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Johns Hopkins Spinout to Bring CancerSEEK Test to Clinic

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CHICAGO (GenomeWeb) – Newly launched cancer screening firm Thrive Earlier Detection is aiming to be among the first to bring genomic pan-cancer early detection tests to the clinic, confident that the relative simplicity and cost effectiveness of its approach — coupled with extremely high specificity — will ease a path to adoption.

The firm announced last week that it had formed, following a $110 million financing, to push a test developed by researchers at Johns Hopkins through to the clinic. Unlike many molecular testing startups, the company is beginning its operations with a 10,000-person prospective trial, and conversations with regulators already underway.

The Hopkins-developed CancerSEEK test received Breakthrough Device designation from the US Food and Drug Administration last year after investigators published a study in Science describing the assay and reporting initial sensitivity numbers.

Among other findings, investigators reported that the test — which algorithmically assesses mutations in 16 genes alongside levels of 11 protein markers — could detect a variety of cancer types while maintaining high specificity. At a specificity cutoff of 99 percent, for example, the median sensitivity for Stage II tumors was 73 percent, though it dropped to 43 percent for Stage I cancers.

"We do certainly emphasize the minimization of false positives because [we are targeting] a primary care audience and an otherwise healthy population, so we think focusing the follow up — psychologically, medically, financially — on those patients whose positive detection is truly a cancer is really critically important," Thrive CEO Steve Kafka said in an interview.

Thrive's next step toward commercialization — the Detecting Cancers Earlier Through Elective Mutation-Based Blood Collection and Testing (DETECT) study — is already fully recruited and underway with the first data read-out expected to come after a one-year follow-up.

"It's an explicit one-year follow-up, and then there are future time points built in as well, so we'll have the opportunity to continue to learn from that and all of that is being taken into account as we continue to engage with FDA around the design of future studies," he added.

In a glimpse at some of the DETECT results, shared earlier this year at the Advances in Genome Biology and Technology meeting, Hopkins researcher Joshua Cohen said that the test had already detected cancer, including colon and ovarian cancer, in nine study participants.

Cohen also reported on the team's development of algorithms that not only identify cancer, but predict the tissue of origin — something crucial for future clinical implementation in order to focus follow-up tests and treatments as efficiently and cost effectively as possible.

According to Cohen, performance for this location pinpointing differs by cancer type, with accuracy topping out at about 80 percent correct for colorectal cancer.

DETECT was initiated before early discussions around Thrive's investment and founding began, when CancerSEEK was under the umbrella of Hopkins spinout PapGene. Kafka said that PapGene is not continuing as a separate company, and has been absorbed into Thrive.

Although the current focus is on bringing CancerSEEK to market, Kafka added that Thrive doesn't necessarily intend to scrap the other efforts that PapGene had spearheaded. Notably, the Hopkins researchers who founded the spinout were pioneers in applying a liquid biopsy methodology to samples other than the expected blood or urine. Investigators had been collecting data on methods to diagnose cancer from pap smear or uterine brushing samples, and even in menstrual fluid collected in tampons.

"The focus of the company is really around advancing CancerSEEK primarily, but [we recognize that this is] a platform where other biopsy samples … are also really amenable to utilizing this kind of targeted approach," Kafka said.

"That was part of what was interesting to us too, actually – that there is a portfolio opportunity here to not only come to market with Cancer SEEK in an average-risk population but also potentially to bring other products around that that would allow us to extend the reach into other risk-defined populations where some of those approaches would be indicated," he added.

The CancerSEEK methodology, which combines sequencing of a panel of defined targets with measurement of cancer-associated proteins, has become somewhat of an outlier as other early detection firms have turned their focus toward broad genome-wide patterns that reflect aspects of the epigenetic contribution to cancer.

Guardant Health's research-use LUNAR assay, for example, combines mutation and methylation data. The company also made a move this year to acquire University of Washington spinout Bellwether Bio, whose technology complements Guardant' internal experiments analyzing DNA fragmentation patterns.

Grail had been assessing multiple approaches in parallel in its Circulating Cell-free Genome Atlas (CCGA) study, including targeted gene panels, genomewide copy number analysis, and methylation. The company has now named methylation as the primary methodology it will advance to the clinic, based on its superior performance compared to these other two signals.

Other firms have also launched in recent years without consideration of cancer mutations at all — starting out of the gate with purely epigenetic methods.

According to Kafka, the CancerSEEK test being used in the DETECT trial is largely the same as what was reported in Science, and won't change substantially in terms of what the firm eventually brings to the clinic.

"This focused or targeted approach … we embrace that term, because it gives us both the performance that we see in terms of specificity, in particular, but it also gives us a test that will be affordable and we think that's going to be critically important in building this into routine use," he said.

"It's tough to say that there won't be additional product development over time of course, [and] we're watching what's happening in the space in terms of methylation and in terms of other biomarkers that might become important over time," he added.

"The fact is it's early days … so there is work to do to show what works best and what's going to actually have an impact in being integrated into routine care because that's ultimately where this is measured," Kafka said. The question, he noted, is whether doctors actually use it and whether it brings benefit to patients."

Sensitivity numbers, reported by various parties, have varied and can be difficult to compare, as studies cite sensitivity at different specificity levels. But in its most recent data, presented at the American Society of Clinical Oncology annual meeting this week, Grail reported that it was able to achieve 77 percent sensitivity for Stage II cancers at a 99 percent specificity cutoff — a bit higher than what investigators showed for CancerSEEK in their Science study last year.

According to Kafka, incremental improvement in sensitivity may not be necessary to prove the value of an early detection assay, at least in some cancer types where any ability to identify tumors would offer a welcome improvement. "The sensitivity for early screening of pancreatic cancer is now essentially zero because there are no tests," he said.

This was also part of what drove the interest in funding Thrive, he added. "Its what got us really excited … in the Science paper – that [among] the retrospective cancers studied, there were a significant handful without current screening methodologies including pancreatic and ovarian."

Thrive's DETECT study with Geisinger marks the first foray for the field in terms of prospectively testing the impact of a genomic early detection test via returning results to patients and their doctors.

In his AGBT presentation, Cohen said that patients in the trial who get a positive result in both an initial and a confirmatory second test proceed to additional testing, either based on the localization prediction — a colonoscopy if the assay predicts colorectal cancer — or, if the origin of the cancer cannot be predicted, a PET-CT scan.

But other firms are not far behind. Grail, for example, believes that it will be ready to start returning results in the next year, based on new data presented at the ASCO meeting this week.

Kafka said that the diversity of approaches being explored, and the financial enthusiasm behind what are now multiple competitors seeking to launch cancer screening tests, is more heartening than intimidating.

"So much of our energy as an industry is and has been going into understanding and treating late stage cancer. It's what I've done my whole career in therapeutics companies and it's most of what the venture money is going into," he said.

"This earlier detection opportunity is such a sea change in our thinking … I'm not that surprised actually. I think I'm actually really excited that there is attention and money turning to this area."

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