Good afternoon and welcome to the Insight Molecular Diagnostics virtual KOL event. At this time, all attendees are in a listen-only mode. A question and answer session will follow the formal presentations. If you'd like to submit a question, you may do so by using the Q&A text box at the bottom of the webcast player. As a reminder, this call is being recorded and a replay will be made available on the Insight Molecular Diagnostics website following the conclusion of the event. I'd now like to turn the call over to Andrea Susan James, Chief Financial Officer at Insight Molecular Diagnostics Inc. Please go ahead, Andrea. Thanks, Tara. Hi everyone, welcome. We're so thrilled you could join us on this Friday afternoon, and we're also so thrilled to be hosting Dr. Anthony Langone for our KOL call. If we could pull up the agenda slide, please. Okay, before we begin, Josh, with Dr. Langone, Josh Riggs is going to briefly touch upon our strategy. Then we have the wonderful presentation from Dr. Langone, and then we have a Q&A session which features those two, plus Chief Science Officer Dr. Ekkehard Schutz. Before Josh begins, we're going to spend about 10 seconds on the forward-looking disclaimer slide. Okay? Go ahead, Josh. Thanks, Andrea, and thanks everybody for joining us today. You know, when I took over about two and a half years ago, we made a commitment to take our technology and get it out of our lab and into the hands of clinicians and researchers around the world because we believe that local care is better care. The first step on that journey for us has been in the transplant space. I'd like to talk to you a little bit about the transplant market that we have here in the United States. If we'll go to the next slide. The market here is really for donor-derived cell-free DNA, which Dr. Langone is going to spend some time talking to us about today. Over the past six, seven years, it's become generally standard of care, but it's dominated by a couple of central labs that are based in California. We saw an opportunity to put the transplant centers themselves in business of managing their patients. That's what we've been working on for the past two and a half years. We're making progress towards the FDA. One thing to note here is the transplant in the United States is a highly concentrated market. You've got maybe 250, 255 transplant centers, but about 100 of them do most of the volume. I think we have the opportunity to take advantage of what's become generally standard of care and make that accessible in the local environment. I'm going to go ahead and talk to you a little bit about our approach on how we get to the market with our technology. We'll go to the next slide, please. We have three ways we touch the market. The first is through our service lab, and that's here in Nashville, Tennessee, alongside Vanderbilt University Medical Center. This is where we create the new technology, where we validate it, how we interact with payers to establish both the clinical value of the technology and the reimbursement. Outside of that, we have an RUO product that has been on market for well over a year now. That gives us a chance to interact with the community and find out what they would like to do with the technology, how we can improve it. All of those improvements roll up into our IVD kit. That's what we're taking into the FDA. We call it the land and expand strategy. We've been out here working with transplant centers around the world to land our technology out there, get some of that positive interaction, and then we'll expand once we get the IVD kit out. That lets these centers take advantage of the clinical claim and start managing their patients locally. Go ahead and go to the next slide. When we went to the FDA, we realized we needed to prove out two points. One is basically assessing how well our test does at ruling a patient in or out for active rejection. We're going to validate that accuracy in the clinical study. What we're doing is when a patient comes into the transplant center, they're drawn a tube of blood, and then there's a biopsy that's done. We match up the results. If we say positive and the biopsy says positive, that's great. That's what we want to see. We think it's going to take about 125 patients- 150 patients to prove that our test does what we say it does. We'll get that into the FDA as a part of a dossier by the end of this year. We're working with about five transplant centers here in the United States. We expect another one or two to come online. We're going to have at least one center out of the EU to support a follow-on IVDR submission. Last slide, please. Our primary endpoint is non-inferiority to currently used dd-cfDNA tests. All of this that you're seeing here on the screen comes out of our clinicaltrials.gov listing. You can go and pull that information yourself if you'd like to look deeper into it. We can see the values that we seek to prove that we're at least as good as. This would be considered the minimum. Based off of our 10 years of publishing history with this technology, we expect to meet and exceed what is here to the right. This has all been reviewed by the FDA multiple times through the Q sub process. We feel really good about our path forward through the FDA. Dr. Langone is our NPI on this study. We're very happy to have him here with us today. We'll go ahead and go over to his slide. It is my pleasure to introduce Dr. Anthony Langone. He is an Associate Professor of Medicine at Vanderbilt University Medical Center. Some of you may already know him as a leading expert in solid organ transplant. He has authored multiple publications looking into the clinical value of donor-derived cell-free DNA. His work focuses on finding better treatments and improving patient outcomes. He is recognized across the country for his expertise. This slide here contains his numerous distinctions. We are lucky to have him here today with us. Dr. Langone. You're on mute, Dr. Langone. Can you hear me now? Sorry. All right. Let me start over. I'm Tony Langone. I've been at Vanderbilt since 1999. I've been a faculty member here since 2002. I've trained in many parts of the country, and I've been in transplant the whole time. I have gotten interested. I've actually