A Blood Test That Uses Next-Generation Sequencing

March 30. 2020. 7 mins read

If you arrived at this story wondering if someone had found a new way to detect the coronavirus, we’re sorry to disappoint you. This article has no direct connection to the pandemic that is emptying your 401K and threatening the lives of your grandparents, except that we will be talking about viruses, bacteria, and other nasty microorganisms that can ruin your day. However, the startup that we’re going to talk about today, Paris-based PathoQuest and its next-generation sequencing technology, could potentially play a role in the final production of a COVID-19 vaccine. We’ll talk more about that later. What’s really piqued our interest is how the company has applied its metagenomic analytics for a different type of blood test.

Some Applications for Blood Testing

Blood testing is a competitive and lucrative market, with the various prognosticators out there estimating the industry at somewhere between $50 billion and $60 billion. Over the years, we’ve covered a number of blood-testing startups, beginning with the biggest and baddest (literally), Theranos, about five years ago. And we’ve actually been profiling companies that are developing blood tests for cancer (also known as liquid biopsies) even longer, beginning way back in 2013 with a startup named ApoCell (since acquired in 2018 by a healthcare services company called Precision Medicine Group). 

Mobile blood-testing labs from Genalyte.
Mobile blood-testing labs from Genalyte. Credit: Genalyte

The basic premise is that from a single drop of blood, we’ll be able to screen for dozens if not hundreds of diseases. It sounds great in theory but harder to achieve in practice, though progress has certainly been made. For example, a startup we profiled previously, Genalyte out of San Diego, has developed a mobile lab that will be able to return results on 90% of standard tests in less than 30 minutes using a small amount of blood. Another startup we covered, Athelas, is testing a device that uses a prick of blood to measure white blood cell count for detecting infections. It even has FDA approval at point-of-care for limited applications.

Why We Need Different Types of Blood Tests

It’s one thing to know that a patient has an infection, but actually identifying the pathogen that is responsible is much trickier. In the past, doctors would just order an antibiotic carpet bombing that would annihilate the bad and good bacteria in the body. There’s at least two problems with that approach. First, it wipes out the beneficial bacteria that live in the gut microbiome and elsewhere in and on our bodies that help us digest sketchy street food and even fight disease

The bigger problem is the fact that we’ve used these drugs with such wanton abandon that bacteria with antibiotic-resistance called superbugs are killing more people with wanton abandon. Last year, the U.S. Centers for Disease Control and Prevention issued a major report that said more than 2.8 million antibiotic-resistant infections occur in the United States each year, and more than 35,000 people die as a result. The World Health Organization has noted that new cases of multidrug-resistant tuberculosis hit nearly a half-million people just six years ago.

If we could identify specific pathogens, then we could deliver more precise medical care without blasting people with antibiotics and helping bacteria evolve better resistance. 

A Different Kind of Blood Testing Startup

Click for company website

Enter PathoQuest, a biotechnology spinoff out of Paris’ Institut Pasteur that has raised about $22 million since it was founded in 2011. The most recent round came in September 2019 when the company raised about $9 million through financing and loans. Here’s what the company’s newest investor, Swiss-based VC firm investiere, had to say about PathoQuest:

[T]hey represent an exciting healthcare company that delivers novel solutions addressing challenges faced by biopharmaceutical companies in their quest to deliver safer, better treatments to patients. PathoQuest’s expertise has also enabled the company to broaden the application of next-generation sequencing into clinical microbiology through the development of iDTECT Dx Blood, a promising new test designed to assist clinicians with their efforts to implement effective antimicrobial stewardship initiatives.

Now let’s break that down so we can understand what PathoQuest is offering, starting with the second half of that statement.

Next-Generation Sequencing for Identifying Pathogens

Next-generation sequencing (NGS) refers to a broad set of different technologies that enable scientists to “read” the genetic information carried in a particular DNA segment quickly and cheaply. Illumina (ILMN) and Oxford Nanopore Sequencing are examples of two companies that have developed different technologies around high-throughput sequencing. In fact, PathoQuest relies on equipment from those exact manufacturers to enable its metagenomics approach. Metagenomics simply refers to the study of individual species within an entire community of microorganisms without the need to isolate and cultivate them in a lab.

