It's Paul Knight here from KeyBanc Life Science Research, and the CEO of Castle Biosciences, Derek Maetzold. Derek, you know, I think I started following molecular diagnostics somewhere around 2001, and you know, we've had our cycles since then. Where do you think we are now today in diagnostics? Is it obviously the IPO market's been shut off, but firms like Castle are now starting to rate cash? Where do you think the industry is in terms of reimbursement, profitability, and potential? I think from a—let me write those things down real quick here—potential. I think from a reimbursement perspective, what we've seen is, I mean, it was a good commentary there, cycles, right? Thankfully, I think there's more clarity, I guess, maybe a little less uncertainty on timing of reimbursement from CMS for new diagnostic tests, but at least there's a clarified pathway there through the MolDX program as one example. I think on the commercial reimbursement side, many of us had expectations of having the state biomarker laws actually be followed, I guess, or to have the local state insurance plans actually follow the intent of the law, and that doesn't seem to be—that did not happen the last couple of years. We have seen those some nice bright light pathways in 2024 and earlier this year. Hopefully in three or four years, we see more consistency of commercial plans on a state level where biomarker laws are in place actually following the intent and spirit of those regulations so that patients who will benefit from biomarker information regarding their treatment options actually get access to those testing services. I think that's a positive looking forward. From a profitability standpoint, you're right, I think there is still a balance between investing in R&D to developing your first or second molecular diagnostic test, creating appropriate adoption, getting reimbursement—that sucks a lot of cash investment out. As you mentioned, there's only a few of us who are in a position now where we've gotten to be sized, I guess, in a relative basis to be able to be functioning as a cash-generating organization, which lets you, of course, go ahead and put more dollars back into either growing the business on the top line or else moving it through from a new product standpoint. That feels pretty good overall. What do you see in the development pipeline? Are products going to have to be more mature before a Castle would acquire it? Is there any dynamics about early-stage companies in the industry that you see, or are there just not as many? From a Castle perspective, we have followed for the last several years kind of philosophy of sort of three buckets of using of our capital use. One of them is clearly pushing investment into our commercial structure to go ahead and drive adoption reimbursement of available tests today. The other one is supporting internal pipeline, which, as you noted, may require more time to go from a concept to a test and from a test to being reimbursed compared to acquiring tests that have either been fully validated and developed, maybe are commercially available, maybe have reimbursement already taken care of through Medicare or some other payer process. Certainly at Castle here in the last several years, we've done all three of those things, right? We've expanded our commercial footprint to go ahead and try and meet the needs of a marketplace for our currently marketed tests. We've acquired a couple of companies, most notably, of course, was our TissueCypher acquisition with Cernostics, which was a test that had been well validated clinically. Performance was consistent across multiple studies, was reviewed, and has coverage through Novitas on a claim-by-claim basis. Of course, such a great demand opportunity there. We had talked more recently about our most advanced internal pipeline test, which is a test what we hope will meet our product profile goal of being able to help dermatologists figure out which systemic atopic dermatitis patients their drug, their patient will respond best to, and also which they probably won't respond well to. That's a mixture of sort of capital investment, our commercial structure, pipeline, and acquisitions. I think we would see ourselves going forward on all three of those buckets. You know, we'll eventually have to talk about SCC, but I'd prefer to go in reverse because it's more interesting and timely, right? TissueCypher has been getting a ton of traction. Can you talk to TissueCypher? Sure. That's a marketplace where we believe there's over 400,000 patients who are undergoing an endoscopy, an upper GI endoscopy each year with a diagnosis of Barrett's esophagus disease. The majority of those patients, the vast majority, 90% plus, will be diagnosed with what's called non-dysplastic Barrett's esophagus disease, which is certainly Barrett's esophagus, but no dysplasia being seen by pathology. The standard of care for those patients has been to sort of, I'll see you back every three or every five years to re-scope you and hope that your disease doesn't progress to cancer or to high-grade dysplasia in that time period. It's a watchful waiting approach, which is appropriate on a population basis. If you get patients who are diagnosed with low-grade dysplasia or high-grade dysplasia today in the US, those patients are recommended or referred to undergo an intervention. Most typically, it's called radiofrequency ablation, which is essentially trying to wipe out that Barrett's lesion. Sometimes that's used alone. Sometimes it's used in combination with a surgical procedure, but the goal is to get rid of that lesion because the chance over five years of progressing to cancer outweighs the risk of doing nothing. What that means practically, of course, is that because we sort of treat and try and kill off the likelihood of those patients progressing to esophageal cancer, the majority of patients who progress to esophageal cancer are those non-dysplastic patients