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Why Cancer Patients Still Die From Infections We Can't Diagnose - Karius · Diagnosing Dx

• David Filby: welcome to the show this week, Alec. How are you? Alec: David, thank you so much for having me. I'm doing fantastic. It was a lovely weekend. David Filby: Awesome. And where in the world are you? Alec: I am in Redwood Shores, California. I live in San Mateo, but I'm in Redwood Shores near the home original home of Oracle. David Filby: there we go. lovely time of year to be in in California, I assume. Alec: It is. It's a very lovely. our warmest time of year is September, early October. we get a little spoiled here, David, in Northern California. hot day is seventy-seven and chilly day is sixty-eight. So apologize for the Fahrenheit, but we we definitely have beautiful weather here. David Filby: That's right. I I'm used to Fahrenheit now after nine years in the States. But actually I'm back in London for summer and we had ninety four in a country that doesn't have air con. So that's Alec: I saw that heat wave come through. Is it still present or has it moved on? David Filby: Yeah, it's cooled down a little bit but it's coming back we've got quite a lot to get into that there's there's so much we could talk about. We could probably record for hours if I'm honest, but we'll try not to. before we get into carriers and everything that's really exciting, with what you guys are doing and have done. I'd love to know more about yourself, your background and career and an introduction to yourself. That would be awesome. Alec: Yeah, thank you, David. I really appreciate, like I said, we're grateful for the opportunity to talk about Carrias. my history professionally, I started working for Pfizer when I was 21. And so I had just come out of college, and Pfizer was seventh or eighth in the industry. It was this, if you can believe, scrappy, entrepreneurial, growth-driven company. they had about four or five hundred sales reps in that whole company when I started. they had tens of thousands when I left, 11 years later. I was very lucky to join this extraordinary high-performing team. I had a great boss. Sometimes you get lucky, sometimes you don't. I had a great Great boss, and so I spent the first 20 years of my career in therapeutics, a little time in vaccines, and I've spent the last 16 years in genomics. So that's the net net of my professional career. The thing that I'll tell you brought me to carry us. My first 11 years at Pfizer, I worked in infectious disease. sales, sales management, marketing research, product marketing, payer marketing. And so I spent this whole time in infectious disease when people were still launching and developing new anti-infectives. That is less the case now than it has ever been in the last 50 years. Set that aside, that was the first 11 years, and then I spent prior to this role, I spent 11 years in a cancer genomics company, prenatal and cancer genomics. So the chance to combine infectious disease at my beginning and genomics in the trailing 11 years in cancer genomics was a really, really rare chance to contribute and find a company that was kind of introducing and bringing genomics to I. David Filby: Interesting. And and how did that transition from therapeutics to diagnostics omics happen? And and I guess what was the thought process there? Alec: Yeah, you know, I had spent, like I'd said, a little under 20 years in therapeutics. I was in a vaccine industry. I was working for Novartis. when they spent a small time in vaccines after they acquired Chiron in Emeryville, California. Chiron, if you remember, had some manufacturing issues with their influenza vaccine. And Novartis decided they wanted to step into the vaccine business. And they actually helped develop and we launched the first meninja cockle vaccine. for adolescents and infants. And so that was a three or four year period. I had a college roommate that worked for this cancer genomics company that for years had said, come on over, it's fantastic. This is a new thing in medicine. so I finally took him up on his offer. There was a chance to lead that commercial organization. you know, over three to four months I got to know people in that organization. They were headquartered in Salt Lake City, Utah. I was living in Berkeley with my family at the time, young daughter and wife, and really fell in love with the idea of identifying patients who have yet to have their first cancer and give them either screening or surgical choices, however challenging they might be, to prevent a preventable cancer. There aren't a Lot of cancers you can prevent. Inherited cancer is one of them. And so it was an extraordinary opportunity. And as an aside, David, about 10% of all cancer comes from an inherited gene mutation, 10% of lung, 10% of ovarian breast, etc. And so it was a very mission-driven company. It was very well run at the time, and it was just a phenomenal 11 years. I really enjoyed it. David Filby: Did you find there more purpose and motivation in the genomics side when you entered that industry? did you find that more enjoyable in terms of the impact it was having? Alec: Well, it's it's interesting, you know, we're still at the very beginning of genomics and medicine. it's only been 30 years since genomic health. They had the first test to identify whether or not a woman might need adjuvant therapy along with early stage cancer treatment surgically. So it's only been 30 years, right? We had genomic health, we had prenatal testing, huge impact on families in terms of making important family planning decisions and understanding the health of their arriving infant. This whole idea of cancer genomics, it was very