Perfect! Good afternoon, everyone. This is Rachel Vatnsdal with the Life Science Tools and Diagnostics team at JP Morgan. Thank you so much for joining us today for Guardant Health's presentation. So as you've seen with most of these, it's going to be 20 minutes roughly of presentation, followed by 20 minutes of Q&A. If you have any questions, feel free to either ping me directly or submit them via the portal. And with that, I will pass it off to Helmy. Thank you.
Thank you, Rachel, and, it's great to be here. So thank you everyone for joining us today. Here's our forward-looking statement. So we founded, Guardant Health 11 years ago with the bold mission of giving us, our families, friends, and loved ones all more time free from cancer, a disease that we believe could be ultimately conquered using vast amounts of data as our weapon. And in those eleven years, we have delivered on that promise. We now have a robust suite of precision oncology products addressing both late and early-stage cancers, as well as recurrence monitoring for cancer survivors. And now with our new screening assay, Shield, Guardant is the first company that has liquid biopsy product offerings spanning the entire continuum of cancer care.
At Guardant, we have always been trailblazers, and this year we will continue to blaze a trail in a groundbreaking cancer screening category as we eagerly await the planned launch of Shield IVD in 2024 for colon cancer screening, pending FDA approval. With that, I would like to start our presentation with a patient story for our newest product category, Shield.
My name is John Gormley. This year, I was diagnosed with stage II colon cancer.
He hadn't had any screening done since 2003. But it's difficult to get patients to do it on a colonoscopy because it requires multiple steps. The stool test for DNA, still a lot of obstructions to getting it done correctly.
He said, "We can have you go get a colonoscopy, or I could give you the Shield blood test," and I chose the blood test.
It takes about 30 seconds to draw the blood. I get results in two to three weeks.
He called me a few days later with the results.
So his test came back an abnormal signal.
He handed me off to Dr. Dhaliwal for the procedure.
Then we found a mass in his colon, and the biopsy of that came as a cancer, and patient was scheduled for surgery.
It turned out well. The recovery was quick.
Patients will recognize right away that this is an easy, fast test that simplifies colon cancer screening enormously.
I would certainly recommend to my friends that they get screened with the Shield blood test because it works.
These stories are the fuel that drive our relentless work. We have made great strides and have administered more than 500,000 cumulative tests. Additionally, these achievements have resulted in a remarkable financial track record with strong revenue growth, with a five-year CAGR of over 44%. Finally, as we have previously forecast, we did in fact reach our goal of becoming cash flow breakeven in therapy selection by the end of 2023. Now let's dive into each one of our product franchises. First, we're going to start off with therapy selection, which is a market consisting of around 700,000 advanced cancer patients in the United States, with a total addressable market opportunity at scale of $10 billion.
Since launching Guardant360 in 2014, we have built a comprehensive portfolio of four precision oncology products that address multiple aspects of the therapy selection market. First, we have our FDA-approved Guardant360 CDx, as well as our next generation Guardant360 test, that helps physicians match their patients to biomarker-driven therapies using a simple blood draw. Combined, these two products are the most ordered and clinically validated liquid biopsies for comprehensive profiling on the planet, with over 450 peer-reviewed publications in support of their utility. We also have Guardant360 TissueNext, our tissue CGP product that works hand in hand with Guardant360 CDx, and Guardant360 Response, the first blood-only liquid biopsy for monitoring of therapeutic response to IO and other targeted therapies.
We are thrilled with the strong uptake we are seeing from oncologists for our newer products, and that excitement is further increasing adoption of Guardant360 CDx in a very nice, virtuous cycle. Now let's take a look at our clinical testing volumes, which are a key driver of revenue. We've seen rapid expansion over the last five years, with clinical testing volume growing at a five-year CAGR of 43%. While these charts include all the products in our oncology portfolio, the vast majority of the tests have been Guardant360, which, as you'll see in a moment, continues to have strong momentum even in its ninth year. Indeed, in 2023, we delivered 173,000 clinical tests and have a number of tailwinds to continue that growth for 2024 and beyond. The key to a financially strong diagnostic business is robust gross margins.
