used to further lower the age recommended for colon cancer screening in official guidelines.

"Most likely, we see the guidelines staying at age 45 for some time. It's an opportunity, though, for us to evaluate performance in that even lower age group," he added. The company is also including patients with family histories of colorectal cancer or genetically linked syndromes such as familial adenomatous polyposis.

Conroy also said Exact is expecting a bit of a drop off in the performance of Cologuard 2.0 as the company goes from a case-control study to a prospective study. However, he added, the company is "fairly confident" that it can maintain specificity greater than 90 percent.

The company's other major priority, Conroy said, is to advance its blood-based cancer diagnostic program. As the company has noted in earlier conference calls, it plans to start by developing a diagnostic for liver cancer. Exact is presenting data at the American Association for the Study of Liver Diseases meeting next month to demonstrate "superior performance of our liver tests compared to the alpha-fetoprotein test," which is the standard of care, Conroy said. The firm will provide more details on this data after that presentation.

Exact is enrolling additional patients in its study of the liver cancer diagnostic in order to finalize test development and plans to make the test available in the second half of 2020. The goal of the study is to generate real-world evidence to support guideline inclusion, broad reimbursement, and adoption of the test, Conroy noted.

Further, Exact also plans to collect and store blood samples from participants in the BLUE-C study to support the validation of its blood-based colorectal cancer screening test, though it's still early days for that.

"We have recently completed a case-control study demonstrating strong performance with the blood-based colorectal cancer test," Conroy said. "A blood test has, like any of the data that we have seen, lower performance than even the [fecal immunochemical] FIT test in terms of pre-cancer detection. [This is] really important as a model — the data then feeds these models."

Through this kind of data collection, the company hopes to develop a blood test for colorectal cancer that has similar performance for cancer detection at a similar specificity as current screens, he added.

Conroy further noted that a blood test would likely be more of a niche test that would have to be conducted once a year, rather than every three, five, or 10 years, like Cologuard or colonoscopy. Therefore, such a test would have to be priced appropriately, most likely at about a third of the current price of Cologuard.

"That doesn’t leave a lot of room for all the costs associated with the DNA sequencing, which is why we are focused on a lower cost approach so that we can bring the test to market for people who refuse both Cologuard and colonoscopy, which we think will be a small fraction of the overall opportunity," Conroy said.

"The other thing to know about a blood-based program is we don't anticipate having this study completed until after it's too late to be in the next [US Preventive Services Task Force] USPSTF guidelines. That's true, we think, of any other entrants in the space," he highlighted. "So, the first time a blood-based test would potentially be in the USPSTF guidelines would be in the 2026 to 2027 timeframe."

Until that time, he said, Exact intends to increase the market penetration of Cologuard, which currently stands at about 5 percent.

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