Karius is a life sciences company focused on generating genomic insights for infectious diseases with a non-invasive blood test that helps clinicians make rapid treatment decisions. By mapping each patient’s microbial landscape from a single blood draw, Karius moves closer to a vision of a world where infectious disease is no longer a major threat to human health. In this interview, CEO Alec Ford discusses the company’s advancements as a world leader in liquid biopsy for infectious diseases.
Please share the story behind Karius: What sparked the idea and how has it evolved so far?
It is quite an amazing story, the two founders of Karius came out of a very well-known lab run by Dr. Stephen Quake at Stanford University where they had seen cell-free DNA being used in prenatal testing, and it has transformed non-invasive prenatal testing over the last 10 to 15 years. They then watched cell-free DNA go on to transform oncology. People used to only do somatic testing and would actually test the tissue involved in a tumor. Now people can use cell-free DNA to look for evidence of that tumor and what might be driving critical mutations in that tumor. The question that they were asking at Steve Quake’s laboratory at Stanford many years ago, was “Can we isolate microbial cell-free DNA to diagnose infections, without actually needing a sample of the infected tissue or fluid? Can we find small elements of genomic structures of pathogens in the bloodstream that could help us understand what is causing the infection?”
There was a clinical case of a child with an underlying hematologic malignancy, who caught an infection and was being treated at Stanford. There was a race in that laboratory to try to identify what was causing her infection. Sadly, the researchers lost that race and the child passed, but they vowed at that point, to stay focused on developing this technology for patients, especially those who are immunocompromised, and to identify the source of these infections in critically ill patients.
Fast forward three or four years later, the test became commercially available and approved through the College of American Pathology. It is now also approved by New York State, and now more than 200 hospitals a month order from us. Those hospitals focus on identifying infections and people who are immunocompromised, meaning those with HIV, hematologic malignancies, solid tumors, autoimmune disease and other things that may compromise someone’s immune system.
What are your key areas of focus?
We are really focused on first educating a variety of our customers around how important the threat of infections is. A lot of people don’t realize that more cancer patients die from infections than from their malignancy. In almost 60% of all hematologic malignancies, people pass from infection. It is a significant threat to the successful outcome of treating someone with cancer. People get super excited when there is a new cancer therapy, whether that be an oral or intravenous cancer therapy or genetic cancer therapy or things like CRISPR, but perhaps fail to realize that the greatest threat to someone with cancer is not the unsuccessful treatment of their cancer — the greatest threat is an infection. So, our focus is helping providers take patients that have a threat to the successful treatment of their cancer and identify what the cause of their infection is as quickly as possible, such that we can inform their care and get them back on chemotherapy or other cancer therapy that is going to ensure that successful outcome.
What makes Karius unique to other diagnostics companies?
The first really important difference between the Karius test and any other infectious disease technology, is that there is no need for an invasive procedure, or an infected sample. Should you or I end up in the hospital with pneumonia, every other diagnostic tool the clinician might use in a hospital setting requires the doctor to go in and get a sample of infected tissue or fluid — for example, a sputum culture, a bronchoalveolar lavage, or do a biopsy to get a piece of tissue from someone’s lung to understand what is causing the infection. The big difference between Karius that is so important is, we are the first commercially-available metagenomic cell-free DNA test capable of large depth and breadth of detection (over 1000 pathogens) via a single blood draw – with the potential to eliminate invasive diagnostic procedures like tissue biopsies. The test detects microbial cell-free DNA (mcfDNA) — fragments of the pathogen’s DNA circulating in blood — even at exceedingly low concentrations. The power and uniqueness of the Karius test comes from its ability to clearly see and accurately measure mcfDNA in low abundance. To achieve this feat, the Karius team pioneered ways to remove the background “noise” in the form of human DNA and other contamination. Karius uses AI to make sense of massive amounts of deep DNA data, teasing out specific microbial signatures tied to an infection. The result is a clear, accurate picture of the infection, which could be caused by one or more pathogens from a long list of more than 1000. This list includes culprits of disease, including those pathogens that are very difficult to identify, and Karius continues to add to it.