compelling. I think from a business standpoint, David, the thing I'd share, therapeutics, you can have breakthrough therapeutics and things that are extraordinarily game-changing, but many, many therapeutics are hyper competitive, where small clinical differences, progression-free survival, efficacy, clinical impact, those differences in therapeutics can be modest. I kind of found over sixteen years in diagnostics. Diagnostics is a little more difficult. I think it's a little more challenging because the differences can be greater. People don't assign necessarily the same significance to treatment as they do diagnosis. And so there's this amazing opportunity to elevate people's beliefs about how important the right diagnosis is. And the the example I'll offer, David, we've had genomic testing to inform a cancer patient's treatment for 25 years. David Filby: Mm. Alec: Today, as of a publication of maybe a month ago, today only half of patients who get cancer get any kind of genomic testing. So you have all of this information that can inform exactly what is driving the growth of a tumor, make sure someone gets on the right therapy to address that malignancy, and we're still only at a point where half of people get a test like that at all. when you're talking about building markets, when you're talking about elevating clinician over. awareness, having doctors feel comfortable with something that is new and a brand new set of technologies to inform care, I think it actually can be a little tougher than therapeutics. And and for me that made it more interesting. David Filby: That's awesome. That's awesome. There's a chance to really innovate and actually make a big impact if people are up for the fight. so Carrius. How did Carrius come about? What's your role there? and then that can lead us into who are Carrius? Alec: Yes. Yeah, the the history of Carius is both compelling and a little bit sad, David. There was a a young boy at Stanford Medical Center about 12 years ago who was critically ill. The young boy had a hematologic malignancy and was going through treatment for that blood cancer. there was a a laboratory at Stanford run by a gentleman by the name of Steve Quake. Very well-known innovator in genomics. Many of the first cell-free genomic technologies came out of his laboratory. Many companies have spun out of Stanford and his extraordinary work. And just in the last couple of years, he published Cell Atlas. People have given that a lot of attention. just an extraordinary kind of discovery hub. Well, They were looking at sequencing data for this young boy being treated for cancer who was critically ill, and they saw a very, very small signal. They knew if they were able to remove the human DNA from that sequencing signal, they might understand could this be the cause of why he was critically ill and he had an infection at the time. Now, that young boy did not make it at Stanford. But what it did is it inspired some of the early folks at Stanford to identify this signal that is hundreds of fold less abundant than human DNA. I'm sure you know this, David, but were more microbial cells as Humans than we are DNA. It's like 52 to 48 percent microbial cells versus DNA cells. And so they were able to extract this signal. It's hundredsfold less abundant than human DNA in a blood sample. And eventually they figured out if they had the right controls, controlled for contamination, got rid of the human signal, got rid of all this background noise, they could see the sequencing signal from these. David Filby: Mm. Alec: Fragments of DNA they found in the bloodstream. And these fragments they found were actually fragments of organisms that were causing infection. And they're varying lengths, but relatively smaller fragments, 20 to 50 base pair fragments. And so they isolated this signal. They found out that they could identify organisms at a species level. And the reason they were in the bloodstream in the first place is anytime you or I get an infection. Infection, a couple things predominantly happen biologically. One, there's a large inflammatory response in the body associated with that infection. And then there's an immune response. So even if you don't know where the infection is, your body does. It goes to that place, it generates inflammation and an immune reaction. And then those organisms causing disease get chewed up by the inflammatory and immune process, and they David Filby: Yep. Alec: End up in the bloodstream as waste. And so they found this secret key to unlocking microbial DNA from a sample of blood. That was a dozen or so years ago. A couple of the thought leaders there decided to start this company. There has never been a microbial cell-free DNA test for infectious disease that ever existed before that. They call them cell-free metagenomics. David Filby: Right. Alec: And so they started a company. Our test has been available for about 10 years, and I can tell you what it does. We can identify at a species level right around 1,300 causes of infection for any DNA-based organism. That's a parasite, a mold, a bacteria, or virus. and we can do that for those 1300 organisms that can cause disease. We can do that with a sample of blood for an infection that is anywhere in your body. Because if the infection is in your hip or your lung or your brain or your gut, it doesn't matter. Those fragments of DNA are going to end up in the bloodstream. And we can find them, we can speciate them, we can tell people if there's antimicrobial resistance with those organisms, and then people can get put on the right antibiotics. so that's a little bit about David, what the test does. Does that make sense? David Filby: Absolutely. Yeah, absolutely. And so the company