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Oxford Gene Technology Bets on Design, Flexibility to Woo Clinical Labs With New NGS Cancer Panel

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NEW YORK (GenomeWeb) – Oxford Gene Technology is looking to expand its presence in the next-generation sequencing market by building out its portfolio of optimized content for custom cancer panels.

The British molecular genetics company recently announced a menu update for its SureSeq myPanel NGS Custom Cancer Panel offering, with new content available for genes and regions linked to colorectal, lung, and prostate cancers, as well as glioma, melanoma, and sarcoma.

This adds to a catalog that already included content for chronic lymphocytic leukemia, acute myeloid leukemia, as well as ovarian and breast cancer. OGT first introduced its SureSeq myPanel offering last October.

In total, its menu now covers 70 genes. The panels are designed for use on Illumina instruments.

Emma Shipstone, executive vice president of marketing at the Oxford-based company, said that OGT is targeting clinical research laboratories with its products, especially those that are either disappointed with the performance of amplicon sequencing panels, or that still rely on Sanger sequencing to interrogate difficult cancer-associated genes. Some labs use both amplicon sequencing panels and Sanger to look at genes of interest.

"I think it's something that amplicon-based panels have not been able to deliver on, and when it's a gene of interest, customers have had to do a second assay to understand what's been going on in a particular gene," said Shipstone. "If you can remove the need for that second assay, you can get the data analysis done much faster without having to do additional techniques."

There is no shortage of fixed and custom cancer panels on the market.

Thermo Fisher Scientific is certainly an OGT competitor with its Ion AmpliSeq NGS Panels, while other firms have opted for a one-panel-meets-most-needs approach, such as Asuragen, which sells its QuantideX NGS Pan Cancer Kit, or Integrated DNA Technologies, whose x-Gen Pan Cancer Panel delivers information on 127 mutated genes across 12 tumor tissue types.

According to Dave Cook, senior product manager at OGT, the company is aiming to beat its competition both on data accuracy, thanks to its hybridization-based bait design approach, as well as its flexibility in delivering an ever-increasing array of optimized, custom content.

Founded in 1995 to protect the IP estate of microarray pioneer Ed Southern, the company began to expand in 2005 with the appointment of CEO Mike Evans by introducing a variety of array products, as well as probes for fluorescence in situ hybridization and sequencing kits and services. It is this background in array hybridization that guided OGT's NGS bait design technique, where the firm synthesizes capture probes optimized to capture regions of interest, adding baits when necessary to capture GC-rich or repetitive regions that are considered to be difficult to sequence.

"What we have found is that using hybridization overcomes many of the issues that you find with amplicon-based library preparation," said Cook of OGT's approach. He said that OGT's bait design eliminates biases found in amplicon-based sequencing, such as obtaining duplicate reads from a single template, as all fragments generated from a single primer set are identical. Primer competition and preferential amplification of some regions over others can also lead to non-uniform enrichment, he noted.

"What we are finding is that the uniformity of coverage gives greater confidence in the ability to make a call in the data, because you are getting much better coverage," Cook said. "We are using design methods that have been honed over a number of years on the array side and with our FISH probes as well and utilizing it on the sequencing side now," he said. "By putting that effort in, we are able to get superior coverage in very tricky areas."

It may very well be that trickiness that has encumbered growth in the market for custom panels. While the technology is there, and the pricing always becoming more favorable, especially in the clinic, uptake may be less than anticipated due in part to questions about its reliability and applicability.

"The translation of next-generation sequencing into routine cancer care has been slower than many would have anticipated," said Sarah Wordsworth, an associate professor at the University of Oxford's Health Economics Research Center, and a co-author on a recent PLoS Medicine paper that assessed the clinical applicability of an Ion AmpliSeq Hotspot Cancer Panel from the vantage point of the National Health Service.

"Some healthcare providers are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single-gene testing," said Wordsworth.