been involved with everything related to cell-free DNA, all the major trials since the original DART trial was published in 2017. I helped write that protocol. The history of cell-free DNA is interesting. Cell-free DNA has been known about since 1948. It actually predates Watson and Crick's understanding of DNA and the double helix, which was discovered several years later. I think there were German scientists that found this DNA floating in the blood. What did this mean? Cell-free DNA basically is cells that are turning over, and the DNA gets into, it's not inside cells, it's freely floating in the serum. It has a relatively short half-life. You can pick this up with various assays, and you could determine self from non-self. You can have a person's DNA, which all of us have DNA turnover. If we had a foreign organ in us or a baby or something else that's not us, that would also put off DNA. The theory was that the average human weighs, say, 180 pounds, but the average kidney weighs about six ounces. If everything is equal and all cells are turning over at the same rate, the cell-free DNA rate that's foreign from a kidney transplant would be less than 0.2%. Lo and behold, we said if the kidney's mad and it's in rejection and it's turning over cell-free DNA quicker, we may be able to pick that up. That's what the DART study showed us in 2017. It was actually a blinded study. It led to CMS covering this first test, this first cell-free DNA test. It led to the initial cutoffs, like you showed, Josh showed up. 0.5% is considered now a positive test based on their assay. The original assays suggested that 1% was the threshold. Over time, we've come to learn to use this test better. There are now two different large registries. There's a study called COR, which I helped write. There's 1,500 patients. Another study called ProActive, which we participated in with over 5,000 participants. As these publications start to come out, we're really learning how people are using the test, what the true cutoff should be. With more data coming out, we're able to come up with propensity scores to try to actually improve the accuracy of the test. The test was always very good at ruling out rejection. The cell-free DNA test has, depending on which, all the assays are about the same, about a 96% negative predictive value, meaning that if the test is negative, the patient does not have rejection. This is important because a rejection or a biopsy to determine a rejection is not a small matter. It costs over $30,000. We have to put the patient at house. There's a fee from the pathologist. They have to prepare the slides. I get a fee. The radiologist gets a fee. The tech gets a fee. It's a big deal. When I went to CMS to show them how many biopsies can be avoided, that's when CMS said, this is actually a money-saving idea. That's why they approved the test. What's interesting is after initial approval and kind of like the wild, wild west, CMS started to push back on it. They said, wait a second. There was one or two people internally that said, this isn't so good. Maybe it's not going to be such a great benefit. We don't have the outcomes data. As these data are being published now, all of a sudden, CMS is coming back and the payers are coming back. They're not only allowing for-cause biopsies, which they had always allowed, but they're now allowing surveillance biopsies. Last year alone, there were over 27,000 kidney transplant patients, the 27,500. CMS is now saying you can not only do for-cause biopsies, but you can do at least four in the first year and then two the years after that in surveillance. We're actually writing letters to the FDA and CMS to allow more than that. We think that's a missed opportunity because what we're finding from these registry trials is that we are picking up rejections way earlier than we were before because the creatinine, which had been the gold standard prior, is such a poor indicator of what's going on histologically. There was also a hope that gene tests would matter. Think about it. Cell-free DNA is after damage is starting to occur. Creatinine goes up. The kidney function goes up way after the damage is there. You're not way beyond the microscopic level. Then there were these gene tests where we can discover these genes that might actually help determine a rejection even before there's actually DNA damage. Those tests have largely failed. The cell-free DNA is actually the best test we have and the earliest test we have to determine and find rejection. This is important because historically, if you waited for the creatinine to go up, by the time you got to the case, the patient had fibrosis, gone himself, cannot reverse fibrosis and scarring. The damage was already done. In these registry trials, where we're following these patients longitudinally, we're picking up rejection at the earliest stage and the easiest stages to treat them. There is no doubt in my mind that this is going to improve overall survivability of the patient and the kidney, and that should lead to better outcomes and less need for more kidneys going downstream. I think CMS is going to increasingly cover this assay. I think a lot of the private payers will as well. What do we do this test for? In addition to ruling out rejection, like we talked about before, or finding a rejection in patients that the creatinine doesn't tell you what's going on, but the test is saying during surveillance that there's something bad going on and it creates a biopsy that finds rejection you wouldn't have found otherwise. It's been very useful to determine the response to treatment. We can actually see the cell-free DNA come down if the person responds to the treatment. I've been using it to find patients who have actually had failed allografts and have gone back to the public. If that kidney starts heating up and they don't know what it is, they think it's an infection because the patient's having fevers, the cell-free DNA can be sent to their house and you can get the result back and then know that the patient needs to have it removed. A hot area that is really interesting is that cell-free DNA may actually be picking up cancers. In these studies that I mentioned before, they're actually picking up cancers when the