To this end, we have recently made great strides in improving ASPs for Guardant360. Specifically in November, Medicare finalized its proposal for the Guardant360 LDT price to be crosswalked to the price of Guardant360 CDx. This took effect on January 1st of this year, increasing the Medicare price of Guardant360 LDT from $3,500 to $5,000. We're also starting to see the positive impact of Guardant360 ASP from commercial payer coverage wins and believe that this is a tailwind that will continue to play out in the coming year. As a result, we expect that in the first quarter of 2024, Guardant360 ASP will increase by approximately $200 compared to Q3 of 2023.
In line with some of these commercial coverage tailwinds, we have continued to make excellent progress in working with other stakeholders to help pass biomarker testing coverage mandates. These mandates have now passed in 15 states, representing well over half the U.S. population, with the most recent bills passed in California and New York. And importantly, the majority of this legislation impacts not only the treatment selection business, but also MRD and monitoring. This legislation will help serve as an important ongoing catalyst for private payer coverage for the entirety of our existing portfolio and for future products. We believe we are still in the early phases of growth for utilization of therapy selection. Specifically, we see three key drivers of growth for the overall therapy selection market. First, increasing liquid and tissue adoption.
Second, the ability to detect emerging markers or extend the use cases of current biomarkers, and then third, moving to earlier lines of therapy. Very excitingly, and in line with the first key driver, the NCCN lung guidelines were just updated this month to include the use of concurrent testing with both liquid and tissue for patients, in order for physicians to be able to maximize both biomarker detection, sensitivity, and speed to results. We look forward to this recommendation being adopted across other cancer types in the future. Now, I'll detail more initiatives we are working on that we believe will also help support growth of our therapy selection franchise. The first focus area for us is streamlining the customer experience. To this end, we have made excellent progress integrating with the three largest EMR systems in the oncology space, which encompass approximately 2/3 of practices.
We are pleased to report that we have now integrated with more than 475 accounts, exceeding our original target of 400 by year-end. We are seeing great increases in efficiency and ease of ordering, leading to a 75% reduction in ordering time. We believe these integrations will serve as a catalyst for increasing ordering depth per account throughout the year. Another critical growth driver is not only increasing adoption of biomarker testing bottoms-up at the physician level, but top-down at the large group practice level, especially in the community where most patients reside. Accordingly, we are pleased to announce that we are partnering with US Oncology, one of the largest community oncology practices in the country, to help support adoption of biomarker testing for their patients in their network.
Next, I am pleased to announce that this year we will launch an updated version of Guardant360, built on our Smart Liquid Biopsy platform. We believe this will mark a significant leap forward for the field of therapy selection by taking it from comprehensive genomic profiling to comprehensive molecular profiling, whereby broad genomic and epigenomic biomarkers are tested for each and every patient. Guardant360 on our Smart Liquid Biopsy platform will help identify more patients for existing therapies that are undetectable by current CGP tests, identify novel targets for new therapies for our biopharma partners, and provide detailed phenotypic information about the tumor, such as histology subtype, and more. New features will be continually added to the test as we clinically validate additional functionality.
Finally, we have seen excellent uptake of our TissueNext product and are also planning to launch an upgraded and greatly expanded version of the test this year. We believe another important driver for volume growth in 2024 will come from international expansion, which has historically been a relatively small portion of our volumes. We are continuing to make good progress in Asia with the recent launch of Guardant360 for clinical use in Japan, which represents the largest international clinical testing opportunity within our portfolio. We are also seeing good momentum in the U.K. as The Royal Marsden's Guardant-powered laboratory was awarded an expression of interest by NHS England to launch liquid biopsy for non-small cell lung cancer, potentially making this technology accessible to thousands of patients across the country.
