The concept of walking into any clinic in the world, getting a blood draw to detect an early-stage tumor, and, if necessary, starting treatment to nip a solid malignancy in the bud has gotten just a little bit closer to becoming a reality.
Labcorp, a global laboratory services company, and Ultima Genomics, a burgeoning next-generation sequencing (NGS) company, today announced a collaboration to enable new whole genome sequencing (WGS) in liquid biopsies for clinical applications, such as detecting rare cancer events and molecular residual disease (MRD) in patients with early-stage solid tumor cancers.
“Labcorp is well-positioned to provide a single source solution for testing in patients with cancer, including the utilization of precision medicine assays in oncology,” Taylor Jensen, Vice President, Head of Oncology Science, Labcorp, told Inside Precision Medicine. “Collaborations like these enable Labcorp to be at the forefront of leveraging technological innovation, both internally and externally, to provide testing that can impact the lives of the patients that we serve as part of clinical testing or pharmaceutical trials.”
The needle in a haystack
Gilad Almogy, PhD, founded Ultima Genomics on the idea that next-generation sequencing is a data-generating business. Since the company’s inception, Almogy has sought solutions for applications requiring generating and analyzing billions of genomes, such as single-cell analysis, AI model training, or when a clinical lab transitions from gene expression panels to whole genomes.
Ultima’s solutions, the UG 100 sequencer, and the Paired Plus Minus Sequencing (ppmSeq) method made a big splash in April 2022 when the company emerged from stealth, touting $1 per gigabase sequencing—the equivalent of $100 per human genome.
Following its launch, Ultima announced an early access program that drew major players such as NVIDIA, Regeneron, and The Broad Institute. However, with the collaboration with Labcorp, a global leader in making clinical tests affordable, Ultiima is entering one of the world’s largest biomedical stages. Almogy believes Ultima’s technology is a perfect fit for LabCorp’s goals in NGS-based oncology testing.
“Our focus has been to work with the largest users or the ones that have the potential to become the largest sequencing users and enable them,” said Almogy. “From day one, we’ve targeted low-cost and high-throughput, and we came out with the $100 genome. It’s also an extremely high-accuracy platform for detecting base substitutions or SNPs, which you’re looking for in oncology.”
According to Almogy, this is all about ppmSeq’s unique capability, which provides an unprecedented accuracy useful for specific applications but not required for all sequencing on the UG 100. What makes ppmSeq unique is that it distinguishes between true SNVs and sample damage-induced miscalled bases without over-sequencing by capturing and sequencing both strands of the template simultaneously and then filtering out any base variants that appear only on the plus or minus strand, leaving only true SNVs detected.
The pairing of UG 100 and ppmSeq is an ideal solution for detecting cancer recurrence, or MRD, in a liquid biopsy, an extreme example of the “needle in the haystack problem.” To provide context, humans have approximately 30 trillion cells, each with three billion base pairs, thousands of which are mutated. When many of these cells die, they shed into the bloodstream, producing cell-free DNA (cfDNA), and it is possible that healthy cells also actively release cfDNA fragments. Cancers also shed cells, with late-stage tumors shedding significantly more than early-stage or recurring tumors. As a result, detecting cfDNA from cancer in the presence of highly variable cfDNA from healthy cells necessitates extreme sensitivity. To find these extremely rare cancer cases, says Almogy, you need technology to spot a one-in-a-million occurrence with pinpoint accuracy.
“If you’re going to find a needle in a haystack, you better look at a lot of hay, and when you see a needle, you need to know it’s a needle,” said Almogy. “To look at extremely large datasets, you need the throughput and the accuracy for rare events—in this case, somatic accuracy and not germline accuracy. That’s critical. So, Ultima’s technology was born for this application, which is the needle in the haystack problem—you’ve got to see a lot of data, and you’ve got to trust the signal you read.”
The strategy pairs Labcorp’s Plasma Detect—the first clinically validated, tumor-informed, WGS-based circulating tumor DNA (ctDNA) MRD solution for research and investigational use—with Ultima’s UG 100 platform and ppmSeq technology. Preliminary data demonstrates that this strategy enables the detection of rare variants at extremely low limits, improved sensitivity and specificity, and more efficient, scalable, and cost-effective workflows.
“During a preliminary evaluation of the Ultima Genomics platform and ppmSeqTM technology, we observed promising data that could potentially lead to improved performance in certain areas of testing like molecular residual disease (MRD),” Labcorp’s Jensen said. “When combined with the cost and throughput benefits that Ultima provides for applications like whole genome sequencing (including Labcorp’s MRD solution), we are excited to collaborate around current and future product development.”
Walking the walk
According to Almogy, if this deal with Labcorp is to succeed, Ultima must deliver high-quality products on time and be able to scale as Labcorp implements this test.
“We’re not a clinical company; we’re a technology provider,” said Almogy. “LabCorp does all the clinical work, all the solution work, and integrates everything. They are the ones coming up with the patient-facing solution, whereas Ultima provides the tools.”
Since Ultima produces all of its tools and reagents, Almogy said his company should be more than capable of handling the workload resulting from its partnership with Labcorp, which has services in around 100 countries.
“We’re a fully vertically integrated supply chain in California,” said Almogy. We have the ability to scale with our customers and give them all the assurances.”
Ultima’s partnership with Labcorp will need to run almost flawlessly to advance whole genome sequencing applications and oncology testing. At the same time, Ultima must continue to expand and innovate to realize Almogy’s vision entirely.
“This is a big moment of recognition for what we have done,” said Almogy. “But really, its the beginning of the road. It’s not about one tool or test. It’s about helping patients, and we still have work to do there.”
Almogy added, “Whatever is good enough for now won’t be good enough in five years. We have to keep developing our next-generation [tech]. We’ve said it publicly: we started on that genome, which is a great start, but that’s not the end goal. We have to keep driving it.”
Ultima faces a difficult challenge in meeting its end of the bargain with Labcorp while trying to innovate and grow. Regardless of how smoothly that goes, this is a step toward improving access to affordable genetic testing in emerging markets with significant unmet needs and in every corner of the world.
“The trend is that every solid tumor will be tracked to an MRD event,” said Almogy. “But as much as it seems like sequencing has caught on, sequencing is still incredibly early. MRD testing is having a moment now, but it’ll go beyond MRD. Genomics tests are not only for cancer. Eventually, screening will be everywhere.”