cell-free DNA suddenly pops, especially to a very high number, and the biopsy is negative for rejection. Say, what's going on here? It turns out the patient ends up having a lymphoma or some kind of cancer. Cancer is DNA that is self that has turned to non-self. These assays are being looked at now more and more to possibly picking up cancers. Picture a day that the PSA tests or mammograms and things like that may go away by way of the Dodo bird. That is actually a very hot area to look at. Last but not least, historically, something called antibody-mediated rejection was the worst thing that could happen to a transplant. We have no effective therapies. There is a part of the big study nationally that's doing this. There are these new CD38 drugs that appear to work really well to treat antibody-mediated rejection. They basically are plasma cell killers. They go downstream. Once the plasma cell starts to differentiate and make a clone against the kidney, they can actually stop the proliferation of this clone and actually hopefully not reject, but reverse the AMR or rejection that was happening in the kidney. The early studies, the phase two studies have been very positive. Now we're entering the phase III era. If this teaches us anything and this ends up being FDA approved and the benefit, then cell-free DNA will be integral at finding these cases before they become fibrotic and scarred. I think going forward, this is a great area. I think it's becoming more and more common for centers to incorporate it. As I mentioned before, there are maybe as many as 400 transplant centers doing it. It's been expanded beyond kidneys. I mentioned the DART study was kidney. It's been validated now in lung transplants, heart transplants, and pancreas transplants. We're even learning how to do it when patients have kidney pancreas transplants. It's been validated because think of it, you have more mass. It's hard to tell which organ is causing the DNA to come off the cell-free DNA. They're actually figuring out ways now to determine if you hit a different threshold, and that means one or both organs are rejecting. At Vanderbilt, we're the largest transplant center in the world now. We did 918 total transplants in fiscal year 2025. We're number one in hearts eight years in a row. We are using cell-free DNA almost exclusively instead of doing biopsies to determine if our heart transplant patients are rejecting. We have excellent outcomes. That's why we get a lot of patients coming from 22 different states. I think since 2017, incorporating this test has helped. Lastly, I must say it's been difficult to get the test sometimes. As you know, EMRs. We are one of the many centers that uses Epic, but there are several different EMR companies out there. These tests had to be sent off. They would actually have to be boxed up and sent by FedEx or some kind of courier to California. There was a turnaround time expected between five and seven days. In fact, if it did not get to California in a certain amount of time, the test was invalidated. There were a lot of times they said, sorry, I know you had the patient come in and do this test, but it just did not get to us in time. Therefore, the test was invalidated, which is problematic and delays care. Our joke is that time is kidney, right? If you have a rejection, just like if you have a heart attack, you want to get seen quickly and get treated so you do not have more damage. This has been a real problem for us. Even the institution worries about these send-out tests because who is billing for it and who is paying for the blood draw and all of this other stuff. I got really excited when this company came out saying, hey, we have got this new technology, a new way of doing PCRs that can be returned to you within a day. You will run the test yourself. It will be integrated into your own EMR. The institution is excited because it can actually bill for these tests and maybe make their own share and not have to worry about being a middleman and helping to get the patient's insurance to pay for it. If not, go after the patient. I am really excited by this. The study that I mentioned, that CD38 study, the phase two, was actually using this company's assay. I have validated tests at Vanderbilt that we sent over to the central lab in Nashville to prove that it works, proof of concept that works just as well as the others, but much quicker. I cannot wait to get this in our house as the company, I think, is going to put units that run the test to the actual organizations of the transplant centers. They will not even have the capital expense of setting that up in the first place. I think that is pretty much a good summary. If you guys have any questions, let me know. Great. Thank you, Dr. Langone. At this time, we will be conducting a question and answer session with our speakers. As a reminder to our audience on the webcast, please submit your written questions via the written text box underneath the player. To our analysts who are joining us live, please use the raise hand feature to indicate you have a question. Please hold for a brief moment. Our first question comes from Mike Matson at Needham. Please go ahead, Mike. You're on mute, Mike. Sorry about that. Thanks, Dr. Langone, for the overview there. That was very helpful. I guess first, just a couple of questions related to this trial. If you take a number of centers and the number of patients they're expecting, it works out to seems like around 20 patients per center. How quickly do you think you could get 20 patients enrolled in your center? Yeah, so this study, the FDA study, is going to be similar in terms of enrollment as the DART study and the ProActive study, which are being published as we speak. We were able to enroll patients very quickly because it's such a low-risk assay. It actually, because the companies are covering it or companies are expediting it, I can get research personnel to help us with this. It's been a lot easier than what I had mentioned before, where I had to try to order it commercially. The patients that got in it benefited from it. I'm looking at my own internal results and I'm saying, oh my goodness, this is amazing how much quicker we're picking up rejections at an earlier stage than