NEW YORK – Mercy BioAnalytics is developing an early cancer detection test using tumor-specific extracellular vesicles (EVs), a relatively nascent category of diagnostic biomarkers in the oncology space.
The Natick, Massachusetts-based company recently presented proof-of-concept data demonstrating that its Mercy Halo Ovarian Cancer test outperformed the widely used CA125 in distinguishing women with early-stage high-grade serious ovarian cancer (HGSOC) from those with benign conditions.
Mercy Bio plans to eventually launch a clinical trial to support a commercial test following the completion of a Series A funding round currently underway.
Although applied to ovarian cancer in the current study, the Halo assay can theoretically be used for any cancer.
Joseph Sedlak, Mercy Bio's scientific founder, explained that all cells release EVs, and they are both more abundant and stable than cell-free DNA, allowing them to better persist and accumulate.
"If you have a one-gram tumor and a 100-kilogram individual," he said, "you would say maybe 1 in 100,000 EVs would be tumor-derived from a stage I cancer, but since you have so many of them per milliliter plasma, the math becomes favorable that you can actually have a large number of tumor-derived extracellular vesicles in every milliliter of blood."
Isolating the tumor-derived EVs consists of finding those with two or more unique tumor-associated markers colocalized to the same EV, thereby minimizing the chance of false positives due to normal EVs that happen to share one or the other biomarker with a cancer cell.
Sedlak refers to this as the firm's "secret sauce."
"That's what other players in the field aren't doing," he said.
The patented assay has five steps, beginning with size exclusion chromatography and immunoaffinity capture to isolate EVs. Tumor-derived EVs are then enriched by the addition of two DNA oligonucleotide-conjugated antibodies targeting cancer-specific epitopes colocalized on the same EV. Those oligonucleotides are then bound and ligated and the cancer EV-associated signals are detected via qPCR.
In preliminary data presented earlier this month at the American Society of Clinical Oncology annual meeting, the Halo assay distinguished HGSOC from benign cancer with 89.9 percent sensitivity at 98 percent specificity. It distinguished stage I/II HGSOC from benign cancer with 84.6 percent sensitivity at 98 percent specificity.
In that study, Mercy retrospectively compared Halo's performance to CA125 in 42 HGSOC and 26 benign ovarian tumor samples, followed by validation using an independent cohort of 89 biobanked HGSOC samples and 124 health controls. The firm further assessed the assay's performance in plasma from 87 women with off-target cancers and 42 women with inflammatory conditions.
Although not included in that study, Sedlak pointed out that the information made available by the EV-associated biomarkers extends beyond merely detecting the presence of cancer, to tissue-of-origin and cancer subtype identification.
Another advantage of working with EVs is their stability relative to nucleic acids, remaining intact at −80° C for long periods of time.
"We can use samples that have been banked for over 15 years," Sedlak said, adding that this enables Mercy Bio to accelerate its discovery process by using biobanked samples.
"We're hoping [to boost] our commercialization prospects by tapping into biobank samples that we can run studies on for regulatory approval," Sedlak said.
Johan Skog, the founder of Exosome Diagnostics (ExoDx), also highlighted stability as a key advantage in using exosomes, compared to analytes such as cell-free DNA or RNA.
"There's so much RNAse activity in a biological sample," he said during a presentation at this week's Precision Medicine World Conference in San Jose, California. "Plasma has so much RNAse activity, for example, that you can't even titer it out."
Skog founded ExoDx in 2008 and his company was acquired by Bio-Techne in 2018. He commented that while the exosome diagnostics field remains relatively small, ExoDx benefits from having gotten in early.
The company has already launched and obtained insurance coverage for its EPI test for prostate cancer.
"We detect around 30 percent more high-grade prostate cancer among those tested with EPI, compared to other tests," Skog said.
Aspira Women's Health, meanwhile, is aware of the potential benefits of EVs, but remains hesitant to commit resources to pursuing commercial EV-based diagnostics until more is known. Aspira's OVA1 test currently evaluates seven proteins as a means of early ovarian cancer detection.
"We have not done a side-by-side review versus EVs," said Valerie Palmieri, Aspira's Executive Chair. "Based on our scientific assessment, EVs are still early, and we do not truly understand their mechanism of action."
Aspira is currently collaborating with the Dana-Farber Cancer Institute to evaluate the latter's microRNA technology in conjunction with Aspira's tools to develop a more highly sensitive and specific test for early detection of ovarian cancer.
Another group at the University of California, Los Angeles is separately developing an EV-based method called "EV Click Chip" — which uses a custom microfluidic chip that integrates nanowires and a network of microchannels — to detect early-stage hepatocellular carcinoma.
Mercy raised $22 million in a seed round in late 2020, said Paul Blavin, Mercy Bio's cofounder and CEO, enabling it to grow from seven employees to now approaching 25.
"That capital raise in 2020 allowed us to really fill in significant positions and accelerate our growth and accelerate our progress towards a commercial assay," Blavin said. The firm did not disclose how much it is aiming to raise in its current Series A round.
Although the exact timing of a commercial launch for a diagnostic test remains in the air, the firm anticipates being able to more immediately realize revenues related to the Halo test from biopharma partnerships.
"We envision being an aid to biopharma and preclinical drug development, accelerating early-stage patient enrollment, therapeutic response [monitoring], and also detecting minimal residual disease," Blavin said.