How did Karius first come into being?

Through research at Stanford in 2014 looking at cell-free DNA, we realized that there was a faint but informative signal coming from microbes. Digging deeper into that signal, we realized it could be applied to infectious disease diagnostics.

In what ways is genomics impacting the infectious disease space?

The current paradigm centers on hypothesis-based testing by the clinician. This can be a long and tedious investigation process, resulting in empirical treatment with broad-spectrum antimicrobials and potential confusion and suffering from wasted time and money. The introduction of genomics into infectious disease diagnostics allows us to capture a broad range of clinically relevant microbes within a single test. The way this is done is by looking at the genetic material that these microbes shed into the bloodstream as they infect the patient. Every bacteria, fungus and virus has a genetic code, and that genetic material is shed into the bloodstream as it replicates. This is the microbial cell-free DNA (cfDNA) that we detect. With sequencing, digitizing and applying machine learning and analytics, we can produce a report that tells the clinician which pathogens are present in their patient’s blood.

What are the differentiators of Karius’ platform from others available?

The Karius test gives physicians a single blood test that can deliver a potentially life-saving diagnosis, often more quickly than traditional testing methods such as blood culture, when time is critical. With cell-free DNA, there are three main benefits: everything, everywhere, in real-time. Firstly, cfDNA allows us to see nearly every class of microbes with a single test. Secondly, an infection can also be picked up anywhere in the body, meaning that the patient may not need to undergo an invasive biopsy. Lastly, cfDNA closely tracks the level of infection in real-time – if a patient has an infection and it clears, the cell-free DNA signal disappears.

Compared to other diagnostic companies, our main differentiator is that we are a comprehensive test, and most others are narrow panels or tests for single pathogens. While blood cultures are fairly broad and can grow a variety of microbes, they are prone to becoming sterile once the patient is put on antibiotics. Once this happens, the patient is even harder to diagnose, but our test can still detect the pathogen DNA for some time after treatment is intiated. The genomics approach therefore carries many advantages to all alternative options.

How rapid has the uptake been for the test?

After proving the test’s clinical utility, we launched our early access program last year. This enabled a set of high-profile institutions such as Rady Children’s Hospital to use the test and provide feedback to us. This year, we are launching the test nationwide. The uptake has been exciting, especially in immunocompromised patients, pediatrics and sepsis.

Could you elaborate on the advantages of the test in immunocompromised patients, pediatrics and sepsis?

Immunocompromised patients include every oncology patient that has gone through chemotherapy. These patients are susceptible to a wide range of infections, making our broad approach especially helpful. We have seen a lot of success here in identifying pathogens that in some instances were not even on the radar of the clinician. There have been some jaw-dropping results, honing in on the specific infections these cancer patients have and allowing clinicians in some cases to narrow the incredibly strong, toxic, broad-spectrum antifungals to a single targeted anti-fungal, for example.

In pediatrics, time is often crucial. There is also inadequate blood volume to test many things in parallel. The ability to diagnose from a single blood draw is therefore extremely powerful in pediatrics. And for sepsis, we ran a study last year enrolling 350 patients that presented with sepsis. We followed their diagnostic odyssey and found that using all available traditional diagnostic tools, only 40% of patients were diagnosed after 8 days. On day 2, only 18% were diagnosed. Results for many standard tests are relatively slow. Running the samples through the Karius system, we were able to identify 60% of the infections on day 2.

What work is being conducted internally to further develop the technology?

Internally, we have extensive R&D to create the next version of the technology. We also work with the pharmaceutical industry to empower them in their clinical studies. One benefit to the pharmaceutical vertical involves facilitating enrollment in clinical trials. Enrolling the wrong patients in clinical trials is a major setback. Equally, it is important to know that they do not have any other background infection that could cause them to fail on the therapy. We recently announced one partnership with Nohla Therapeutics, which has a cell-therapy for oncology patients to reduce the rate of infection after chemotherapy. They are using our test for a range of measurements within that study.

Karius has also made two grants available for research institutions. What are the intentions behind this funding support?

The idea is to really move the needle for a researcher or fellow and provide them the resources to collect required samples and kick off their projects in applied infectious disease genomics. Infectious diseases are the number two cause of death around the world, above all the cancers combined. We want to elevate the problem in the minds of researchers and scientists as an area worthy of focus. Millions of people are dying from undiagnosed infections and in many cases precise and timely medical intervention could prevent this.

What are the next steps for the company in terms of new developments?

The first priority for 2018 is to touch as many patients as possible, first in the United States and then beyond. As we do that, it is important that we keep listening  to our customers and implement their feedback. However, taking a novel approach to the market requires us to be not only reactive but also proactive. A blend of these two factors is what carves out the road map for the future.

Looking a little bit further, I am confident that in five or six years, genomics will be the standard way to diagnose infectious diseases. It makes little sense to wait for microbes to grow in a culture when the DNA signal is there in the blood at the time of the draw. It makes just as little sense to require an invasive biopsy from the patient in the case of a deep-seated infection when the signal is available in the blood. Our team is proud and humbled to be leading this paradigm shift.