we would have if we were relying on creatinine alone. To answer your question, say 20 patients, 25 patients, when we're expected to do 400 in a year, I, in theory, could be done recruiting in a month or two. We're going to follow these patients longitudinally for a set period of time and the other studies that were three years each. In terms of recruitment, that shouldn't be a problem. OK, got it. In terms of the endpoints as specified in the clinicaltrials.gov website, the lower bounds for sensitivity and specificity are 56% and 75% respectively. What level of these two measures do you think would be a success and would cause you and your colleagues to move most of your testing to GraftAssureDX? Do you think hitting, if it came in close to the minimum on one or both of those numbers, do you think that would still be viewed as a success? I think we're learning more as we do these tests and as we have experience. Some of these, like the COR and ProActive that are active, when we look at the white people, because it's open label, the physician can do whatever they want. We're just kind of monitoring that. We're finding that their tests are turning positive or the statistical difference five months before they're actually even doing a biopsy. Some centers, some people are still not familiar with the test. They're learning it. I think that will change over time. In terms of absolute numbers, for the FDA, we got to give them endpoints. What we're learning is it's a lot like a PSA test. If your PSA today is 1, a year from now it's 2, a year after that it's 3. 3 is still below that cutoff of 5, but something's happening. Something's going on. It's probably not good, even though you haven't crossed the absolute threshold. I think with the use of AI and measurement of slopes, and more data, I said 1,501 study, 5,000 others, this data gets collected. I think we're going to have a better idea based on slopes of change whether someone's turned positive or not. There's actually talk of these different devices like iBox and others that will help teach people. There's a propensity score that this company is coming up with that will teach people, hey, this is a high-risk situation. You probably should biopsy, even though it hasn't crossed a certain threshold yet. OK, great. My last question is just, it sounds like you see some advantages of doing the testing in your own facility. What do you think the biggest obstacle is going to be for Insight Molecular Diagnostics Inc. in terms of getting doctors to switch from sending the test out to the established market leaders and doing it in their own facility with the GraftAssureDX test? How do you think they can overcome that obstacle? The oldest company out there was CareDx. They're the ones that did the DART study. We were involved with them early on. With us doing ProActive and making it a little bit easier to order the test, we switched very overnight and started using the Natera's test. To answer your question, we were one center. We switched to another assay like overnight based on a preference, something that made it better. I think we'll take all of this business and switch them over to Insight Molecular Diagnostics Inc. if we get in-house to test. My faculty will follow my lead and do that. OK, got it. Thank you. Thanks for the questions, Mike. Our next question comes from Thomas Flaten at Lake Street. Please go ahead, Thomas. You're unmuted. Sorry about that. Dr. Langone, you mentioned earlier that you were writing letters to CMS to try and increase the number of tests that were going to be allowed for payment from the 4 plus 2, et cetera. What do you think that appropriate number is? What are you requesting? When we did the DART study, it was seven in the first year and then four every year thereafter. Some have been pushing we should do seven in the first year. I'd be happy with four every year. I think a quarterly amount. The interesting thing is when we looked at our data from our internal data, all the tests that we've done, not just the ones part of a study, we're finding rejections 10 years out. The patient's never not at risk. Especially as they get further out from their transplant, they're seen less and less in the medical center. As we become victims of our own success, if we do 400 a year, year on year, if we could set up a system and these companies do that, where they actually remind the patient, go get your test done and get it done at a local center or get it done at Vanderbilt. Regardless, they get it done. We could just follow those tests. The companies have been good about alerting us. A negative test or a low propensity, no big deal. If it's a positive test, they alert us, say, hey, this patient probably has to come back to the medical center. If I can get the government to do what I want, I think four a year, year on year, would be perfect. I know that we would be reducing graft loss. There's 130,000 people waiting for the grafts. The largest growth component is patients waiting on their second or third kidney because they've rejected their first one. If we can prevent that or get to their rejections early, then I think we can get better longevity and get more people transplanted that have been waiting. There are more people dying waiting for kidneys than are actually getting it. If we can keep those who have it already without losing it, those patients will have an opportunity. I think four a year, I mentioned we did a record number countrywide, 27,500 transplants last year. The growth is up. That was up like 10% the year before. There are many pushes by the government to advocate for transplant. In fact, when I get a patient on the transplant list, I have carte blanche. I could order the silliest test in the world, and the government will pay for it. I can order PET studies, even though there's no reason to. There's no prior auths or anything like that because the expense of dialysis is so ludicrous in comparison. To put in comparison, a hemodialysis patient costs the system between $100,000 and $125,000 a month with all the water and everything that they do, whereas a transplant is $85,000 plus the meds they got to take going forward. It is definitely a cheaper activity and better for the patient, God forbid. Certainly, from