Good morning. My name is Rob. I will be your conference operator today. At this time, I'd like to welcome everyone to the Exact Sciences fourth quarter 2022 earnings conference call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question-and-answer session. If you would like to ask a question during this time, simply press star followed by the number one one on your telephone keypad. If you would like to withdraw your question, again, press the star one. Thank you. Megan Jones, Senior Director, Investor Relations, you may begin your conference. Thanks, Rob. Thank you for joining us for Exact Sciences fourth quarter 2022 conference call. On the call today are Kevin Conroy, the company's Chairman and CEO, and Jeff Elliott, our Chief Financial Officer and Chief Operating Officer. Everett Cunningham, our Chief Commercial Officer, will also be available for questions. Exact Sciences issued a news release earlier this afternoon detailing our fourth quarter financial results. This news release and today's presentation are available on our website at exactsciences.com. During today's call, we will make forward-looking statements based on current expectations. Our actual results may have material differences from such statements. Discussions of non-GAAP figures and reconciliations to GAAP figures are available in our earnings press release, and descriptions of the risks and uncertainties associated with Exact Sciences are included in our SEC filings. Both can be accessed through our website. I'll now turn the call over to Kevin. The strength of our foundation supporting the best brands in cancer diagnostics puts us in a leading position to continue delivering innovative cancer tests, consistent revenue growth, and profitability. We are using this platform to help prevent cancer, detect it earlier, and guide treatment for more patients globally. Achievements in 2022 that helped strengthen our leadership include surpassing 12 million cumulative people tested for cancer, including 10 million with Cologuard, expanding our global network of ordering healthcare professionals to more than 350,000, growing core revenue $380 million year-over-year, becoming adjusted EBITDA profitable in the fourth quarter, completing enrollment of BLUE-C, our pivotal study to support our next generation Cologuard and colon cancer blood test, and generating evidence for our multi-cancer early detection and molecular residual disease tests. Over the past decade, we've built a high-quality platform to deliver advanced cancer tests at scale. We've invested heavily in our people, lab infrastructure, technology systems, clinical evidence, plans, and customer experience. This platform is fueling efficient growth for our current tests, and over time, it will fuel the next wave of novel cancer diagnostics. Our health system customers employ most U.S. healthcare professionals and seek to improve the quality of care while reducing costs. They are incentivized to focus on preventive care, including cancer screenings. Today, many face a staff shortage, leading to a trend of more in-home services such as Cologuard. Advanced cancer testing. In advanced cancer testing, health systems continue to ask for fewer partners to meet their needs. A complete range of high-quality, impactful tests, broad insurance coverage, EMR integration, and data-sharing capabilities. Exact Sciences is uniquely positioned to deliver on these needs because we have the broadest offering of innovative cancer tests, patient-focused services, EMR integration capabilities, and payer relationships. This year, we'll increase adoption of Cologuard and Oncotype DX, create an even better customer experience, and advance our key pipeline programs in colorectal cancer, multi-cancer early detection, and molecular residual disease. Jeff will now discuss our financial results and outlook for 2023. Thanks, Kevin. Good afternoon. Fourth quarter revenue of $553 million grew 17%, or 28% excluding COVID testing. Screening revenue of $404 million increased 45%, including three points of growth from professional genetics. For the year, screening revenue increased 30% organically. During the quarter, 10,000 new healthcare professionals ordered Cologuard, bringing the total to more than 302,000 since launch. Precision oncology revenue decreased 4% to $143 million. Excluding the sale of our prostate business and a $2 million FX headwind, growth was 1%. COVID testing revenue decreased 87% to $6 million. Fourth quarter GAAP gross margin was 70%. non-GAAP gross margin, excluding the amortization of acquired tangibles, was 73%. Net loss was $128 million. Adjusted EBITDA was $5 million, an improvement of $120 million, demonstrating the power of the Exact Sciences platform. We ended the year with cash and securities of about $630 million. Our total liquidity is about $840 million, including available credit facilities. In terms of guidance, we expect total revenue between $536 million and $551 million during the first quarter and $2.265 billion and $2.315 billion for the year. This assumes screening revenue between $390 million and $400 million for the first quarter and $1.66 -1.69 billion for the year. Precision oncology revenue between $143 million and $148 million for the first quarter and $60 -620 million for the year. COVID revenue of $3 million for the first quarter and $5 million for the year. For the year, this implies 18% growth for screening, 5% growth for precision oncology, excluding the sale of our prostate business, and 14% overall growth, excluding COVID testing and the prostate sale. We exited last year with broad momentum, which is driving a strong first quarter. This is especially true in our screening business, where we're seeing the benefits of past investments and great execution from our team. We expect to generate up to $25 million of adjusted EBITDA for the year. This assumes non-GAAP gross margin of about 73% for the year. Our industry-leading gross margins are powering positive Adjusted EBITDA and a clear path to free cash flow as we continue investing in growth and efficiencies. We expect total GAAP CapEx to increase mid-single digits for the year. This includes an absolute decrease in sales and marketing, offset by increased G&A and R&D. Last year, G&A was reduced by $57 million, primarily from a non-cash gain related to the Thrive acquisition earn-out. In