All right, we'll get started here. Thanks everyone for joining us. I'm Mason Carrico, I'm the Diagnostics and Genomics Analyst at Stephens. Today, we have Frank Stokes, CFO, with us from Castle Biosciences. If anyone has any questions, feel free to hop in at any point. Before we get started with questions, Frank, maybe for those who are less familiar with the story, you can give us a high-level view of Castle and who you guys are, what you're working on. Sure. So Castle is a diagnostics company. We perform diagnostic testing services. We do that across three therapeutic areas. We are in the areas of dermatology. We have three tests in the dermatology area. We're in gastroenterology, and we have one test in GI. And we're in PGx or pharmacogenomics, and we have a test in pharmacogenomics that's targeted at mental health conditions, eight of them, including major depressive disorder. So we'll start off here with your melanoma test. It's clearly been a great growth driver for the business. Test volumes are up 20% year to date. I think market penetration is around something like 25%. You guys essentially make up all of it. Where do you see penetration tapping out? Are there any tests in the market today, maybe for a different cancer indication that we can use as somewhat of a proxy for peak penetration? And ultimately, what's required to get to that level? Yeah, sure. So, a couple of proxies that you can look to, and one would be our uveal melanoma test. We have a test, I didn't mention it earlier because it's a very small piece of our business, but our uveal melanoma test, we test about 85% of those patients every year. Now, the asterisk there is that's a small disease state. There's a small number of prescribers. There's maybe 1,800 patients a year diagnosed with uveal melanoma, and there's just a handful of physicians that see them. But we do have a competitor there, and so, you know, aspirationally, maybe that's the right number. The breast cancer test, there are a number of breast cancer, you know, led by Oncotype DX and MammaPrint. I think 85% or 90% of all breast cancer patients are tested that are eligible at this point. So those are aspirationally on the high end, maybe. There's a really good analog in the thyroid space. So, Veracyte has a test called Afirma. Interpace has a test that competes with them, and I think Sonic Healthcare has a test. And I think Veracyte's estimates are about 60% of all thyroid patients are tested. So I don't know why any of our tests couldn't get to that 60% level. If you take melanoma, the similarities to thyroid are, we avoid a surgery, we are providing a prognostic answer, we're stratifying patients, getting the right patients in higher acuity care and the right patients out of that higher acuity. So, you know, potentially 60%'s a reasonable number. If you look at the prostate cancer area, prostate cancer testing, I think maybe 35% of those patients are tested today. And if you just look at the timeline, this is rough and tough close. I think Oncotype was launched in about 2004. Afirma for thyroid was launched in about 2011. Our test was launched. Our melanoma test was launched in about 2015, and I think the prostate cancer tests were launched in maybe 2014. So if you look at the time to that level, that kind of gives you a little bit of a sense. So, could we be at 85% or 90%, ten years out? You know, that seems twenty years out, you know, that seems to be we seem to be on track, we seem to be on trajectory for that. But I guess the way I look at it is, if we were only to get each of our tests to where the thyroid cancer market is, you know, the numbers get a little goofy. So I—we are targeting that 90%. I think 60% feels difficult to argue with. But in any case, we've got a lot of room to go, and I think importantly, it suggests our melanoma test, which you referenced, we still have plenty of growth there. If we were to only get to 50% penetration, that's roughly 60,000 patients. You know, that's a $225 million-$250 million revenue business, so plenty of growth yet in melanoma. With our other tests, the penetration is just, it's not even—we're not even meaningfully penetrated there, so plenty of room to go. Got it. And then on the NCCN guideline opportunity, I think the committee met in July. Maybe we see an update by year-end or early 2024. The NCI collaboration data, the Dhillon study, I think both of those were submitted and included in the July meeting. So could we talk about, you know, maybe the significance of having those studies submitted? And, and when it comes to guideline inclusion, what, what type of upside opportunity or, or, you know, driver to ASP and volumes could that bring? Sure. So the NCCN meets every year in July. They want their data, all your information in by June 30. So we did have those two publications in and included in their review or available for their review. And then they usually put their update out at the end of December. Now, there was an update from the committee on melanoma last month, I guess. That was not, we don't believe, their review. That was really an update for a new drug approval. It is typically their practice when a new drug is approved for melanoma, they will include it in the guideline, as an available therapeutic. So