Personal Genome Diagnostics Aims for FDA Clearance of NGS-based Cancer Products

Wednesday, February 25, 2015

John Hopkins University spinout Personal Genome Diagnostics plans to develop cancer diagnostic products that it will bring through US Food and Drug Administration clearance.

At last week's Molecular Medicine Tri-Conference in San Francisco, PGDx Founder and CSO Victor Velculescu told GenomeWeb that the company is in the midst of "moving from being a service company to a product company," and aims to bring both tissue-based targeted sequencing tests as well as NGS-based liquid biopsy tests through FDA clearance in the next couple of years.

As part of this push the company plans to complete a Series A financing round this year. Last year, it raised $2.8 million in private financing.

PGDx currently offers a clinical targeted sequencing panel and a variety of research-based sequencing services for both tissue- and blood-based tumor profiling.

Its laboratory-developed test, CancerSelect, analyzes 88 genes and has a turnaround time of three weeks. The firm sequences the entire coding regions of 76 genes, does copy number analysis for 13 genes, rearrangement analysis for 14 genes, and microsatellite analysis for five genes. Sequencing is done to over 500x coverage using Illumina instruments. The test has a sensitivity of greater than 99 percent and a specificity of greater than 99.99 percent.

PGDx also offers an expanded, RUO version of CancerSelect that analyzes 203 genes. The company also offers RUO tumor exome sequencing and targeted assays that analyze circulating tumor DNA — the 63-gene PlasmaSelect assay, as well as METDetect, which looks for MET amplifications.

In addition, through a business segment it calls Enterprise Solutions, PGDx works with labs to develop standard operating procedures and bioinformatics to run the CancerSelect tests themselves. Both its 88-gene and 203-gene CancerSelect tests are available through this model.

"It's a turnkey solution," PGDx CCO Antony Newton said. "We do the R&D … figure out the genes to include, the panel design," he said, and then "enable individual labs to get it up and running."

Velculescu said that once the company has FDA-cleared products it would bring them to clinical labs in this same model. As PGDx improves on the panel, the latest version would be available to those labs as an upgrade, he said.

"Over time, these kits will become FDA approved and that will be the way in which we move forward to make sure the technologies we develop get to as many patients as possible," Velculescu said.

Currently, both Illumina's MiSeqDx and Thermo Fisher Scientific's Ion PGM Dx NGS systems are designated as Class II devices. However, the intended use of those systems is for analyzing germline mutations from blood, and do not extend to analyzing somatic mutations from formalin-fixed paraffin-embedded tissue. FDA has said that either a test developer or system manufacturer would have to submit an assay and accompanying software to add tumor sequencing to the intended use of the platform.

Velculescu also said that PGDx would focus more on its circulating tumor DNA assays. Last year, PGDx licensed technology for analyzing cell-free tumor DNA from Johns Hopkins University. Known as PARE, for personalized analysis of rearranged ends, the technology enables identification of structural changes. The CancerSelect, PlasmaSelect, and METDetect assays all make use of the PARE technology.

Velculescu said both the PARE technology and additional technology developed at PGDx "puts us in a good position" to tap into the liquid biopsy field.

Many researchers and companies have recently expressed interest in this market, including Guardant Health, which already offers a clinical test based on targeted sequencing of ctDNA. Many of the larger companies, like Illumina, Sequenom, Thermo Fisher Scientific, and Foundation Medicine have also stated plans to develop ctDNA assays.

Being able to analyze tumor mutations from blood would offer many advantages over biopsies, Velculescu said. Often, patients with metastatic disease have tumors in multiple sites and it is too difficult to take biopsies from every site. In addition, a blood-based test would enable physicians to monitor cancer progression and drug response and resistance over time, or to look for residual disease following surgery or treatment, he added.


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