NEW YORK (GenomeWeb) – Mitochondrial DNA diagnostics firm MDNA Life Sciences announced the launch of its first noninvasive blood-based cancer test this week, with Phi Life Sciences as the assay's first US distributor.
Though the company got its start developing assays for analysis of tissue samples, researchers have more recently found that the firm's mitochondrial DNA-based approach is similarly sensitive when applied to blood samples. Based on this, the company has now shifted its focus to the liquid biopsy space.
"Our very early work was in tissue, and the first product was a prostate biopsy tissue test," Chris Mitton, MDNA's CEO, told GenomeWeb. "But then we found that some of the same [genomic features] — the same 3.4 kilobase deletion that was used in the [tissue-based prostate test] — was also present in body fluids. So that was really the catalyst to continue to work toward developing a liquid biopsy test."
Since then, Mitton said, MDNA's vision has crystalized around a blood-based pipeline, which is now its exclusive focus, although it still plans to continue to offer its first and only tissue-based assay, the Prostate Core Mitomic Test.
MDNA was formed in November 2014 for the purpose of acquiring the assets of predecessor company Mitomics, which had gone into receivership.
The firm's technology goes back further — about 15 years, Mitton said — to academic work at the University of Newcastle Upon Tyne in the UK and at Lakehead University in Canada.
MDNA's technology is based on a core methodology which involves real-time PCR detection of alterations, mainly large-scale deletions, in mitochondrial DNA, which signal cellular changes linked to the development of cancer.
Mitochondrial DNA is present at very high copy numbers in cells, and mutations occur frequently and accumulate at high levels without cells dying or becoming dysfunctional.
MDNA has built its testing method around research that showed that it is possible to detect mitochondrial DNA changes associated with particular diseases, which also appear to occur very early in disease inception and accumulate over time as the disease progresses.
The company's initial tissue-based Prostate Core test is intended as a follow-up to an initial negative biopsy in men who still have clinical signs of cancer, like elevated or rising levels of prostate specific antigen. According to MDNA, the test is able to distinguish a "true" negative from a false-negative biopsy with a negative predictive value of 92 percent.
The newer blood-based assay, called the Prostate Mitomic Test, is designed to predict which patients with an elevated PSA level need to have a biopsy in the first place, thus helping to avoid unnecessary procedures in men whose high PSA levels don't indicate the presence of a high-grade developing cancer.
Growing recognition of the limitations and the relative inaccuracy of PSA testing has spurred development of other new molecular tests that MDNA's new assay may compete with.
MDxHealth, for example, launched a test it calls SelectMDx for Prostate Cancer in March of this year. SelectMDx is a urine-based assay that, like MDNA's test, is intended to further stratify patients with clinical factors that suggest a risk for prostate cancer, like high PSA levels, in order to avoid unnecessary biopsies.
Also, German firm Chronix Biomedical offers a next-generation sequencing-based test that analyzes circulating cell-free DNA to gauge whether a patient is at high risk for prostate cancer and should go on to receive a biopsy.
Chronix launched that test out of its clinical laboratory in Göttingen, Germany in 2015, with plans to expand to the UK, other European countries, and the US.
Mitton said MDNA believes its Mitomic approach offers advantages over other molecular assays in its simplicity and robustness, and that that the performance the company has seen in validation studies of its own assay demonstrates that the test meets or outperforms the sensitivity and specificity of alternatives on the market.
Because of its high copy numbers, there is a lot of mitochondrial DNA to sample, and MDNA can perform its tests using simple real-time PCR.
Mitton said that the firm is platform agnostic overall, with the goal of being able to license its technology to other labs that could develop their own tests using whatever PCR platform they wanted.
In house, he said, the firm's scientific team prefers the BioRad CSX, which it is using to develop its assay pipeline.
In terms of test sensitivity, he said the company hasn't done head to head comparisons with other blood-based molecular methods, but in its validation work with the University of Cambridge, it concluded that its assay has 87 percent sensitivity and a 97 percent negative predictive value in distinguishing men with Gleason score-7 or higher prostate cancers.
Chronix Biomedical, in contrast, has reported that its test could discriminate prostate cancer from controls with an area under the receiver operating curve (AUC) of .92, representing a diagnostic accuracy of 83 percent. For distinguishing prostate cancer from benign prostate hyperplasia and prostatitis, the test's diagnostic accuracy jumps to 90 percent.
MDxHealth lists an AUC of 0.89 for its SelectMDx on its website.
"We think a lot of [our accuracy advantage] has to do with the platform itself — the fact that the mitochondrial DNA is so abundant and we have this copy number advantage," Mitton said. "In every sample, without additional amplification, or library preparation in the case of NGS, we have a lot of clinically relevant material so we can get a very good signal."
Though the company hasn't published its analytical validation of the new blood-based test, it has published on the earlier tissue-based Prostate Core test. Mitton said the firm plans to submit a study detailing its work on of the liquid biopsy version in January.
Next in line in MDNA's pipeline of liquid biopsy assays is a test for endometriosis that the company has been validating in collaboration with the University of Oxford and plans to launch in the third quarter of 2017.
Although the firm has completed proof of concept studies in about ten different cancer types, including lung and pancreatic cancer, Mitton said that MDNA plans to focus in the near term on other assays in the women's health space, namely tests for ovarian, uterine, and cervical cancers.
These will fill similar niches to the company's prostate cancer test – as adjunct screening tools for high-risk patients, helping to distinguish who needs intervention and who does not.
According to Mitton, MDNA has also begun to collect evidence that its mitomic approach can distinguish between different stages of cancerous or pre-cancerous disease, patients with Gleason 6 and Gleason 7 prostate cancer scores, for example.
"As we evolved the product line … we have seen that we do have differentiation between different subgroups of disease, so the goal is to launch second-generation products that help stratify risk or grade aggressiveness of each disease as well," he said.Â