Earlier today, we announced an agreement with Hikma Pharmaceuticals, a multinational pharmaceutical company, to promote our portfolio of liquid and tissue biopsy tests across the Middle East and North Africa. In this region, there are more than 400,000 new cancers each year, and cancer incidence is expected to double by 2040. We are excited to partner with Hikma and leverage their strong commercial capabilities and regional expertise to equip oncologists in the region with the necessary tools for cancer screening, recurrence, monitoring, and guiding treatment selection. Turning to our biopharma business, we ended the year with nearly 30,000 samples, up 15% from the prior year. Guardant Infinity helped pave the way, representing more than 30% of our biopharma testing volume. Notable achievements included successful entry into China with more than 30 partnerships in our pipeline.
Looking forward, our robust companion diagnostic pipeline, coupled with a backlog of deals won, positions us for significant growth in 2024. Furthermore, we believe our active engagement with biopharma leaders for strategic partnerships, especially in exploring the potential of epigenomics for their pipeline of assets, will drive even more demand for our products and services. In summary, we are very pleased with the progress in therapy selection over the course of 2023, but believe there's much more to come from a number of these drivers in 2024. Now, let's take a look at our MRD business. The market is comprised of about 15 million early cancer patients and cancer survivors, which represents a $20 billion TAM in the U.S. at scale. There are two main approaches in the MRD space.
The first is called tumor-informed, where one needs to physically obtain a tissue specimen for the tumor and sequence it to be able to test the patient. And our approach, which is tissue-free, which only requires a blood sample. The tissue-free approach is certainly more difficult, but we believe it'll be ultimately the modality that has much greater product-market fit, and thus will capture a larger part of the market for three main reasons. One, it's faster, enabling results in days rather than weeks. Two, it's easier, enabling monitoring of patients that don't have tissue in the neoadjuvant, adjuvant settings and for survivors that are years out from surgery. And finally, three, it's in a category of its own in terms of power and utility.
Rather than just telling a physician if a cancer has recurred, our tissue-free MRD test, Guardant Reveal, built on our Smart Liquid Biopsy platform, will uncover the why and what to do next. I am excited to share, as of this year end... As of last year's end, we have upgraded Guardant Reveal to our Smart Liquid Biopsy platform. With this broad methylome-wide technology, we can now achieve high performance since our methylation chemistry is tracking hundreds to thousands of active alterations per patient versus just the 16-50 mutations from tumor-informed assays. As we detailed at our Investor Day, we have a low background methylation chemistry that leads to ultra-high specificity, and we maximize overall accuracy by applying machine learning to thousands of clinical samples.
Finally, physicians will be able to use the test to quantitatively track and quantify tumor fraction, sorry, in the MRD setting with high precision using our epigenomics-based technology. Guardant Reveal is currently available for CRC, breast, and lung cancers and will be expanded to other tumor types over time. We previously shared data from our COSMOS colon study, looking at Stage II and III patients, and showed that Guardant Reveal on our Smart Liquid Biopsy platform achieved 80% surveillance sensitivity with 99% specificity. One thing we are learning is that sensitivity of MRD assays is highly dependent on the compositions of patients in a particular study. This is because the site of recurrence greatly affects the shedding rate into the blood, with some metastatic sites shedding much less than others.
At this level of analysis, it's very exciting to see that Reveal performs favorably to other MRD approaches when comparing the dominant metastatic sites for CRC patients. We are finalizing the manuscript for this data, and it will be included in our submission to Medicare for our surveillance indication. We are also pleased to report we have now assessed three clinical breast cohorts with our Guardant Reveal assay and Smart Liquid Biopsy. We achieved a blended 82% surveillance sensitivity for distant recurrence, with 97% specificity on this very sizable combined cohort. We are very excited by this data, as both of these numbers are in line, and if not favorable, to other approaches in this space. We also look forward to sharing more details about this data this year and including this in our submission to Medicare.
