NEW YORK—Exosome Diagnostics Inc. has tapped London-based DxS Ltd. to partner with on the development of blood-based companion diagnostics for key cancer gene mutations, such as KRAS, BRAF and EGFR. If successful with the initial mutations, the program will be extended to others. The collaboration will use DxS' industry-leading Scorpions real-time PCR mutation test kits in conjunction with Exosome's xOS technology, which harvests high-quality nucleic acids from blood exosomes.
The collaboration will initially focus on developing blood-based measurement for predicting patient response to targeted therapies. Blood-based mutation measurement is particularly valuable in circumstances where tissue bioavailability is limited such as in lung, pancreatic and ovarian cancers.
"There are over 180 companies investigating over 370 different molecular targeted cancer therapies, many of which will require high-quality, molecular companion diagnostics," says James McCullough, CEO of Exosome. "DxS is the gold standard in detecting these mutations."
Exosomes are small microvesicles shed by all solid tumors into blood and other body fluids. They contain virtually the entire cancer tumor transcriptome. Exosome has identified most mRNA and miRNA in circulating tumor derived exosomes, all protected in the exosome lipid bi-layer from any blood-based RNase. The company's initial research findings were published in the December 2008 issue of Nature Cell Biology.
"We isolate the exosome and extract the nucleic acid," McCullough says, noting that exosomes provide a pure nucleic acid fraction that is present in a relatively high concentration. "We can extract 200 to 500 ng/ml of serum and higher when there is a good tumor burden."
DxS' Scorpion probes target key mutations directly from blood.
"Our relationship with Exosome is R&D-based," notes Dr. Stephen Little, CEO of DxS, differentiating it from his company's recently announced collaboration with Boehringer Ingelheim, which involves drug therapy. "We're striving to improve the usability of our products by moving from biopsied tissue to blood, which is a much easier test to do. The challenge is primarily one of sensitivity in the diagnostic sense. If you don't get 100 percent, you have to balance convenience against sensitivity."
Little notes that availability of tissue samples is one key; in colorectal cancer, for example, something like 90 percent sensitivity might be required, whereas in lung cancer, where you can't get a sample easily, maybe 75 percent would suffice.
Exosome will be responsible for the methodology to extract the tumor cells, which will then be transferred to DxS for testing. Exosome's McCullough adds that the two companies are also investigating tumor profiling by looking at a number of genes expressed in exosomes that create a fingerprint for cancer type—melanoma, brain cancer, pancreatic cancer, and so forth—that would be important for early detection and monitoring disease progression.
The IP position of the joint effort may not be clear for a year or two, Little states.
"To me, this is a technology that is 'yes' or 'no,'" he says. "From our perspective, it makes the testing process simpler and easier and will make adoption for clinical use that much faster. If the technology works, it can be extended to any mutation as an ideal solution in personalized medicine. The nub of the project is, does it work well enough?"
To that question, McCullough and Little are of like mind—in a year, they should have their answer.