For OGT, the main competing technology in this context is not other NGS kits, but a reliance on the standard approach of single-gene Sanger sequencing, though Cook noted that OGT's approach enables users to detect low-frequency variants consistently down to a 1 percent variant allele frequency, versus the 20 percent VAF common with Sanger.

"There is a desire to be using NGS, but there have been some issues with certain regions," Shipstone said. "Customers are still using Sanger orthogonally, and that is a problem that we are looking to overcome with what we are able to offer in terms of design with our panel," she said.

Reception to SureSeq MyPanel since its autumn launch has been positive, Cook said, in particular because the firm is committed to adding new content as it is identified and optimized.

"When we are talking to customers, they certainly appreciate our goal to manage the fact that discoveries in cancer biology are occurring all the time, and if you've got a fixed panel of content, that can become out of date, which is why we have adopted a very fluid, custom approach," said Cook.

Cook declined to provide pricing information, but said that it is calculated based on content — i.e. kilobases per panel — rather than the number of genes or regions covered. That also gives OGT an advantage over fixed panels, he said, as clients pay for their 10 or 15 genes of interest, rather than generating unnecessary data on larger, fixed panels that contain those same genes. "We are looking to minimize the content on the panel, as opposed to maximize the content," said Cook. "We can offer very competitive panels because of it."

One early adopter is Anna Skowronska, an R&D scientist at West Midlands Regional Genetics Laboratory, which moved to using an OGT SureSeq myPanel last fall when the product first became available, after doing Sanger sequencing for 20 years.

"We decided that using NGS testing gives us better sensitivity and can improve turnaround time," Skowronska said. "If we are talking about a big panel, like 25 genes, it is also cheaper, because time also comes into account," she said. "We can't multiplex so many amplicons in Sanger but we can easily do it in NGS."

Birmingham-based West Midlands Regional Genetics Laboratory has evaluated other technologies, including amplicon sequencing panels, but elected to use a hybridization approach, in part because the lab would like to add other tests to its battery in the future, such as copy number and mutation analysis. Skowronska said that her lab is also using Illumina's Nextera DNA Library Prep Kits with the same rationale. "We think that hybridization gives us wider possibilities, and it also deals with difficult genomic regions," she said. "This we know based on our experience."

While the West Midlands Regional Genetics Laboratory is sold on using OGT's kits for now, some believe that some of the kits might fare better should they receive a CE-IVD marking. Gert Matthijs, head of the laboratory of molecular diagnosis at the University of Leuven in Belgium said that while his lab has not used the kits, OGT's "reputation … gives us confidence about the quality."

Matthijs said it's a "pity" that the kits are available for research use only.

"The claimed uniformity is an asset for sequencing, and especially for diagnostic applications," said Matthijs. "It would be nice if the company would offer a CE-marked version of the kits, for clinical use," he said. Should OGT obtain such marks through cooperation and validation with other labs, "everybody benefits for the work, and no one has to re-invent the wheel," he said.

Matthijs also suggested that given the uniformity of the data produced using its kits, OGT's panels could also be used for gene dosage analysis — determining the number of copies of a gene present in a genome. While he suggested that OGT's proposed limit of detection of 1 percent "may be on the optimistic side," he noted that the firm's technology has been shown to be "repeatable and robust in a diagnostic context."

OGT appreciates the market's desire for CE-IVD-marked products, and will "certainly be considering [them] in the future," Shipstone said. In the short-term though, customization of content on sequencing panels will be the firm's main focus.  "As panel content becomes better defined and locked down over time, it would certainly facilitate the process of CE-IVD marking," she said.

OGT will now continue to build on its SureSeq myPanel offering as it wins over more customers. "We plan to make more content available both across the disease areas we are already covering and new genes of interest that customers can add to those virtual panels," she said. Shipstone noted that OGT recently launched a custom panel to detect variants associated with familial hypercholesterolemia. "So we have capabilities in the rare molecular diseases," she said, "alongside solid and hematological cancers."

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