NEW YORK – Backed by $830 million in new funding, Caris Life Sciences expects to launch a blood-based version of its comprehensive genomic profiling service for late-stage cancer patients later this year and has plans to expand liquid biopsy testing in other areas.
The new test will run on a backbone of whole-exome sequencing of cell-free DNA and sequencing of cell-free RNA, dwarfing the targeted panels used by most competitors in the market.
Relying on the breadth of this platform, the firm intends to then use the same clinical sequencing pipeline to rapidly add products for cancer screening, monitoring, and residual disease detection.
Caris has discussed its ongoing development of liquid biopsy solutions in past years, but the new formalization of its plans and timeline is being buoyed by a large influx of cash via an $830 million equity round the firm announced last week.
David Spetzler, Caris' president and CSO, said that some of this money will help the company finish building a new lab space to enable it to offer its suite of liquid biopsy tests on an expanded scale.
"Right now, the construction timeline to have [the new lab] finished is about August," Spetzler said. "I've never seen a construction project finished on time, but that's what we're waiting for [and] we'll do a beta launch before that with very limited access. But for commercialization, we need that new lab to be complete."
According to Spetzler, growing data from competing platforms has already begun to cement the clinical utility of blood-based cancer profiling in the minds of the oncology community.
But the fact that liquid biopsy has become more solidly established in recent years also means Caris will be facing significant competition — including from companies like Guardant Health and Foundation Medicine that have already had their assays approved by the US Food and Drug Administration.
Spetzler said the company believes it can offer significant improvements over the most prominent commercial tests based on the ability of its dual DNA and RNA platform.
"What's different in the way that we're approaching it from everybody else is that the assay that we built is measuring the whole exome in cell-free DNA and the whole transcriptome out of cell-free RNA … much like we do with the tissue," Spetzler said.
"What we've found is that by adding in the RNA component, we've solved the 'non-shedder problem,' where about 40 percent of metastatic cancer patients don't have sufficient amounts of cell-free DNA to run the typical cell-free DNA assay."
"By adding in the RNA, that number drops to basically zero," he said. "In other words, we're getting sufficient amounts of nucleic acid out from nearly all patients to be able to run our assay."
Some other precision oncology firms, like Personalis, now offer broad transcriptome-sequencing in tissue. RNA liquid biopsy approaches for narrower targets have also been explored for various applications. But the leading companies currently offering comprehensive liquid biopsy-based genomic profiling have largely stuck to DNA.
Spetzler said that this is probably because sequencing RNA is "really hard."
"Everyone says [that] it's an unstable molecule, and that's true. But it's not unstable because of the nature of RNA, it's unstable because of the laboratory processes that have thus far been used to work with it."
Typically, RNA sequencing fails in 30 to 40 percent of tissue samples "but we have our own proprietary method … and our failure rate is .03 percent," Spetzler said.
According to Spetzler, while it hasn't published results yet, Caris has already collected the necessary validation data to support the use of its platform on blood samples for genotyping advanced cancer patients. But for its other planned applications — in monitoring, MRD detection, and early detection — the company will need to complete prospective trials.
"We've started those trials already, but a lot of this [new] money will also go towards financing those," Spetzler said. "To do a screening diagnostic, you need thousands and thousands and thousands of patients to go through the FDA."
In this arena, Caris will also be facing significant competition. For MRD, Natera has been offering a testing service called Signatera, which uses tumor whole-exome data to create patient-specific MRD and monitoring assays. Inivata has advanced a similar technology, and Personalis said recently that it plans to do the same. Also, Guardant Health has launched a tumor tissue-agnostic MRD assay that relies on detection of genome-wide epigenetic signals.
In early detection, Grail is expected to launch its Galleri multi-cancer early detection test during the first half of this year, and other firms, like Burning Rock and Delfi, are not far behind advancing similar multi-tumor platforms. Still others, including Guardant Health, Exact Sciences, and Freenome, have staked initial claims in colorectal cancer but have stated they expect to expand to other tumor types in the future.
Almost all of these methods either exclusively use or include the analysis of epigenetic signals — patterns of DNA methylation or fragmentation. Caris' approach will instead reflect its current tissue-based methodology of capturing changes in DNA and RNA.
Spetzler argued that not including methylation is not an issue for the firm, because its analysis of the transcriptome reflects the downstream biological effect of epigenetic alterations like DNA methylation.
According to Spetzler, Caris is also at an advantage due to its history of comprehensive tissue testing, with over 300,000 patients profiled thus far. This has led to a variety of discoveries, including a methodology for predicting tumor tissue of origin in patients with cancers of unknown primary.
"We've already built algorithms in the tissue … [and] in the creation of those signatures, each one of those becomes a molecular definition of that disease type," Spetzler said. "So we already know exactly what we're looking for … and we can look for those signatures in the blood data."
"We just need to know which ones are conserved, basically, which elements are highly reliable in the blood that are part of our signatures in the tissue, so it's a very different kind of development approach from the idea of 'let's take blood from healthy people and blood from people that have cancer and see what's different.'"
Spetzler said that taking its approach to the clinic for MRD and disease monitoring will likely take two or three years. However, the screening indication should advance faster because for early detection, following up on positive cases — whether via imaging, biopsy, or other tools — offers an immediate "gold standard" answer as to whether a participant with a positive blood test has cancer or not.
"We've got breast and colon already underway, and really, it's just a numbers game. The number of patients enrolling in those trials during COVID is way down, but [they] will start to go back up, and once we hit 10,000 or so patients, we'll probably have the cohort we need to fully validate that," he said.
"That is sufficient to get a test out there," Spetzler said. "But then it'll take decades, really, to understand how much we can move the needle in terms of curing people of cancer, because now we're finding it at stage I and cutting it out."