the government perspective, it is better. Life, liberty, and pursuit of dialysis is guaranteed in this country since 1972. It's now Medicare's budget. It's about 13% goes to end-stage renal disease and dialysis of the entire Medicare budget. That's why they're partnering with us. The government wants us and it wants the private practice physicians to send their patients for transplant at a higher rate. Got it. One follow-up question, if I may. You mentioned you guys have a particularly large catchment area. I'm curious, you mentioned turnaround time, trying to get that to kind of same-day turnaround. What are the logistics around that? If you have someone come in, do you usually have them around the center the whole day so you could actually realistically wait for the test to be turned around before they fly home or drive home? With a commercially available test to go to California now, they may drive in from Arkansas. They may drive in from South Alabama. They come in. I'm worried about their trajectory. I order the test, and then a couple of days later, the test comes back positive or negative. I bring them back, so they're actually doing another trip. If I could say, hey, just like checking a creatinine, which I can get back in a couple of hours, hey, it's 8:00 A.M., can you stay here, eat lunch, and then if the test is positive, I'll admit you and do the biopsy. As a matter of fact, these companies, these other companies tell you do not order it on a Friday. Like today, if I saw a patient in clinic, I couldn't even order it because the stuff's going to sit. If I had it internal, I can get the answer back the same day and admit them on a Friday and start empiric treatment or do a biopsy or whatever I need to do. I am excited by the technology and the turnaround because I think this could be a game changer. Great. I appreciate that. I'll jump back in the queue. Thanks. Thank you for the questions. Our next question comes from Mason Carrico at Stephens. Please go ahead, Mason. Pairs to the important data points that clinicians will be highly focused on or what they need to see in terms of driving broader adoption commercially. No one can forecast what the FDA is going to want. I could tell you when we went to the CMS the first time, the reason why it got approved was because it reduced biopsies. Biopsies are an expensive process. They were excited by that because the negative predictive value was so good. Clinicians want that, but they also want to pick up real rejection. They don't want to be doing a lot of biopsies on patients that have false elevations. I think with time, as more data comes available, propensity scores are made, AI is used, we're able to get the positive predictive value up quite a bit. Like I stated before, slopes matter in addition to an absolute that matters. There's even a couple of the assays, including Insight Molecular Diagnostics Inc.'s assay, that actually gives you an absolute DNA score, not just a ratio. Can you picture the situation where someone is in an earthquake and they have massive damage to their body? That peripheral DNA could be so high that it will make the actual kidney part, if it wasn't damaged directly, look low, even though it could be in rejection. There could be other, or the background may be less for some reason. It may make it look higher as a percentage, but the absolute may remain low. I think the combination of the absolute and the relative is going to improve the PPV. It's going to be something that clinicians are going to like better because they're going to not be doing false biopsies. I think the FDA is going to like that too, because when they weren't seeing the benefit of following patients longitudinally, they felt there were so many negative values. In our own study, in both assays, both the COR and the ProActive, we're finding 12% of patients are having positive tests that would not have been picked up by creatinine alone. We're getting to them at the cellular rejection point, which is a very treatable and easily treatable point. Their grafts should last longer. I think that's what's going to come more and more with these new studies. They're going to do more and more outcomes to prove the benefit. We're using AI now. There's this thing called the iBox. There are others out there that could put all this data together. Instead of waiting till a kidney fails, which could take 10 years to do that, or compared to a kidney that lasts 20 years, they can actually, based on trajectories of creatinine, know how long a kidney is going to last. The FDA is accepting that now as an outcome parameter. I think this is why I think there's been a flipback that I think they realized they were too harsh at one point, stating that it could only be for causes. Now they're actually starting to approve some of the surveillance studies because they realize there's value in it. DART program impacted your daily practice. Have you seen an increased use in marginal organs? What are your high-level thoughts on that increasing? Yeah, we're part of the Save 34 Kidneys. You know, you probably heard of that. There's this company. I think it's maybe for-profit, not for-profit. Basically, there are 34 people dying on the list every day or some. They're trying to, it's called 34 Kidneys. We're integrally involved with it. One of my surgeons, Dr. Cornell, is leading the charge here. You can't increase the volume without taking more marginal kidneys. There's no doubt that historically, we might have been overly conservative, that we looked at things that we didn't realize may not have been as important, like certain things on the biopsy and stuff as we thought they were. AI is actually helping with that now. They're actually telling what things, what factors on the history or the physical or the laboratories are really what matters. That said, we are taking a lot of very stressed kidneys. What was nice about this test is these patients often don't get creatinines like we hoped. They get creatinines of 3 instead of 1. What I'm seeing a lot of people doing is they're biopsying these kidneys to see if they're rejecting or what's the reason. If they did cell-free DNA testing, it would show that there was no activity. It's just that the kidney has