What has been your biggest accomplishments since launching Karius?
The thing we talk about a lot internally, is the impact this is having on patients. Every day we hear a story about someone, especially children, who goes through cancer treatment, who has a significant threat to their life in terms of an infection. We hear about clinicians ordering the Karius test when they have had 3-7 different diagnostics in a row fail to identify the cause of the infection. We increasingly hear from providers about what it means to be able to send us a sample and get an answer 24 hours after we’ve received it, on exactly what is causing that infection. The typical journey for a lot of providers and a lot of patients is to try blood culture, serology, and then various microbiology tests. Sometimes that kind of approach can take anywhere from 3-14 or more days before the doctor actually knows what is causing the infection. In fact, for up to 80% of patients in the hospital, the cause of their infectious disease is never identified in terms of which specific pathogen is making them sick. For years, we’ve thrown every antibiotic we can think of at patients that are in the hospital to cover all types of microbes, and as a result, these antibiotics get overused and don’t work as well. Then we see antibiotic resistance. To be able to find out in 24 hours what is causing an infection allows a doctor to dramatically narrow their treatment such that they’re only treating the cause of the infection.
We also need to remember that these anti-infectives are not side effect free. They can put significant strain on people’s major organ systems, kidney, heart, liver. So, getting someone on the narrowest therapy possible is the safest approach to treating them.
In your opinion what has been the most significant development in Biotech in the past few years?
I get excited about advanced molecular diagnostics and the impact on prenatal care, oncology, and now infectious disease. One of the first companies in this space had the first test to look at a woman’s breast cancer and understand how aggressive that breast tumor is 25-27 years ago. And to see people move into liquid biopsies as an alternative for somatic testing, to see the adoption of germline or inherited breast cancer screening has just been amazing. But we still have a little ways to go to see cell-free DNA move into liquid biopsy and replace somatic testing. And then to see new tests like minimal residual disease, homologous recombination deficiency, and see all these advanced genomic enabled technologies have an impact in disease states, like oncology has been incredible. I think the opportunity here is where do we go from oncology — people get super excited about advancements in treating cancer because we’ve all been touched by it. Everybody has a family member, everyone has someone they know who’s been impacted by cancer, but now is the time where we need to take these advanced technologies and move them into other areas of medicine, mental health, infectious disease, and other places where advanced genomics can have a dramatic impact on the care and outcomes of patients.
What are some other trends and technologies that you find particularly interesting these days?
I think that people are getting better and better at assessing how effective these new technologies are. At Karius, what we would love to be able to do in the future is be the company that helps people developing new anti-infectives, also identify the cause, have the best objective way to identify the presence of an infection, and what’s causing an infection so that those clinical trials can be even more and more powerful over time.
I think the other thing that is exciting is people are understanding what the tradeoffs are between clinical benefit and economic benefit. It’s not just enough to have something that has an impact on a clinical outcome, we have to show that it has an impact on economic outcome. At Karius something we’re very much focused on, is demonstrating to providers if you use the Karius test, what the impact is on things like mortality and what the impact is on the economic side, for example, what floor of the hospital you’re in, the number of consults you need, the number of drugs that are used, did you need an invasive diagnostic, do you get out of the hospital sooner, etc. We have to look at both of those deliverables in our healthcare system; it’s just going to be super important for any breakthrough new technology in the future.
How do you envision the future of biotechnology in the next five years?
Right now, there’s a lot of conversation about making sure that we’re leveraging technology so that people get the best therapies, based on the best information possible. Because a one-size-fits all approach to medicine won’t really give us the best results. So even though precision medicine is only really starting in oncology, and now infectious disease, I think the chance to bring precision medicine to many other areas of medicine is very compelling.
