NEW YORK – BCAL Diagnostics is preparing to conduct studies in support of commercializing a breast cancer diagnostic assay based on the lipid profiles of extracellular vesicles.
The Sydney-based firm, which went public last year, recently filed a patent on its lipid detection method in Australia. It intends to seek global patent approvals and has partnered with an analytical lab in North Carolina in anticipation of marketing the assay within the United States.
The provisional patent covers a method of diagnosing a subject with a breast cancer by measuring the levels of one or more circulating lipid biomarkers. While the company could not yet discuss details of the method, it involves isolating extracellular vesicles followed by mass spectrometry analysis of their lipid profiles.
Although less widely used in cancer diagnostics, the lipid compositions of extracellular vesicles (EVs) from cancer cells differ from those of healthy cells and contribute to cancer progression.
BCAL licensed the original method that led to the company's technology from the University of Louisville in 2013.
"We funded a lot of the work in the University of Louisville until about 2017, when we brought it back to Australia," said John Hurrell, the company's CEO. Hurrell joined BCAL earlier this year, after serving as chief commercial officer at Jana Care.
At the moment, the lipid signature that the firm has identified is broadly applicable to breast cancers in general, although BCAL intends to investigate whether separate EV signatures for breast cancer subtypes exist.
Hurrell commented that the assay has shown high accuracy and sensitivity among approximately 750 patients and controls tested to date, spanning stages zero through II of early breast cancer.
"We're now looking to expand our cohorts and validate all of the work we've done to date and expand out the diversity of patient population," Hurrell said.
As part of that effort, BCAL intends to run clinical studies in the US, where Hurrell says researchers will have access to a different demographic composition than in Australia.
The company has partnered with an as-yet-unnamed analytical lab in North Carolina, which will analyze samples for BCAL, both in relation to the planned study and as part of the firm's broader effort to expand into the US.
"We're now looking at setting up a legal entity in the US," Hurrell said, "and then based on the results we get with our partners in North Carolina, we'll decide what we want to do."
Although the assay is primarily meant as a cancer diagnostic at the moment, it may also find use in cancer screening and in treatment response monitoring.
BCAL currently has in place a master services agreement with GenesisCare, an Australian cancer and cardiac care services provider, to evaluate the efficacy and utility of the assay among patients who have already been diagnosed and are undergoing treatment.
Through that research effort, said Hurrell, "we'll see how the signal changes. Firstly, does it change with different modalities of therapy and then whether or not we can predict anything from those changes."
In following studies, the company intends to evaluate whether it can use its assay to surveil patients post-treatment and, in general, to investigate what other information can be obtained from the lipid signature as patients progress through diagnosis and treatment.
Research into the use of EV-associated lipid profiles as cancer biomarkers lags behind that of more established molecules such as circulating tumor DNA.
"EVs certainly possess a promise in cancer detection," said Tony Hu, the director of the Center for Intelligent Molecular Diagnostics at Tulane University, "but better gold standards for EV isolation and marker identification [and] quantification are urgently needed."
Hu and Sudhir Srivastava, a researcher with the National Cancer Institute's Early Detection Research Network, recently published a review of the use of EVs in cancer diagnosis, in which they identified a need for standardizing EV isolation and purification methods, for clearer EV nomenclature, and for standardizing analyte assays.
Hsian-Rong Tseng, a professor of pharmacology at UCLA and the CEO of Eximius Diagnostics, anticipates the needed improvements in EV science to come in relatively short order.
"There is a fast-growing interest in EVs for diagnostics companies globally," Tseng said.
Tseng's company is based around the EV Click Chip, which he invented for collecting and purifying circulating EVs to identify early-stage hepatocellular carcinoma biomarkers via reverse-transcription Droplet Digital PCR.
Eximius, he said, "is in the process of licensing the IP associated with EV Click Chip. They will soon put this product into the regulatory pipeline."
Other firms investigating the diagnostic use of cancer-related lipids include Berg, which has also been pursuing mass spec-based lipid biomarker discovery.
While Hurrell said that the firm's current commercialization plan is to remain focused on breast cancer, other cancers likely have their own lipid signatures that can form the basis of similar assays.
"For example," he said, "the patent that we licensed from the University of Louisville also covers lung cancer. Once you've made the investment in building a platform to allow you to to pursue signatures in other directions, we'll definitely do that."
BCAL raised A$10 million in an IPO last year (US$7.36 million at the time), and Hurrell said that the firm has sufficient funds to carry it through the end of 2024.