and the the test has been a bait available for ten years. When did you join the company and what did you come in to do? Like where were they in their life cycle and and what did you come in to achieve? Alec: Yeah, so it was about just about six years ago I joined the company, David. like I said, I had been at a cancer genomics company previously. the opportunity at Careyus that I would articulate that existed when I arrived just about six years ago was you have this extraordinary technology, it's the first time it's been available, it can do dozens, if not hundreds, of different things in terms of diagnosing infection. But as you know, From your experience, David, you have to make choices. You have to decide what markets you're going to go into. You'd have to decide what clinical evidence you have to generate. You can't boil the ocean. You can't go after 25 priorities. You need to narrow your focus so that you can have the kind of clinical impact you want. So we had to make a decision. And that decision with the leadership team that we were pulling together at the time, that decision was to exclusively focus on immunocompromised patients. And I'll put that in context for you. Those include cancer, HIV, solid organ transplant, and people going through autoimmune treatment for things like Crohn's, colitis, inflammatory bowel disease. I'm sure you see on TV every five minutes there's an advertisement for an autoimmune therapy. David Filby: Mm. Alec: That compromises someone's immune system where they tell you you're at risk of certain infections. The reason that immunocompromise choice was such a big deal, David, one, huge morbidity and mortality. In the United States, there are there's about 640,000 cancer deaths in the U.S. a year. 52% of those cancer deaths in the United States are due to infection. Not David Filby: Mm. Wow. Alec: The underlying malignancy. People go on therapies, either the cancer or their cancer therapy compromises their immune system. The reason that's so important, if you and I get pneumonia, there's 10 or 12 organisms that are likely to cause our pneumonia. There are little, really simple PCR tests that we can take to identify one of those 12, and we can get on the right antibiotic. If you have cancer, There are 600 organisms, David, that can cause pneumonia because your immune system isn't functioning the right way. So that was the first part of the decision. Very high morbidity, very high mortality, and a huge unmet need. If you have cancer as an example, hematologic malignancy, and you're a Medicare patient in the United States, over 65, and you're admitted for infection, and by the way, there are 4 million admissions for infection among cancer in the United States every single year. If you're admitted for infection, the average length of stay is 19 days. And that will happen anywhere between four to six times during the course of your cancer treatment. So we're talking about massive risk. In fact, that 52% number of cancer patient primary or secondary cause of death, David, in hematologic malignancies, it's over 60%. David Filby: Mm. Alec: So we're talking about an extraordinarily unmet need. We're talking about a huge problem. The tests in the hospital are adequate if you are immunocompetent, if it's you or me going to the hospital. If you have cancer, HIV, you're going through organ transplantation, you're on autoimmune therapy, the tests in the hospital do not take care of doctors the right way. In fact, we s we articulate existing literature that says the standard of care. A week of everything in the hospital that's used to diagnose an infection has up to an 80% failure rate. That's things like culture, PCR, serology, antigen testing, a very high failure rate. Four things that have, when we talk about infections and cancer, the number one infection is pneumonia. The mortality rate in cancer with pneumonia is up to 65% in 30 days. So we're talking about a massive problem with life and death stakes in terms of how this impacts patients, David. David Filby: Can ask you a c a a commercial question, Kyle? Because I mean, the stats are absolutely wild and and like I think anybody hearing that will absolutely believe the unmet need and the purpose of Carrius is so profound. But when you made that decision to go after immunocompromised patients and try and help them Was there a commercial decision there that it actually meant your market was potentially smaller, but ultimately the goal so worth it? Alec: Yeah, I think no matter what it's smaller. there are there are many more. David Filby: Yeah. Comp then compared to boiling the ocean. Yeah. Alec: Yeah, many more admissions to the hospital among lots and lots of people where this test would work great. It would it would work fantastic. But if we were to prioritize, and this is what we did six years ago, greatest unmet need, highest morbidity, highest mortality, patients, you know, we'll spend five hundred to eight hundred thousand dollars treating a cancer in America. And the number one thing threatening both that clinical investment. David Filby: Yeah. Yeah. Alec: As well as that financial investment is infection. You look at solid organ transplant, it's the same, David. Half of them fail from rejection, half of them fail from infection. And so we're talking about making choices where we think we can move the needle in terms of the greatest patient need. David Filby: I think that's awesome. So what's happened in the last six years then? Take me through that since you made that decision. Alec: So Carrius had had some efforts commercially. You mentioned your questions around a commercial. We needed to rescale the commercial organization when I arrived. There was one commercial