NEW YORK – C2i Genomics has taken the first step in a planned global launch of its whole-genome sequencing-based test for solid tumor minimal residual disease (MRD) detection, having recently received a CE mark for the assay.
The company and its partners will now offer the C2inform assay clinically to patients in European countries that recognize CE marking. The label is also a prerequisite for reimbursement of diagnostic tests by health authorities.
C2i said that early adopters include undisclosed cancer centers in Denmark, Switzerland, France, and the UK, as well as genomics firm OncoDNA which signed a strategic partnership with C2i earlier this year.
Meanwhile, in the US, CLIA certification for the firm's lab is "very close," said C2i CEO Asaf Zviran.
To support adoption, the firm is releasing new data, beginning with study results from several clinical trials reported this week at the annual meeting of the American Association for Cancer Research.
Like others in the growing solid tumor MRD space, C2i aims to provide better tools for cancer treatment decision-making, Zviran said. "Although we have a very nice portfolio of many different treatments with immunotherapies and targeted therapies … the diagnosis and the monitoring of the treatment that basically allows the decision of when to treat, when to stop, [and] when to switch is done with technologies from the '70s," he said.
The company's platform and strategy differ from that of competitors in a few ways. For one, C2inform is based on analysis of whole-genome sequencing data, using patient-specific discriminators developed via AI-based pattern recognition and error suppression methods that recombine weak signals for highly sensitive detection of tumor-associated DNA.
In contrast, leading technologies from other companies either use fixed epigenetic panels, or create bespoke, patient-specific assays from initial tumor tissue sequencing data.
A recent preprint publication from a team led by C2i Scientific Cofounder Dan Landau, a professor at Weill Cornell Medicine and faculty member at the New York Genome Center, described an update to the original methods upon which C2inform was built.
Investigators reported that their improved analysis method, called MRD-EDGE, increased SNV signal-to-noise enrichment in WGS by 300X compared to the initial MRDetect approach.
According to Zviran, this academic report isn't directly connected to the company's activities, but it does reflect some of the work done on the commercial side as C2i has fine-tuned the C2inform test over the last few years.
Another differentiator is C2i's strategy of supporting ex-US testing through a model of disseminated software and wet lab protocol provision.
"We wanted to build the company to allow accessibility all over the world," Zviran said.
Because allowing multiple labs to perform the sequencing aspect of its assay would require US Food and Drug Administration approval, the plan there is to follow a more traditional LDT model, operated out of a single central lab.
But for customers in Europe, labs can perform their own local sequencing of samples and run the firm's test through a remote analysis and reporting system housed in what the company calls the C2intelligence cloud-based platform.
The process includes stringent training of international partner labs. "We are validating every lab that is working with us but allowing them to basically to do the processing in house," Zviran explained. "We are actually sending out protocols. We are training, sending them samples, validating them, and we are monitoring the quality of all of the wet lab processes."
According to the company, its analysis software is compatible with sequences received from any Illumina NovaSeq instrument. On the ground, the sequencing protocols require only a 4-ml blood sample.
"They do the sequencing on their own geography that they don't need to deal with all the regulatory restrictions of sending samples," said C2i Chief Technology Officer Boris Oklander.
"All of this is very appealing to [ex-US] labs, but also to pharma companies, because with clinical trials in different geographical locations, this is super convenient for them to operate in this way," he added.
According to Oklander, one of the most crucial elements supporting this model is C2i's demonstration of high reproducibility across different labs and geographical regions. At the AACR meeting this week, the company included results from matched samples processed at its own lab and by collaborators in Denmark.
Investigators reported that ctDNA status was identically called by the two labs in 97 percent of samples.
Researchers also presented a study at AACR showing that C2i's test could detect MRD in a small cohort of patients with pediatric brain tumors. Liquid biopsy technologies have historically struggled in these cancers because of the blood-brain barrier and its prevention of tumor DNA molecules from entering circulation.
The results are preliminary, but the ability to detect and monitor cancer in these patients using a blood test could potentially be an improvement to clinical care over current cerebral spinal fluid methods. Oklander also argued that the findings provide further evidence of C2i's high sensitivity.
Next steps for the company include achieving CLIA certification for its New York lab, publishing or presenting more data from European partners, and supporting what Zviran said are multiple interventional trials to build up the necessary utility data for payor reimbursement.
The question of utility for solid tumor MRD testing is being paid increased attention as commercial activities and marketing by companies like Natera and Guardant Health have accelerated in recent years.
A recent study of Natera's tumor-informed patient-specific Signatera technology, for example, reported no added value from the test in terms of early detection of tumor recurrences in colorectal cancer patients.
However, Natera and other companies have collected compelling data supporting other use cases, like single-timepoint, or "landmark" testing to identify cases of surgical or adjuvant treatment failure.
C2i is focused on the latter, particularly in two clinical niches: organ preservation in cancer patients after neoadjuvant therapy and before surgery, and the aforementioned landmark testing for patients after standard-of-care surgery and adjuvant treatment.
The company's interventional studies for the first use-case are focused initially in rectal and bladder cancers, Zviran said. For the second indication, trials are exploring pan-cancer use of the test, including a recently announced trial with Paris' Gustave Roussy Institute, in which patient are receiving surgery and any standard-of-care adjuvant treatment, with post-treatment C2inform testing.
Those found to be MRD-positive are then randomized to escalation of treatment or continued standard of care.
"We are hoping to really benchmark the ability of this to intervene," Zviran said.
Compared to targeted panels, whole-genome sequencing carries a higher cost. But Zviran argued that the expense of a test is relative to its impact in terms of cost savings. "That's why we are not going for … surveillance, like other companies, where you may detect a few months before imaging, but we are actually going towards applications in clinical decision-making," he said.
In the organ preservation context, for example, by avoiding surgery, "the immediate cost savings for patients, beside the quality-of-life improvement, which is huge, is more than $50,000 or $100,000 if you consider both the surgery costs and morbidity and hospitalization," he said.
The MRD community continues to lack direct head-to-head comparison data for competing solid-tumor MRD assays, leaving the question of ultimate superiority open. But Zviran hinted that some of C2i's data at AACR could be indirectly matched to studies in the same population by other companies.
He added that an unnamed pharma validation study has also directly compared C2i's test to other companies' assays but declined to elaborate.