addition to cycling against that gain this year, we expect $19 million in non-cash expense as we accrue for the earn-out payment. R&D is increasing to support our multi-cancer and MRD programs. We expect CapEx this year to be about $120 million. I'll now turn the call back to Kevin. Thanks, Jeff. Cologuard is becoming the preferred colorectal cancer screening choice. During the fourth quarter, nearly 116,000 healthcare professionals ordered Cologuard, a new record. The rate of people rescreening hit an all-time high. We are starting 2023 with tailwinds, including stronger healthcare professional conviction in Cologuard as their frontline screening test, increased consumer awareness, improved electronic ordering, and an enhanced digital patient experience. Also reached half a million people screened with Cologuard between ages 45 and 49. As of the fourth quarter, we estimate Cologuard grew to 9% penetration of the more than 90 million people ages 50 to 85 in the colon cancer screening market. For the nearly 20 million 45 to 49-year-olds, penetration grew to more than 8% just 18 months after it was included, that age group was included in USPSTF guidelines. Screening people in their mid to late forties will provide recurring revenue for decades as we work to keep them screening every three years until they're 85. Cologuard growth is supported by the most powerful sales and marketing team in cancer diagnostics. We engage with healthcare professionals more than 1 million times each year and have more than doubled the revenue generated per interaction in the past year. We build brand recognition and loyalty by generating more than 15 billion impressions annually. Our commercial team, supported by rigorous analytics, will get even more efficient over time and help decrease sales and marketing costs as a percentage of revenue while supporting growth. Our precision oncology team has guided treatment decisions for more than 1.75 million cancer patients around the world, including a record 220,000 people last year. Oncotype DX will revolutionize breast cancer care. It is internationally recognized as standard of care for patients with early-stage HR-positive, HER2-negative breast cancer, which represents about half of breast cancer cases. We have an opportunity to impact even more lives by making Oncotype DX easily accessible to more women globally, offering OncoExtra, our enhanced therapy selection test with DNA and RNA analysis, and working with our biopharma partners to develop new targeted cancer therapeutics. Thanks to our team, trusted Oncotype DX brand, and deep oncology relationships, we can power better treatment decisions that are specific to each patient's disease. Our advanced R&D expertise and platform spanning screening and precision oncology will help get our pipeline tests to more patients quickly. We made meaningful progress in each of our key pipeline programs last year by completing enrollment of our BLUE-C pivotal trial, which included more than 26,000 people. Presenting two studies, including 4,200 samples, showing the power of our multi-cancer early detection test and initiating and enrolling studies that will answer key questions clinicians and payers have when evaluating our molecular residual disease test. We are completing the final steps of our BLUE-C trial and expect to have top-line next-generation Cologuard data mid-2023 before submitting to the FDA for approval. We expect to have two additional sets of multi-cancer early detection data this year, further validating our multi-marker class approach before we move to a larger prospective trial. We also plan to validate and make our tumor-informed molecular residual disease test available to colon cancer patients later this year. Our mission is to make earlier detection a routine part of medical care to help eradicate cancer. Our platform, deeply embedded standard of care tests, and pipeline of life-changing diagnostics will power years of growth and continued profitability, helping us to achieve our mission. Thank you. We're happy to open the line for questions. At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad. We ask that you limit yourself to 1 question only with no follow-up questions. Your first question comes from a line of Derik De Bruin from Bank of America. Your line is open. Derik De Bruin, your line is open. Hi, it's Derik. Sorry about that. I had the mute on. A couple of questions. I think the first one is, what were the key market changes that drove some of the increased momentum in Q4? You know, the guide was better than expected, particularly for Cologuard and for 2023. That's one. Just I've gotten a bunch of questions from investors lately about the competitive landscape outside of liquid biopsy. There's a couple of companies that are advancing some of their stool-based colon cancer screening test and also just sort of the landscape for Oncotype as it sort of goes OUS. There's a little bit more competitive opportunities out there. Can you just sort of talk through them, those couple of questions? Thanks. I'll shut up. Well, let's first address the momentum that we saw throughout the fourth quarter and the start of the year. A lot of this is just the result of the investments that we have made over time, the strong need for non-invasive screening, colon cancer screening tools. You have some structural tailwinds, including the ease of electronic ordering that has taken, you know, a significant amount of effort, time, engagement with large health systems to deliver electronic ordering through our Epic and EMR capabilities. Increased brand awareness around Cologuard. Health systems are highly incented to drive their colon cancer screening scores, and they're frequently now reaching out to us to ask for a partner who can help them improve their quality measures, care gaps, et cetera. We're seeing GIs have a staff shortage, there's a greater focus in the endoscopy suite on diagnostic colonoscopies. GIs are ordering Cologuard at a higher rate as primary care physicians are, certainly. Our sales and marketing team, I just can't tell you how proud we are of the work that they have done and continue to do. Be it their efficiency, their engagement is turning the tide and really making Cologuard a first-line screening choice. Also, of course, the 45 to 49 year age group. 