NEW YORK – Ultima Genomics continues to demonstrate the performance and utility of its sequencing platform in the clinical space, recently applying it to blood-based minimal residual disease (MRD) detection of cancer.
Last week, precision oncology firm Inocras launched MRDVision as a clinical test, which uses Ultima's platform and is designed to detect MRD from circulating tumor DNA (ctDNA) in blood.
Separately, a recent study, published by researchers from Weill Cornell Medicine and their collaborators, also illustrated Ultima's suitability for blood-based MRD monitoring, using whole-genome error-corrected sequencing of ctDNA.
According to Inocras CEO Jehee Suh, the company had been developing and validating MRDVision for clinical use since last year. The test leverages Ultima's paired plus minus sequencing (ppmSeq), a duplex sequencing method that promises to achieve at least 1-part-per-million accuracy for calling single nucleotide variants (SNVs).
"We realized that we needed an approach on the back end to remove a lot of the errors that you see on the sequencing of ctDNA in order to get to a lower limit of detection," said Suh. "After assessing a number of technologies, we zeroed in on the Ultima Genomics ppmSeq."
MRDVision is a panel-free, tumor-informed liquid biopsy assay. Patients first receive the CancerVision assay, an existing product from Inocras that performs tumor-normal paired whole-genome cancer profiling. This generates personalized tumor mutation signatures for each patient, serving as a baseline for subsequent MRD testing.
Inocras Chief Medical Officer Erin Connolly-Strong said the company performs target-enhanced whole-genome sequencing for CancerVision, which aims for 40X coverage for the tumor sample while achieving greater sequencing depth for over 500 key biomarker genes. For the germline sample, the sequencing coverage is around 20X, she noted.
For MRDVision, the test starts with two 10 ml tubes of peripheral blood from the patient. The assay performs WGS on ctDNA extracted from the blood, with a targeted sequencing depth of about 90X, Connolly-Strong said.
As part of the clinical validation for MRDVision, Suh said, the company applied the assay to cell-free DNA (cfDNA) samples from 20 postsurgical ovarian and 20 lung cancer patients with different disease stages. Overall, the assay detected tumor-derived signals in 6 percent of cases that were not identified by a commercially available comparator assay, which the company declined to identify.
Using analytical simulations with high tumor mutational burden tumors and plasma sequencing at 100X coverage, MRDVision could achieve a limit of detection (LOD95) of 1 part per million, Suh noted.
As the first lab to provide ppmSeq as part of an MRD clinical test, Suh said the company "worked very closely" with Ultima throughout the clinical validation process. "There is no playbook," he noted. "Every decision has been a first-time decision ever."
MRDVision can be ordered through providers, Suh said, and has a turnaround time between two and four weeks. The MRD assay, which is not yet covered by insurance, has a list price of $3,000. Meanwhile, the list price for CancerVision to establish the tumor mutational baseline is another $4,000, Suh noted. If a patient has already received the CancerVision assay previously, the test does not need to be repeated.
For the first 50 customers, Inocras is offering one baseline cancer test and two MRD monitoring assays for $4,000, Suh said, adding that each customer can order multiple sets of tests within the promotional period, which lasts through the end of the year.
Suh said the target customers for MRDVision include pharmaceutical companies that are using MRD as a surrogate marker in clinical trials as well as clinicians. The company has "a few places that are lined up to use [the test] immediately," he added.
Inocras is not the only group that is tapping Ultima sequencing for solid tumor MRD testing. Quest Diagnostics, for instance, announced a partnership with Ultima last year to potentially develop assays for solid-tumor MRD testing for clinical and biopharmaceutical MRD applications. Additionally, Myriad Genetics has also teamed up with Ultima to explore the potential for improving the performance and cost of its MRD test with ppmSeq sequencing.
Moreover, a team of researchers led by Dan Landau, a faculty member of the New York Genome Center and Weill Cornell Medicine, has also been leveraging the Ultima platform liquid biopsy-based cancer monitoring.
Landau's team showcased their efforts in a Nature Methods paper published last month, some results of which were previously described in a preprint posted on BioRxiv in 2022.
Landau and his collaborators used the Ultima platform for deep WGS at about 120X coverage of plasma samples, detecting ctDNA within the part-per-million range, according to the study.
Enabled by Ultima's lower sequencing cost, Landau's team further implemented duplex error-corrected sequencing of circulating cfDNA (ccfDNA) at a genome-wide scale, which helped achieve "three orders of magnitude reduction in error rates" compared to standard sequencing, they wrote. This error-corrected approach allowed the researchers to assess disease burden in individuals with melanoma and urothelial cancer without matched tumor sequencing.
The goal was to show "whether we can use the lower sequencing cost to do something that is not just incremental," Landau said, applying duplex error correction at the scale of the entire genome in cell-free DNA.
As part of the study, Landau's team performed a head-to-head comparison between matching libraries for the Ultima and Illumina platforms. The results indicated that Ultima worked "just as well" for detecting copy number variants while having a competitive edge for SNV detection versus Illumina, Landau said. Meanwhile, when it came to homopolymers and indels, Ultima slightly underperformed compared to Illumina.
Still, "in the cell-free DNA world, we care much more about the SNV accuracy than that of homopolymers," Landau noted. "The advantage of SNV accuracy far outweighs the limitation of the homopolymers."
Landau currently serves on the scientific advisory board of molecular diagnostics firm Veracyte, which acquired C2i Genomics in 2024. He was the scientific cofounder of C2i Genomics, a joint venture and spinout from the NYGC and Weill Cornell Medicine that has been commercializing a WGS-based liquid biopsy test for solid tumor MRD detection using the method developed by his team.
Veracyte said it plans to launch its first MRD assay in muscle-invasive bladder cancer in the first half of 2026, with other cancer indications to follow.
Moving forward, Suh said Inocras will continue to generate "a lot more clinical evidence" for its MRDVision test. "The initial clinical validation is a very simple approach, where it shows that the test works," he said. "What we would love to do is bring this to bigger clinical studies of hundreds of patients."
Generating clinical evidence is also vital for obtaining reimbursement for MRDVision, which is "next on the horizon" for the company, Suh said.