With digital PCR OncoBEAM and NGS Plasma SafeSEQ technologies sensitive to 0.02% and 0.05% MAF respectively, expect to hear more from Sysmex-Inostics for biomarker development, companion diagnostic commercialization and patient testing
It isn’t unusual for me to be found at different conferences, whether ASHG, AGBT, AACR or occasionally Molecular Tri-Con or ASCO. And it is also not unusual for a person I know to walk up to me, and the first thing focus on the company affiliation on my name-tag, curious as to what company I’m associated with! I am happy to announce a change of affiliation (again), this time to Sysmex-Inostics.
A great six months in San Diego
The past six months have been enlightening on several different dimensions. In the context of Singlera Genomics, learning first-hand about the complexities of In Vitro Diagnostics development, working with potential collaborators, getting to legal and business agreements as well as establishing vendor and supplier relationships all take time and effort, and was very rewarding.
Outside of work, wow San Diego sure does have a constellation of interesting startup companies (one of which I’ve highlighted here – Cardea Bio and SeqOnce I’ve written about, and several others that I haven’t written about) and many people involved at various levels of the life sciences industry I had the privilege of either meeting for the first time or renewing prior friendships. I am grateful for the opportunities to learn that these interactions afforded!
Cell-free DNA still represents the future of cancer diagnostics
Liquid biopsy in its various forms represents a secular change in how disease, and especially cancer, is treated, monitored, and detected. For example, this MIT Technology Review piece from 2016 lays out how a Johns Hopkins group working with a group in Australia demonstrate specifically how which survivors of colon cancer are at high risk of recurrence, through a simple blood-based test.
Through a sensitive method, only made possible through next-generation sequencing (NGS) as well as novel library preparation chemistry, coupled with digital PCR to look at a narrower range of circulating tumor DNA mutations, could there be a $20B market created. Guardant Health has a current market cap of some $5.7B as of this writing, on $50M in 2017 revenue and perhaps $82M in 2018 revenue; startup GRAIL has attracted $1.6B in investor money (so far) with names like Bill Gates, Jeff Bezos, and Google Ventures. This interest on the business side is for a good reason: it represents the future of cancer diagnostics and treatment. The figure below, borrowed from the consultancy DeciBio, indicates how crowded this market is across the spectrum of liquid biopsy use-cases.
Helpfully the image above distinguishes between cfDNA and CTC analysis, as well as ‘other’ (including exosomes) to help keep things straight. Nonetheless there are companies entering in all the time, and the image above is just a sampling of the >100 companies that DeciBio keeps track of. For example, at least in Early Detection / Screening I can think of CellMax Life out of Taiwan using CTCs for early-detection of colon cancer, and Bluestar Genomics for early-detection of pancreatic cancer using a novel 5’-hydroxymethylcytosine enrichment.
A matter of market fit, technology fit, culture fit, people fit, and potential
From a career perspective, there are many questions to ask and have answered when considering a move to a new organization. A primary question is what market will the company be operating in? I could have gone to a research market company, I could have gone into a different business altogether; in the end I decided to stay in the area of liquid biopsy, knowing that this clinical market, while highly crowded and competitive, remains full of promise as ever.
Within this market, the other questions are germane: what has the best technology fit to the problems they are trying to tackle, what is the company culture like and would I fit into that culture, what are the people like and in particular the hiring manager, and what kind of potential would this role have as well as the potential the company has in the markets it currently is in and markets it may want to enter.
I’m happy to say that Sysmex-Inostics answers all these questions for me, and the potential will come true in the coming years with me being part of that realization.
Sysmex the company
Sysmex is well-known in the clinical laboratory, with a large share of the hematology and coagulation blood-testing markets. Having had it’s beginning in the 1960’s with the first commercialized blood-cell counter in Japan, Sysmex has grown to a $2.5B revenue (last fiscal year) / $11B market capitalization company. On the Sysmex website, there is a nice Basics of Hematology and on its last page, ‘The Future of Testing’, points to this page with Sysmex’ vision of Personalized Medicine, with an emphasis on reducing the burden on patients.
What I can tell so far, from both in-person interaction as well as broad corporate philosophy communications like this one, is their emphasis on customers and meeting customer needs. In addition, emphasis is also made on the high standards they place on their employees, and the need to return value with the highest ethics back to their business partners, shareholders and to the wider society. It is interesting to see their latest emphasis on holistic, intuitive laboratory workflow optimization called ‘Beyond a Better Box’.
And as far as the potential of their technology on the cell analysis side, this page describes their current research effort on imaging flow cytometry, licensed from Merck. The first product in development is called Flow Fish, which automates the currently manual process of fluorescent in-situ hybridization. Here’s a YouTube video that describes the concept.
A little Inostics background
Sysmex Inostics is a subsidiary of Sysmex with a CLIA-certified laboratory in Baltimore MD and a CGP laboratory in Hamburg Germany. Both the digital PCR technology OncoBEAM and the NGS-based Plasma SafeSEQ are complementary technologies; a menu of 20 OncoBEAM tests are offered as a service, and 3 additional Plasma SafeSEQ tests are offered.
Below is a figure borrowed from this SafeSEQ Technology Fact Sheet (PDF) – six-fold higher analytical sensitivity (down to 5 mutant molecules per 10,000 wild-type, or 0.05%) with extremely high concordance between the NGS-based Plasma SafeSEQ and the digital PCR-based OncoBEAM as illustrated.
Being able to reliably detect 5 mutant molecules in 10,000 is remarkable technology. The fact remains that less than 1% MAF between four different liquid biopsy vendors that concordance between assays is low per this recent JCO Precision Oncology comparison (Stetson B and Dougherty BA et al 2019 JCO Precision Oncol “Orthogonal Comparison of Four Plasma NGS Tests With Tumor Suggests Technical Factors are a Major Source of Assay Discordance”). Quoting several of the authors and vendors in this GenomeWeb piece (“AstraZeneca Liquid Biopsy Comparison Details Concordance Failures”, subscription required) there is ‘substantial variability’ across calls in 24 matched tumor / plasma samples, and Dr. Mark Li of Resolution Biosciences is quoted as saying “many vendors who claim super low detection rates may be reporting false positives, in one case even more false positives than true positives. We believe a false positive is the worst thing we can do.”
OncoBEAM Webinar May 8, 2019
On May 8, 2019 Sysmex-Inostics is sponsoring a GenomeWeb Webinar entitled “OncoBEAM ctDNA Testing for Early Response Prediction and Therapy Surveillance in Melanoma and Pancreatic Cancer”, featuring Dr. Evan Lipson of Johns Hopkins on the clinical utility of ctDNA measurements as an adjunct to radiographic imaging for monitoring disease activity in advanced melanoma patients undergoing treatment with targeted therapy or immune checkpoint inhibitors. Also Dr. Stefan Holdenrieder of the Technical University of Munich will examine the value of KRAS-mutant ctDNA as a highly specific marker for early response prediction and treatment monitoring of advanced pancreatic cancer patients receiving chemotherapy. You can sign-up on this GenomeWeb page for the May 8, 2019 (Wednesday, 11am ET) presentation.
If you are interested in what Sysmex-Inostics can do for you do reach out to me directly – dale (at) yuzuki.org