NEW YORK (GenomeWeb) – With several new milestones under its belt, including the CLIA certification of its lab and the launch of a kit version of its RNA-based immune profiling technology (recently rebranded as ImmunoPrism), Cofactor Genomics is hoping to provide tools to a well-established community of sequencing labs for investigating and developing cancer biomarkers in their own facilities.
At the same time, the firm has completed validation of the assay, which it believes will help it lead and support the clinical translation of these biomarkers.
ImmunoPrism, which Cofactor has been performing in-house since early last year, is designed to define RNA signals that reflect cancer biology and the body's response to it in order to help guide the use of a new generation of immune-focused cancer drugs.
The approach relies on a proprietary database of so-called immune reference signatures, which the company says involve thousands of disease- or cell-specific RNA patterns.
In a webinar last month outlining the process and results from its CLIA validation of ImmunoPrism, company leaders reported some of the first public details of how the assay performs in differentiating or detecting eight different cell types that make up important actors of the adaptive immune system. These are CD-4+ T cells, CD-8+ T cells, CD-14 monocytes, CD19+ B cells, CD56+ natural killer cells, M1 and M2 macrophages, and T regulatory cells.
According to Cofactor CSO John Armstrong, various performance and reproducibility experiments concluded that the assay "is able to differentiate between relative amounts of different immune cells within a wide reportable range of zero to 45 percent for all cell types," and that it is robust in the face of confounding factors.
The assay also achieved low limits of detection, down to 1 percent relative abundance for several cell types.
Cofactor is not alone in seeing growing interest in the cancer research community for new RNA-focused technologies.
At the International Cancer Immunotherapy Conference in New York last October, for example, multiple presenters highlighted results demonstrating that both tumor immunogenicity and the body's response to that prompt are factors in the success or failure of immunooncology drugs.
Having a readout on both of those questions — whether the tumor is immunogenic, and whether there is a robust immune response taking place — may be crucial in the future for making decisions about how to treat patients, attendees argued.
In Cofactor's webinar last month, Natalie LaFranzo, the firm's director of market development, cited the limitations of the currently established biomarkers for cancer immunotherapy, like PD-L1, and mentioned a statement by the European Society for Molecular Oncology that suggested that PD-L1 immunohistochemistry "is not suitable as a biomarker for selection of anti PD-1 inhibitors," and recommended the field focus on developing "multi component" approaches.
Cofactor is banking on the potential of its immune "reference signature" approach to help fulfill this call by comprehensively measuring the immune cell component of a cancer rather than the single immune-associated genes or proteins that have been explored thus far.
The firm is not alone in turning attention from tumor genetics or transcriptomics to looking at the way the body responds to a cancer. Other firms that have launched tools for this type of exploration include NanoString Technologies, which offers a tumor inflammation signature assay, and Thermo Fisher Scientific, which recently launched a set of TCR-beta short-read and long-read assays.
Jarret Glasscock, Cofactor's founder and CEO, argued that the company's methodology is in a very different category than other takes on RNA profiling that exist on the market. "We took a departure from [most methods] which … rely on a gene list, usually a ranked gene list," he said. "When you are looking at differential expression and coming up with a measure based on a single gene observance … there's a lot of issues with that in terms of statistical significance … and muddiness in terms of both your specificity and your sensitivity."
"We're not doing it the way everybody else is doing it," he explained. Rather than amalgamating various single genes, ImmunoPrism is built on an architecture of the firm's "reference signatures."
"We build models, full global models of transcription for every one of these immune cell types," he said.
Before this fall, Cofactor offered the assay largely as a service through its own lab, with just a few early-access partners beginning running beta versions of the now-available ImmunoPrism kit.
Launched in October, the kit is identical to what Cofactor performs in its own lab. According to Glasscock, the company had been planning to develop a kit version of its technology for several years. "We realized that the things that we wanted to accomplish and what we wanted to bring to the market didn't necessarily just have to happen in our lab," he said.
Strategically, the move reflects a recognition of growing desire in the cancer clinical research space for RNA tools, which Glasscock argued represents a large market.
"Quite frankly, when you look at some of the recent announcements [or reports] from groups like Illumina, you see that there are [more than 10,000] instruments out there in the wild and this represents … a distribution channel for Cofactor."
"We believe that RNA in particular has some very interesting and valuable applications that it lends itself to and it would be silly for us not to go the distributed route and take advantage of these customers, which have already invested a significant amount of time [and] money building their sequencing infrastructure there. They're wanting access to new applications, to valuable applications to run within their own labs," he said.
"What we hope is [that] within three years' time, the majority of our business will be based off of these kits," Glasscock added. "The idea is that we'll be enabling all of the labs which have invested in sequencing resources, so I suspect that in terms of number of samples … that opportunity is larger than a centralized model."
Cofactor has only made public a few users and partnerships so far, some of which predate the kit launch. These include work by researchers at the Fred Hutchinson Cancer Research Center in sarcoma — some of which was presented early last year at the Molecular Medicine TriConference in San Francisco — as well as a deal with the National Cancer Institute and three other unnamed academic and pharma groups, focused on demonstrating the clinical utility of the company's assay in measuring immune profiles of patients with conditions including prostate cancer, lung cancer, breast cancer, and bladder cancer.
"[For] some of them, we were running the kit in-house … but more recently [our partners] have been running the kit within their own facilities," Glasscock said.
Cofactor also said in December that ImmunoPrism will be used in a Phase I/IIa clinical study of Genocea Biosciences' personalized cancer vaccine candidate GEN-009, in which the pharma firm is hoping to comprehensively characterize the immune responses generated by clinical trial participants in response to vaccination.