that we watch and wait. Where TissueCypher really stepped into a high unmet clinical need was to say, "Hey, we can use spatial omics by looking at biomarkers and where they're located on that Barrett's esophagus pinch biopsy and tell you if this particular patient's non-dysplastic Barrett's disease is highly likely to progress at a rate that's similar to or higher than low-grade or high-grade dysplasia, in which case we would say just because this patient biologically has been shown to progress rather than pathologically, why wouldn't you treat them the exact same way?" I think most gastroenterologists around the US, when we get to them and present the benefit of our test here, say, "Well, of course, I'm treating patients with ablation or other interventions to stop progression." That's based upon my expectation of how many would progress over the course of five years. If your test can be that similar or better, why not use it? I think we walked into a very, very important opportunity to help people avoid progressing to esophageal cancer. Today we have no good tools to find those people in that non-dysplastic bucket. That is a really, really fantastic outcome. I think what you've seen in the meantime is that when you appropriately educate doctors, you're seeing quite nice adoption across the space. DecisionDx- Melanoma is your largest test, rapid growth in 2024. What's your outlook there, Derek? I think that if we look at sort of where does it get to, maybe that kind of question, we sort of benchmark other molecular diagnostic tests that have sort of a similar use. They're able to kind of remove a procedure, in our case, that's removing a sentinel lymph node biopsy surgical procedure. Does that marry the same kind of clinical use as, for instance, the thyroid test where you're removing a potential thyroidectomy procedure, right? If we think that that's a comparable market, then I would say we believe we exited 2024 at around, what, 28%, 29%, 30% market penetration. Getting up to the 55%-60%-65% should not be a huge stress. I think more of the question is timing, you know, how fast do we go ahead and double volume overall in the next several years? There's going to be another decade before we get there. I think ongoing evidence development, we have seen last year a number of plans on a commercial basis move from non-coverage to coverage based upon the fact that when you use our test, people live longer. I think that ongoing march of evidence will help go ahead and drive that penetration forward. I guess, you know, touching on now SCC, I guess your options are what? You've submitted more published work that may get reviewed. Is that kind of the possibility on SCC? Yeah, I think there's—we had eight publications in 2024. Half of them were sort of tied to the ability of our test to predict responsiveness to adjuvant radiation therapy. That was—we had, of those four papers, two of them were separate multicenter trials, which showed that when you compare to matched control patients, the use of our test identifies patients who receive no benefit from adjuvant radiation therapy, which is a majority of patients who'd be eligible. We find a small proportion of patients who get a tremendous, nearly a 50% reduction in the likelihood of progression compared to those patients who don't receive ART. Great clinical utility on directing radiation therapy. Those weren't available for either one of the LCDs when those were reviewed in 2023. Those are important publications. We also published last year a fairly basic direct cost analysis model to the Medicare population showing if you actually take the number of people who underwent radiation therapy of the Medicare age bracket over the course of a single year, and if you had applied our test to help rule in or rule out radiation therapy, you just took the cost of radiation therapy, which we estimated based upon reimbursed rates of around $60,000 for a full course of therapy, and you deducted the cost of our test being paid for by Medicare, the overall savings to Medicare, I think it was up to $970 million in savings in the course of a year. That really shows you the value of being able to rule out an intervention which is used in this disease state. If you do so, has tremendous opportunities not only to avoid complications from patients undergoing ART who do not benefit, but also removing overall cost dollars. I think that data going in, we would hope would be enough evidence to say, "Hey, the use of our test tremendously allows people to rule out ART," and the few that need it, you really can push them hard towards that. The overall cost savings to the system is just fantastic. In effect, that's a clinical utility test? Yeah. That would be the—sorry. Oh, yeah, yeah, yes. That would be the primary clinical use. Now, it turns out, if you look at, say, NCCN guidelines, the majority of patients, I want to say upper 90s, might even be 99% of the people who we test actually meet NCCN high-risk or very high-risk SCC disease. It also happens that under NCCN guidelines, you would be eligible for radiation therapy under either one of those two categories. If that ends up being the final intended use group or coverage group, that sounds like it's basically covering the people who are testing today, which I think is appropriate from a medical care standpoint. Okay. Would you view that as kind of your best study on cost analysis done yet to date? Yes, on the ART approach, yes. You know, let's say SCC continues, well, eventually is not reimbursed. Were your commercial sales force, what do they get reallocated to, or is melanoma growing fast enough that you just wouldn't hire because of melanoma growth? Yeah. So we are sitting, I think, at the end of 2024, maybe mid-70s in terms of sales territories across the US, single layer. We think there are 10,000 plus medical dermatologists, but you have another few thousand dermatology clinicians who are nurse practitioners or