At our Investor Day, we laid out the vast size of our clinical cohorts for establishing validity and utility for Guardant Reveal. The biobank and trials we've amassed are comprised of over 20,000 patients and 80,000 samples across many solid tumors. And these samples are going to be used to essentially support additional indications for reimbursement over time. Now I'll hand it off to Amir Ali to detail our progress on screening.
Thanks, Helmy. At Guardant, we are pioneering a new category of blood-based cancer screening tests. Our mission has always been improving patient lives, and with our cancer screening test, we will deliver an accessible test that will detect cancers at earlier stages of the disease. Early detection is the key. Looking across 26 different solid tumor cancers, which comprise 87% of all cancers, the survival rate is just 14% once the cancer is metastasized. However, when the cancer is diagnosed as regional or localized disease, the survival is much, much higher, at around 65%-90%. To change these outcomes at the population level, we must not only develop a high-performing test that can detect cancers at the localized or regional stage, but it must be an accessible test that consumer will actually follow through and complete.
A blood-based screening test does all of that. We believe the best approach to an accessible multi-cancer screening test starts with colon cancer indication, where there is an established reimbursement pathway and a huge clinical need to improve patient compliance for screening. Looking at the market for colon cancer screening, there are 137 million people in the U.S. between ages of 45 - 85. Of this group, 120 million individuals are considered to be average risk for colorectal cancer. 70 million individuals are up-to-date with their CRC screening. The vast majority is through colonoscopy, and about 15 million people are getting screened with stool-based tests. You can see that even with these available screening modalities, there are still approximately 50 million people that remain unscreened.
The lack of compliance contributes significantly in making CRC the second leading cause of cancer-related death in the United States. 76% of CRC deaths are in the individuals that are either not up-to-date or have never been screened for colon cancer. The first factor for any screening test is to demonstrate its clinical performance. To this end, we successfully conducted our registrational ECLIPSE screening trial. We enrolled more than 45,000 patients and used roughly 23,000 samples to run for our PMA submission. Our PMA study demonstrated the performance of Shield to be at 83% CRC sensitivity with specificity of 90%, both within the performance range of other guideline-recommended modalities. We have approximately 20,000 additional blinded biobank samples that can be used for future IVD studies and device upgrades. 2024 is a turning point in our journey for Shield.
We are making steady progress in FDA review, and we'll go through an advisory committee panel discussion as the next phase of the review process and are preparing to launch the test following FDA approval. Under our milestone-gated investment in our PCP commercial channel expansion, we are planning to have a field force of 100 FDEs to support Shield IVD launch. As we get close to USPSTF guideline inclusion, which we expect in 2026, we plan to expand our field team to about 300. After guideline inclusion, we plan to expand the team to about 700 FDEs at scale. With our early commercial experience with Shield, we are witnessing the real-world evidence of its effectiveness of driving unparalleled compliance in completing cancer screening.
In over 20,000 ordered Shield tests, the adherence rate was 94%, which is much higher than the range of 38%-65% with current modalities. In a health system setting, a randomized study was conducted at Kaiser Permanente and demonstrated that when individuals who hadn't completed FIT were offered Shield, the rate of screening increased by more than two times. This highlights the significant impact of what Shield can do when this blood test is added as a new and accessible option for CRC screening. It's so exciting to hear from physician how adding Shield to their testing menu has positively impacted their practice. Feedback on Shield has been nothing short of exceptional.
We are hearing how compliance has skyrocketed in PCP practices and how individuals who've never been screened due to existing barriers are now getting screened due to the opportunity to test right in the office. This collective response from ordering PCPs underscores a significant endorsement of Shield's value and utility even prior to receiving regulatory approval and guideline inclusions. Just like we've seen with John moments ago in the video, we are excited to see the impact of Shield to give patients more time free from cancer in the near future. CRC screening indication for Shield is just the beginning. Our goal has always been to have a blood test that can detect multi-cancers at early stages. Our second strategic indication is lung, the leading cause of cancer-related mortality. We are continuing to make good progress in enrollment of our cancer screening, our lung cancer screening study.