18 months ago, the guidelines changed to lower from age 50 to 45, we believe Cologuard is leading in terms of market share today. The penetration is impressive. If you take the fourth quarter, number of tests and extrapolate that, we believe the penetration is about 8%, as I mentioned earlier. Jeff, I don't know if you want to add any color to that. Just to add what Kevin said, electronic ordering is a huge year last year. Recall when we started at the pandemic back in early 2020, 30% of Cologuard orders were electronic. In Q4, that was up to 63%. That has implications not only for Cologuard, to make it easier to get orders, it has implications down the road. As we launch new products, they'll launch right into that foundation. It will grow deeper connections to health systems. In Q4, I think as we talked before, Derik, we picked up a little bit of extra upside from enhancements we made both to our patient compliance engine and our billing systems. Again, these added to the upside, they weren't the sole cause of it. The reason I bring those up is because when we added these enhancements, which will benefit on a run rate basis, we'll get better compliance and better ASPs going forward. When we added those enhancements, we pulled forward a bit of revenue from Q2 to Q3. Consider that catch-up revenue that add a little bit more in Q4. You really can't take Q4 and extrapolate that. Now when I've got half of Q1 in the books now, I think a little bit of that catch-up revenue, again, from the billing enhancements, patient compliance enhancements is going into Q1. It's part of the strength in Q1. Then just everything Kevin said should continue. I know there's questions on competition. Yeah. In terms of competitive dynamics, when you look at Cologuard set a standard of care and a very high bar in colon cancer screening. Cologuard 2.0, or what we call the next-generation Cologuard, will raise that bar. We just haven't seen data indicating any other testing modality that approaches that high level of performance for detecting cancer or detecting precancerous polyps and having a high specificity rate. You have to be careful when you take a look at data, is it apples to apples? What are the underlying drivers? How large is the study, how well powered, et cetera, et cetera. We feel great about the competitive positioning. There's so much more to Cologuard than the test. There's enormous investment, altogether about $1 billion invested in an IT infrastructure, a commercial team, a lab team and capability that is, you know, multi-billion dollar investment to be able to reach the hundreds of thousands of ordering healthcare providers and the tens of millions of patients. Oncotype DX is in a class of its own. It's the only test with the level of evidence that you've seen with TAILORx and RxPONDER. As a result, it has a leading position in the U.S. and globally. These are the two best brands in diagnostics. We will keep investing in them, and they have become, a standard of care without peer in terms of that, Cologuard and its sample type and Oncotype DX. It'd be very difficult to replicate that level of effort. We're proud of these programs and continue to expect big things in the future. Your next question comes from a line of Andrew Brackmann from William Blair. Your line is open. Hi, guys. Good afternoon. Thanks for taking the question. Kevin, maybe one for you and sort of building off some of that stool-based commentary there. Just sort of recognizing 2.0 data is gonna come, I think you said around mid-year. Can you just sort of give us an update on where you expect those data to come in? Anything in particular you'd point to as we put together those scorecards for that data and sort of the longer term benefit to the model? Thanks. We expect Cologuard 2.0 to have improved specificity, so a lower false positive rate. We on a secondary basis, would hope to see some improvement in the advanced adenoma detection rate. The main goal is to lower the false positive rate. We have designed Cologuard with more specific markers. We also expect to see improved cost efficiencies and other aspects of Cologuard testing. That's what we expect. Of course, we won't know until we complete all of the validation testing. We expect that to occur mid-year. Your next question comes from a line of Dan Brennan from Cowen. Your line is open. Great. Thanks for the questions, guys. Maybe, first one just on the rescreening of 45 to 49, and then just one question on the EBITDA guidance for 2023. Jeff, can you just clarify? 8% penetration run rate in 4Q seems like a really big number. We're coming down like 130,000 tests. Is that in the zip code? It's, what, 20 million people in total, and you divide that by three to get the addressable for Cologuard, so that's like 6.6 million on a... Then you got 8% penetration in 4Qs, so we just took a quarter of that and 8% of that. Maybe a little clarity on the math there and how we... You know, kinda how we think about it. I know you guys don't wanna disclose too much on these, but since they are material, it'd be great to understand how you're thinking about the impact for rescreening 45-49 in 2023. The second one would just be on the +$25 million of adjusted EBITDA ex comp in 2023. If you exited Q4 with $5 million, just wondering if that's a conservative number since I would expect you guys would have some nice momentum despite all the investments that you're doing. I would have thought it'd be a high number in 2023. Maybe you could just speak through some of the drivers there. Thank you. Sure. A lot there. Obviously, Kevin talked about 45 and rescreen just being significant growth drivers, and that will continue for a long time. Last year, we had put up guidance for 45 of at least $100 million of revenue. We beat that nicely. For rescreens, we said at least $220 million, and we beat that nicely. Both are, have really good momentum. This year, we expect rescreens to be about 20% of revenue in total, and that should grow from there. Eventually, this becomes half our revenue, and 45 should have a pretty similar trajectory as rescreens. Huge drivers there. In Q4, you know, Kevin talked about the overall penetration rate for 45. Just to be clear on the definition here, we're looking at the pool of patients, which is nearly 20 million people. In that Q4 run rate, call it roughly 125,000 people tested. If you adjust that for the interval