person in the company on my arrival. We brought in a very talented initially, a great, a very talented chief commercial officer who helped us scale this initial team. It was it was pretty small, David, when I started. eight territories. Each territory had two people. So there were only 16 people when we started. There were about 45 people in the organization at the time and things, and we needed to build an effective commercial motion. People who wanted to be a part of a journey like this. Ideally, they needed to have some infectious disease experience or genomics experience. And so we had a chance to build and scale the organization. We brought in a chief medical officer with deep genomics and idea experience. We bought in a very strong intellectual property chief legal officer. Chief financial officer with deep category and genomics experience. We elevated the role of our chief people officer then leveraged the history we had with our chief technology officer and chief scientific officer. So as the company scaled, especially commercially, we needed to prove that that commercial motion was repeatable. David Filby: Mm. Alec: And that we could continue. And today we have 24 territories, each with two people in them, about 60 people out of 180 that are in our commercial organization. And they've proven this commercial motion over and over again. Add a new hospital, train the doctors. They've never had a genomic test in the hospital for infectious disease. Train the doctors on the literature, make sure that they feel confident in using this technology at the right time in the right patient. And work closely with laboratory and infectious disease leadership to make sure that everyone is trying to achieve the same thing in these critically ill patients. David Filby: and you mentioned the educating physicians around this type of test. is that a bigger or lesser challenge now that sort of educating as you open up new systems and customers? Alec: It's interesting. I I think it's gotten easier over time. we have over 350 publications in the peer review literature now. So people have heard about it. The thing I would tell you though, David, I'll flip it around. Early in my career in my early 20s, working in therapeutics, it was my observation, and perhaps obvious to many, but it was my observation that doctors will not do something they don't feel confident doing. David Filby: Mm. Alec: And so this whole idea, whether it's a new therapeutic or a new vaccine or a new genomic test, if a clinician doesn't feel comfortable incorporating this in terms of how they want to take care of people, they don't feel confident about the literature, they don't understand not only how to use a new genomic test, but how to interpret it. If they don't feel confident and comfortable in that process, it's not gonna happen. And so I think that's a little bit of a golden thread over 37, 38 years of doing this is there's an education and a confidence generating activity that has not changed. Clinicians need to believe the literature, they need to understand how to use something, and they need to feel confident using it such that they know how their care is going to change as a result. David Filby: That's interesting actually, and I think there's an honesty to it. I think it is hard for adoption, right? Even, you know, if the science is great and you've got your regulatory even reimbursement and everything, you know, you've still got to get out there and educate. But we as an industry that is difficult. But it's interesting that you're saying it's not a diagnostics problem, it's a healthcare problem. You know, across therapeutics and vaccines as well. And you've taken that into genomic testing as well. That's really interesting. Alec: Yeah, I think clinicians, my observation would be once clinicians get there and they get a chance to build some experience with something new, whether it's a cancer test, a prenatal test that uses genomics, or even in our case, an infectious disease test, once they get their their legs under them and and feel both confident with the clinical perspective and and what the literature says and and how to use it, when to use it, I think people can move on. And we've seen that. Like we said in cancer genomics, we're still only halfway there for informing how to treat someone's cancer. So it takes time. That education piece is very important. David Filby: Yeah. Yeah, crazy. give us an insight into how adoption has gone, because obviously it's been successful. You guys have gone from, you know, forty-five, fifty people, one salesperson, you know a hundred and eighty people with, a really I think you said forty-eight sales reps and so how has adoption grown? Alec: Yeah, a couple ways that we look at that. the first I would tell you in 2025 we had about 600 unique hospitals that ordered a test. There's about five, six thousand in the United States, so that's a relatively modest number. I'll qualify that in a moment. The other thing is we had 10,000 unique physicians that ordered a test in 2025. And those are infectious disease, pathology, pulmonology, cardiology. HEMONC and MEDONC, as well as critical care and hospitalists who spend all their time in the hospital. So a really nice diverse set of clinicians who are building experience ordering it. That qualification I spoke to a moment ago, out of those five or six thousand hospitals in the United States, there's about 200, David, that admit 10 immunocompromised patients for infection every single day. These are leading cancer center, organ transplant, CAR T centers, patients that have large HIV populations. These are some of the largest academic and health systems in the United States. There's another group of