But we are not going to continue to add cancer types one by one. We are also working on adding the early detection of a panel of cancer as an indication expansion into the same Shield test. Now, turning to our full-year performance. 2023 was another very strong year for Guardant, with full-year revenue growth of 25%. This increase in revenue was fueled by strong performance across both our clinical business, with test volume growing 39%, and our biopharma business, where testing volume grew 15%. We continue to be laser-focused on managing our cash and driving down a path to break even. In 2023, we successfully lowered our cash burn to our target of less than $350 million, while continuing to grow our therapy selection business and make significant investments in both MRD and screening.
We close out 2023 with $1.2 billion in cash, and as we look ahead to the next five years, we are confident that by starting to generate positive cash flow from therapy selection, by driving MRD to profitability-
... and by carefully managing the spend in our business in our screening business, we can continue to lower our cash burn each year, so that by the time we reach 2028, we'll be cash flow breakeven. As we look ahead to 2024 and beyond, we have a number of upcoming milestones in each of our key business across business areas, including liquid biopsy upgrade for Guardant360, volume expansion across therapy selection, data publication for MRD, and finally, Shield IVD launch for screening. With that, I'll turn it back to Rachel to open it up for question.
Perfect. Thank you so much for kicking that off with the presentation. So first, I wanted to dig in a little bit more on the pre-announcement from this morning. You announced a strong revenue beat behind clinical volumes, or excuse me, volumes in both clinical and biopharma. So I was wondering if you could walk through some of the trends that you saw in that core business exiting the year, and then what sort of organic momentum does that lead you up into 2024?
Yeah, no, I mean, we're very excited by the performance we had in Q4. Q4, at least for clinical businesses, tends to be, you know, a little bit challenging just because of the holidays and some of the storms that are there. And so the fact that we continue to see really nice strong sequential growth, I think sets us up for a really nice 2024. I think we saw a stabilization in terms of some of the breast pressure that we had seen before. We're now, I think, in a good spot in terms of really just continuing to grow volumes. And biopharma, I think, was especially exciting.
I think that has been an area of pressure for, you know, many players in the space, but for us, it really has been a really nice area of growth and strength, and we are really deepening a lot of the collaborations with some of the larger biopharma companies in this space. And this really sets us up. Our backlog and pipeline has continued to grow, and yeah, we're looking forward to next year.
Great. And then speaking of next year, I wanted to touch on 2024 and kind of a framework for that. So at your recent Analyst Day, you laid out your new financial targets, which assume over 30% total growth from 2023 through 2028, with therapy selection and MRD both growing over 20% in that same time frame. So in terms of 2024, you know, given some of the puts and takes, whether that's ASP, lapping some of these difficult comps on the volume side as well, how should we think about 2024 on that core business?
Yeah. Yeah, in the core business, yeah, over the next five years, we've sort of laid out, yeah, this 20% CAGR. And as Helmy was mentioning in what was in the presentation, I think, you know, we see that we're really set up very well for 2024. You mentioned the ASPs. We've had really good traction in those ASPs. We'll see something like a $200 hike for Guardant360 ASP in 2024. We've had gonna get really good traction on volume as well, coming on the international side, as well as in the U.S. And I think, you know, TissueNext, Response, and Reveal are also set to be drivers next year as well. So that, on top of the pipeline we've seen on biopharma, I think it sets us up really well.
From a guidance perspective, I think, you know, we'll have our earnings call in February, and we'll sort of lay out more specifics on the, on the revenue guidance for next year. But I think at the moment, we're feeling very confident for 2024.
Perfect. That's helpful. And then I wanted to dig into Guardant360 ASPs there. So on the LDT side, that was crosswalked to $5,000 recently. So how should we think about Guardant360 ASPs into next year? And then how does that impact the gross margin line as well?
