Skip to main content
Premium Trial:

Request an Annual Quote

Cofactor Pushes RNA-Based Dx Goals With New Immuno-Oncology Assay

Premium

SAN FRANCISCO (GenomeWeb) – Cofactor Genomics has launched a new RNA-based cancer assay called Paragon, advancing its goal to develop a suite of products that move molecular assessment of cancers away from DNA sequencing and toward the realm of gene transcription and expression.

In addition, at the Molecular Medicine Tri-Conference held here this week, researchers working with Cofactor presented data from a study that demonstrated one clinical application of the assay: generating an immune-specific molecular profile of sarcomas.

Cofactor is more than eight years old but only recently crystallized its focus on developing RNA-based tests with the launch last year of a gene expression assay called Pinnacle.

Last week, the firm announced a new product, Paragon, which is focused on both specific genes with relevance to the rapidly expanding field of immuno-oncology, and on the associated tumor microenvironment.

The test is designed to serve clinical researchers who are working to define which signals — not only in the molecular architecture of tumors themselves, but also in immune cells and other elements that make up body's response to cancer — can help guide the use of a new generation of pharmaceuticals.

According to Cofactor, Paragon is designed to address a need that isn't well met by other technologies that interrogate the cancer's interaction with the immune system.

It's not alone in looking beyond the genome itself. Gene expression, or transcription, as opposed to the fundamental genetic code, has driven a number of already successful diagnostics, for instance in the prognostic assessment of breast cancers.

Meanwhile, companies like NanoString have worked to develop and disseminate platforms that allow digital, multiplex analysis of gene expression — offering a less variable readout of many of the markers that are currently analyzed clinically using individual IHC stains.

For its part, NanoString has focused more on instrument sales but has also developed specific assays targeting some of the same areas that Cofactor is pursuing. For example, the firm promotes an assay panel alongside its nCounter instrument called the Tumor Inflammation Signature or TIS, which was developed in collaboration with Merck to predict patient response to cancer immunotherapy — a similar application to Cofactor's Paragon.

Cofactor does not market a platform or a system. Instead it is hoping to advance assays performed out of its own CLIA lab, in the manner of many genomics-based laboratory-developed test firms.

The company describes its assays, both Pinnacle and Paragon, as reliant on a proprietary database of immune reference signatures — what it says are thousands of disease- or cell-specific fingerprints.

The Paragon assay is cancer type-agnostic, supported by expression databases that the firm says are pre-built for more than 25 different tumor types.

The analysis couples an assessment of the expression of known immuno-oncology genes with measurement of more general signatures that speak to how the body is responding to a cancer on a cellular level.

For example, Cofactor said that the assay differentiates cells like M1 and M2 macrophages, as well as cancer-specific expression signals from escape genes including PD-1, PD-L1, and CTLA4. For these escape genes, the test analyzes expression relative to a tumor type-specific reference, and reports not only the expression readout, but also a confidence interval.

In recent years, researchers have begun to echo a conviction that the path to identifying the most patients who will respond to immunotherapy will be through a combination of biomarkers, including genes like PD-L1, the activity of individual immune cells, and assessment of overall cancer mutability.

Based on Cofactor's description of its approach, it seems poised to potentially answer this call.

At the Molecular Medicine Tri-Conference meeting, Seth Pollack, a member of the Fred Hutchinson Cancer Research Center, reported on experiments in which he and his colleagues were able to define soft-tissue sarcoma subtypes using the Cofactor assay, which are now informing new immunotherapy trials.

The same researchers have also used Cofactor's Paragon to analyze patients before and after initial treatment regimens, looking for signals that can identify the 50 percent of patients that will not be cured by standard treatment from those that will.

According to the researchers, the Paragon assay has been able to define gene expression signals and identify immune cell signatures that differentiate patients who remain disease-free after three years from those who recurred within one year.

Interestingly, researchers have also applied the NanoString platform to sarcoma. A team based in British Columbia published a report on their validation of a gene fusion-based sarcoma subtyping test in the Journal of Molecular Diagnostics last November.

Cofactor Founder and CEO Jarrett Glasscock said in an interview this week that the company expects to make additional announcements over the next few months about collaborations with research groups in a variety of different cancer types and therapeutic areas.

He also said Paragon is building the capability to call genomic mutations in addition to the current readout of the expression of immune escape genes like PD-L1 and various aspects of the immune cell response to cancer.

"We have been very encouraged over the last three months with that development, and … that will be a component of Paragon in the near future," he said.

The company has mentioned publicly that the Paragon assay could also be harnessed to assess tumor mutational burden (TMB) — providing a surrogate measure of a cancer's neoantigen load. Presumably, this could come from the firm's work to be able to report mutation calls.

After several years of research and debate, the precision medicine field is now coalescing around the utility of TMB in guiding cancer immunotherapies, either in lieu of, or in combination with other markers. Most recently, Bristol-Myers Squibb reported data from a study of its immunotherapies Opdivo (nivolumab) and Yervoy (ipilimumab), which could support regulatory approval for the regimen in lung cancer patients identified at having high TMB by Foundation Medicine's next-generation sequencing companion diagnostic.

Foundation began offering TMB analysis using its 300-gene FoundationOne sequencing assay in 2016, and has said more recently that it is that it is advancing a blood-based version as a companion diagnostic to Roche/Genentech’s immunotherapy drug Tecentriq (atezolizumab) in first-line treatment of non-small cell lung cancer patients.

Other firms, like Personal Genome Diagnostics, have also said they are developing assays that use a measure of how mutated a tumor is to predict immunotherapy response.

"The question is really what technologies are going to be able to take part in this consolidation, of TMB, expression, [and] immune cells," Glasscock said. "And [we believe] this is an assay that can offer consolidation of all of those factors."

The Scan

Highly Similar

Researchers have uncovered bat viruses that are highly similar to SARS-CoV-2, according to Nature News.

Gain of Oversight

According to the Wall Street Journal, the Biden Administration is considering greater oversight of gain-of-function research.

Lasker for mRNA Vaccine Work

The Scientist reports that researchers whose work enabled the development of mRNA-based vaccines are among this year's Lasker Award winners

PLOS Papers on Causal Variant Mapping, Ancient Salmonella, ALK Fusion Test for NSCLC

In PLOS this week: MsCAVIAR approach to map causal variants, analysis of ancient Salmonella, and more.