physician's assistants that are also in that same group that are doing medical dermatology. So maybe call it 13, 14, 15,000 might be the right number. Being sized in the mid-70s to cover that universe of clinicians is about the right size, whether or not you have one product or one test in our case that you're offering educationally or two tests. I don't see any kind of a reduction that would be thoughtfully thought out. Plus, as you point out earlier, Paul, this is our single largest revenue base of the company. To have us make some kind of a change short-term-wise does not seem to be in the best interest of patient care, doctor care, or Castle's employees. Okay. When is the expiration date on reimbursement for SCC right now, Derek? There was an extension provided in January that has the sort of effective date of the Novitas LCD being April 24 of this year. Why do you think it was—why was it extended, do you think? There was a press release issued by another laboratory, which seemed to suggest that the extension was provided by the incoming administration, so they would have time to go ahead and review the LCD. I don't know the weight of that or not, but at least that was what was out there already. That's my assumption there. Obviously, we've had a lot of changes going on in Washington, including layoffs. Do you think clinical utilization rates will go up under this scenario of rising unemployment? Clinical utilization rates of our test specifically? Will people do more physician visits, diagnostics, testings while they're still on a health plan? Oh, I think as it relates to Castle's test specifically, no. Yeah. You're more Medicare age. Yeah. Yeah. I mean, one could argue maybe, well, for other cutaneous squamous cell carcinoma or melanoma, those are usually a mixture between patient-driven, like that mole in the back of my neck's bleeding, or they're clinician-driven, where maybe you might see a few more dermatology visits being snuck into, but I don't think we would be able to discern that, Paul. I think where maybe it'd be more likely, maybe you might see an uptake would be to say, "Do you have employees in the federal government or other locations that would say, 'I've had this ongoing GERD. I'm taking Pepcid over the counter. I chomp that for three or four a day. I still have this thing. I might go in then.'" Maybe that's a scenario, but I don't think it's going to be a heavy driver to be able to see them yearly. Okay. Has PAMA worked as well as we'd hope? I think our core tests are all advanced diagnostic laboratory tests. Yap We thought that was important, one that you could call it a good housekeeping seal of approval to say, "Hey, we made a decision to take our investor dollars and develop and build or acquire innovative first-in-class tests by and large." That is kind of a badge of honor to the employee base and even to our clinicians to say, "Hey, we hadn't liked it before. We have something now." On the other hand, that also means that we get priced annually. There is a lagging price structure, but that means that we have to collect the median private payer rate, so what the commercial payers pay us on average from a fully allowable amount, and we get priced that with our Medicare rate. For us, PAMA has worked in terms of saying, "Hey, I don't think there's a problem by having Medicare reimburse the cost of a test for Castle at the same rate that's being reimbursed by commercial insurance." I think from our standpoint, PAMA has done a wonderful job of saying, "Let the commercial marketplace set the rate for Medicare as opposed to having different negotiations that might disadvantage Medicare or vice versa." I think PAMA for the other thousands of tests out there that are not advanced diagnostic tests has been delayed, as you know. I don't know at the end of the day if that means Medicare is overpaying as a whole for those testing services or if they're underpaying relative to commercial markets. I know from our perspective, it feels good to be transparent with the marketplace saying, "All we would ask you to do from a Medicare standpoint is to reimburse us the average weighted price that we get paid on a private basis." That seems to be a very transparent give and take. Another question we've had regarding the new administration is new leadership at CMS. Do you sense that there could be any change in terms of CMS view on reimbursement or approval in the early days of the RFK HHS leadership? One that's probably above my pay grade in general, Paul. I would say I don't know how one could affect the reimbursement. I think PAMA adjustments would require a change through Congress. That's pretty well established. Maybe they would go ahead and push PAMA compliance as opposed to delays. Maybe that's an impact on the reimbursement side. I think on the approval side, assuming Oz is confirmed, there certainly is interest in personalized medicine from his perspective. You would think that might have an elevated approach in CMS, at least under the value of biomarkers. Maybe that has a benefit for the industry overall, but that's a possible upside there potentially. Yeah, that's the question I think we're disseminating is maybe somebody knows RFK's history more than we do, is the interest that he may have in personalized medicine. I guess that's it. Yeah. Regarding other products, MyPath, where are we with that, Derek? We are on the Uveal Melanoma Test, just for the audience here, that's our last of our sort of early chapter one test at Castle Biosciences. It serves a small marketplace of rare cancer. We think we're testing 80-85% of all patients diagnosed each year. That's fairly fully penetrated. I think our goal there is to make sure that we're serving patients well. There are obviously 15-20% of patients who aren't accessing our tests on a routine basis. We have some small upside there. On our MyPath Melanoma test, we are beginning to look at investing in that test on a broader basis