Dr. Helmy Eltoukhy, CEO and co-founder of Guardant Health, will be giving a talk at the upcoming Personalized Medicine World Conference Silicon Valley. He recently shared his views with us on clinical sequencing and liquid biopsies.
AllSeq – Liquid biopsies are one of the hottest new applications for NGS. How does Guardant Health stand out from the many companies trying to get in this space?
Dr. Eltoukhy – We stand out in many ways. We were the first liquid biopsy company to offer a comprehensive test, both for research use and commercially, and we’ve established a strong intellectual-property position from day one. We have a patented digital sequencing method that provides us the highest specificity of any NGS cancer diagnostic, which is critical in a clinical setting. We’re the only company that has run more than 10,000 commercial tests, and we have gleaned critical insights as a result. And we have the only comprehensive liquid biopsy test that profiles all four major classes of somatic alterations. Some companies developing ctDNA tests are trying to follow our lead, while many others are using “hotspot” assays that survey a limited set of exons. While economically attractive, these tests fail to identify many activating mutations in oncogenes. Complete exon sequencing has been shown to improve outcomes by identifying less common mutations in these “undergenotyped” patients. Furthermore, we are well poised for the future and are fortunate to be well capitalized in a tough funding environment, which improves our competitive position versus many companies trying to enter the market.
AllSeq – ‘Liquid Biopsy’ today primarily seems to mean cancer diagnostics. Are there other applications in the liquid biopsy space down the road?
Dr. Eltoukhy – Though commercial use of cfDNA testing began with non-invasive prenatal testing, the largest market will soon be in cancer care. Today liquid biopsies are largely a tool for therapy selection for advanced cancers, but soon their utility will cover the entire cancer-care continuum. Liquid biopsies may be a tool for early detection, an aid in neoadjuvant and adjuvant therapy, and a non-invasive method for residual disease monitoring and recurrence or relapse monitoring. Because the technology is capable of isolating, detecting, and profiling both DNA and RNA molecules at low concentration in the blood stream, many non-cancer uses can be imagined as well. Researchers are already looking to liquid biopsies in transplant diagnostics, and the same technology may be applied to any case where there’s a need to isolate specific molecules from blood. There are many unmet needs.
AllSeq – In terms of NGS, how far along the clinical adoption curve do you think we are?
Dr. Eltoukhy – It depends on the application. There are simple single-gene and small-panel NGS tests for inherited disease diagnostics that are widely used in the clinic today. But overall we’re just scratching the surface of a market estimated to be worth between $20 billion to $30 billion within five years. For cancer, we are still in the early adoption phase. The potential benefit to patients when this reaches the mainstream is huge, and we’re seeing rapid adoption in academic medical centers as well as in community oncology. It’s not a question of if, it’s a question of when.
AllSeq – What’s the biggest factor preventing NGS from more widely adopted in the clinic?
Dr. Eltoukhy – It depends on how NGS is being used. Whole genome or whole exome sequencing is still expensive relative to yield, and so the cost-benefit ratio isn’t appropriate for many applications. But for cancer applications, where the number of actionable genes is smaller, and the clinical need is critical, we’re seeing terrific adoption and growth. The real point is that the technology for technology’s sake isn’t important – technology needs to be useful, in a cost effective way, for an unmet need. For advanced cancer patients NGS is extremely relevant, and while it takes time for practice patterns to change in medicine, it’s happening. We’re also confident that we will see more NGS use as more targeted therapies receive FDA approval. These therapies are the future of oncology and are already saving lives, but we’ve only seen the tip of the iceberg.
AllSeq – What are your thoughts on targeted vs exome vs WGS in clinical sequencing?
Dr. Eltoukhy – Although our platform is capable of whole genome or exome sequencing, yield will always be higher with a targeted approach, so we always think about the specific needs of an application. While there are some rare diseases where it’s impossible to make a diagnosis without sequencing the whole exome or genome, in cancer the universe of relevant genes is relatively small, especially for clinical applications. But we need to sequence at great depth to achieve the extremely high sensitivity and specificity required to confidently detect the small quantity of cfDNA molecules in the blood. As a result, we don’t see whole exome or genome sequencing applied to cancer applications in the near future. Oncologists need actionable information, so we provide sensitive and targeted sequencing. We see WGS sequencing primarily as a tool for discovery research today.
AllSeq – The market has mostly been focusing on driving down the cost of sequencing. Is there still a need to drive the cost down even more, or do you think other factors are becoming more important?
Dr. Eltoukhy – While a decrease in costs is always useful, what will be more useful is further improvements in the data. There’s still a lot of missing information – variants that aren’t assessed, molecular pathways that aren’t understood, etc. – and this is probably more important than simple cost. We will also benefit from instruments with higher throughput. Every day a specimen sits on a sequencer is a day a patient’s cancer is progressing.
See Dr. Eltoukhy’s presentation at “Personalized Medicine World Conference – Silicon Valley” where he will give a talk entitled “Cancer’s Tweet: 160bp Snapshots into Cancer’s Hidden Evolution”