23 Mar Q&A with Mickey Kertesz, Chief Executive Officer, Karius

Dr. Kertesz co-founded Karius in 2014 to bring the novel pathogen detection technology he and colleagues developed at Stanford closer to the bedside. Based in Redwood City, California, Karius now provides a Next-Generation Sequencing based test that is able to identify over a thousand pathogens from a single blood draw. Prior to founding Karius, Dr. Kertesz was the CEO and co-founder of Moleculo, a long-reads DNA sequencing company, which was acquired by Illumina in late 2012. Read his full bio.

PMWC 2018 Michigan takes place June 6-7, 2018.

Q&A with Mickey Kertesz

Q: Tell us a little bit about Karius – what problem(s)/need(s) are you trying to address and what technology is behind it to achieve this?

A: The challenge we see is that patients are suffering needlessly from undiagnosed infections. Infectious diseases have a profound global impact, responsible for roughly 20% of all human deaths each year. This includes patients we commonly encounter with sepsis, compromised immune systems, and difficult-to-diagnose infections.

Current diagnostic methods may be invasive, limited in their ability to detect pathogens, challenging to interpret, or susceptible to contamination.

A rapid, accurate infectious disease diagnosis can enable clinicians to improve patient care and outcomes by tailoring more effective antibiotic/antifungal therapy, eliminating unnecessary procedures, and guiding antimicrobial stewardship.

Karius provides a comprehensive, CLIA-certified, CAP-accredited test capable of identifying more than 1,000 pathogens from a standard blood draw. It uses next-generation sequencing to detect cell-free pathogen DNA circulating in a patient’s bloodstream, with a typical turnaround time of one day from sample receipt.

Q: Can you discuss a couple of use cases that demonstrate Karius’ approach?

A: The Karius™ test is being used in a number of applications, including detecting pathogens in diagnostically challenging or culture-negative infections like sepsis, endocarditis, fever of unknown origin, and patients who have received antibiotic pre-treatment.

We are also able to quickly and accurately identify many deep-seated infections such as invasive fungal infections that might otherwise require invasive biopsies, and monitor immunocompromised patients who are susceptible to a broad range of pathogens, including stem-cell transplant recipients.

Clinicians across the country are using the Karius test to be able to precisely target antimicrobial therapy in some cases where blood cultures are negative, including febrile neutropenia and infections with fastidious organisms.

Q: You are developing cell-free DNA testing for infectious disease diagnostics – is there enough signal (material) to make this happen?

A: For infectious disease detection, the pathogen DNA signal in plasma is about one millionth the level of the human DNA signal. The signal for individual pathogens is often much less than that, unless the patient is very sick. This makes it hard for widely available technologies to be able to extract meaningful information.

Karius is the first team to characterize this microbial cell-free DNA signal (cfDNA) and offer a commercial cell-free test in the United States to detect pathogens.

We do this by putting great focus on the rigorous standards of our laboratory procedures. These include reducing environmental contamination, enriching the pathogen DNA signal to increase the signal:noise ratio, and controlling for known sources of bias. This combination of techniques gives us far better sensitivity and precision than standard NGS protocols, allowing us to accurately and rapidly detect and identify pathogens from the cfDNA signal.

Q: What are the advantages of cell-free DNA testing and what are some challenges that still need to be overcome to make its detection a routine in the clinic?

A: With cell-free DNA, there are three main advantages: we can rapidly detect a broad range of pathogens from infections throughout the body. 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 also dissipates.

Compared to other diagnostic companies, our main differentiator is that we are a broad 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. In these ways, the genomics approach carries many advantages to the alternative options.

The challenges to making this a routine part of clinical care include changing the current paradigm of diagnostic testing and helping clinicians trust that there can be a better way than the current standard protocols.

Q: What needs to be achieved and how should we all work together as a community to take infectious disease diagnostics into the genomics area? What are some of the major challenges we need to overcome?

A: As a precision medicine community, we can work together to raise awareness in our networks about the opportunities for improved patient outcomes as a result of genomics. We can demonstrate the benefits with clinical studies, and share our findings openly. We will need to overcome existing hospital infrastructure, work our way into standard medical training, and find early adopters within the medical system to champion this wave of precision medicine for the benefit of patients.

Q: Is there anything else you would like to share with the PMWC audience?

A: We believe that in five or six years, genomics will be the standard way to diagnose infectious diseases.

To sum up, Karius arms physicians with a single test that can deliver a potentially life-saving diagnosis, often more quickly than traditional testing methods, when time is critical. Compared head-to-head with several traditional methods, the Karius test proved faster and more sensitive; in many instances, detecting pathogens missed by standard culture-based methods.

A number of clinical trials are currently underway to gather data about the impact of Karius testing on invasive fungal infections in immunocompromised patients, fever and neutropenia, endocarditis, and other culture-negative sepsis syndromes. Karius is well positioned to become an important tool for clinicians working in infectious disease, oncology, transplantation and critical care.

We are open to collaborations with doctors and researchers across the US, and have launched a Clinical Investigator Awards program to grant $50,000 to two promising research projects in the field of Applied Infectious Disease Genomics. You can submit your application here before June 30, 2018 – http://events.kariusdx.com/CIawards.