and annualize it, we're at about 8% penetration into that younger age group. The reason we highlight that is because Cologuard got there in about 18 months after USPSTF guideline inclusion for that younger age group. You contrast that to the 60 and above age group, that's been, you know, the biggest diagnostic launch in history. We're at 9% there today. The point there is really 45 is growing very, very quickly. The question on adjusted EBITDA, what we're guiding to is flat to $25 million adjusted EBITDA for the year. This really speaks to the power of the platform. You know, you'll recall that we had accelerated the path to profitability. It was gonna be 2024, then mid-2023, and eventually we got there, in end of 2022. For the year now, what we're guiding to is over $150 million of adjusted EBITDA growth. On an incremental adjusted EBITDA margin basis, we're talking over 75% incremental. The guidance is the most likely outcome. I'm proud of what the team has delivered here. You know, I'm very proud of these numbers. It's a significant improvement year-over-year, and it puts us in a position to really continue investing in growth and efficiencies and delivering profitability to investors. Your next question comes from the line of Vijay Kumar from Evercore ISI. Your line is open. Hey, guys. Thanks for taking my question. Jeff, one, and your, I guess I had a two-part question. This 2.0 Cologuard 2.0 results, I know you mentioned increased specificity, and you expect an increase in advanced adenoma sensitivity. Is there any risk as you take up that specificity that the sensitivity for cancer perhaps it, you know, drops? You know, I know given AA sensitivity going up, perhaps that's not the case, but maybe just talk to us, is there any risk here from a sensitivity perspective heading into these results? On adjusted EBITDA, Jeff, how should we think about those leverage levels going forward? The incremental leverage map that you just laid out, should that hold true when we think about 24 and 25? Thank you. Why don't I take the first part, Jeff, and you take the second part? We would expect the cancer sensitivity to be at or above 90%. We would expect somewhere in the neighborhood of 100 cancer samples in the study. As you recall, in the DEEP-C study, we had 65 samples. What have we done to improve the likelihood of success? We've, number one, increased the powering of this study. Number two, we've done a significant amount of work to compare the current version of Cologuard with the next generation version of Cologuard in samples, including samples from the DEEP-C study. We have a head-to-head comparison, which gives us confidence that Cologuard 2.0 performs better than Cologuard 1.0. You can never control all of the risks, because if the fundamental population is changed or, for example, you see a lot more smaller cancers, harder to detect cancers, you don't know that, and you can't control for it. What we have done is, develop the very best test with the best markers, the, most efficient and powerful DNA capture technologies and deployed that into the study. We look forward to opening, the results of the study and sharing them with you. That's our thinking on that. Jeff, maybe you take the second one. This is Jeff. On the leverage question, look, this model was built to scale, to scale efficiently and ultimately deliver positive free cash flow, which we expect to reach in 2024. Can we sustain 75% plus incrementals? I hope so, but that's a, that's a pretty tall order, Vijay. You know, when I think about leverage going forward, the best way to do it is to drive a really strong top line. I know Everett and the team are gonna do that. We've got some nice levers to pull when I walk through the P&L, thinking of gross margin. We're targeting over 80% gross margin for the two key products here, Cologuard and Oncotype. Oncotype is there. I'm confident Cologuard will get there over time. I expect some good gross margin improvement. The G&A, you know, this year I talked about that Thrive earn-out payment. It's driving higher G&A growth on a GAAP basis, but you adjust for that, it's mid-single digit growth. Over time, the G&A leverage will improve. Sales and marketing, you know, the mandate there is really to make sure we're always investing in the smart growth. Everett's done a nice job there. We're seeing a really good leverage within sales and marketing. R&D, the way we'll get leverage there is to focus on the highest impact opportunities. Kevin has talked about those today. Over time, as we get the benefit, Cologuard 2.0, the MRD programs, multi-cancer, as we get the benefit from those programs, that will help drive additional leverage through the P&L. Your next question comes from a line of Catherine Schulte from Baird. Your line is open. Hey, guys. Thanks for the question. Thanks for showing that slide on rep productivity. It's great to see Cologuard revenue per field call continuing to trend upwards. I'm curious, you know, what's that number would've looked like pre-COVID, and if you can talk to where you think that number should go over time. Catherine, this is Jeff. You know, pre-COVID, I think there's a lot of moving pieces there, you know, when you think of the Pfizer relationship. It's a great partnership. It, it just does change the dynamic as well, which is why we focused on the quarters that we displayed on the slide deck. Going forward, where can it go? I can start, but Everett, you know, please chime in then. There's a long ways to grow when you, when you think of that market penetration number, the 9% in that 50-plus age group. Longer term, I'm confident we can get to at least 40%, and I think we've already got a strong team in place, so I expect that productivity to go way up over time. Everett? No. Thanks, Jeff, and thanks, Catherine, for the question. I'm really proud of what the commercial team has done over the past years since we've launched Cologuard, and we continue to evolve the commercial team. There's many things that are contributing to the productivity. I'll just highlight a couple of things. Number one is- The way in which we've evolved our territories, we've cleaned up the overlap in territories, which has driven deeper customer relations. I think that's driving a lot of the acceptance of why now Cologuard is a preferred choice for screening. Number two, we use data and