they were clear that they didn't review the other data, and it wasn't a guideline update as their regular cycle. That was really just the drug inclusion. So are those two studies enough? Is a great question. I guess we would think, you know, of course, it's enough. How do you not? I mean, you've got two well thought out publications that clearly demonstrate that patients who are tested with our test have better outcomes than patients who aren't. And if I'm arguing to the NCCN, I'm saying, "So it's your judgment then, that you want to guide physicians to the care pathway that has worse outcomes for patients. Are you comfortable? That's your position, right?" Of course, you can't put it that way. But we would think that's enough. Now, in practicality, they move very slowly. I think that if you ask, and this gets to the second part of your question, if you ask many physicians, you know, "Is NCCN cutting edge of medicine and science?" They're gonna say, "No." The NCCN is a lag. It's a trailing indicator, if you will. So if we were to be included, what does that mean? I don't think that it means a lot on volume. As I said, I don't think there are many physicians who are saying, "I would use your test, Castle, but the NCCN doesn't say use it, so I'm holding off." I don't think—I'm sure there are some, but I don't think that's a big number of physicians. Where I think it helps you is on the payer side with ASPs, and I think it's a lot harder for a payer to say, "This testing service is investigational and experimental," when the NCCN includes it as a criteria or as a recommended test. And that's another point, just to... As you think about it, there's sort of three levels of inclusion. There's the recommend against, there's the, you might consider this, and then there's the recommended. Our uveal melanoma test is in the recommended, it's in the care pathway. The NCCN says, "If you have a patient with uveal melanoma, you should test them for gene expression profile testing." So the second part of your answer is, I would not expect to go from here to here. I would expect to go iteratively, and so we would go from don't consider, to you might consider, to eventually a care pathway. So I think it. The biggest impact is just on payers. It really gets difficult for them with a straight face to call something E&I if it's in the guidelines. Docs are, there's a handful who, you know, might drop back and say, "Well, until NCCN says use it, I'm not gonna use it." But I really think it's an ASP issue more than a volume issue. Okay. Then moving to TissueCypher a nd what about timing? Yeah, so we're fortunate that they, that they do meet annually. So NCCN, the melanoma committee meets every year, and that's good. I mean, the ADA, this is directly right. I don't think they've changed their guidelines in five years, and so at least you get an annual shot on goal. And they typically always meet in July. They have a follow-up, I don't know how they do it, some kind of follow-up in August, and then usually it's about the third week of December, they publish the update. And they're pretty consistent with that. They don't have to. There's no, you know, there's no obligation, but that's kind of what they've done. So as an industry, you kind of use, you know, July to June to assemble your information and if you can get things published. That's the other thing, is they want data... They typically will only rely on data that's published in a peer-reviewed journal. So if you have a study that's completed and you're presenting it in poster format or, you know, abstract format at meetings, they really, that's a great excuse not to consider it for them. So they really want it published, and that's why for us, this, the second quarter, it was critically important to get those two publications in: the SEER data with our collaboration with NCI, and then the, the... We call it the Dhillon paper, which was three academic care centers who did their own independent, their own independent study. And that's the other thing, that, in our business, that we get, payers and, NCCN will push back and they'll say, "Well, look, yeah, you've got all this data, but that's all Castle sponsored. You sponsored those studies." And, and what, what we would say back is, "Well, you know, you recommend Opdivo. Who who sponsored those studies? That was the drug company. They spon-- You know, it wasn't American Cancer Society that sponsored it, it was, it was drug companies." So, so they, they criticize what is inherently the nature of, of evidence development. But what was great about the Dhillon study, and, you know, you could say shame on us, we didn't even know what was going on. I mean, they gave us a heads-up just before and said, "Hey, by the way, this thing's about to hit." And, you know, it was good, so that's okay, right? But it was three academic centers and there are three kind of thought leaders, you know, you would call them KOLs for sure, who lead these centers. And they looked around, they said, "You know, we've got some doctors that use this test with melanoma, and we've got some that don't. I wonder if it matters. I wonder if it matters." So they independently looked at all their patients over... I don't recall how long it was, it was a very