donor-derived issues, like arteriosclerosis or fibrosis or something that came over from the donor. The tests are validated at least at 4 weeks, if not 6 weeks. All the implantation errors and things that can occur, injury that can occur, by 6 weeks, certainly, the test should be validated and used. That's what the DART study showed and others. I think this is a new opportunity with the IOTA that we could be using cell-free DNA more on the front end to prevent biopsies. If someone really did have a hyperacute rejection or something like that, and that's why the kidney's not waking up, that would be found. You would go ahead and do the biopsy. Got it. Thank you again. Thanks for the questions, Mason. Our next question comes from Bill Bonello at Craig-Hallum. Please go ahead, Bill. Hey, of course, my phone rings exactly when. Thank you very much. I want to touch on a couple of the things you talked about, just maybe from a slightly different angle. I really appreciate your willingness to talk to us. The first thing is, you know, again, thinking about sort of data that's necessary. As you said, this has become somewhat standard of care with a lot of still room for penetration. What do you think centers beyond your center maybe and the surgeons at those centers, what do they need to see in terms of data to feel comfortable saying, OK, I'm good with this testing being done internally by our hospital with a kit rather than sending it out to one of the other two providers like we've been doing? Do they have to have a peer-reviewed publication? Obviously, the FDA study is a lot smaller than DART or ProActive. How is that going to play out? I think an easy way to do this is what the company did for me. They came to me a couple of years ago, and they said, hey, we got this assay that can run faster. I had patients in studies already that I was using as standard of care with the other commercial companies. What I did was I actually ran my own little study internally where they would not charge. They said, let me just give three patients. I did that, and I had data from those same three patients having the blood drawn the same day. They were very close, not statistically different. The test is fine. I think that they're equal in their efficacy. The advantage here is how fast you can get the result back and how quickly you can act upon it. I don't necessarily think that, and the other companies have kind of, from a CMS standpoint, have gone on their own coattails. One gets approved for doing something. The other one's data gets that approved too because even the FDA and CMS is not seeing them as different assays. They're seeing it as like one aggregate. If a person was loyal to a company out in California and they really had any concern, I think the company here would be smart to say, look, run your tests like you do. Here's five free ones. Compare it. You may be shocked to find out it's not any different. You'll hear things about different numbers of SNPs and all that stuff. That doesn't seem to matter. When they've looked at the two commercial players out there, the two commercial companies right now, they're just not statistically different, even though one has a lot more SNPs than the other. OK, that's very helpful. It sounds like, I mean, it's almost like any other IVD that a lab would perform as long as your team knows it's been validated and it's accurate. They don't need to see yet a third or fourth large study. What they're going to do, I understand, is that when they put in the hardware, the capital expense that the companies, like the institutions like mine, have to pay for, they can do an internal validation study. That will actually make the HLA Director happy and say, this is clear fine. This is great. I think they're going to do that too at the level of the Lab Directors. From the clinician standpoint, they just have to feel that all the tests are the same. I think that's the way we are feeling. It's just a matter of the convenience of it. As long as payers don't say, you have to use this test like you do with drugs or something like that, that hasn't happened. I don't know if that's ever going to happen. CMS certainly isn't going to dictate that. They don't care which assay you use. It really comes down to convenience and ease and not affecting the workflow. If I can order this test like I would order a CBC or a creatinine, then that's going to be part of my panel. The utilization will go up crazy amounts. The companies can help me by even pointing out a positive test. It'll integrate into my EMR, and I'll be able to see trends and everything instead of having it faxed to me. That's what we've been doing up to this point. It's been very laborious. We believe enough in it, we'll do it. It's just a problem with workflow. If we can do this internally, this would be, it's a game changer. That's really helpful. If I can, just a couple more quick ones. Really appreciate it. The decision-making process, I mean, you made the comment, hey, if I want to go this way, the other docs will follow. What all would typically be involved, do you think, for transplant centers to internalize something like this? Do you need the buy-in of presumably the Lab Director? Do you need C-suite buy-in? Do the surgeons sort of all put their heads together and talk about what they want to do? What's kind of the process? I could give you my scenario. I've been working on this for years. Even though I was one of the lead authors and came up with the DART study, the COR study, everything that's published, my own institution was always worried about us losing money. Picture a situation where you order this test that costs X amount of dollars, and then the insurer doesn't pay for it. If Vanderbilt took on the cost, like paid whatever company, CareDx, paid them the $3,000 for the test, and then they don't get reimbursed, they would be out the money. CMS would reimburse them. A lot of the private payers at the time were not reimbursing, or at least not at the full rate. The companies would say, all of them, that we're not going to charge you. We're not going to do it. They couldn't do that legally. They couldn't put that in a contract. I know of no patient in the seven, eight years I've been doing this that actually