analytics now in terms of who to call on, when to call on, how often we call on those customers. We're just much better now at looking and knowing exactly who to call on for the growth. We review those analytics and who we're calling on a weekly and monthly, very rigorous process in our commercial organization. We just don't do it centrally, but we're now doing it at the market and area level, where that execution is happening. You know, Jeff mentioned, Kevin mentioned in terms of we're gonna always invest for growth. We're really focused on health systems. That's where a lot of our customers and patients are. We've increased our amount of account executives at the health systems level. The conversations now that we're having around the screening is our health systems are now coming to us on how can we partner for those hard-to-screen patients where they need to close the care gaps. We saw a lot of that at the tail end of 2022, that's gonna continue in 2023. I feel bullish that our productivity will continue to improve. Your next question comes from the line of Brandon Caron from Jefferies. Your line is open. Hey, thanks. Good afternoon. Just a two-part question in terms of the guide for the year. Jeff, what's in bed for the stock comp expense? Kevin, conceptually speaking, if the top line is, let's say, running ahead of plan as we move through the year, would it be your preference to reinvest some of those dollars, but still deliver on the profitability target, or would you let that drop down? Thanks. So Brandon, this is Jeff. I think the first one on stock comp. I think we've given you the, you know, kind of all the pieces between when you look at a GAAP, the sales unit growth and OpEx of just unit down. I think you can. Stock comp is probably the biggest piece between there. If you look at last year, what you have, you'll have in the K if you don't already, it's going to grow from there as if you look back at the headcount growth over time. I think that that's enough to give you all the math between the GAAP number and the just unit down number. Second question on reinvestment? In terms of investment, we're still making enormous investments in new product programs. We've touched upon the three big ones: colon cancer, multi-cancer early detection, and the MRD program. We also have some minor programs that we're working on in liver esophageal cancer and endometrial cancer. We're making those investments today. We're making significant investments in our IT infrastructure. Would we selectively reinvest some of those profits? Yes. Are we biased towards and leaning towards letting that flow through? The answer is yes. The whole company is on board with that. They're driving to it. We're all rowing together as one team to show the profitability engine that we have, and that's very important to us. Your next question comes from a line of Matt Sykes from Goldman Sachs. Your line is open. Hi, good afternoon. Thanks for taking my questions. Maybe the first one just on compliance. Jeff, you mentioned some of the enhancements you were making to compliance, and if we add in the rescreen opportunity, over time, could you maybe help us frame where you think compliance can go to for Cologuard over the next year or two? Just secondly, I'll ask them both upfront, but secondly, just on Oncotype outside of the U.S. I think you mentioned that's sort of the main growth area for you. Could you maybe talk about what you see as sort of the growth rate for ex-U.S. within Oncotype for this year? Thanks. Yeah, this is Jeff. I think I'll handle both of those. Cologuard patient compliance, the way we typically report this out is looking at tests sent out 12-18 months prior. That rate is in the mid-60s%, so about two out of three patients comply with Cologuard. Over time, I expect that to go above 70, possibly to 75. The reason why I'm confident we'll get there is that on rescreen patients, the overall patient compliance rate is 50-20 points higher than first-time patients. Over time, that's gonna be a big driver of overall lift in the patient compliance rate. We're making significant investments to enhance that customer experience, better ways for outreach, better ways to make it even simpler to do Cologuard. Over time, that will naturally bring that patient compliance rate up. The second question on Oncotype DX international growth, there's a significant runway ahead, thanks to the strength of the team there, the strength of the evidence that Kevin alluded to. Oncotype globally is opening up in new markets through reimbursement and access. What we've baked into this year is in the U.S., growth there is approaching prevalence plus a point or so. Think of kind of low to mid single digits. International will grow faster. It can be easily into the double digits depending on new markets that launch within a given year. This year, we expect Japan, which could eventually be the biggest market outside the U.S. We expect Japan to come on potentially mid-year, and that can be a big driver, starting mid-year and into next year. Your next question comes from the line of Jack Meehan from Nephron Research. Your line is open. Thanks. Good afternoon. My questions for Kevin are on the blood screening programs. First, can you give an update on the blood portion of BLUE-C, when you expect that to read out? Second, on MCED, talked about validating additional markers. Can you just talk about, you know, how that might be similar or different to what you presented at ESMO and what that might mean for timeline for the SOAR study? Sure. On the first program, we haven't given specific guidance as to when the colon cancer blood program will read out. The team that is focused on our colon cancer programs are focused both on stool, Cologuard 2.0, and blood. There's a huge amount of effort that is required prior to testing samples. There is a rigorous set of analytical validation studies that are required, verification studies, software development, and validation. There is an enormous amount of rigor that goes into that in preparing the automation, entire program and submission that goes to the FDA. You don't make changes easily, so you need to make sure that the manufacturing capability and all the studies are locked down. The Cologuard 2.0, or next-generation Cologuard, is first, and then that team will shift its focus to the validation and