large N. And they said, "Okay, let's take the patients that were tested. Let's take the patients that weren't. Let's see what the outcomes were." And what they found was the patients who were tested had better outcomes. And so you would say, "Why is that?" What—you know, or NCCN might say, "Okay, but why? Granularly help me why." Well, the why is the patients who were tested and who were high risk by our test, our test is a Class 1A, 1B, 2. The patients who are two, Class 2, biologically are more likely to metastasize. So what that means is these centers were taking the high-risk patients, and even though by pathology, so they might have had a very small, thin tumor—they might have had a small tumor that didn't have... You know, the high-risk things they look at are like regression. That means the tumor was bigger and has gotten smaller. They look at, has it scaled? Does it bleed? Is there perineural invasion, which means the cancer's kind of gone down the nerve deeper. All these are factors, and so what they found is that patients who didn't have those factors by pathology, they would have been sent home. "Good job. You saw a lesion, you came in, you saw your doctor. We got it early. Well done. Come back next year, we're worried about new cancers, not that one." Well, if they tested Castle high risk, instead of sending them home, they put them in the surveillance program. So they probably did monthly or bi-monthly imaging. You know, they palpate, touch, squeeze. They'd squeeze the lymph nodes and say, "Yeah, that doesn't feel right. You got some cells there." They did that much more frequently, which means that when the cancer left home and started to metastasize, and melanoma unfortunately goes to the lung or the brain, typically, they picked it up earlier. So they were, because they were imaging these patients every month, they were finding those first couple of spots, get them in for lung, and you go, "Oh, there's three little spots there. We got metastasis." So they were able to get them on drug therapy when the tumor burden was way low. And without the test, what would have happened for those patients who were low risk by pathology, but actually biologically high risk? They would have been sent home, and you know, you don't know anything's going wrong until they show up throwing up blood, or, you know, they pass out 'cause they got a big brain met, or, you know, they're throwing up blood 'cause the lungs are... And then you get them on imaging, and it looks like, yeah, I mean, if you're a bird hunter, it looks like you've birdshot against a paper target. It's just like all these spots, you know, and it's just like, "Ah," you know, that's a bad day. There's not much you can do 'cause the tumor burden is so high. So the reason they did better is when you find a high-risk patient, you know it sooner, you get them in surveillance, and you find the cancer when it's low tumor burden, and the drugs we have work much better. So that's why, so that's why if you're, if you're NCCN, that's why you should want to test patients, because the numbers are only, right, only 10,000 people or 8,000 people die in melanoma a year, only. And there's only 130,000 patients. But melanoma, like a lot of the other things that we test for, is very treatable early, and so there should be far fewer. And so, what NCCN should be saying is, they should be saying: "We want to know if the... Because," so, so what 80% of melanomas are stage one or two when they're diagnosed, so local non-metastatic, 80%. But because the number is so big, that's where the deaths come from. Most of the deaths come from that 80%. So when you talk to a dermatologist, most of them have, in their memory, that patient that had a very polite little melanoma. They did a wide, or right here, they did a wide local excision, got it, clean margins. You did the right thing, you're all good. And then that patient died because it metastasized, even though it looked low risk. So doctors all have that in their memory, and so what you're trying to do is you're trying to find the one who looks low risk and is high risk, and, and so that's one of the, the answers our test gives. The other is there's a surgical procedure called a sentinel lymph node biopsy surgery, which sounds kind of easy because it's got biopsy in there, but it's inpatient, especially for Medicare, general anesthesia. You know, if the melanoma is here, they're going in, they're rooting out those lymph nodes and pulling those out, and they're looking in those lymph nodes to see if there's a cancer cell. And if there's one cancer cell, that's a stage three now. That's local metastasis to the lymph nodes. So that surgery, for many, many years, was thought to be therapeutically beneficial. Makes sense. The lymph nodes are how a cancer moves. We're going to pull out the highway, cancer can't move. In 2014 and 2015, the societies of dermatological cancer, the American Society for Dermatologic Surgery, something like that, they did two studies, MSLT-I and MSLT-II, which proved that patients have the same prognosis whether you pull those out or not. So all that procedure is a prognostic. It's just a prognostic procedure. Well, how does it perform? So for every 100 surgeries you do, you find 12 positives. So