got a bill. The companies have held true. They have not actually gone after the patients. The C-suite was worried because they're looking they could be on the hook for millions if that was the typical billing. What they said to me and others in my department, you do it independent of us. That made it even more difficult. It's like my lab people couldn't even do it. That's why you almost had to do it in a study format to get it covered or get it done. Then my study coordinators that are under me would be able to draw the test and send it off as a study format. Now, if they do it in a way where they are actually running the test, they're actually making most of the money off of the actual test, that which would have been done in California. Now they see this as a profit center. In times as tight as they are, you may have heard Vanderbilt is, I mean, they cry poor, but $500 million, $600 million in debt with NIH and all this other stuff. They fired a bunch of employees and everything to tighten the belt. This might actually look very attractive to them because now it looks like something they can make money on, and legitimately. As far as a, I don't do things to make money. I don't get it directly. I don't order tests to get paid. I do the tests because I think they're valid and they need to be done. I think if the leadership within the Medical Directors say this is a good thing to do, they may set it up as a protocol and it may become protocolized. What we have done, we have independent practices. We're all part of one team. If I'm the biggest user of it, others that I've trained may follow me. You don't have to do it. We're not forcing it. In centers that get protocolized, it will become part of the routine. The Nurse Practitioners will order it at a set rate and such. I think most centers do try to protocolize things just to make things easier and have less variability. I think as long as there's buy-in and people, and most centers, there's 400 of them doing it, are starting to recognize that this is the way to do it. In fact, I worry centers that aren't doing cell-free DNA or genetic testing is another thing to think about. If they're not doing it and that's becoming standard of care, they are putting themselves at legal risk because you didn't do everything that could have been done when other centers couldn't do that for that same patient. I think there's going to be more and more push for centers to have to use this test no matter what their prior biases were because it's becoming more uniform throughout the country. Excellent. Thank you. Just the last one. This gets to the turnaround time and the patients staying around, not having to come back in, et cetera. How big of a deal is, I don't know what you want to call it, patient leakage? Patients that just simply lost in follow-up. Does that happen? Or because this is transplant, you get pretty good compliance that people come back? One of the reasons you do the test is because some patients aren't compliant. I ran the VA program for almost 25 years. In the VA, there's no excuse because we give the meds for free. The veterans don't pay, yet some of them still don't take their meds or show up for their visits. It's just human nature. When you have that history, then you're even more worried that they're rejecting no matter what their creatinine is, that they haven't taken their meds for X amount of time. It's kind of like when you sell a car. If the guy walks out of the showroom, he's most likely not coming back. I want to keep him in front of me and know whether there's a problem and admit him if I can and get things going. As I stated before, time is kidney. If you were having chest pain today, you don't want me to do the cath on Monday. You want to know today, am I having a heart attack? That's what this test does. There are similar tests called troponins in heart attacks. If that were negative, the negative predictive value is great, go home. You're fine. That chest pain is not real. If it were positive, I can get that test back within a few hours. I'm bringing you to the hospital and getting you into the cath lab. I think that's the advantage here because some of these patients, they're limited socioeconomically. If they go down to Mobile, Alabama, if they saw me on a Friday and I call them on Wednesday, hey, I need you back up here, that means they have to take off time from work again and everything. Some of them just don't have gas money. It's really somewhat pathetic, actually, but that's the truth. I really do see a great benefit in being able to not disturb the workflow and order it in real time and get things done going forward. Thank you so much for taking all those questions. Really appreciate it. Thanks for the questions, Bill. Our next question comes from Yuan Zhi at B. Riley. Please go ahead. Thank you so much for all the insights. If you have to put a value to this test, what will it be? Is it based on how early this test can help you detect rejections, or how many kidneys you can save and justify this monitoring? I think time will tell as we figure out how many. The problem is at this point, it's become standard of care. It would be cruel not to offer the test to some and give it to others. I don't think that study will be done. I don't think you can randomize people. It's like randomizing people who have heart disease to no aspirin when aspirin at least is the baseline that you have to have versus the drug you're trying to test. I think there will have to be always offered going forward for these folks. We could look at historical data. We could certainly look at patients who presented. First of all, we can look at graft half-life. If people's half-lives are increasing in an era where they're using this test, that would suggest that the test is adding value in that sense. I think from a global standpoint, from a government standpoint, these kinds of values, it's huge for them. That's why I think transplant in general is being recognized as the standard of care. That's why I think the government is allowing some of the accommodations to make transplant happen. That may be one of the reasons why they're loosening their reins on this test in particular. I mentioned organs. I said there's about 130,000 active