hospitals out of instead of those 200, about 2,000 that admit somewhere between four and eight immunocompromised patients for infection per day. And I don't think people Really realize if you look at the average hospitalized patient 40 years ago, David, versus the average person who goes in the hospital today, people are much, much sicker. Hospitals have all these financial pressures. The average person who's admitted to the hospital is much, much sicker because there's many things we can treat at home now. Everything is done to try to treat people on an outpatient basis. And so the people arriving in these 2,200 hospitals in the country absolutely need the most advanced, sophisticated care possible. And the data point I'd share with you, you know, out of the Fred Hutch. Cancer Center, they have a large group focused on kind of immunocompromised patient advocacy and therapeutics development. They estimate that 7% of people in the United States are immunocompromised, whether that's cancer, HIV, organ transplant, autoimmune, or advanced age. so we're talking about a very large portion of the population. So the average patient showing up in the hospital looks entirely different than it did perhaps 50 years ago. David Filby: Wow. And so talk to me about a couple of these milestones. Talk to me about reimbursement. Obviously such an important topic in diagnostics. How's your reimbursement journey developed? Alec: Yeah, we have a dynamic in how we're paid for, David, that has never existed before in diagnostics. I was just at a a meeting last week in Southern California, and it was primarily diagnostic companies, cancer genomics, minimal residual disease companies, companies developing diagnostics for immuno oncology drugs, looking at drug response. So the majority of molecular diagnostics, very sophisticated diagnostics. is in cancer. I think the piece that is most notable for us is we're not in cancer, we're an infectious disease, and we're only ordered by hospitals. And so the challenge that all those companies have is launching a test, getting Medicare to pay for it, and then eventually adding commercial coverage thereafter. Today, every single test that is ordered, the hospital sends us his test, we send them a bill, they pay the bill. That's it. So we don't have many of the headwinds involved in reimbursement that are a real challenge for our colleagues in outpatient diagnostic testing, because those tests require a lot of reimbursement to get momentum. So every test that we get is paid for. And so we've got an engine where hospitals are not only voting clinically that they absolutely need this test, but they're also voting with their pocketbook because we have a $2,200 test that hospitals order, we send them a bill and they pay us. So our reimbursement landscape is very, very different than the typical diagnostic company in the United States, David. David Filby: That's awesome. And have you had to raise capital along the way and and how much? Alec: Yeah, so there was a a series B raise about three or four months before I started. that was led by Softbank. and that capital was capital I was able to use to scale that company from 50 or so people. we completed a little over two years ago, we completed a series C. And that series C was designed to do a couple things. One, let's raise enough capital that we never need to raise capital again and we can get to profitability. We are still on track for that. If we never raise another dollar, we can get to cash flow break-even. And economically it's interesting, perhaps only for those of us in molecular diagnostics, but There's a decent chance, David, we could be the least capital in to profitability of any molecular diagnostic company in history. David Filby: Wow, that's amazing. Alec: I hope so. there's been so many challenges in molecular diagnostics in the last 30 years. Many companies that never make it. companies that end up in Delaware court or sold for parts to other players in the molecular space. The chance to demonstrate a very rapid and very capital efficient path to profitability is something I think that's great for our industry. and to to demonstrate Mm-hmm. David Filby: I I actually completely agree. I think that kind of success story is a story that needs to be told time and time again. what's been the key to that? Because there's plenty of companies in molecular diagnostics that are probably sitting around forty, fifty, sixty headcount at the moment. Maybe they're currently, flipping from that. R and D development engine into a commercial engine, which tends to happen around that time. And they're on this long road that you've been on. But when you look back, what's been the key to the success and the growth and the milestones and adoption that you've seen? Alec: Yeah, I think a couple things. One, we do have an advantage that we're paid directly by hospitals. That is a dynamic that no one else has been able to enjoy in our space. I think, but for the company, I think the pieces that I would offer, you know, when you go through a strategic exercise, and I did that with some of my leaders when I came on board just about six years ago. When you go through a strategic exercise, you have to make choices, which means the inclusion of things like an exclusive focus. On immunocompromised patients. You have to make very difficult choices, and when you make those, you are excluding everything else. And I think, David, the cultural dynamic that I think can be present in organizations is people don't like picking. Right? Picking engenders risk. If I pick one thing, I'm not picking 10 others. And I think the thing I would applaud among the people at CARIAS. All we talk about are immunocompromised