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Exosome Dx Presents Data on New Combined Exosomal RNA and ctDNA Liquid Biopsy Platform

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NEW YORK (GenomeWeb) — Exosome Diagnostics presented data last week on a new platform it has developed to simultaneously isolate and analyze circulating exosomal RNA and cell-free tumor DNA.

According to the company, the combined platform, called EXO52, had a higher cancer mutation detection rate compared to analysis using only cell-free DNA in samples representing multiple cancer types.

Exosome has previously focused on the isolation and detection of nucleic acids present in exosomes, a type of microvesicle ejected from cells into plasma and other body fluids. Exosomes contain mostly RNA, but also small amounts of DNA.

Johan Skog, the company's CSO, told GenomeWeb that the firm has been working for some time on broadening its technology to simultaneously capture and analyze both exosome-borne nucleic acids and cell-free tumor DNA in a single column, but the data it presented last week at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Barcelona is the first to be released at a scientific meeting.

"There are several sources of mutations from a tumor you can detect and monitor in biofluids, including exosomal RNA, also some DNA from exosomes, apoptotic bodies, and cell-free DNA," Skog explained.

Cell-free tumor DNA and other circulating DNA is released as part of the death of tumor cells, while exosomes are released as part of an active process of living and dividing cells. As such, by adopting a dual platform, "you get both the RNA and the DNA," he said. "You are seeing both the living process and the dying process, which increases the number of copies of the mutation you can pick up."

Exosome plans to launch several exosomal nucleic acid diagnostics in 2015 with an initial focus on tests for lung and other solid tumor cancers, including prostate cancer. Vince O'Neill, the company's chief medical officer, told GenomeWeb this week that the planned diagnostics in the lung cancer area will cover detection of ALK fusions and the EGFR T790M resistance mutation, as well as a sequencing panel initially covering about 10 cancer-associated genes.

Skog said that at least some of these assays will include analysis of both exosomal RNA and ctDNA depending on the particular target. For example, ALK fusions are not easily detected using circulating DNA because of their length and location, so that particular target will be addressed specifically in circulating RNA.

Exosome faces competition across its planned test areas, including ALK and other mutation detection in lung cancer. For example, Biocept launched OncoCEE-LU earlier this month, a blood-based test that detects mutations in circulating tumor cells to guide treatment strategies for lung cancer patients with ALK fusions who don't have sufficient tumor biopsy material for analysis by conventional tests.

But in its presentations at the EORTC-NCI-AACR meeting last week, the company highlighted the ability of its technology to detect low-prevalence mutations, potentially much more sensitively than technologies that rely on only a single source of circulating tumor DNA, such as CTCs, or cell-free DNA.

At the meeting Skog highlighted data demonstrating that the company's new EXO52 dual platform has the ability to capture both exosomal RNA and cfDNA from plasma and detect actionable mutations including KRAS, BRAF, and EGFR in various cancers such as melanoma, colorectal cancer, and lung cancer.

He described a study of 30 melanoma patients showing that EXO52 could extract as much cell-free DNA as a standalone cfDNA extraction method, and that combined exosomal RNA and cfDNA analysis detected more gene copies than cfDNA alone in the same cohort.

The platform also outperformed cfDNA analysis alone in determining total gene copy number, as well as BRAF, EGFR, and KRAS mutation copy number in a cohort of colorectal cancer patients.

Two posters by Exosome and collaborating researchers further detailed these studies. The first described the development of the platform itself and its superiority to cfDNA analyses alone. In this study, the team co-isolated exosomal RNA and cfDNA from 16 late-stage metastatic colorectal cancer patients using the EXO52 platform, and compared analysis of both DNA and RNA to DNA alone, enriching BRAF, NRAS, KRAS, PIK3CA, MEK1, and EGFR targets, and sequencing on the Illumina MiSeq.

According to the authors, the addition of RNA analysis to cfDNA alone allowed the detection of an additional eight mutations. Moreover, all the mutations found in cfDNA alone were detected with increased copy numbers using both exosomal RNA and cfDNA.

A second poster also provided early results of an ongoing study of the platform in detecting BRAF mutations in melanoma patients. The report included data from the first six metastatic melanoma patients in the study, where the platform is being used to detect BRAF mutations prior to therapy and then again at five serial time points post-therapy to track changes in response to treatment.

In this cohort, the combined EXO52 platform also yielded substantially more mutant gene copies than cfDNA alone, increasing the overall assay sensitivity, the authors reported.

O'Neill said that the results highlight the clinical potential of Exosome's approach, especially the utility of being able to analyze all sources of circulating nucleic acids, which the company believes it has demonstrated offers significantly increased sensitivity over analysis of cell-free DNA alone.

The company's work in melanoma specifically, and in other undisclosed tumor types is ongoing, O'Neill said. Exosome is also researching the use of its technology for early detection of cancer, an area of great interest across the liquid biopsy field.

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