NEW YORK – Glycoproteomics diagnostic firm InterVenn BioSciences is developing a test for the early detection of colorectal cancer.
According to Klaus Lindpaintner, the company's chief scientific and medical officer, a pilot study found the test was able to detect colorectal cancer with 98 percent sensitivity and 91 percent specificity and advanced adenomas with 98 percent sensitivity and 85 percent specificity.
Those performance numbers were generated in a small retrospective cohort and considerably more validation work is needed to determine whether they hold up. If they were to hold, the InterVenn test would be a significant improvement over existing non-invasive tools for colorectal cancer screening.
Based in South San Francisco, InterVenn launched in March of 2018 to commercialize glycoproteomic analysis methods developed by University of California, Davis professor Carlito Lebrilla and Stanford University professor Carolyn Bertozzi, both cofounders of the firm. At the end of 2018 it raised $9.4 million in a funding round led by Genoa Ventures.
Protein glycosylation, in which sugars modify various amino acids, is a common post-translational modification and an important phenomenon in the biology of various diseases, including many cancers. Given this, researchers have long considered glycoproteins to have high potential as protein biomarkers, and, in fact, more than half of the cancer protein markers currently approved by the US Food and Drug Administration are glycoproteins.
Glycoproteomic analysis has been challenging, however, due in large part to the wide variety of possible glycosylations, called glycans. InterVenn is using approaches developed by Lebrilla and Bertozzi to streamline glycoprotein analysis that enable mass spec-based analysis of hundreds to thousands of glycopeptides in serum simultaneously.
In the colorectal cancer work the company analyzed 120 blood samples, roughly two-thirds of them from patients with colorectal cancer and one-third from patients with advanced adenomas, which precede the development of colorectal cancer.
They compared these against a set of healthy controls, splitting the cohort into a training set they used to develop their diagnostic panel and a testing set they used to evaluate its performance.
Lindpaintner noted that further validation of the results will be needed. In addition to being relatively small and retrospectively collected, the cohort used to develop the test was all Caucasian.
"But given the fact that we saw this high performance, we are very optimistic that we will be able to provide that kind of [result]," he said.
Lindpaintner said the company is now working with a number of academic collaborators to recruit patients for prospective studies of the test.
Colonoscopy is the gold standard for colorectal cancer screening. However, it is an invasive and relatively time-consuming procedure with a small but real risk of negative side effects. Stool-based tests like fecal immunochemical tests, which look for hidden blood in stool samples are also commonly used for colorectal cancer screening, though they are not as accurate as colonoscopy, especially when it comes to picking up precancerous advanced adenomas.
Exact Sciences' Cologuard test adds detection of cancer linked DNA markers to FIT testing, which has boosted the performance of the test, though sensitivity remains low for advanced adenomas, and it has a higher false positive rate than FIT testing. In a company-funded validation study looking at 9,989 subjects, Cologuard had sensitivity of 92.3 percent for colorectal cancer and sensitivity of 42.4 percent for advanced adenoma with a specificity of 89.8 percent while FIT had sensitivity of 73.8 percent for colorectal cancer and sensitivity of 23.8 percent for advanced adenoma with a specificity of 96.4 percent. In October, Exact Sciences released data on a new version of Cologuard that identified colorectal cancers with sensitivity of 92 percent and advanced adenomas with sensitivity of 65 percent at 92 percent specificity.
At the level of performance achieved in the recent study, the InterVenn test would catch significantly more advanced adenomas than Cologuard or FIT though with the trade-off of a higher level of false positives. The test could also benefit from being blood-based as opposed to stool-based, with the former being a more convenient sample source.
InterVenn is not the first proteomics to company to pursue a colorectal cancer test. Now defunct diagnostics firm Applied Proteomics developed a protein test called SimpliPro Colon for evaluating symptomatic patients to determine whether they should receive a colonoscopy. It was also planning to launch a test for screening asymptomatic people for colorectal cancer before it closed at the beginning of 2018. Its assets were purchased by Khosla Ventures-funded startup DiscernDx, but DiscernDx said that it was primarily interested in the company's mass spec technology as opposed to the colorectal cancer test itself.
InterVenn also continues work on its ovarian cancer test, which is intended to assess the likelihood that a pelvic mass is malignant, similar to Vermillion's OVA1 and Overa tests. Lindpaintner said that the COVID-19 pandemic had slowed recruiting of patients for the company's ongoing prospective validation study but that to date it had enrolled around 350 patients across the US and Southeast Asia and had recently started recruitment in Australia.
Previously, InterVenn CEO Aldo Carrascoso said that in data from 200 prospectively analyzed patients, its test distinguished between benign and malignant masses with a sensitivity of 91 percent and specificity of 92 percent. He did not provide a breakdown of the test's performance by cancer stage but said that it had performed well across all stages.
Lindpaintner said the company planned to release data from a second interim analysis towards the end of the Q1 or beginning of Q2.
In addition to its internal diagnostics development, InterVenn offers research services to outside firms and Lindpaintner said it is "currently engaged with a number of large [drug] industry partners to apply this tool to target discovery and target validation."