NEW YORK – Multiomics diagnostics firm DiscernDx presented data last week on its assay for nonalcoholic steatohepatitis as it works toward development of a rule-out test for the condition.
The blood test is the lead product for the Palo Alto, California-based company, which in 2018 purchased the assets of defunct proteomics outfit Applied Proteomics (API) and has since applied them to its focus on chronic disease.
"We think [chronic disease] is a good opportunity and a good application for a multiomics approach," said DiscernDx CEO Christopher Hall, noting that it was a less crowded space for omics test development than areas like oncology.
He said that the company's ultimate goal is to build a blood-based assay that can provide information on a number of chronic diseases, much like liquid biopsy firms in oncology are aiming to provide early detection for a variety of cancers.
"We picked NASH as our first indication so that it can be a vector to work with patients across many cardiometabolic conditions," Hall said, "because NASH patients are uniquely overlapped with heart disease patients, diabetes patients, metabolic syndrome patients, hypertension patients, etc."
The company's NASH test is designed to identify patients with nonalcoholic fatty liver disease (NAFLD) who are unlikely to progress to NASH and can safely avoid the liver biopsies commonly used to diagnose the condition.
Typically, Hall said, patients suspected of having NAFLD are given blood tests and ultrasounds to confirm the condition. Around 50 percent of NAFLD patients are classified as low risk for NASH with the other half considered at-risk for the condition.
"For those [at-risk] patients, they apply a combination of imaging techniques or they do a liver biopsy," Hall said. Only around 40 percent of these at-risk patients will have NASH, however. DiscernDx aims with its test to identify those NAFLD patients without NASH who can avoid undergoing biopsy.
The company is using for its test the mass spectrometry technologies it acquired through its $1.8 million purchase of API's assets. At the time of that purchase, Alex Morgan, a partner at venture firm Khosla Ventures, which backed API and is the sole investor in DiscernDx, said that while DiscernDx was not necessarily interested in continuing development of API's proteomic colorectal cancer test, it was attracted by API's success in "productizing" its mass spectrometry workflows.
"Basically all the little things that you need to do to operationalize a business, they've done over years," he said following the acquisition. "It's not a single technology improvement. It's figuring out all the little things you need to do to make something work more efficiently. Reducing the coefficients of variation, getting things down to a per-sample cost basis that is attractive and tenable. Those are important [challenges] that the company did a very good job at solving."
API was focused on proteomics, but DiscernDx has expanded the scope of the company's mass spec assays to cover lipidomics and measurements of metals, as well. The company has also been using DNA methylation data that it acquired as part of its 2020 purchase of Luminst Labs, through which it also acquired many of the patient samples used in development of its NASH test.
In the preliminary results, which DiscernDx presented last week at the 2021 NASH-TAG annual meeting in Park City, Utah, the company found that in a set of 90 samples, its combined proteomic, lipidomic, metal, and methylation measurements could distinguish between patients with and without NASH with an area under the curve of .92.
"The AUC curve would suggest that we could stop half or nearly half of [unnecessary] biopsies from happening," Hall said.
He said the company is now looking to integrate additional data sources and further optimize its model and then conduct a larger prospective trial evaluating the assay. In the study presented a week ago, the researchers looked at 326 samples from a cohort of 517 total patients collected prospectively from 29 centers across the US and Canada.
"We're going to continue to refine [the assay]… and then test it on some more prospective samples that we have, and then we will begin enrolling patients in a prospective clinical trial to be able to confirm [the results] in a bigger sample size," Hall said, adding that the company aims to begin enrolling for that trial this year.
Currently, DiscernDx uses mass spec for all of its clinical measurements, though Hall said the company could in the future incorporate epigenetic data like the methylation information included with the Luminist samples or transcriptomic data if it appeared helpful.
Hall said the company uses separate mass spec experiments to collect the proteomic, lipidomic, and metallomic data from each sample, though he said it plans ultimately to put the measurements in a single assay and could potentially move from mass spec to a different clinical platform. DiscernDx plans to offer the assay as a laboratory-developed test, though Hall said the company has not yet begun developing a CLIA facility out of which it could offer it.
"We're still largely in the R&D space, still a small, early-stage company," he said, noting that it currently has 10 employees.
DiscernDx's founding CEO, Bruce Wilcox, who was formerly senior vice president of research and development at API, left the company in November 2020 and is now vice president of proteomics at PrognomiQ, a clinical testing company spun out of proteomics firm Seer in September.
Hall said that while the company is currently backed solely by Khosla, he anticipates that it will at some point bring in additional capital to support its test development efforts.