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Genosity Latest Entrant to Growing ctDNA Residual Disease Monitoring Market

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NEW YORK – Biotech firm Genosity said last week that it has received approval from the state of New Jersey, where its CLIA laboratory is located, to offer a new liquid biopsy assay called AsTra (Assessment and Tracking) for cancer monitoring and residual disease detection in biopharmaceutical research and clinical trials.

Similar to other platforms commercialized in recent years by companies like Natera and Inivata, AsTra uses tumor exome sequencing to derive a panel of patient-specific genomic targets. These are then used to design bespoke liquid biopsy assays for the detection and monitoring of minimal residual disease in cancer patients.

The platform aims to detect a signal of residual disease based on the presence of circulating tumor DNA. As similar tools have been developed and advanced, researchers have accumulated increasing evidence that detecting MRD after putatively curative treatment can identify cases of treatment failure that are likely to result in later recurrence. Such tests can also detect signs of these emerging recurrences earlier than available surveillance methods.

The first component of Genosity's offering, which is calls Astra Profile, involves whole-exome sequencing using the Illumina NovaSeq 6000 platform. Genosity President and Chief Technology Officer Robert Daber said that this is the core of what his firm brought to the development of AsTra, with library prep and informatics technology from an undisclosed third party supporting the follow-on ctDNA assay creation.

"One of the big things [for us in being able to launch this] is that NovaSeq has dropped in price so much that we could think about running tumor-normal sequencing in a cost-effective manner," Daber said. "We don't like to bring expensive tests to the market. We want cost-effective [methods] that can impact broad numbers.

Once a tumor exome has been generated, Genosity uses the resulting data to create a patient-specific liquid biopsy sequencing assay using the aforementioned third-party library prep technology. This is similar to the approach taken by Inivata, which is NGS-based, but differs from Natera's offering, which uses PCR.

According to Daber, depending on the specific application or biopharma partner there might be different thresholds for how many targets these bespoke assays need to include.

"Each project is [different], so there may be a target number of locations, and that's really dictated on the collaborative project we're doing — whether someone wants to have something in the teens, in the 50s all the way up to 200 or so," Daber said.

"Not every tumor has that many alterations though," he added. "So even within a project, when we have a target number, it's going to really be dependent upon the tumor. What we end up working with is a minimum threshold and then a target threshold. And as long as we hit the minimum, the sample will move forward."

Once a patient-specific assay has been created it can be used in two ways. What the firm calls Astra One comprises an initial liquid biopsy MRD assessment. This can then be followed up with Astra Next, a program of ongoing monitoring.

Daber said he could not disclose with whom Genosity worked to create the liquid biopsy assay portion of AsTra, but he said that the collaboration has been going on for multiple years.

"We had developed our exome about two and a half years ago and that became the basis of the collaboration since we had the exome component, but what we didn't have were the liquid biopsy component or samples to do research collaborations on."

Following the collaboration the technology evolved into the current service offering, he added.

Earlier this year, Daber and other colleagues were listed publicly as coauthors on a presentation by researchers from the University College London and genomics firm ArcherDx at the American Association for Cancer Research annual meeting. In their presentation, investigators shared data from an expanded investigation of ctDNA patterns in pre- and post-surgery samples from lung cancer patients in the TraceRx study. The group reported, among other things, that by creating personalized ctDNA MRD assays, the team could reliably detect low-frequency variants. They also found that MRD surveillance lead to earlier detection of relapse, often significantly ahead of standard-of-care imaging.

Based their collaboration in that study, it's possible ArcherDx could be the unnamed third party whose technology underlies the liquid biopsy assay portion of Genosity's offering.

Archer is also already engaged in a comarketing agreement with Genosity, which the companies announced this February. Under the agreement Archer is comarketing Genosity's line of consulting and laboratory software services for genomic research, including Genosity's Genome Explorer platform, which is being integrated into ArcherDx's Archer Analysis Unlimited bioinformatics pipeline; its Laboratory Information Management System for NGS workflows; and its Cortex application for population-level analysis and cohort identification.

Daber said that Genosity's collaborators will likely publish a peer-reviewed paper detailing its early work later this year or early next. In general, he added, what Genosity has seen through that effort, as well as in other partner projects, reflects the kind of findings that have been published by other players in the field: that ctDNA MRD detection might be able to identify patients that need additional adjuvant treatments and that it could in turn help pharma firms better identify subjects for trials of new adjuvant drugs.

This application — the use of MRD detection in research and clinical trials — is Genosity's commercial focus. The firm isn't aiming to provide testing for oncologists in general clinical practice, according to Daber.

"Our business model has been to leverage [genomic technologies] in the context of either research collaborations or in clinical trials … but not directly to oncologists who are looking to do this on their patients today," he said. "There's no real reimbursement tied to this yet and Genosity, as a company, we primarily focus on servicing the biopharma and IVD space." 

Other firms with commercial ctDNA MRD assays are also largely research-focused, though this is poised to shift. Describing his company's new RaDaR product earlier this year, Inivata CEO Clive Morris said that while the firm anticipates clinically validating the tool for use by oncologists eventually, it would probably need at least at one to two years to obtain actionable data that could translate to clinical use, with additional time to pursue regulatory clearance and reimbursement.

Natera (which is engaged in an ongoing legal tussle with ArcherDx related to liquid biopsy patents) was the first company to announce a commercial ctDNA MRD product.

When it launched its Signatera technology in 2017, the company made clear that it intended to provide clinical ctDNA MRD detection for ordering oncologists. Securing coverage decisions from insurance payors has been a long road though, and in the meantime, the firm has kept its focus on supporting pharmaceutical companies.

Last year, Natera saw its first major milestone in making the shift to the clinic, obtaining a draft local coverage determination from Medicare contractor Palmetto for use of Signatera in colorectal cancer. The company said at the time that it would launch the test clinically for this indication after that LCD was finalized, which was expected to take place this year.

For its part, Daber said Genosity is looking mainly to demonstrate where ctDNA MRD has value and utility, but does not see itself as "the traditional central lab where we expect those assays to stay here forever."

"Our vision is that we run these labs here and they get matured into our platform and then … we're able to support the flow of these technologies out to the decentralized local lab setting," he explained.

Moving forward with liquid biopsy, the company hopes to now extend the work it's done in more limited cancer types to a broader population. "We are trying to expand as we find either pharma partners or academic partners who have rich cohorts of a given cancer type," Daber said, adding that the biggest challenge is finding studies with tumor normal and matched plasma samples.

"Folks have started banking plasma, but there's not as deep a history as there is for just tumor blocks themselves," he added.

Another area for future development is experimenting with whether patient-specific ctDNA MRD assays can be created without the need for tumor tissue: by using ctDNA itself to support the initial exome sequencing aspect, something Natera has also been exploring.

"With the second version of the exome Genosity is running in our lab, we can actually run a 500x exome off of circulating tumor material," Daber said. "So we're starting to pilot running whole exomes off of plasma, but what we don't know yet is: Can we still detect a true tumor profile or is the sensitivity just not there yet? We know we can't do the same type of error correcting on a 500x exome that you can do if you sequence to say 20,000x and we don't think we can sequence to 20,000x, at least not cost effectively."

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