patients, all we publish on is immunocompromised patients, all we talk to clinicians about is immunocompromised patients. And that's what we do all day, every single day, all the time. And so for a whole company of people to understand that this is the choice we've made, can we do many other things? Of course. Are we going to right now? No. David Filby: Yeah. Mm-hmm. Alec: And I think that that process of excluding so many areas of optionality as a company and making sure that all the capital and all of the talented people you have are focused on a single thing, I think that can be a scary prospect for many. David Filby: Do you think then there's a there's a point where that has to happen? So if you're a seed, you know, just coming out of some sort of academic platform and you've got some interesting science, you know, is there a point where it's too early to make that sort of discipline, and implement that disciplined approach, but then at some point it's like, okay, we now have to know who we want to be. Do you think there's some sort of perfect point to do that? Alec: I don't know about perfect. You know, I spend a lot of time talking to my colleagues and learning from them about their kind of company evolution history. I think there does come a point in any technology, right? This is a company that started with a technology. It didn't start with a product. I think there is a point where you have to pick the first application. Right, and that application has to be informed by clinical science, not technological story. you have to compare it to standard of care, you have to show that doctors are going to change what they do. And that first step into that first product choice is, I'm sure, a very, very difficult one for many organizations. David Filby: I love that. I love that. we had a a great chief medical officer on the show a few months ago and and her opinion was that one of the biggest challenges in diagnostics is we lack products. We have great science everywhere, but we don't have great products and we don't have great market fit. And that's where the the disconnect happens or the failure rate happens in the industry. And it sounds like you're saying a similar thing. Alec: you know, David, I'll I'll introduce this what I think will be our second choice. we will make a choice to offer this test on an outpatient basis. We we expect that to arrive in 2027. If you could imagine a cancer patient who's at home, and let's say they're going through chemo for their solid tumor, they get a fever, which happens very often in cancer, they get a fever, and that medical oncologist has to make a decision. Today, though you have one choice, David. Go to the ER. That is what they tell a patient who they think has a suspected infection. Can you imagine all of the medically, otherwise medically stable cancer patients, organ transplant, and other patients? All of a sudden, patient has a fever, they're medically stable, and you can just say, hey, come by the infusion center, we'll get a sample of your blood, and then you can go back home. Let's find out what's causing your infection. And don't go to the emergency room. The reason patients in like this, cancer, HIV, autoimmune, organ transplant, the reason they have to go to the ER is everything that's used to diagnose their infection, David, is in the basement of the hospital. Right? Culture, serology, PCR testing, it's all downstairs in that hospital. They go to the ER, they might wait six to eight hours to be seen, they might wait half a day for a bed, or maybe 24 hours for a bed. Maybe they're put in observation before they're decided to send up to a floor for a bed. and then because they have a suspected infection, they're given multiple antibiotics because no one knows why they're sick. And so to think about our model for diagnosing infection, that model, go to the emergency room, use the stuff in the basement of the hospital, that hasn't changed in a hundred years, David. Nothing. So to think that there would be another option that I can take someone. David Filby: Mm. Alec: Who I think has a suspected infection, I can diagnose them, they can stay out of the place that may confer additional risk of infection, like the hospital, because it's not the best place to go if you're immunocompromised based on your risk for other infections during your admission. And I can treat them, I can diagnose and treat them at home. David Filby: Mm. Alec: For 1,300 different causes of infection, a technology and tool and test that has never been available for it before in the history of medicine. Take everything in the basement of the hospital and give it to the patient on an outpatient basis where they can diagnose disease. I think some people are gonna embrace it. And some people, because not everybody likes new things, David, some people aren't gonna like it. David Filby: So it's the same test, it's the same immunocompromised patient, which is what you guys have been disciplined about, which you've been passionate about, and which there is obviously this incredible, profound unmet need that we should be supporting. How does that change carry us as a company? Because that it's a really significant move, right? And and there's a commercial model there that changed, but is this carrier sort of 2.0 in effect? Alec: I think I think you're right, David. I think it is. I think there's a couple things to think about for me that are different in those markets. In the hospital, you have multiple decision makers. You've got a laboratory director, you've got infectious disease, even though 70% of cancer patients do not have access to an ID in the United States. So you've got ID, you've got hospitalists and critical care physicians, you've