you've done 88 surgeries you didn't need to do, told you nothing. You found 12 positives. You'll have 11 complications. So your complication and positivity rate's about the same, and then you're going to have 18 false negatives. So 18 negative biopsies, and they still metastasize. So if I came to you to finance that as a diagnostic test, you'd tell me to go pound sand. It's terrible. So you're telling me the complication rate and the... So you're going to do 88 of these tests to—you do 100 to find 12? It's terrible statistics. So the other thing our test does is inform on the likelihood of a patient being sentinel lymph node positive for cancer. And we have a paper we published in, I think, 2019, maybe 2018 or 2019, that shows that if you test all these patients, you can reduce 75% of that surgery. You can take three out of four of those surgeries off the table. You know, what we said quite simply to CMS is, "You don't even need a model for that." You test four people at $7,000 each, that's $28,000. You take three off the table at $25,000 each, that's $75,000. You're $50,000 good. You don't even need a model. All good. Not to mention, that's better for patients. So that's the first question we answer, and that is why we would suggest, and they would possibly, probably have a different... We would suggest that's why we've had friction at NCCN, because the committee is largely made up of surgical oncologists, who spend a lot of their time performing, publishing, teaching on that surgery. And here come these guys from Texas with this little black box that says, 75% of the time, you were doing bad work for your patient. 75% of the time, you were treating your patient badly. Well, they don't like that. So we would suggest that some of that friction is why we've had such a hard time with NCCN and melanoma. Now, our second derm test is our squamous cell test. We expect to have, not this year, probably not, but at some point we expect to have a better outcome with NCCN on the squamous cell side, because there isn't that inherent bias against change of practice that you see in melanoma. And on squamous cell carcinoma of the skin, it is probably not a great analogy, but doctors will call it the Wild West. Nobody knows what to do. We all do different things. We all treat these patients differently, and there's a million of those a year. 80% of the time, no problem. They do a surgery called Mohs surgery, and it's like if you go to the Baskin-Robbins, it's like dipping ice cream. They go in, they dip a little bit, and they run over the microscope and look at it. "I don't have clean margins." They go back, they dip a little bit more, go look at it, and they keep dipping until they get a layer, a scoop that has clean margins, no cancer. They say, "Okay, we're good." That's... But 80% of the time, that works. Now, that's not a trivial squamous cell of the skin tends to be over the shoulders. So, if you've ever been in a country club locker room, and you see the old guys playing pinochle or gin rummy, and the guy's got the big bandage on top of his head, that's probably a squamous cell. He probably had Mohs surgery, 'cause that's where you get it, 'cause that's where your exposure is. And it's sort of a, it's a fairer skin, male, average diagnosis, 67, I think. So clearly, triggered by sun exposure, things like that. So it's not trivial, but it works 80%. Well, there's 20% that the doctors don't know what to do, and what is typically done is adjuvant or prophylactic radiation therapy. And so, again, back to the fact, you know, 80% are above the shoulders, and in our experience, two-thirds are Medicare age. So, you know, I always use my dad as the example. If Dad's got a squam up here, he's 85, 86, got a lot of challenging health issues anyway. Am I gonna say yes to adjuvant radiation therapy, which what? He can never do it again, so if he gets another cancer, you can't... You've shot your bullet. High likelihood of radiation-induced dementia, lots of complications, and it's like $50,000-$60,000. So, you know, of this high risk, this 20%, only about one out of five is gonna metastasize. So if you're a physician, what do you do? Do I treat all five? Well, that's, that's a tough call. Do I treat none and just hope I catch it when one starts to metastasize? Well, that's a tough call, too. So, so what do I do? And when we were developing our squamous cell test, the physicians came, some of who were on NCCN, by the way, who came to us and said, "Look, the current staging we have is about 20%-30% positive predictive value. So one out of five to one out of three high risk by our staging are actually gonna metastasize, and we don't know what to do about that. If you could say 50%, if you could be 50% positive predictive value, that'd be overwhelmingly compelling to us." Well, our data is about 60%. We're about 60% positive predictive value. Conversely, we have a better than 90%, it's actually 92% negative predictive value. So if you have a low-risk score by our test, that means your risk is exactly the same as that 80% that we're not worried about. So we're taking that 20%, and we're moving the ones into care that need it and out of care that don't. And I think that's why we're getting good uptake from physicians, is that