verification studies for CRC blood afterwards. In the coming quarters, we'll provide more clarity as to when that pivotal study from the blood portion of the CRC program will be complete. In terms of the MCED marker validation study, we have interim and full readouts of the test design, kind of the lockdown study, prior to moving into the large prospective study. That study we expect to read out this year. Two different studies will read out during the year, and that is a much larger version of the data that you saw at ESMO last year. That will lock down our final marker classes, and then we expect SOAR to start next year. We would expect that to start in the first half of next year. The team right now is working on perfecting the test, making sure that that test and the automation surrounding it is locked down before we start that study. Once you start a prospective study for a cancer screening test, you don't make changes to that product, so it's totally locked down. Your next question comes from the line of Mark Massaro from BTIG. Your line is open. Hey, guys. Thanks for the questions and congrats on the progress. My first one is on MRD, it's great to see your planned LDT launch later this year in colorectal cancer. When can we expect to see additional data which would support reimbursement, have you had discussions with any Medicare contractors? My second question is on the Thrive multi-cancer initiative. I appreciate that additional data will be rolling out this year. Maybe, Kevin, can you just give us a sense... You know, this is not like you're rolling out an LDT. This is kind of a higher risk, bigger opportunity. What types of, you know, factors do you think might change in the landscape over the next few years that could perhaps increase the probability of success? Can you give us a sense for the size of the patient enrollment? Is it somewhere near the 80,000-100,000-plus mark? Okay. The first question in terms of what are the things that are gonna change to make a multi-cancer early detection, this whole category of testing, more likely to be successful. Certainly, Congress creating a Medicare benefit category is one. That's important. We expect that legislation to be reintroduced in this Congress. Remember last year, there were more than 50% of Congress were co-sponsors, equal number of Democrats and Republicans. We're working hard right now to make sure that Medicare beneficiaries will have access to this incredible new category of testing. The evidence that is being built by Exact, by others in this field, shows great promise for the ability to shift the stage of cancer detection broadly across many, many different types of cancers. From later stage, more difficult to treat cancer to earlier, cancers where the therapy frequently is surgery with an intent to cure. That's a big shift. The more evidence that is generated, there is more excitement that is being built in this space. We believe that we have a significant advantage because of the strength of our Cologuard screening team, infrastructure, lab capability, etc., perfectly positions us for success. This is gonna play out over a long period of time. We believe there are well north of 100 million people in the U.S. alone, many more outside the U.S., that are gonna benefit from the test. The key takeaway here is that there is no therapy as effective as earlier detection. Earlier detection means your therapy plan is going to be very different. That's the goal of the program. We're excited about it. We're committed to making this happen. We're doing the rigorous scientific work to develop the best test. Mark, you had also asked on MRD. We plan to publish data at an upcoming scientific conference in the tumor-informed version of our test. Recall we're working on both tumor-informed and tumor-naive. That tumor-informed data in colon cancer puts us one step closer to bringing that test to market, which we plan to do later this year, first as an LDT. Next year, we'll submit retrospective prospective data to MolDX, hoping to secure reimbursement with that. Behind the scenes, we've been working on pivotal studies for both colon and breast that eventually will help set, we think the standard for evidence in this space. We feel good. Same thing with multi-cancer and leveraging the foundation we built in primary care. MRD, given our positioning with oncologists, what Everett and team have done there, building deep, deep relationships. As you know, 98% of oncologists have ordered Oncotype DX from us. We think we can leverage that same strength of that commercial foundation into MRD. Your next question comes from the line of Dan Arias from Stifel. Your line is open. Afternoon, guys. Thanks. Kevin, back on the pipeline, just any update on the thoughts around commercialization for Cologuard 2.0? I think at one point that was a potential 23 event. Just curious if that's still a possibility, and then how dependent on that would commercialization be on just performance and data around the test versus other factors like sales training, reimbursement, et cetera? Thanks. Sure. We expect to submit this year, and it's at least six months with the FDA before approval. That puts us into next year with the launch. A lot of pre-launch activity will go on. Certainly, that launch will incorporate the new and different sensitivity and specificity. Some of the more mundane aspects of launch would include the billing code for the new version of Cologuard. Does it change? Doesn't it change? Payer relationships, Medicare, et cetera. You need to do a lot of work there before you switch over to a new test. Lab automation, changes, et cetera. That will be a very thoughtful transition from the great current version of Cologuard to an even better version of Cologuard. The nice thing is we have a great test in Cologuard today, and it's all upside for patients, health systems, and Exact Sciences shareholders, when we bring the new innovation to patients. Just to add to that, recall that late last year, we pulled ahead one of the key benefits of Cologuard 2. We pulled ahead to internally what we call Cologuard 1.5. What Cologuard 1.5 did is it extended the stability of that patient sample by a third. That's important because it helps get more of those tests back to our lab with a sample we can still use that's not expired. To date, this new version of the kit, this