going forward. That's a small contributor today, but it's important for us because I think to our overall customer base, it says, "Hey, we care about melanoma. We want to make sure we can assist you in getting the diagnosis correct, which is what MyPath does. And then when it comes to saying, "Okay, this is melanoma and it's invasive," our DecisionDx Melanoma can fit right into that same customer group and say, "Now, we can provide you with additional information you can get nowhere else that lets you understand, does this patient need to undergo the surgical sentinel lymph node biopsy procedure, or can we kind of have a conversation and defer that? And then how do I treat the management afterwards?" I think that's a nice one-two punch there. ID genetix, sorry. Yeah, we had pivoted last fall or late last year, I guess, to looking at the value of having us largely promote that from our inside sales support as opposed to on the feet, ground support. That was an attempt to really see if we can get this into a profit line of business. Kind of stay tuned on that after the first quarter here to see how that's going. You know, I've seen companies in the molecular diagnostics industry use the inside salesforce approach. In what situations does that seem to really work well, Derek? That's a good question. I can't comment on other people's experience sets there. Certainly, when we have seen vacant territories and switched over some support, we see good support of those vacant territories. I think with the IDgenetix team, we have customers who like the assay. And the assay, of course, as you may recall, it provides really a three-in-one kind of report. It lets clinicians get not only drug gene data, but gene-gene data as well as lifestyle factor data so that a physician who's seeing a patient with depression or anxiety, one of the other covered mental health services, doesn't have to go back at night and figure out how do these things all fit together. We try and do that for them. That has great value. I think when you look at our current customers, being able to support those through inside sales is probably an appropriate approach to think about. Good. Any sense on the commercial payer environment? Is it as same as historical and usual in the market today? For which? Just in general? In general, I mean, it seems to have been always difficult in most of our career watching or dealing with commercial pay. Do you think there's any hope that it could get quicker? I think that clearly building evidence makes a difference. It takes a while to get there. As I mentioned earlier, we were seeing some plans last year take a hard look at the NCI's SEER data, which shows, of course, that in patients who were tested clinically with their melanoma test compared to a matched group using NIH's approach of three-to-one matching, they lived longer than patients who were not clinically tested. I think that kind of data shows this is an outcome improvement. Clinicians order our test because they use the results to inform how they want to follow that patient or care for that patient. If you get tested, all the things being matched equally, including socioeconomic factors, people live longer if you actually have received this information on top of what you already have. That kind of movement is always needed, I guess, in the diagnostics industry. We are seeing some movement in some of the state biomarker laws. As you may know, I think over half the population is now covered under biomarker law. I do not believe the spirit or intent of the legislation was actively followed by many commercial carriers. We are seeing movement on some states going back and trying to recorrect that behavior. Hopefully, at the end of the day, the states that passed legislation to say having biomarkers inform better patient care is something we care about will actually happen. I do not think that happens overnight, but I think we are seeing the march in the right direction, which is hopeful for all patient care and for companies too. Yeah. Routine doctor visits seem to take forever to get scheduled now. It kind of signals to me or asks the question, how are they keeping up with the many new data points and diagnostics? Our clinicians specifically, I think that's where the mixture of both personal, non-personal education and communication efforts takes place, right? I think nothing really substitutes for being in person and having a well-trained commercial group and having a well-trained medical science liaison groups who can actually add value to that clinician's base of knowledge, which will have them either say, "I see where I can get better value out of your test more often," or have them say, "Actually, I'm getting the right value out of your test. Thank you very much." Mixing that in with non-personal promotion activities is a way to kind of move business forward from an educational standpoint. You're right, with the advent of new tests, of new therapies, of more patients coming in and less reimbursement from a clinician standpoint, there's a balance of saying, how do they keep up? I think we play an important role in keeping up. Yeah. Yeah. Derek, any closing comments on what you're thinking about with Castle's 2025? Yeah. We closed out last year, I think, very, very strong ahead of our revenue guidance. We generated cash last year. We were operating cash flow positive for the course of 2024, which all hit our milestones for 2025, by the way, already. That is quite positive. I think, as you noted, we have good growth under our current belt from 2025 expectations. We have this overhang potentially of this April 24th pumpkin date for this coverage decision with DecisionDx-SCC. Otherwise, we believe that we have the resources in place, the people in place to go ahead and have another productive 2025. Congratulations on many years of running a successful molecular diagnostics firm, Derek. Thank you. Thank you. Yeah. Good to see you, Paul.