there is such a conundrum. There's such a lack of consensus of what to do, and we have two negative policies on our squamous test, if you follow the sector, and one of them is poorly written, so it's not worthy of going through the fundamentals. But the Palmetto policy, they miss that adjuvant radiation therapy piece. And they actually say it in the policy. They say, "We don't think that anything... You You know, we don't think there's any treatment change here." So what we did is, post that draft in the comment period last summer, is we showed them a study we've done that shows, one, doctors are widely using adjuvant radiation therapy. Two, you're paying for it. Three, you're paying about $60,000 for it, and we can reduce about 80% of those. We can take 80% of those things, those and take them out, take them off the table. So we've supplied that information, submitted it, and discussed it, and that's why we although we've taken squamous cell out of our guidance, and we've asked the analysts and investors just to assume that it's not there, at the same time, we think at some point it has to be covered. If we lose coverage, it has to be recovered at some point because the data is so good. And I'm always careful to say we're happy about something when it means more people are sick. What's interesting about squamous cell is even though we're only testing about 20%, there's about a million of those a year versus 130,000 melanomas. So that means a doctor is thinking about squamous cell of the skin eight times more often than melanoma. So even though we're not testing all those patients or suitable to test all those patients, it's still top of mind. It's still something that physician is thinking about, is thinking about that, that condition, that disease, and the impact on their patient. So you've got a bigger pool to shoot against, and you've got a more frequent physician engagement. And it's one of the things we get on our melanoma test is, you know, how do you when have you lost a doctor? Well, that's kind of hard to say. I mean, if you, you know, a dermatologist in Brentwood, Tennessee, might see five melanomas a year. So if he orders and then six months later, we haven't gotten an order, what does that mean? Did we lose a doc, or he just hadn't seen a melanoma? And our area managers are very good at trying to figure that out and make sure we haven't lost a doc. Whereas a squamous cell, you know, they're seeing those every week, not testing, not a testable or not a candidate for testing every week, but they're seeing that patient every week. That cover a couple questions there? Yeah. No, that was great. I mean, on that point, you were talking about the negative Palmetto draft. You presented the adjuvant radiation data during the open meeting, so maybe could you talk about, for both MACs, Novitas and Palmetto. But I guess, could you talk about if we were to see a policy flip positive, which MAC are you more optimistic on and why? So I'm not predicting a flip in either case, but Palmetto clearly is making sound evidentiary reviews, and the example validating that I can give you is a private company that might not be on your radar, but it's called Scipher, S-C-I-P-H-E-R, Scipher. They had a rheumatoid... They had an RA test. I believe it's a therapeutic indicator, therapeutic guide test, and about a year ago, a little over a year ago, they got a negative policy. So Palmetto said, "We're not gonna cover this test." And then in that period of time, they supplied additional data to Palmetto, and when the policy went positive, maybe August or September, Palmetto reversed itself and is covering the test. The other thing Palmetto has been clear is, they're not saying: "Okay, the data submission is this, and then we're gonna pretend, you know, anything after that date, we don't know about it." Palmetto has been clear that we want to make a decision with the entirety of the information base. And in fact, we know they want that even on LCDs they're not reviewing. So, you referenced the SEER data and the Dhillon paper. We've supplied that to Palmetto. They're not reviewing our melanoma test, but we've sent that to them and shared it with them and actually met with them about it. You know, you call Palmetto, you say, "We'd like to send you this new data. It's relevant to an LCD you have in place." "Yeah, we want to see that." So we present it to them, and they ask questions and are engaged, and okay, that's... You know, doesn't change anything, but that's supportive. So we have supplied that adjuvant radiation therapy data to Palmetto. They did not have that when they did the initial review. So I can say that they have a practice and history of using a reliable evidentiary review process to come up with what they want, what they see as the right answer. My opinion is Novitas had the answer, and they backed into it. In fact, the Novitas LCD is. There are so many flaws in it, but one of the flaws I can highlight is Novitas said, "Well, on Castle's test, we can't find publications confirming analytical validity." Well, analytical validity is such an early step. I mean, that's way back in the signature optimization process. What it says is, does your test really do what you say it does? If you see these overexpression of