new Cologuard 1.5, has helped over 45,000 samples to come back to our lab without expiring. Now some of those we could have gone on to recollect before, but it creates an overall better patient experience, more revenue for us, better gross margins for us. The team is not standing by idly by any means. They're pulling ahead, this big benefit. Overall this year, that will increase completed tests by at least a point. Commercially, we're already there. We know our targets. Obviously, as Kevin said, with Cologuard on the market now, it will be a seamless transition from a selling and marketing standpoint. Your next question comes from a line of Puneet Souda from SVB Securities. Your line is open. Yeah. Hi, Kevin, Jeff, thanks for taking the questions. First one is, you mentioned the 8% penetration for 49, 45-49-year-olds. What's the ceiling for that penetration given the momentum you're seeing here? On the MCED data, I mean, should we be expecting that at AACR or ASCO or later in the year at ESMO? Thank you. I'll take the first part, Jeff, you take the second part. In terms of the ceiling, we think that the ceiling is higher than the 40% penetration that we've long guided to for Cologuard in that earlier age group because people who are 45 to 49 typically are busier than retirees, and it's more of a challenge for them to schedule a screening colonoscopy, which can take a day and a half out of your life. Typically your, a portion of your week that you're normally working. We also have been able to educate and reach people digitally. Our digital investments and social media marketing will increase over time. Cologuard is a test that fits within their lifestyle. Do we get to 50% to 60% penetration? That wouldn't surprise me over time in that age group. What you're seeing is you're seeing the endoscopy suites are very, very busy today. Any notion that Cologuard was going to slow down the business of gastroenterologists and endoscopy suites is just not proven to be accurate. In fact, it's allowed them to focus. There is an opportunity for Cologuard, and it's being ordered more frequently in that patient population because the risk of colon cancer is lower, and GIs are and health systems are focusing on getting those people screened, which goes into their colon cancer quality ratings through Cologuard. Visiting last week with primary care physicians who have very busy practices, they are focused on Cologuard. One office I met with switched 100% to Cologuard. Why? The GIs are so busy in that part of the country that they don't want to see more average-risk patients. We see that Cologuard will continue to grow because it's easy, it's at home, it's accurate. Jeff, I think there was a second part of that question, too. Puneet, this is Jeff. The MSI team has done a really good job generating a wealth of evidence to help build out this new category. As Kevin talked about, there's two sets of data coming this year. The first one, I don't think will be at AACR. I don't know the conference for sure, but I would think mid-year on the first set, and then the fall timing for the second set. When we know what conference, though, we'll let you know. Your next question comes from the line of Patrick Donnelly from Citi. Your line is open. Hey, guys. Thank you for taking the question. Jeff, maybe one for you just on kind of the cadence of the year coming out of the strong four Q. You know, I know even going back to the conference in January, you were talking about, you know, four Q had some benefits. I think you mentioned the billing enhancements on the call here. You know, no surprise, one Q down sequentially on Cologuard. Can you just talk about, are we getting back to that normal seasonality? Obviously, again, four Q had that great inflection. You talked about all the factors there. How do we think about that going forward into 2023? It's been a weird couple years, obviously, in terms of the impacts you guys have seen. How do you think about the cadence of this year, you know, both on the top line with Cologuard and then also, you know, maybe on the EBITDA side, if there's anything we should be looking out for there in terms of expense timing? Thank you, guys. Patrick, the typical cadence of Cologuard, you know, hasn't changed. It's really driven by primary care utilization trends. What those are is that you typically start the year, if people are coming off the holidays, deductible just reset, so primary care use is typically lower in January. Things build up until Memorial Day at the end of May, and then over the summer, they're typically flatter as people go on vacations and aren't focused as much on primary care. About mid-August or Labor Day, things tick back up, and, you know, typically climb pretty steeply until Thanksgiving timing, and then slow down over the holidays as people go on to again, onto vacations. What that means for Cologuard, there's about a 30-day lag between a primary care visit and we would recognize revenue. That's typically why you'd see a step down going from Q4 to Q1. I don't expect that to change going forward. However, our business is becoming more predictable. More predictable. You know, we've got more stable growth drivers as Everett and team have done a really nice job building out a whole wealth of different drivers. It's not just tied to one thing anymore. From a Q1 of this year standpoint, there's a couple unique things that are happening. Everybody's seen the flu data. The flu is really mild this year. Relative to most years, you know, flu is normally a headwind to us and others in early Q1. That headwind is really nonexistent this year. I think all else equal, Q1 a little stronger this year. Also, some of the carryover benefits that I talked about earlier from enhancements to both our patient compliance engine and our billing systems, we're picking up a little bit of catch-up revenue on both those things. All told, Q1 seasonally stronger this year. As you think about phasing throughout the year, don't expect that same sequential build Q1 to Q2 this year as you would normally. From an adjusted EBITDA standpoint, Q1 typically has the lowest profitability of the year because of the top line being a little lighter seasonally, and expenses are a bit higher as you roll into a new year. We've got some unique sales and marketing events in Q1 also. Lighter profitability in Q1, but