got multiple stakeholders trying to figure out what's going on with a patient. So I think that makes it very different from the outpatient setup. David Filby: Right. Yeah. Alec: In the outpatient setting, and this is true for oncology genomics, there's one decision maker. The thing I think that can be so powerful about that, David, though, is you are literally putting the test in the hands of the person who is responsible for the clinical outcome of the cancer. Whereas today, go to the ER, it's a whole different team trying to diagnose that and treat that infection. All of a sudden now hematology oncology, medical oncology, all having access. The person who's on the hook for the clinical outcome, the person who is accountable to the family for successfully treating that cancer now has a tool to diagnose an infection sooner and get them back on their cancer therapy. If you, by the way, David, if you interrupt cancer therapy for as little as five days, outcomes change. We talked about that Medicare patient spending three weeks in the hospital. That's more than five days. So the alignment between the person treating the cancer or HIV or Autoimmune disorder and giving that test to that same person who can diagnose the thing that's going to prevent them from treating that patient successfully. I think that is the sweet spot. And so it's one doctor, and that doctor is the same person who wants to address their autoimmune therapy, treat their infection the right way, and get them back. on their autoimmune therapy so their autoimmune disease can be managed the right way. True for cancer, organ transplant, and all those too. So I like the fact that we're going to put that tool right into their hands in terms of getting it closer to the treating position. David Filby: Mm. Yeah, it's it sounds amazing. the accessibility, the access to decision makers to make them decisions quickly, that give patience decisions quickly. just sounds like a slam dunk. So so what what happens from here then? What's what's the future look like for carriers and what are the milestones we should be looking out for for people who want to follow the story from here? Alec: Thank you. I really appreciate that question, David. There's a couple pieces. One, as I said, we expect Medicare reimbursement for the test in 2027. It will be some subset of all these patients that you and I just spoke of. You know, one of the unique things that we don't talk about very often, but is very important in cancer, is there's a subset of cancer patients that are extraordinarily high risk. Hemanologic malignancies are a great example. The chance to use a test like this for screening these highest risk of high risk patients. We can identify a bacterial infection five days before someone feels clinically sick, and we can identify a fungal infection up to 30 days, David, before they feel clinically ill. So if we can define a narrow subset of the most at risk patients, provide a surveillance tool where you can identify an infection long before it would have been found otherwise, we can drive a different clinical outcome in these patients. David Filby: Mm. Alec: I think that's a really big part of this dynamic. So that's one milestone. Put this in the hands of outpatient clinicians. We won't offer the outpatient test until Medicare has decided decided to support it. We're already in seven clinical guidelines today for these immunocompromised patients. We'll add commercial payer coverage conservatively and kind of in a stepwise fashion in the years that follow. So we have the core symptomatic patient that you think of today. We have high-risk surveillance. That will be a new market for carrier and a new way that we can serve these high-risk patients. And then the third piece, the third milestone, David, per your question is there are a lot of patients who require very long sustained therapy for the treatment of their infection, sometimes up to six months. So we can offer a monitoring tool because one of the things that makes the carrier test unique is we actually quite The microbial burden in every single patient. So it's not just do you have David Filby: Mm. Alec: haemophilus influenza, you have haemophilus influenza at 20,000 fragments per nanoliter of blood. We can actually quantify that signal. So the chance that someone can use this test and watch that signal go down over time and know that the patient is clinically responding. I would underscore that as a critical part of our journey, David. Is one out of five of our tests today is actually used more than once. People already have figured out this tool to make sure that someone is clinically responding. They order it in the hospital, start them on the right treatment, and then they order it at some interval of time later to understand that they're clinically responding. David Filby: Alec, I love everything about this. And maybe I'm lucky because I'm talking to you in terms of, you know, where you guys are in your life cycle. Would have been interesting if I spoke to you six years ago when you joined. maybe you knew you were gonna be this successful, maybe you didn't, but I think there's so many elements to this that when you're hearing you talk about it, it just makes so much sense as to why you've been successful. I love the discipline. To know who your your end patient is and and go and solve that unmet need. I think that that's amazing. But we've talked about the difference between science and product. We've talked about the future development and continuous innovation, but still in the same unmet need because it's so big that you really are still even with your success just scratching the surface as to what could be achieved. But then also just