these genes and the relationship of each other, does that really mean there's higher risk? That's analytical validity, and you don't typically publish on that. You know, it turns out New England Journal doesn't really care about that. That's not something they're interested in. So, Novitas said, "We can't find publications, so we don't, we can't be sure they have analytical validity." But the other part of the Novitas policy is, if you're recommended by NCCN or if you're in the MSK database of mutational listing and one other, well, then we can confirm analytical validity. Well, that's factually 100% inaccurate. Those groups, NCCN and MSK and the other, the third, I'll remember when I quit trying, they don't examine analytical validity. So the Novitas policy says, "Because you're recommended by these, well, we know you've got analytical validity." Conversely, our tests are regulated by CAP and CLIA, who do confirm analytical validity. So the Novitas policy is 180 degrees wrong on that, on that issue on both sides, and it's one of those things where, you know, they, they wrote it. And I mean, man, if you understand diagnostics, you read that, you're kind of, "Oof, ah, that's embarrassing." You know, that's one of those things, man, I mean, we should take that back, you know? And so, I don't believe Novitas is making a legitimate evidentiary review, in my opinion. I think they have a legitimate problem, and that is that the cost of testing services has gone way up. I think their approach to resolving that is the wrong approach. So, without predicting either one, I do have a lot of confidence in Palmetto's process. I think all of us can be... You know, you can be comfortable that they when they come with an answer or a position, that is a well-considered, thoughtful, justifiable position on coverage. Now, if they say no, what does it mean? Well, we'll very carefully look at the reasons, and we'll if possible, and I believe it will be possible, we'll develop evidence to answer their concerns that weren't answered, and that's what you do. You know, if they say this shouldn't be covered because of, I don't know, the whatever analysis they think isn't met, well, then you develop evidence to do it. So, and then the last point there is the timelines are uncertain on both. The Novitas draft went up in July, the Palmetto draft went up in June, and the only requirement, timeline-wise, is if an LCD is not finalized within a year of the draft, it expires. So that's the only backstop, is that sometime within that year, they have to act. Mm-hmm. And then maybe jumping to TissueCypher here, another good growth driver for you guys. Can you walk us through the dynamics that have made that test so successful from an adoption standpoint? I mean, why has that test resonated with GI docs so well? How does it fit into their existing clinical workflow? Sure. So when we first started looking at TissueCypher, we kept seeing these things about it, and we kept thinking: Man, this, this feels like melanoma five years ago. This feels like our melanoma test five years ago. How is that? Well... You got a large number, and it's not a cancer test, it's a Barrett's esophagus test, which is a precursor to cancer. But you've got a large number of Barrett's esophagus patients who are non-dysplastic or low-grade dysplasia. That's the majority. It's 90%, I don't know, 90%. 90% of the patients, 80%, 90% are in that, that low risk by pathology. So how do you find that? Well, the doc is doing a surveillance endoscopy, so he's got the scope down there, that's got the camera on it. He's looking around, he sees Barrett's tissue, which is abnormal tissue, which is caused by... The precursor to Barrett's is GERD or reflux disease. So what's happening is the patient is having stomach acid coming up in the esophagus, and it's damaging the tissue. And if it happens all the time, it begins to create permanent damage. So that's Barrett's esophagus. So the doctor goes down there, he sees Barrett's tissue, and he's got a pinch biopsy on the scope, and it's all. It's like a colonoscopy. You know, they got the light, the camera, the irrigant, and the pincher. They got everything right there. Well, the same thing on an endoscope. And so they take a pinch biopsy, they send that to the pathologist, and the pathologist grades it non-dysplastic, low-grade, indeterminate is one thing they'll sometimes do, and then high-grade. If it's high-grade dysplasia, no need to test, the doctor's gonna get that patient ablated because Barrett's is like... The, The, you know, analogy I use is cervical cancer. You know, 25 years ago, 30 years ago, 52,000 women a year in the US died of cervical cancer. This year, it will be about 2,500, and the majority of those 2,500 are patients that just didn't have healthcare. They didn't have access. Why is that? Well, if a woman has dysplasia, the doctor can do a procedure, it's called colposcopy, remove the dysplastic tissue. There's no tissue to progress to cervical cancer, you never get there, so you never have the death. Barrett's is the same way. If the doctor ablates the tissue, you remove that damaged tissue, there's no tissue to progress to into, to esophageal cancer. So if it's a high-grade dysplasia, the doctor will immediately