Yeah, again, with the LDT uplift going from 3,500 to 5,000, that's a $200 uplift overall for Guardant360. The other thing that we've seen, early in 2023, we got coverage from United and Anthem, and we said that would take time for that to come through into the ASPs, and towards the back end of the year, we've started to see that. So we started to see faster and better payments from those payers. So I think as you know, that $200 for 2024 is based on the Medicare LDT rate only. I think if we continue to see the same traction from the commercial payers, we could have some upside on that.
So again, I think we're confident on the ASP, we're confident on that $200 uplift as a minimum, and yeah, there could be some upsides.
Perfect. That's helpful. And then on the NCCN guidelines for lung, you know, can you walk us through that? Had you expected that to come this month, or would this represent more upside to 2024 from either a volume or ASP perspective or both? And then walk us through the significance of that guideline inclusion for therapy selection.
Yeah, no, we're very excited about it. I think it was kind of a surprise Christmas present for the space here. So I think it was nice to see that, you know, the guideline committee in lung, which tends to be the sort of kind of lead indication when you think about solid tumors. It's the canary in the coal mine, so to speak. And so we believe that this bodes well for other cancer types, really taking what we think is the right stance in terms of maximizing sensitivity for patients. Essentially, they recognize that liquid and tissue are both valid sort of means of getting this information. They both have false negatives, potentially. They sometimes miss things.
And so when you think about those important biomarkers and the fact that finding one can change a patient's life, I think the fact that they recognize that testing both modalities at the same time is net beneficial for patients, I think bodes really well for expansion for the space and for the market.
Great. And then just shifting over to MRD, I was wondering if you could spend a minute talking about the competitive dynamics right now. You mentioned some of the tumor-informed versus tumor-naive approaches. So anything you're seeing in the landscape there would be helpful.
... Yeah, no, we continue to be very pleased with how the Shield is really spacing out. We really don't see almost any competitive pressure on the tissue-free side. We think it really is apples and oranges in terms of where we can go. We think that a large part of the market is not gonna have ready access to tissue, and right now we're only—we're really the only player in this space. So, yeah, we're looking forward to just being heads down, focusing on reimbursement, and expanding our ASP.
Great. Then I wanted to ask about the biopharma business. Can you just walk through how should we be thinking about that segment in 2024, given some of the macro environment, some of the funding constraints, and things like that?
Yeah, look, I mean, despite those constraints, we did extremely well in 2023, and we really see nothing different in 2024. I think we continue to see great collaborations with our biopharma partners, a lot of interest, and a lot of really strategic conversations, especially around our Smart Liquid Biopsy and epigenomics, where there's a potential that some of the studies that we're doing could even extend you know exploratory aspects even beyond oncology. I mean, I think it's too early to bank a lot there, but there's just so much excitement in terms of what we can unlock from a tube of blood with our Smart Liquid Biopsy platform.
Great, that's helpful. And then maybe as a follow-up to that, just regarding the smart liquid biopsy, can you talk about how much is left in terms of investing into those assets and that technology upgrade? Is there more to be done on that front? And then how much of a margin lift will you see once all those assays are ported over to that smart liquid biopsy technology?
Yeah, the nice thing is, you know, I think Shield is the first really test that's coming out of that platform. And, you know, one, in the near term, it's gonna just provide a step-level difference in terms of differentiation, in terms of biomarkers, in terms of capabilities and performance. But as we get the engine of Shield and really high volumes going in terms of the operational scale and efficiency and automation that's there, a lot of that is gonna essentially carry over and be leveraged by the entire portfolio, which will, I think, expand gross margins over time. So, I think it's gonna be a gift that keeps on giving.
Great. And then maybe sticking with Shield, can you give us an update on that approval timeline for Shield, following the FDA advisory panel review that's set for later March? And then how long after that meeting could you really expect an approval, and is there any other expectations for that specific meeting as well?
Yeah, sure. You know, we continue to expect FDA decision about Shield approval sometime in 2024, as we communicated at the time that we submitted our PMA last March. Although over time, we thought that the probability of this outcome was going down and down, still, there was some residual probability, and that's why, you know, we had this broad range of when we thought the FDA decision would be. So we are still, based on everything that has happened and the progress that we are making, we are on track to get FDA decision sometime in 2024.
