NEW YORK (GenomeWeb) – Liquid biopsy firm Resolution Bioscience has maintained a tight focus over the last several years on its strategy of developing narrow, clinically focused liquid biopsy assays for use as US Food and Drug-approved companion diagnostics to guide targeted cancer therapy.
The company has been relatively quiet in what has become a crowded space in which many other firms regularly announce financing rounds and names like Guardant Health have now become publicly traded.
But its more circumscribed path has not hindered Resolution, CEO Mark Li said in an interview earlier this month. The company saw its first full year of profitability in 2017, and the firm, which currently employs about 40 people plus various outside contractors, is now moving into a new lab facility and "hiring aggressively" with the potential to grow its staff up to 60 or 70.
According to Li, Resolution is hoping to be part of shifting the discussion around liquid biopsy tests forward — from the question of blood-tissue concordance to cementing and refining an understanding of the clinical utility of blood-based cancer testing.
Reflective of that, the company saw a study published in late November in which investigators at Memorial Sloan Kettering Cancer Center used the ResBio assay to search for informative mutations in blood samples from 210 individuals with non-small cell lung cancer who were enrolled consecutively.
The team reported in the Journal of the National Cancer Institute that the Resolution test could quickly and accurately identify targeted treatment-relevant mutations in the patients studied.
In blood, the team found somatic mutations in 135 of the cases with a test turnaround time span of four to 22 days, and a median of nine days. Nearly 90 percent of the somatic changes found by liquid biopsy also turned up with NGS on tissue biopsies, which took 13 to 69 days, with a median of 20 days.
Importantly, the researchers reported that the overall concordance between the somatic mutations found in blood and tissue increased to more than 96 percent when it came to uncovering oncogenic driver gene mutations. The group also reported clinical responses to liquid biopsy-directed targeted therapy in 46 cases.
"It's an ongoing study, so the data set is actually quite a lot larger than what was in that paper now," Li said.
"What we and MSK are really focused on is [figuring out] how can we can [provide] the data to help drive the next set of guidelines and real clinical application of blood-based testing," he explained. "The idea of turnaround time … is something that [they] focused on in the paper. And that's really changed, from talking to the thoracic oncologists there … to be able to get a report before you get tissue back and put the patient on therapy quickly. So those kinds of things remain our focus and those kinds of studies are super important for us.
"Really the goal [of this and of our other studies] is to move the discussion past … 'Hey look what I can see in plasma' to clinical utility," he added. "That's what's really going to be critical to move the industry forward with payors."
As part of this shift of attention to clinical utility, the liquid biopsy field may also be poised to begin paying more attention to the landscape of available platforms — and whether there are substantive differences between various commercial assays that might lead to preeminence of one technology over another.
Comparisons like this have already been spearheaded by firms like AstraZeneca, which has led technology "bakeoffs," reporting, for example, on a head-to-head comparison of four unnamed companies in a 2017 liquid biopsy workshop co-sponsored by the US Food and Drug Administration and the American Association for Cancer Research
"Our original goal remains to prove out our [approach] and eventually have our technology power the majority of liquid biopsy tests globally," Li said.
As the company has emphasized before, one way Resolution believes it can differentiate itself is through a system that was developed specifically for cell-free DNA, rather than adapted from a sequencing methods designed for tissue samples.
"We've talked about this in the past but you know we have very short probes — 40 bases — whereas I think a lot of the rest of the competition are still using [Agilent] SureSelect which is 120 bases," he said. "We've always felt that this is different than tissue and so applying tissue-type technologies like long probes isn't the way to do this."
Li also highlighted the fact that Resolution has designed its system to have a very high on-target rate. "We're running very large panels that have routinely 99 percent on-target in clinical samples. This needs to be commercially viable for labs to adopt, which means it can't waste sequencing with off-target."
Another differentiator for Resolution has been its decision to develop narrower panels focused on specific clinical areas rather than a larger pan-cancer approach.
"We are still are more focused on clinically actionable panels … as opposed to signal searching … because I think it makes it hard on reimbursement and we have seen that played out now," Li said. "You can see what others are getting coverage for, and its very limited parts of their panel."
Despite Resolution's confidence, there is one reason that smaller panels might not be preferable to a comprehensive or pan-cancer assay, which is the growing excitement around tumor mutational burden (TMB), or mutational load, as a biomarker to predict patient response to cancer immunotherapy. To calculate TMB, you need to sequence a large enough portion of the genome.
But in Li's view, the practical and economic downsides of trying to do TMB in liquid biopsy seem severe. "You have to sequence at least 150 to 200 genes to do it. That's easier if you're doing it in tissue where you've got a high tumor content but not in plasma."
"I mean we can certainly do it as a technical problem and you know we can run a global trial for it and we can probably get an approval for it. But can anyone make money running that particular panel on blood?" he added.
That said, Resolution is definitely exploring the immuno-oncology area, and has reported on work in which it was able to use its technology to analyze certain aspects of the cancer-immune system interaction like the T-cell repertoire.
In regard to the company's progress in seeing its kits approved by FDA, Li couldn't discuss timelines. "Its one of those fun things with working with drug companies. Everything is confidential," he said.
But he said that Resolution is running registration trials, and working on a premarket approval for a global companion diagnostic, so it is "fully engaged with the regulators" and has had two "very successful interactions" with them to date.