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Profile Feature as seen in Nature 25th September 2014

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Since its founding in 1982, Quintiles has become a leading clinical research organization, from first-in-human studies to post-launch monitoring. In 2013, Quintiles acquired Expression Analysis (EA) to expand its genomic testing analysis services throughout the entire process of drug discovery and development. Dr. Patrick Hurban, a trained molecular biologist and geneticist and EA’s Global Head of Genomic R&D, tells Nature how the marriage between EA and Quintiles benefits researchers.

Q: How does Expression Analysis help advance drug development?EA was spun out of the Duke University Medical Center’s Microarray Core Facility in 2001, primarily performing high-quality, high-throughput RNA expression services on microarray chips. Since then, we have expanded so that almost anything you can think of that would help scientists understand the impact of genomics on patients and disease is something that we might support. Without giving a laundry list of technologies, our primary focus is on nucleic acid extraction technologies, array-based technology for both genotyping and expression, and sequencing assays we can use for somatic mutation detection—essentially genotyping by sequencing. And of course our heritage in gene expression analysis positions us to thoroughly understand and exploit RNA expression analysis by sequencing.

For each of those different technologies, we have the ability to do very broad-based assays, such as whole exome sequencing to identify particular biomarkers of potential interest, down to very targeted assays, such as profiling for a single gene or a set of genes and mutations. Importantly, our bioinformatics team is just stellar, and their reach spans all of our technologies.

Q: What interested Quintiles in EA’s early-stage genomics services?Many of the researchers and companies we worked with were the same folks that Quintiles was working with, but we were talking to different parts of the businesses: discovery on our part, and clinical development on their part. By combining forces, we can now provide comprehensive genomic technologies across the entire continuum of drug development. We can begin with biomarker discovery programs early in clinical development and then progressively develop those candidate biomarkers as market-ready companion diagnostics; this ability is very powerful for advancing clinical research quickly and efficiently.

For example, let’s say we perform retrospective whole exome sequencing on some clinical samples and determine an association between clinical outcomes and specific genes, specific mutations within those genes, or domains within the encoded proteins. We can then make a customized, targeted assay. Depending on the level of resolution that we would need for further development, we can work with one of our diagnostic development company partners on a companion diagnostic strategy so that we can couple the therapeutic candidate to a specific diagnostic platform.

Q: How do you help clients choose which technologies and services are best for their program?First and foremost, we help clients determine how much of a discovery element should be included in their program. We might recommend targeted assays that specifically focus on genes that are involved in a particular disease. The advantage of this type of strategy is that looking at fewer analytes provides greater precision and accuracy. If they suspect that those genes are not telling the whole story then we can do something else, such as whole exome sequencing or our Quintiles comprehensive cancer panel. This approach gives us the ability to look at those specific genes and gene rearrangements that we highly suspect are involved, as well as the ability to discover more.

Q: Can you tell us more about the Quintiles comprehensive cancer panel?This is a targeted sequencing assay of around 200 genes that have shown high frequency of genomic variation in cancer and play important roles in cell signaling pathways that impact drug response and resistance for both existing and emerging drug classes. In fact, the panel covers about 98% of the most common gene mutations currently reported in cancer, and can detect point mutations, insertions, deletions, structural rearrangements and changes in copy number. This panel had its genesis in Quintiles’ Translational R&D – Oncology group, which is led by Sarah Bacus, PhD, and combines their deep oncology expertise with our genomics expertise. Dr. Bacus’ team has even used the panel to identify novel, druggable genomic variations in a rare form of breast cancer, the results of which will be presented in a plenary session at the upcoming EORTC-AACR-NCI Molecular Targets and Cancer Therapeutics symposium in November.

Q: Other than cancer, what disease areas do you think will be impacted by genomics in clinical development? The two that come to mind are infectious diseases and autoimmune diseases. With infectious diseases, we need to consider the genomes of both the host and the pathogen. We already know that many pathogens become more virulent or more drug-resistant via genomic changes, so following these changes during disease progression and in response to therapy will become more common. There’s also an increasing awareness that an individual is actually a collection of genomes—the human genome plus the genomes of the particular milieu of microorganisms that live in the gut and elsewhere. These microbiomes are dynamic, and we are only beginning to understand the impact that changes in the gut microbiome have on disease.

Likewise, genomic developments in autoimmunity are very early-stage and exciting. The link between autoimmune disease and the HLA locus is well established, but the HLA locus is incredibly complex. As genomic technologies become better at penetrating this complexity, it’s very likely that our understanding of autoimmune diseases will increase.

Patrick Hurban, PhD, Global Head of Genomic Research and Development, EA, QuintilesINSI

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By combining forces, we can now provide comprehensive genomic technologies across the entire continuum of drug development.

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