Using proprietary methods developed by PathoQuest, the company prepares blood samples and then analyzes them using those next-generation sequencing technologies to identify genomic sequences of pathogens that are present in a patient’s blood. Those genomic sequences are then compared to a database PathoQuest has built that contains genetic records from more than 1,200 bacteria and viruses. The company regularly updates the database with clinically relevant pathogens such as something like the coronavirus. 

PathoQuest next-generation sequencing platform for pathogen blood tests.
Credit: PathoQuest

A report identifying any pathogens present in the blood sample is then handed over to clinicians to help them to determine the most appropriate treatment approach. PathoQuest got the first-ever European Union approval for a metagenomics NGS test back in 2016.

Is Next-Generation Sequencing Better Than Traditional Methods?

Of course, the question is whether this method works better than traditional approaches – and if it saves money. 

To answer the first part of that question we can look at the results of a small clinical trial involving 101 immune-compromised patients that compared the company’s iDTECT blood test against a half-dozen standard methods such as blood cultures and PCR testing. The PathoQuest test detected clinically relevant pathogens in 36% of patients versus 11% using other testing protocols. So there’s that.

However, the test is currently limited to immunocompromised patients with suspected infections, especially those with extremely low white blood cell counts. That means the blood-based test is being used on patients with blood malignancies like leukemia who are undergoing high-risk therapies; cancer patients whose treatments kill red and white blood cells; and others with a severely compromised immune system where even a minor infection could prove deadly. The company does say that it’s looking to expand the clinical applications of the iDTECT blood test, including identifying infections in biological samples other than blood.

It’s much harder to answer the cost question, as we don’t really have any financial data to compare. On one hand, the company’s next-generation sequencing technology means that labs don’t need to culture or grow the microorganisms to identify them. More targeted approaches should result in better, faster outcomes in treating infections, which would presumably lower costs, including time spent occupying a hospital bed. But even though sequencing technology is much cheaper than in the past, it’s still not cheap. And since the use cases are still limited to more extreme use cases, we assume the tests carry a higher price tag than conventional methods.

Next-Generation Sequencing for Biological Production

While our focus in this article is on PathoQuest’s development of a next-generation sequencing test for identifying pathogens in blood, the company’s platform was also developed for an altogether different purpose – ensuring quality and safety in the production of biologicals. In other words, labs producing biopharmaceutical products like vaccines employ its technology to ensure there are no viral, bacterial or other biological contaminants that could cause quality or safety issues during production.

PathoQuest biologics genomics sequencing workflow.
Credit: PathoQuest

One of the company’s key customers – and an investor as of last year – is Charles River Laboratories International (CRL), a drug discovery support services company with a $6 billion market cap. Besides biologics viral safety testing, Charles River also uses PathoQuest’s platform for what’s called cell-line characterization, FierceBiotech reported. In part, that just means that the cell bank from which biopharmaceutical companies use to draw upon for their products are free of any contaminants.

The important thing to understand is that this multi-billion-dollar company considers PathoQuest crucial to its business. A quote from a vice president-type at Charles River in the FierceBiotech story:

Our partnership with PathoQuest is integral to our ability to provide the most sensitive testing methods to our clients in order to ensure the safety of biological products produced by the biopharmaceutical industry.

Earlier this year, PathoQuest announced it had received a critical lab certification for its next-generation sequencing viral safety testing, which the company says will provide it with “a significant new market opportunity in addition to the current testing we perform in a R&D environment.” 


Our final wrap-up question for PathoQuest: “What’s next?” The company appears equally committed to developing its two core services – metagenomics blood testing and biologics genomics QA. Last year’s infusion of cash will obviously go toward growing the business, and it’s unclear how much is still being poured into R&D to mature its next-generation sequencing technologies. Charles River Laboratories obviously has a strong financial interest in PathoQuest, and one path toward reducing that risk is through acquisition – something Charles River is not averse to doing, having snatched up nearly 30 companies over the years. It’s all speculation, but that’s half the fun for the retail investor.


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