NEW YORK – Just months after launching its first commercial product, a test for guiding immunotherapy in melanoma patients, glycoproteomics firm InterVenn Biosciences is changing direction to focus on the development of a blood-based assay for early detection of colorectal cancer.
The shift was driven by a combination of factors, said InterVenn President and Chief Operating Officer Erwin Estigarribia, including promising early results from the colorectal cancer test and a recognition that commercializing the immunotherapy product, called Dawn IO Melanoma, will require substantial time and resources.
Estigarribia, a veteran of diagnostic firms including CardioDx and Applied Proteomics, was named president of InterVenn this week.
InterVenn launched March 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. Bertozzi won the 2022 Nobel Prize in Chemistry for her work using click chemistry to study cellular glycosylation.
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 biomarkers, and, in fact, more than half of the cancer protein markers currently approved by the US Food and Drug Administration are glycoproteins.
The recent change in strategy is not the first for InterVenn. Upon its launch, the South San Francisco, California-based company was focused on developing a test called Glori for triaging pelvic masses, similar to Aspira Women's Health's OVA1 test. It then shifted focus to developing a test for early detection of colorectal cancer. In 2021, following a $201 million Series C funding round, InterVenn announced that it planned to focus on the Dawn IO test, with John Leite, the company's chief business officer at the time, saying that it would be its "marquee product to go to market and to really introduce [InterVenn's glycoproteomics] platform to the industry."
Leite left InterVenn in September and is now senior VP and general manager of pulmonology and market access at Veracyte.
This week, explaining the move back to colorectal cancer, Estigarribia said that while InterVenn continues to work on the Dawn IO test, it believes that meaningful sales of that product remain a ways off and that the colorectal cancer test could provide a quicker route to revenue.
"Dawn as a product is incredibly complex relative to colorectal cancer in terms of the conversations that happen at the clinic," he said. "Also, the amount of evidence that we are generating to support Dawn is just something that takes a lot longer. You essentially have to wait for patients to expire when you are generating these hazard ratio curves."
Dawn "is a longer play for us, and when we looked at the bucket of capital available to us, and we looked at the performance of our [colorectal cancer] assay, we saw a sightline to make a much quicker impact in the market and in the clinic," Estigarribia said.
InterVenn's colorectal cancer assay is not meant as a population screening tool but rather is intended for use in patients considered at high risk for the disease. The test aims to detect advanced adenomas, which can turn into colorectal cancers if left untreated.
The colorectal cancer detection space is competitive, with colonoscopy established as the gold standard for adenoma and cancer detection and stool-based tests including various fecal immunochemical tests (FITs) and Exact Science's Cologuard offering less invasive options for colorectal cancer screening. More recently, Guardant Health launched a blood-based circulating tumor DNA test, Shield, for the early detection of colorectal cancer. Exact is also developing a blood-based test for colorectal cancer detection. Blood-based multi-cancer early detection tests either offered or under development from firms including Grail and Exact are also likely to play a role in colorectal cancer early detection.
Estigarribia said InterVenn believes that its focus on detecting advanced adenomas, as opposed to already developed cancers, will help it carve out a space in this crowded market. He added that the company believes there is unmet demand for a noninvasive test aimed specifically at the high-risk population, which he put at around 8 million to 11 million people in the US.
InterVenn's Noninvasive Identification of CRC and Adenomas in Early Stages (NICE) study, a prospective study of 3,000 patients enriched for adenomas, is expected to wrap up by the end of the year. Estigarribia said that initial results from the study led the company to believe that it could improve upon the performance of existing noninvasive tests for detecting advanced adenomas in high-risk individuals.
Estigarribia did not provide specific data, which he said InterVenn would present at the JP Morgan Healthcare Conference in January, but said that the test showed sensitivity of well over 60 percent, a figure that he said investors and key opinion leaders had identified as a benchmark. He said the test's specificity in the NICE study was "on par or above tests or publications that have been published to date."
Estigarribia has prior experience bringing a proteomic test for colorectal cancer detection to market. As senior VP of operations at Applied Proteomics, he helped develop and commercialize that company's SimpliPro Colon test, a blood-based assay that was likewise intended to detect colorectal adenomas and cancers in high-risk individuals. Applied raised more than $50 million in financing over its 11 years in business but was never able to achieve commercial traction for SimpliPro Colon. In 2018, the company sold its assets to DiscernDx for $1.9 million.
Looking back at Applied's struggles, Estigarribia said that one of the test's main problems was that while it provided an improvement in patient convenience — allowing for blood-based as opposed to stool-based testing — it didn't offer substantially better performance than incumbent noninvasive colorectal cancer tests.
"The number one advantage was blood versus stool. That's really what it provided," he said.
He said that, by contrast, the InterVenn test offers significantly better sensitivity for detecting advanced adenomas than do existing products.
It won't be possible to judge that statement until the company releases its data in January, and additional demonstrations in additional cohorts will likely be necessary for InterVenn to make its case. That said, if the company's test does indeed offer sensitivity for advanced adenomas of well above 60 percent, it would surpass existing products. Cologuard, for instance, has sensitivity of 45 percent for precancerous lesions, while FIT has sensitivity of around 25 percent. Guardant's Shield has shown sensitivity of 20 percent for detecting advanced adenomas.
Existing tests do better, however, when looking only at adenomas with high-grade dysplasia, which are among the most likely to turn into colorectal cancer. Cologuard offers sensitivity of 69 percent for advanced adenomas with high-grade dysplasia, while FIT has sensitivity of around 40 percent. In January, Exact presented data from a study of a second-generation version of Cologuard in which the test showed 57 percent sensitivity for advanced adenomas and 83 percent sensitivity for advanced adenomas with high-grade dysplasia. The company is currently running a clinical trial for the second-generation test and plans to release results in late 2022 or early 2023.
While InterVenn has put the Dawn IO Melanoma and Glori pelvic mass tests on the back burner, both can be ordered through the company's CLIA lab. Estigarribia described the Glori test as something of a proof-of-concept product demonstrating the validity of the company's approach and platform. Acknowledging the difficulty Aspira has had commercializing a similar assay in OVA1, he said InterVenn sees its test as more of a starting point to branch out into other areas of women's health than a standalone product.
He said that InterVenn has "a very small" sales force for Dawn that is primarily focused on engaging with clinicians at major cancer centers to understand and generate data on how the test is being utilized.