NEW YORK (GenomeWeb) – Qiagen expects to be a dominant player in the nascent liquid biopsy space, with a growing number of the firm's widely-used products finding prominence under that tent. In a recent interview with GenomeWeb, the company offered insights into its liquid biopsy business, and also clarified its business relationship with Exosome Diagnostics.
Liquid biopsies aim to replace painful and costly tissue-based diagnostics with nucleic acid detection — using sequencing or PCR — from blood, sputum, urine, or other bodily fluid. Qiagen has a two-fold strategy when it comes to this market.
"On one hand, [Qiagen has] full solution coverage for the product portfolio — really from sample to the bioinformatics insight," noted Michael Kazinski, Qiagen's senior director of molecular preanalytic technologies and the executive responsible for liquid biopsy solutions in the company's life sciences business.
"At the same time [it also has] the expertise in allowing customers to develop clinical diagnostic tests with no need to change technologies while going down the regulatory path," Kazinski said.
Although liquid biopsy analysis could apply to many diseases, the field is now mostly focused on oncology. Detection in this domain includes cell-free and circulating tumor nucleic acids and proteins, as well as DNA, RNA, miRNA, or proteins that can be found in circulating micro-vesicles or exosomes.
The latter is quite interesting — and remains one of Qiagen's priorities — but it's only one piece of the larger picture. And the exoRNeasy kit, which isolates exosomes and preps the nucleic acid sample, and which was jointly-developed with Exosome Diagnostics, has now led to an additional kit for other analyses.
"What we learned is that the community is also increasingly interested in looking at what is in exosomes besides pure nucleic acids — for example, proteins," said Kazinski. A new kit, called exoEasy, uses a column-based method to isolate intact vesicles, allowing a customer to do "whatever downstream application he or she wants to perform."
An example sequencing-based liquid biopsy workflow might include isolating the DNA out of plasma with the QIAamp circulating nucleic acid kit, either manually or with the automated, high throughput QIAsymphony platform. The latter platform also plays a key role in the firm's efforts in the liquid biopsy space, Qiagen CEO Peer Schatz said in a presentation at the JP Morgan Healthcare conference this week, and new QIAsymphony placements in the fourth quarter exceeded expectations.
Customers could then search for specific targets using, for example, GeneRead DNAseq Targeted Panels. These multiplex PCR primer sets are available tailored to 15 different cancer and risk types, can also be customized, and are "designed for Illumina or Ion Torrent sequencers, which allow you to generate high-quality amplicons from your region of interest," Kazinski said.
The library prep solutions are platform agnostic, so work with Illumina or Ion Torrent, but also with the sequencing platform recently launched by Qiagen, the GeneReader.
"We're expanding on this and we'll soon have these solutions even further optimized to work with the GeneReader NGS System," Kazinski noted, adding the sequencing workflow is just one example to show how Qiagen covers the whole space.
Customers also have the option to use PCR-based solutions. Qiagen offers targeted panels for this workflow, as well as the PCR platforms to run them. "Our liquid biopsy-based companion diagnostic test for Iressa is exactly that workflow — looking into circulating DNA using specific primers ... [and] read out on the RotoGene Q," Kazinski said, referring to the firm's therascreen EGFR kit which is already approved and in use in the clinic.
To analyze reams of data, customers can use Qiagen's widely-adopted informatics suites originating from Ingenuity and CLC Bio, and the firm is also developing informatics tools specific for the liquid biopsy space.
"We are working on solutions — the whole field is really fluid at the moment ... there is a clear focus on cancer, [but] there are other indications where liquid biopsy will play a role, such as neurodegenerative diseases," Kazinski said. "At this point we already have the best solutions in bioinformatics covering everything from pathway analysis to NGS data interpretation, and we're looking forward to more liquid biopsy-specific tailored solutions in future development."
The firm will also soon be launching a product called QIAseq Ultralow Input Library Prep Kit, designed for use with Illumina sequencers. This kit will generate robust, ready-to-sequence libraries which can then be used for whole-genome or whole-exome sequencing from as little as 10 picograms to 100 picograms of input material, Kazinski said.
"We have significant interest from the pharma industry and there are several projects which we cannot disclose at this point," he added. "In addition, we collaborate with clinical researchers to show and prove the feasibility of the workflows we offer solutions for."
At JP Morgan, Schatz noted that Qiagen has five companion diagnostic deals thus far that use liquid biopsy, including one announced this week with Array BioPharma, and also said that he believes the company is processing more liquid biopsy samples than any other firm in the industry.
He further noted that the firm has put together a sales team specifically focused on the molecular oncology market that will sell the GeneReader along with other Qiagen products, such as the theraScreen assays.
Overall, Qiagen is "the only company who has the full solution offering from sample isolation down to the bioinformatics interpretation of results," Kazinski said. Going forward, the firm's strategy is to enable research customers to use the same technologies for both the research and regulatory phases of clinical diagnostic development, eliminating significant challenges customers face in switching technologies or platforms. "We believe this is of extreme importance," he added.
Exosome agreement
In late 2015, Exosome Diagnostics launched a clinical commercialization program to port clinical research projects from the exoRNeasy kit — which was co-developed by Exosome and Qiagen, and is marketed by Qiagen — to a method Exosome had developed in house. The company also offered to work with researchers to take selected biomarkers through the FDA approval process and provide them with royalties from any future sales of clinical tests.
At the time, Exosome asserted that it retained the rights to the clinical market under its agreement with Qiagen. But Qiagen demurred, telling GenomeWeb that clinical research and biopharmaceutical research are parts of the research field to which Qiagen has exclusive rights.
"We received an exclusive license under Exosome's intellectual property rights — meaning patent rights and know-how — to sell products based on these IP rights to the biopharmaceutical and academic research community," said Achim Ribbe, Qiagen's president of corporate business development for licensing. But, "Qiagen cannot convey any licensing rights to [a] CLIA lab to use such products for commercial testing, as defined as a fee-for-service business; such use would need additional licensing rights by Exsome Dx."
Rights to sell future clinical products using the technology would ultimately require CE-IVD or FDA approval, Ribbe added. Those rights reside with Exosome, with the one exception being a future jointly-developed IVD clinical test focusing on a few defined biomarkers being developed as a companion diagnostic test for a pharma partner.
However, Kazinski noted, "Before something goes into an IVD-approved clinical test, what people usually do is look what are the relevant biomarkers associated with this disease ... including using patient material, blood samples for example, [and] this is what we call clinical or translational research."
At the end of this research stage, a customer may come up with a specific biomarker and use it to develop an IVD test, Kazinski added, which could then fall under Exosome's domain. "But in the translational phase, we serve this market," he said, "and it is also important to state that the technology we use with the Exosome portfolio is a technology jointly developed between Exosome and Qiagen."