NEW YORK (GenomeWeb) – A new blood-based cancer testing firm, CellMax Life, made its debut this week with the launch of its first assay — a CTC-based early colorectal cancer detection test available currently through its lab in Taiwan.
The company has amassed about $14 million in venture funding to support ongoing studies assessing the clinical utility of the test, called CellMax CRC-Protect, and development efforts for other tests in its menu.
Though CRC-Protect is its first publicly promoted test, the company also describes several others on its website as currently available for patients to order through its Taiwan lab. These include a germline cancer risk mutation panel, a liquid biopsy mutation-based test for guiding cancer treatment decision making, and another intended to monitor disease recurrence.
Atul Sharan, CellMax Life's co-founder and CEO, told GenomeWeb that the firm has a broad technology platform incorporating both the proprietary microfluidic CTC-capture technology that is at the heart of the new CRC test, and other methods for sequencing-based ctDNA analysis and detection of epigenetic and other blood-based biomarkers.
Though all the tests on the company's website are currently available to patients, they have not been formally rolled out, and are being offered to "properly define utility and use-modalities" ahead of a full launch announcement, according to the company.
CellMax Life's overall goal is to provide a range of blood-based tests that together work to assess cancer in its earlier stages and support patients who do get cancer and progress.
Sharan would not share much detail about the company's technology or design for its tests, but said that the firm's "CMx" CTC isolation platform was initially developed by academic researchers in Asia, and was licensed by the company exclusively.
According to published research, CMx relies on a "chaotic mixing microfluidic chip" that incorporates an anti-EpCAM-functionalized supported lipid bilayer as well as a "non-fouling lubricant-like membrane." Captured CTCs can then be analyzed or counted using immunohistochemical staining and imaging.
The test detects early cancer by counting CTCs isolated using this platform, although Sharan said that the company also incorporates other molecular analytes like ctDNA, as well as clinical factors like age into its analysis.
CRC-Protect is currently only available through the company's laboratory in Taiwan, where Sharan described the regulatory environment as similar to the US, allowing labs to offer clinical testing under a laboratory-developed test (LDT) model.
Eventually though, CellMax does have plans to offer tests elsewhere in Asia, and also in the US, where it could face additional regulatory hurdles.
For example, on its website, CellMax offers an option for patients to seek out testing directly through the company.
Sharan said that patients who take this track do interact with a physician. But in the US, companies offering genomic testing with similar consumer-facing approaches have been reprimanded by the US Food and Drug Administration for employing models that track too closely to a direct-to-consumer paradigm.
CellMax is not the only company interested in blood-based early cancer detection via CTCs or ctDNA. Several others — including Guardant Health, an early leader in ctDNA testing of later-stage cancer patients, and Grail, launched by sequencing behemoth Illumina earlier this year — say they are working on the lengthy studies necessary to prove to clinicians, regulators, and payors that their respective tests are safe and clinically useful.
Some other companies have jumped into the pool with relatively little data supporting the ability of their tests to accurately identify or screen for early cancer. Still others are eschewing CTCs and ctDNA and looking to other blood-borne biomarkers like epigenetic signatures, or using machine learning to support early cancer screening assays.
For colorectal cancer specifically, Epigenomics' PCR-based Epi proColon test was recently approved by the FDA as the first blood-based colon cancer detection test in the US.
Other proteomic tests are also being explored. For example, MDx firm Novigenix has developed an assay, called Colox, which combines a 29-gene host immune response panel with a pair of tumor-derived protein biomarkers to detect not only early-stage colorectal cancer, but also large adenomatous polyps that can be precursors to cancer.
According to Sharan, CellMax's CRC-Protect blood test has achieved higher sensitivity and specificity than these competitors. The assay has been evaluated in two separate studies of over 500 Taiwanese patients at medical centers in Taiwan, which included a mix of asymptomatic and early-stage CRC patients.
Sharan declined to provide details about the results of the study, but the company claims that for moderate- to high-risk patients, the CMx platform correctly identified those who had colorectal cancer over 90 percent of the time.
Data from the studies has been only limitedly described and has not yet been published in a peer-reviewed journal.
CellMax has published some studies on its CTC-based colorectal cancer detection technology, including one in Nature's open access Scientific Reports this April, in which company researchers used the CMx platform to detect CTCs in individuals with normal colon, benign colon disease, preoperative non-metastatic, and metastatic colon cancers. They concluded that the platform could detect CTCs early in disease development, and that CTC count as measured by CMx correlated well with cancer progression.
According to the authors, the average number of CTCs in the group of patients diagnosed with colorectal cancer was significantly higher than the average amongst both the healthy group and the group with polyps.
Within each subgroup, the mean and median CTC numbers also increased with the severity of the subgroup's condition. For example, the authors wrote, amongst patients with colorectal polyps, the mean CRC counts were one, five, and eight, for the subgroups with hyperplastic, adenomatous, and severely dysplastic polyps, respectively.
After two years, non-metastatic cancer patients who had at least five CTCs were eight times more likely to develop distant metastasis within one year after curable surgery than those who had fewer than five.
This is not direct evidence that CellMax can sensitively detect early cancers in otherwise healthy patients — the indication in which the company is now marketing the test — but it does support the CMx platform's utility for predicting outcomes for patients who already have cancer, something other groups have also recently been able to achieve with ctDNA-based analyses.
According to Sharan, CellMax Life's as-yet unpublished 500-patient clinical study provides evidence enough that the test works for early detection — and importantly that it works better that colonoscopy — to support the company's push forward.
"If your technology is not able to detect early cancer you can run studies forever. It really is a question of when you can prove that you can detect cancer early … and [whether it is] better than the standard of care [and whether] it improve[s] things," he said.
Also important to the firm's prospects, Sharan said, is the fact that blood-based testing has the potential to increase patient compliance with screening reccomendations — especially in Asia — more than the currently available stool-based tests, like simple fecal occult blood testing, or potentially Exact Sciences' stool-based genetic tests Cologuard, which proved its validity in a 10,000-patient trial.
Epigenomics' Epi proColon, the first FDA-approved blood-based CRC test, was demonstrated in more than 1,000 patients. However, despite the evidence that persuaded the FDA and also met with approval in China, clinicians have expressed skepticism that this or other blood tests should be widely adopted absent data that shows that they actually improve patient outcomes compared to stool-based methods.
In a viewpoint piece in JAMA last month, Ravi Parikh of Brigham and Women's Hospital and Vinay Prasad of the Knight Cancer Institute at Oregon Health and Science University outlined what they see as the shortcomings in the evidence that supported Epi proColon's FDA approval.
In an email to GenomeWeb, Prasad reiterated "Bottom line: clinicians should not use blood testing until [a] company generates some data on how it can be used to improve outcomes and publishes that data in the peer-reviewed literature. We have other options with much better proof."
Despite having made public relatively limited clinical data compared to Exact Sciences or even Epigenomics, Sharan expressed confidence in CellMax Life's ability to promote its test in Taiwan as an effective alternative to colonoscopy or fecal tests.
He reiterated that since screening is known to improve patient outcomes, and blood-based testing can improve compliance with screening compared to currently available stool tests and colonoscopy, logically, it should improve outcomes.
"The fundamental goal for … CRC-Protect is to improve colon cancer screening with an accurate and accessible test that is conducive to higher compliance," he said in an email.
In addition to the CRC test, the firm is also working on applying its CTC counting approach to detecting early breast and prostate cancers.