patients waiting for kidneys in the United States right now and that there's actually a higher death rate. These are things that are hard to put dollar values on. If you just say, death is cheap, people can die, and that doesn't cost you anything. If you really care and you want them to do better, then yeah, there's a cost savings versus being on dialysis. I also think as the test becomes more ubiquitous, I think pricing will come down. I think the overall, whatever the test cost is now, it's hard to judge when they're doing millions of tests versus thousands of tests going forward. It becomes in-center and quicker and the assays are cheaper and they're producing at a larger amount. I think there'll be some downward pressure on the cost. That will make the overall cost benefit even greater. There'll just be more tests done. It'll be more ubiquitous. Got it. As you mentioned, creatinine and eGFR is kind of the biomarker right now for any rejection detection. You mentioned the iBox earlier. I'm curious, what does it take to replace creatinine or eGFR as a biomarker, whether for iBox or for the cell-free DNA test to replace or make it more sensitive? Right. As I mentioned in these studies, like the COR study and the ProActive study, where they're seeing where people should have been biopsied earlier and they weren't, I think there's a learning curve to trusting the test. I think as you get more used to the test and you have seen the value not only in the rise of creatinine, I mean, rise in the cell-free DNA and doing the biopsy earlier than the creatinine would tell you otherwise, people are starting to replace the creatinine. They've seen that the R-squared correlation of creatinine rejection is very low. Everyone's recognizing that now. There are other biomarkers trying to be developed, but none of them have panned out. Urinary biomarkers have been difficult to validate. I think the use of AI is going to help us even more. I think as we develop propensity scores, and it doesn't have to be iBox. That's just one. Internally, Dr. Ekkehard Schütz has his own propensity score. He's going to show that the PPV will go up based on both the absolute and the relative, the percentage, and then also the ratio, how it's going up, what the change is. Those changes will help us realize or recognize more than our eyes would that that patient's at risk. The companies all say this patient's at risk. This is a high-risk situation, even if it hasn't crossed a certain threshold. It's not just relying on you or the nurse practitioner to make an interpretation. They are giving you an interpretation based on what's being seen or what's happened over time. That's why it's very important not to have an isolated number because you don't know what that means. If you see something increasing over time and their propensity score suggests this is a high-risk situation, that would produce a biopsy. You need more data points. I think the government's starting to recognize that as more stuff is getting published. Got it. Thank you for taking all our questions. Thanks for the questions, Yuan. We have a few more minutes. I'm going to turn the call to Andrea to read the remainder of the questions that came over the webcast. Thank you for sending in your questions. Dr. Langone, thank you so much for all of this. I'm learning just from listening to you here. I'm going to combine this because we do have some questions coming in. Chris Mercado at Wells Fargo asked about the LCD, the recent draft LCD, and you did touch upon that. Vivian Vice at BTIG also asked about testing cadence. I'm going to combine those two, just generally talking about testing cadence, the draft LCD, I know you did address it, and then an appropriate cadence of testing in a patient with suspected active rejection versus the protocol recommended by DART. Would it perhaps be better in your view to let a physician determine the appropriate cadence on an individual patient basis? Yes. There are some patients at higher risk than others. There are patients that are what they call sensitized. They have haplo-reactive antibodies that are elevated, or they're of a certain race and gender that may be higher risk than another race and gender or age. Older Caucasian males have lower rates of rejection. If you want to nail it down to that level, then yes, there are probably differences in what patients should be followed. I can tell you that it's difficult for centers to do that, to individualize it that much. I think it would be good if they came up with some kind of reasonable protocol that they could follow. I'll give you an example. This is not a knock against surgeons, but they like simplicity. We know that, for example, the main drug we use called Tacrolimus has an average dosing that the FDA says is 0.075 mg per kilogram twice daily. You could actually look at the weight and say, OK, they are 100 kilos. I should use 7.5 mg. If you have someone who's half that weight, then use less. What I have seen, and this is uniform throughout, they just like one number. Let's just put everyone on four, and then they adjust thereof. You know what I'm saying? If the experts can come up with what they think should be done for most folks, that could be the standard. It doesn't necessarily have to be exactly what the DART did. The DART did it seven in the first year because we didn't know what we were doing. We didn't know what, you know, we didn't even know if this was going to work. It was blinded. We wanted more data to try to figure out what was going on. The individual didn't know if the cell-free DNA was positive or not. They were doing biopsies based on what the creatinine was. You're right. I think you should, hopefully, the government's not so firm to say, oh, only four in a year, only two in a year, that there's individual cases where you need to do it more. One of the things I mentioned, the utility of this test is actually to see the results of the treatment. If I have a patient that has a cell-free DNA that went to 1.2%, even if the creatinine looks normal, I biopsy them, they got rejection. I could treat them with whatever treatment it is, whatever type of rejection it is, and instead of re-biopsying them in a month to see if I got it, because the creatinine was.