NEW YORK (360Dx) – A lot of people who think heart burn is not an issue don't recognize that it could progress to cancer.
For Cernostics, raising awareness of this health threat could be the catalyst to increase sales of its TissueCypher Barrett's Esophagus test, the firm's CEO Michael Hoerres said in an interview.
Cernostics' assay, which predicts the risk of developing esophageal cancer in patients with Barrett's Esophagus, is undergoing clinical studies. The test has been available since last year from the firm's CLIA-certified laboratory in Pittsburgh, Pennsylvania, and last week, the firm said it raised $2.5 million in a Series A1 financing round with Illumina Ventures being the sole investor.
"With the Series A1 funding, our primary objective is to continue financing follow-on development studies for TissueCypher," Hoerres said. "We want to make TissueCypher the clinical standard for stratifying patients with Barrett's who are at risk, and we know that to make that happen we need to continually invest in doing robust studies and building the level of evidence to support the marketplace and its need."
TissueCypher is a digital platform for multichannel fluorescence whole-slide imaging and includes image reading, image segmentation, biomarker expression, and tissue structure evaluation. The firm developed it to overcome challenges with traditional methods of determining which patients are at risk for disease progression. The platform's performance, Cernostics said, is linked to clinical outcome or progress to cancer, not to the level of dysplasia.
Chronic reflux in the esophagus brings changes to the molecular and cellular features of the esophagus, which often results in Barrett's Esophagus, a risk factor for the development of esophageal cancer.
Gastroenterologists cannot adequately determine which patients with Barrett's Esophagus will progress to esophageal cancer. Therefore, patients with Barrett's must undergo regular surveillance endoscopies to check the status of the condition.
Jeffrey Prichard, director of surgical pathology in the department of laboratory medicine at Geisinger Health System, noted that the Cernostics test not only reduces subjectivity inherent in classic pathology conducted without the assistance of biomarkers, but it also provides valuable diagnostic information not available to pathologists by any other means. Prichard said that he helped Cernostics identify this area of clinical need to inform the development of the classifier, and he facilitated providing clinical samples for early biomarker discovery and training of the TissueCypher system.
Pathologists have a particularly difficult time deciding whether there's dysplasia in Barrett's Esophagus biopsies, he said. It is such a challenge that there is an accepted category called "indefinite for dysplasia," and the American College of Gastroenterology requires that when a pathologist reports a positive result, confirmation of the result must come from another pathologist, he said.
Prichard said that he told the TissueCypher development team that "one of the places in which we are really weak and even a little embarrassed as pathologists is making diagnoses [for] Barrett's Esophagus. We realized that if we could coordinate multiple markers in evaluating Barrett's and be able to correlate that with the morphologic findings that we use classically, then we could advance this and be less embarrassed in trying to diagnose dysplasia and predict the risk."
"Now we are at the point where we can say that if there's a questionable diagnosis, [TissueCypher] is going to tell you more reliably than a specialist pathologist whether it is a significant risk for the patient," he added.
If there are 20 patients with Barrett's Esophagus, he said, the system will identify the one patient that is at high risk of progressing to cancer, and healthcare systems could save "a lot of money" by eliminating the need for endoscopic monitoring in the remaining 19 patients.
The Cernostics classifier has shown "an improved correlation with risk of progression and does a better job than either a generalist or specialist pathologists," he added.
The platform employs multiplexed fluorescence digital imaging of biomarkers to improve on current histochemical methods, Hoerres said.
According to Cernostics, the classifier can quantify multiple antigens per biopsy section, including co-localized antigens, and conduct "objective reproducible extraction of quantitative biomarker, morphology, and spatial data by image analysis software." The platform employs computer vision and machine learning algorithms to capture hundreds of cell and tissue measurements of biomarkers and morphology and quantify complex biological relationships.
Barrett's Esophagus develops when chronic exposure to acid from the stomach leads to the deterioration of the esophageal cell lining, creating an environment for cancer. The total market for screening, diagnostics, and risk stratification is "very large and underappreciated," Hoerres said.
Barrett's and esophageal cancer primarily hits Caucasian males ages 50 to 80, he said, and men are five times more likely to have it than women.
Between 3 million and 4 million American patients receive screening for Barrett's and around 400,000 of these patients are diagnosed with the condition each year after receiving an upper gastrointestinal endoscopy, Hoerres said. Almost all the confirmed cases are candidates for getting TissueCypher testing for risk stratification, and the ailment's prevalence in western Europe likely doubles the size of Cernostics' addressable market, he added.
The incidence of esophageal cancer, once rare, has increased by more than 500 percent since the 1970s, according to Cernostics. It remains highly lethal, with a five-year survival rate of 17 percent, the firm said, citing American Cancer Society statistics.
This "dramatic increase" in esophageal cancers closely tracks with increases in obesity and chronic gastrointestinal reflux in western countries, and both are major risk factors for the development of esophageal cancer, Cernostics said.
In developing the test, the firm hand-curated thousands of patient records and identified which patients progressed to cancer. "We trained our classifier upfront on that outcome instead of trying to peg it to a level of dysplasia that's subjective," Hoerres said. "By eliminating that in the discovery and validation stage, we have now developed something that is predictive of cancer."
The company also identified a broad range of biomarkers that were indicative of Barrett's Esophagus and other gastrointestinal cancers and eventually narrowed them down to nine markers for the classifier.
Cernostics has published two clinical validation studies. The first, published in June 2016 in Cancer Epidemiology, Biomarkers, & Prevention, evaluated the performance of TissueCypher by comparing patients who progressed to either high-grade dysplasia or cancer with those who didn't progress.
In the study, the researchers collected data from Barrett's Esophagus patients at four institutions — Geisinger Medical Center, University of Pittsburgh Medical Center, University of Pennsylvania, and Academic Medical Centre in Amsterdam. They matched 79 patients who had Barrett's Esophagus and who progressed to high-grade dysplasia or esophageal adenocarcinoma after more than one year with 287 patients who did not progress within that time. The group conducted immunofluorescence analyses of biopsies and analyzed quantitative biomarker and morphometric features.
They selected prognostic features using a training set of the population and combined them into classifiers. They then assessed the top-performing classifier in a validation set. The researchers concluded that the test "has the potential to improve upon histologic analysis as an objective method to risk-stratify Barrett's Esophagus patients."
It identified "high risk patients that were 9.4 times more likely to progress to cancer within five years of biopsy" than the non-progressing class, Hoerres said.
Later, in September 2016, the company published a second study in the same journal and conduced with the same clinical collaborators. They tested the platform while excluding patients who progressed to esophageal cancer within 12 months.
The researchers said that their results indicated that molecular and cellular changes associated with malignant transformation in Barrett's Esophagus "may be detectable as a field effect using the test, and that a tissue systems pathology test may provide an objective method to facilitate earlier identification of these patients requiring therapeutic intervention."
In the study, patients identified as high risk by TissueCypher were 46 times more likely to have either high-grade dysplasia or esophageal adenocarcinoma at the time of a baseline biopsy versus the low-risk class.
The investment by Illumina Ventures, an independent, early-stage venture capital firm, brings the total that Cernostics has raised since its founding in 2008 to $13 million.