hearing you talk about and your passion and motivation like for me it's all there like all the elements. You can see why you guys have been successful. What's what's your overview on the the diagnostics industry at large at the moment and where where do you think we are? Alec: Yeah, I think it's interesting. I spent a lot of time learning from my colleagues in our space, David. And I like I said last week, I just spent some additional time. I think diagnostics still has a long way to go for people to understand how important it is. In infectious disease, I'll give you an example. If you don't identify the organism at a species level, right, mortality goes up. Morbidity goes up, length of stay goes up, and cost goes up. That is an established medical fact. And so I think there's a challenge for our entire industry in helping people understand that if you don't get the right diagnosis, you will not increase the likelihood of having the right treatment outcome. And I think as an industry, we can do a lot more. To help people understand that that is absolutely the most pivotal part of any disease state, any condition, any management. You know, I have a very close friend who just tore their meniscus in their knee skiing over the winter. That friend still hasn't had an MRI to understand: do they need surgery or will they have the ability to, on a long-term basis, respond to physical therapy? David, my gosh, he needs to get an MRI. Right? Because we need to know which one of those paths we're on. And at the moment for that close friend, they're stuck. Right? Maybe PT is working a little bit, still some knee pain, can't stay mobile and active, can't do the things that they love to do. It's a very simple, it's a very simple example, but diagnostics can do so much more to help people understand how the failure of a diagnosis will turn it into a negative. The failure of a diagnosis. Is absolutely the first domino in terms of ensuring the right clinical outcome. So I think there's so much more. On the other side, I would say, we have to do a much better job of demonstrating clinical outcome. You and I talked about cancer genomics. Only about 50% of people get them. Only about 30% of doctors actually change what they do when they get a cancer genomic test. So that means 70% of the time their cancer care is not changing even though they received an advanced genomic test to understand what's driving the growth of that malignancy. I think that last piece of demonstrating outcomes, David, has to arrive. David Filby: Mm. Alec: We have to be able to connect the right diagnosis to the right long-term outcome. I think the challenge though, massive amounts of capital, masses of amounts of data. I think we have some things that have happened in the world with data that are going to get us there a little bit faster than we would have otherwise. But if we can't demonstrate as an industry that we can drive a change in clinical outcomes, we can argue about the value of a diagnosis all we want. David Filby: Incredible. thank you so much for coming on the show. I I love this story, as I said. It's got everything. And I think that there's lessons in there for early stage founders and C suite who are trying to bring something novel. through to market, but I'm also incredibly excited about where you're gonna go next. It feels like we're still at the start of this story and there's so much more to be achieved. But thank you for coming on and sharing the insights and and all the best with the future. It was absolutely fantastic. Alec: Thank you, David. I would just make one more request, David, and and just know how grateful we are to share kind of what everyone at Carius is doing to change this reality. I think we all unfortunately know someone who's been touched by cancer. That is the sad part. I lost a sister 12 years ago. It is not academic to me. the thing I would encourage anyone who's listening to this, if you know someone who's going through cancer treatment with as terrifying and upsetting as that is for an entire family, if they end up in a hospital, David, the big difference in our industry in infectious disease. It is very likely that the patient in the hospital being treated for cancer who's been admitted for an infection, the patients and the family will never know what testing is ordered. So if that patient and family does not say, I want a carious test while my mom, like the minute she's admitted to the hospital, if they don't do that, David, they could get anywhere from 15 to 20 tests in the first seven days, 45 tests by day 14, 80% failure rate, and the patient and the family will never know which tests are ordered. And so if patients don't put themselves in a powerful position and families, right? This is someone's son, parent, child, spouse. If if patients don't ask about this test, it is really unlikely they're gonna get it, David. So that would be my only ask at the tail end of our conversation, is if you know somebody or you have families or friends, they have to start asking questions when they show up in the hospital because unlike outpatient. Cancer diagnostics, they'll get a copy of the report. In the hospital, they are blind to testing. And they will not know that they've already had 11 tests that have all failed. And you have a family sitting in a waiting room waiting five days to understand what's happening with their mom. They have no idea what testing has been ordered, and they don't even know what to ask for. David Filby: Mm. Alec: That is the tragedy we're trying to avoid, David. David Filby: Fantastic. Thank you so much, Alec. That's awesome. Alec: Thank you, David. I'm really grateful for the opportunity. It has been a lovely way to start the week.