Helpful. And then just regarding the V2 data that you guys presented at your Analyst Day, I was wondering if you could kind of walk us through the sequence of events needed there for approval, and if you've been having conversations with FDA around the V2 assay? Going off of that, I guess, what gives you confidence in V2 being really grandfathered into this USPSTF, you know, guidelines there as well?
Yeah. So V2 is actually a pipeline activity that we have to improve our core platform technologies and Shield V2. We showed some data in our Investor Day, that the performance for CRC sensitivity is improving relative to V1. In terms of communication with FDA, we are laser-focused on the current version of the Shield and taking that to the finish line, securing the FDA approval, and going to market with that V1 device effectively, and then upgrade it to V2 performance claim in a supplemental PMA in collaboration with agency. So we haven't started those conversations with agency to not distract the review cycle for our V1 right now.
Okay, that's helpful. Maybe just on the investment line for Shield. You know, you've mentioned that $200 million burn for Shield, and you've started to see some of that R&D coming down in 2024. So how much more do we really need to invest into the Shield product, and how does that align with building out the sales force for that channel? And what other types of, you know, commercial infrastructure will you really need ahead of the launch?
So as I presented in the presentation, we are planning to launch this IVD version of the Shield with 100 people in the field in terms of PCP channel, and we are planning to expand it to about 300 by 2026, as long as we are delivering on the milestones that we have in terms of the volume ramp and the revenue projection. These are obviously assuming that we are gonna get FDA approval, and if for whatever unexpected reason the FDA approval doesn't happen, definitely we are gonna have some material operational plan changes accordingly.
So, we believe actually with this roadmap that we showed for investment in the commercial infrastructure, we can keep the contributing cash burn of screening brand in around $200 million, within the next five years, and deliver on the five-year guidance that we talked about during our Investor Day. It's about $500 million revenue contribution to Guardant in 2028.
Perfect. That's helpful. And then maybe a follow-up on V2. Can you just spend a minute talking about the sensitivity, that you saw with that V2 assay, and really, what gives you conviction that you will be able to see broad adoption off of that level, both from physicians and also payers from that perspective?
With V2? So what we are seeing in the marketplace is actually a lot of excitement and adoption of Shield LDT, which is effectively the V1 version that we have. Like, you know, the V2 is not commercially available right now, and when we are thinking about unscreened patient population, 50 million people, 16 million annual testing opportunity, these are the people that their colorectal cancer mainly is getting diagnosed through symptoms, typically in advanced stages, and offering screening option, improving compliance, is the value that we are really offering. So we are already seeing this commercial, anecdotal positive feedback, high NPS scores that we are seeing in our survey results with the current version of the Shield. But definitely, we always want to have the best blood-based colorectal cancer screening in the marketplace.
That's why we invested in the pipeline activity, and that's why we are excited that over time, performance of Shield can get improved. The first version is strong and great, but it's not gonna be the last version.
Perfect. That's helpful. And then maybe in the last minute or two, could you guys spend a minute talking about what is most misunderstood about the Guardant story, and then what are you most excited for in 2024 and beyond?
Yeah, I think a couple of things. There's the fact that we have a core business that is now cash flow break even, and you know, it has really great margins, really great growth still. And that is really the engine that is, like, really at the heart of Guardant. And a lot of the spend we have is discrete. These are investments in specific programs, MRD and screening, that if for whatever reason, you know, the trajectory of those change, we can change the operating profile of the company very quickly. So I think that's one. I think just the... And I think we're underestimating the opportunities we have in our MRD and screening programs. We really don't see, you know, a lot of competitive pressure in those areas.
We think we have products that are very differentiated, and so we think we have the opportunities that I think are much larger than, I think we're given credit for at this time.
Perfect. With that, we are out of time. Thank you so much for joining us today, and thank you to everyone in the room as well.
Thanks.
Thank you.