overall strength to the year, from a profit standpoint. Again, significant pickup year-on-year in adjusted EBITDA. Your next question comes from the line of Andrew Cooper from Raymond James. Your line is open. Hey, everybody. Thanks for sneaking me in here towards the end. Maybe first just, Jeff, you know, you mentioned some of the prior period collections and some of the improvements in compliance. Can you give us a sense for sizing of that in the fourth quarter? Then, you know, I think it was about a year ago, maybe this call last year, you talked a little bit about, you know, a chance for pricing and ASP to continue to climb a little bit. Can you just give us an update? You know, have you been able to capture a little bit more on sort of apples to apples ASP and what that's looked like and how that impacts the move to profitability as well as assuming pretty steep drop down there? Andrew, in Q4, the base business exceeded expectations. This is the things that Kevin and Everett have talked about. It's the strength of the relationships with health systems, the sales force productivity, Cologuard rescreens, 45, all those things drove the upside. The reason I called out some of these other items is because we didn't want people to take Q4 and then assume that's kind of the new base run rate going forward. I look at it as more sweeter in terms of a couple of things. Again, it's the enhancements to our billing systems, enhancements to patients' compliance. What happened here, let's say you turn those on early October. Well, because of those enhancements, we were able to capture patients and revenue that otherwise would have hit in Q2 and Q3. We picked up in Q4. It's, you know, a good guide there on a go-forward basis now. Our revenue per test, or ASP, is higher, and our patient compliance rate should improve on a go-forward basis. You see it in other ways. You see the things like our DSO improvement improved by 50 days year-on-year. Overall, that team has done a really good job at enhancing our overall kind of billing systems and processing. On a run rate basis, ASP for Cologuard, the right way to think of this is around $480 of revenue per test. There are some puts and takes there. You obviously, you've got this newer age group, 45 to 49. You know, for a while, that was a... It carried a lower revenue per test as we built up the insurance coverage. There's also some other classes like Medicaid that rightly so, come in about 80% of the Medicaid oftentimes. Again, here the team has done a nice job, and longer term, I think we can work that rate towards $500. Your final question comes from the line of Dan Leonard from Credit Suisse. Your line is open. Hello. Thank you for taking the question. I have a question on your precision oncology guide. It doesn't seem like you're expecting much from OncoExTra. Is that accurate? Could you walk through the path for some of these new products like OncoExTra and MRD to contribute to the sales ramp in precision oncology? Thank you. Sure. I could start, and maybe Everett can jump in. What's baked in the PO guide globally, U.S., and we've talked about this for a long time, given the strong current market position, as a class, the penetration rate there is over 70%. We do a nice job within that. Given the strong position, the growth in the U.S. for the Oncotype DX business, think of low single digits. This is prevalent plus maybe a point. The strength of that foundation will allow us to launch other programs like OncoExTra, like MRD, like the Riskguard, which is the hereditary cancer product. Internationally, the growth there is... That business, think of kind of $150 million a year right now. Growth there over time should be double digits for many years to come. Year to year can be a little different depending on which markets open up that year. This year, the big new market that we expect to come online is Japan mid-year. What's baked in is stronger growth in the U.S., but it's not that we won't get the full year impact from Japan. It's not strong double-digit growth this year. It's probably high single or low double digits baked in. OncoExTra there, I think it's considered north of $10 million of revenue this year. It is the first year of launch. I know that Everett and the team are excited about the launch, but it's early, so we'll come back to you and, you know, look forward to providing updates as the year unfolds there. Everett, anything to add? I'll just add, we often talk about the productivity of our Cologuard sales and marketing team. My hats off to our precision oncology sales and marketing team. We had the launch of OncoExTra a couple of weeks ago. The training team and marketing team did a great job of preparing our sales organization to launch it day one. And again, the granularity of who we're focused on who we need to drive OncoExTra was really evident at our launch of OncoExTra. We're already generating orders. As Jeff Elliott said, we're gonna look to hit, exceed our target for OncoExTra in 2023. Just to understand the differentiation of OncoExTra, this is an enhanced version of a therapy selection test, which is a ultra-comprehensive panel. It includes DNA and RNA. It detects the clinically actionable mutations and fusions, including whole exome, whole transcriptome sequencing. It also includes patient-matched tumor normal sequencing. It has a incredibly easy to interpret result reports for FDA-approved therapies, immuno-oncology signatures, et cetera. One thing, Dan, you didn't ask this question, I don't think we touched upon was around the follow-up colonoscopy rule changes. Everett, maybe you wanna just touch on that. Absolutely. Thanks, Kevin. One of the biggest objections from our customers around Cologuard was, hey, if they get a positive Cologuard test, that patient is burdened with paying for the follow-up colonoscopy. CMS and commercial last year made the positive development that there will be no copay, zero copay for a follow-up colonoscopy. Our organization is now focused on getting that message out. It takes time. We have to educate over 300,000 primary care physicians and health systems on that new ruling. We're really excited about that new development legislation, and we're out there every day, talking about the positive development. This does conclude today's conference call. Thank you for your participation. You may now.