NEW YORK – UK cell isolation firm Angle is on the cusp of a major shift into the clinical realm as it awaits US Food and Drug Administration clearance of its Parsortix system for the isolation of circulating breast cancer cells later this year.
The breast cancer application, for metastatic patients, represents the first of several indications in which the company plans to establish its technology and drive clinical test development. It marks a significant shift for the firm from what has been a long period of product development and early research.
According to Angle founder and CEO Andrew Newland, the company now has two clinical labs — one in the US and one in the UK — for which it is seeking necessary approvals. Following the breast cancer FDA clearance, the firm’s strategy will be to divide its attention between supplying its product and consumables to customers for clinical diagnostic development and pursuing certain applications and assays internally.
Currently, the firm's clinical labs are being used for pharma services. "We're already actively selling the use of the system for cancer drug trials to measure the state of the patient before, during, and after the drug, so that's an active part of our business, which is growing right now," Newland said.
To service the pharmaceutical market, Angle has created a custom assay development service. "We have our base service, which is to find out what kinds of cells are present, but [we can then] also interrogate those cells and look for the marker of interest to the pharma. And that basically aligns with companion diagnostics to detect likely responders," he said.
"We've just taken on a contract with one customer who wants to look at DNA damage repair genes … [and] we've already done work in house on PD-L1, which is a big target for the immunotherapy drugs.”
Alongside this work, the company has been conducting an ovarian cancer detection trial, which has now finished patient enrollment and is due to give headline results in the fourth quarter. "That will be the first laboratory-developed test to go into our clinical labs," he said.
In previous research, Angle has established that it could use Parsortix to isolate CTCs from patients with ovarian cancer and extract them for downstream molecular analysis. The firm collected pilot data showing that this method could distinguish patients with cancer from healthy controls and set out to further validate it as a tool for early cancer detection and subtyping with collaborators at the University of Rochester.
If it can successfully validate an ovarian cancer assay, Angle would be offering it, at least initially, as an LDT, without FDA clearance. But as the company has said before, its long-term plan has been to seek follow-on 510(k) clearances for its platform beyond breast cancer, with prostate cancer being the next target after ovarian cancer, Newland said.
Parsortix is not without potential competitors in CTC diagnostics. As an epitope-independent technology, it has set itself apart from the CellSearch system and similar platforms, which are limited to capturing EpCAM-expressing cells.
But while several other companies and academic groups have also developed marker-agnostic cell separation systems, Newland said Angle doesn't see Parsortix suffering from substantial competition from these players.
"We're already six years into the process of seeking FDA clearance, and we're not aware of anybody else even having started that,” he said. “So even if anything [really promising] came out, they would be [years] behind."
"The real challenge for us isn't the competition as such, it’s going through the steps to get clinical utility data to prove [this] works and to get people to adopt it. And that's not trivial," he added.
Beyond ovarian and prostate cancer, Newland said Angle also has diagnostic plans that would build directly upon the initial breast cancer cell-isolation clearance that it expects later this year.
"We've already signed a partnership deal for a first application, which will be the measurement of HER2 protein expression in breast cancer,” Newland said, adding that the company hopes to combine Parsortix cell isolation with Abbott's PathVysion kit, which is already established for HER2 analysis in tissue samples.
The firm, in fact, used this as one of the demonstration pieces in its FDA submission. "We showed that we could [isolate] cancer cells and we could run the PathVysion HER2 test on those cells," he said.
The plan now will be to run additional studies to show the benefit of a blood test and then take that back to the FDA.
In the meantime, research using Parsortix has continued to bear various other potential diagnostic fruit.
Investigators from the Medical University of Vienna, for example, presented results of three studies at the Advances in Circulating Tumor Cells conference last month in Kalamata, Greece, showing that Parsortix CTC isolation and downstream molecular analysis could serve as a tool to monitor patients' responses to treatment and predict their outcomes.
The largest study, a Phase II drug trial including 133 ovarian cancer patients, explored longitudinal gene expression in platinum-resistant patients enrolled on the GANNET53 trial. According to the investigators, gene expression in CTCs isolated from successive blood draws correlated closely with significantly improved progression-free survival and response to therapy.
The group reported that gene expression analysis of CTCs isolated by the Parsortix system could differentiate a group of responsive patients, with a survival rate of 85 percent at 120 days, compared to non-responders, with a survival rate of just 30 percent at the same time point.
In a second study, researchers collected early evidence that CTCs expressing p53 protein could be used as a biomarker in small-cell lung cancer.
A third presentation reported results from quantitative PCR analysis of Parsortix-captured CTCs in samples from 118 non-small cell lung cancer patients and 30 healthy volunteers. Researchers found that CTCs expressing EMT (epithelial mesenchymal transition) or cancer stem cell markers had more prognostic value than those expressing the epithelial markers employed by other commonly used CTC capture assays.
One area that Angle has decided to pull back from is the use of Parsortix outside of cancer. The company had done some initial work in pregnant women, showing that it could detect and isolate cells with male chromosomes, indicating a fetal origin.
"That was an initial proof of principle, but while we see that as a very substantial market opportunity, it's just beyond what we can do with the scale of company that we have and the resources that we have," Newland said. "We are in discussions with some other groups that might take that on, but we decided to focus our resources on cancer."