ablate, remove that tissue, and that works. It works the vast majority of the time. You prevent the progression to, to cancer. But what doctors worry about is this lower non-dysplastic or low-grade dysplasia, because, because of the numbers, that's where most of the cancers are coming from, 'cause the high grade, they're ablating them, so they're not progressing. So it's this group they're worried about. And what they don't know is, do I see them every year? Do I scope them next year? Do I scope them in three years? Do I say, "Hey, you're non-dysplastic, just call me if it gets worse?" You know, what, how do I-- what do I do with that? And so they-- we didn't appreciate this, but they call it a Barrett's conundrum. You know, what do I do with this patient? And so what our test does is it says, regardless of dysplastic characterization, except high grade, because we're not testing high grade, it gives the doctor a biologic risk of the patient progressing rather than just a pathological risk. And so why are we having great uptake? Well, when we were doing our diligence on that test, we thought there were 280 or 300 thousand surveillance endoscopies a year. Well, we now know that it's at least 420, so the pool is bigger. The pool of patients is bigger than we can help. When we were doing our diligence, we did probably 20 physician interviews and maybe 200 surveys. And, you know, you're always nervous about what you get. Am I just getting a doc that likes to fill out the survey 'cause he gets an honorarium for it, or am I just getting somebody who likes to talk? You know, you worry, am I getting a real sample? Well, what we found is that the sample we got in our diligence very representative of the physician receptivity. So you've got a large number of patients. Doctors are reluctant to overtreat. They don't want to scope patients all the time if they don't need to. But you also have a very well-validated therapeutic. When we were launching our melanoma test, I mean, the criticism we got is, "Okay, guys, high risk melanoma patient, what are you gonna do? You're just gonna watch them. But if they do start to metastasize, there's no therapeutic." So what's, you know, the benefit? Well, you know, the benefit is you maybe get them in a clinical trial or something like that. Well, now there's well-validated therapeutic intervention. So if you get a high-risk melanoma patient, you image them every month, they start metastasizing, we got a very well-validated therapeutic to treat the metastasis and treat the cancer. In Barrett's, if it is a high-risk patient, you ablate, and that's overwhelmingly vast majority of the time, effective in preventing esophageal cancer. And esophageal cancer is, it has an 80% five-year mortality rate. If you're in the lucky 20%, one of the things they'll do is they'll remove part of your esophagus, and depending on how much they remove, you might be limited to 45 degrees of recline for the rest of your life. So for the rest of your life, this is how you sleep. You got to be at 45 degrees, 'cause if you recline on your back, your esophagus can... and the acid comes up and you're causing damage. And so, it's a bad cancer. You just and like cervical, it's one that nobody should get, 'cause we should be able to catch it, we should be able to prevent it. So one of the things that helps us there is that ablation is well-studied, doctors know it works, and payers know it works. Payers pay for ablation. And what we're seeing anecdotally, and hopefully, at some point, we'll have some kind of good hard data, what we're finding is that if a patient is low-grade dysplasia or non-dysplastic, but high risk by TissueCypher, payers will pay for ablation. So there's a big group. Physicians have a question they need answers for, and if they get that answer, that there's high risk, physicians know what to do. I've got a well-validated treatment I can send that patient to, that's gonna be paid for, and it's gonna be effective. So I think that's why we're getting such good uptake. And what, what is fun from a financial modeling perspective, if we were to get TissueCypher to the penetration level we have in melanoma today. So forget 60%. Don't forget it, but we won't talk about it. So if we get to 25%, that's a $250 million product just TissueCypher by itself. That's, that's bigger than— So, so we guided, two hundred million or better this year for the whole company. So TissueCypher could be 25% bigger than the whole co right now if we get it to 25% penetration. And the hurdles to get there: one, we are under, under, personed. I can't say undermanned, right? Under-personed, at the, at the field rep level. We have about 24 territories. There are probably 12,000 eligible or suitable users of our test that, to be targeted. 24 is not enough. But we are mindful of our, our burn profile. We've committed by 2025 to be operating cash flow positive. Could get there sooner based on coverage, but we're committed to making that guide, and so we're not gonna overstaff or I would say, appropriately staff too quickly and take on that burn. So we're gonna kinda grow that force over time. And what we've said is that we would expect in the first half to add at least a region, which would be another 8 or 10, to that group, because the hurdle to getting there is just education. There's no... There's not a resistance from a doctor saying... Now we have one competitor for that test. It's a small private company. So, you know, at some point, they'll be more impactful than they are today. So that's a potential headwind, but there's no alternative treatment or there's no, you know, the doctor doesn't have a another option than testing for a Barrett's patient. They've only got the old way, which is look at the pathology, non-dysplastic. "Okay, I think that's good. Statistically, it's good, but that's where my cancers are coming from, so, you know, what do I do?" So the hurdles to get to that 25%, I think it's just educating physicians, letting them know about the clinical utility. How does this change your practice? And what you're doing is you're taking patients that you need to see more often, and you're moving them here. You're taking patients you don't need to see, and you're moving them here. So you're getting the right care to the right patients, and it's better outcomes. And so, I don't know why—I don't see a reason why we can't get that testing category to 25% as well or honestly to 60% like thyroid. Mm-hmm. So maybe let's finish up with a couple financial questions here. 2025 targets. Initially, you had SCC revenue built in. You've pulled that from the guide, and you've also reiterated your targets that do not now include the squamous cell test and revenue from that test. So you've talked about TissueCypher, probably tracking better than your initial expectations, but, yeah, can you just walk us through your confidence in reiterating those targets? Sure. So we gave a range of revenue for 2025, and the rationale for the range was the low end assumed that our newer products, so everything other than melanoma, just did okay. And the high end assumed that the newer products, everything but melanoma, did pretty well. And that was 15 months ago, 16 months ago. In the interim, yes, we have a question about squamous cell reimbursement, but the other tests are well ahead of where we expected them to be when we issued that guidance. And so the reason we're confident in that is that even if we lose squamous cell all of 2025, which again, we're assuming that, we're modeling it, and we're encouraging people to model it. To me, that's such a hard thing to get my head around, how with the evidence we have could you not? But okay, let's say we don't. We don't have coverage all the way to 25. The other tests are doing sufficiently well that we'll still be in that zip code, in that range of revenue. So, we would... There are... We haven't talked about IDgenetix, our pharmacogenomic test for mental health. We have 20 territories there. We, you know, our competitor, we do have a competitor, an established competitor to that test in Myriad. Myriad has 180 people dedicated to their GeneSight test, which is the competitor. They're not all field reps, but there are 180 people dedicated. We got 26, you know, 20, 28, including, well, 26, including 20 in the field. So we definitely are under-penetrated there, but again, we're committed to hitting that guidance, and so for us to go hire 180 people and target them against IDgenetix, yeah, we'd grow it a lot faster and that'd be great, but between here and there, it would increase our burn, and we wouldn't be able to meet the targets that we've given. So we're being very cautious in our growth of our marketing effort. We've scaled back a lot of R&D. I mean, frankly, the SEER data and the Dhillon paper, you know, there were a couple studies we were working on that we don't need as much, that the data is provided there. So we've been able to kind of pull some levers back on R&D, and also we've grown sales and marketing more slowly than we might. And so as a result, revenue in 2025 will be lower than it might otherwise have been, but we'll be... You know, we can hit that operating cash flow level that we've guided to. That's helpful, and maybe one more here to end on. If we were thinking about maybe some of the upside to 2025 targets compared to what was initially built in, at least. When I'm thinking about when you guys first gave targets, did you assume NCCN guidelines for melanoma? Did you assume the ADLT rate for squamous cell that you now have? And I know that coverage for SCC- Yeah ... potentially roll off, who knows? But if it were to stay in place, obviously, if ADLT pricing was not baked in initially, that would be- Yeah ... upside. So for, when we gave that guidance, we did not assume ADLT pricing on squamous cell. We, you know, you can read the criteria. So we knew it qualified by the criteria, but there's no, there's no publication date for ADLT, you know, for CMS. There's no, there's no requirement for timeline. There's no... So we just didn't assume that, that, that we would have that. And the other question was? NCCN. NCCN. Mm-hmm. We have not assumed NCCN in any of our analysis for melanoma. Again, I think that it should be recommended. It's. We've got two studies that show that it's better, the patients do better, but that's a very difficult group to predict, and so if it happens, it'll be upside. Perfect. We can end it there. Good. Thanks, Frank. Appreciate you joining us. Thank you.