Good morning, everybody, and thank you for joining us for the Guardant Health 2025 Investor Day. I'm Zarak Khurshid, Vice President of Investor Relations. It's been almost seven years since our IPO and two years since our last Investor Day. Given where we are today and the progress we've made in the last two years, we're incredibly excited to provide an update on the business and share more details about where Guardant is headed. We've got an exciting day planned for you. Hopefully, we can advance the slides. We're going to be making some forward-looking statements. We have our Safe Harbor agreement here. We'll also be reviewing some of the non-GAAP measures throughout today's presentation. A reconciliation of those measures back to GAAP can be found in the SEC filings. Additionally, we won't be providing any color on Q3 or updating our outlook for the year.
We will provide Q3 results and an updated outlook on our earnings call. As I said, we have a really action-packed day here planned for you. The CEOs are going to make some introductory remarks, and then we're going to dive into the innovation engine and Smart Platform with Darya. After that, Craig will do a deep dive into our learning engine. The team will then provide a refresh on our integrated portfolio of products with updates on therapy selection, MRD, biopharma, and Chris Freeman will do a deep dive into our oncology commercial organization. Mike will walk us through that financial roadmap for the next few years, and we'll close it out with the founders again and jump into about 45 minutes of Q&A. With that, I'd like to introduce Helmy Eltoukhy and AmirAli Talasaz, co-CEOs and founders of Guardant Health.
Hopefully, the sound on our microphones works. It's really exciting to see so many familiar faces and to present really the exciting developments we have in our pipeline, as well as some of the new targets that we have for the business. At Guardant, we are on a mission to guard wellness and give every person more time free, not just from cancer, but from most diseases. Thirteen years ago, when we started Guardant, the idea that a simple blood draw could replace invasive biopsies or detect cancer early seemed, frankly, impossible to many. People thought it was naive to imagine that one day a blood test could guide treatment in advanced cancer, or that the same platform could enable early detection during a routine visit to a primary care doctor. Fast forward to today, some of those same ideas are no longer viewed as science fiction.
They are now recognized as some of the most important and largest markets in all of healthcare. The broader industry, competitors included, have validated that vision. For us, that's the ultimate compliment. Over the past decade, we've not only advanced the science, but more importantly, we've turned vision into execution. We've built a world-class commercial team, delivered category-defining products, and established Guardant as a leader in liquid biopsy. Yet, I would argue that we are still just getting started. At Guardant, everything begins and ends with one value: putting patients first. This guiding principle drives the three pillars that make us different. The first, innovation. By blazing a trail with exponential thinking, we pursue bold, unconventional solutions that directly improve patient care. Two, execution. Through commercial and operational excellence, fueled by resilience and grit, we deliver groundbreaking innovations rapidly at scale so more patients benefit faster. Finally, data.
By turning insights and intelligence into advancements, we leverage a powerful data treasury to accelerate progress and personalize treatment for every patient. Together, these pillars reinforce our commitment to putting patients first and transforming the future of cancer care. Since the founding days of Guardant Health back in 2012, 10 years passed, more than 10 years, we made substantial progress delivering on the promise that we made to the patients to offer solutions across the continuum of care. As of today, we are the only company in the cancer liquid biopsy field that has offerings spanning from late-stage cancer management, both on the liquid and tissue front, MRD, and early cancer detection with Shield. We have touched nearly 1 million patients, ordered by over 12,000 oncologists and thousands of primary care physicians. Two years ago, at our last Investor Day, we provided a deep dive into our Smart Platform.
We talked about how it would change the whole field and how it would be the foundational technology driving the next paradigm shift in the liquid biopsy detection. We imagined the days that these new molecular insights powered by a Smart Platform would unleash opportunities and powerful waves of new applications and clinical value. That is exactly what has played out commercially in a very meaningful way just two years later. Our Smart Platform now underpins and is the backbone of all of our products across the continuum of care. It's effectively now the cornerstone of the robust pipeline and the growth driver for our business. Here is the list of all of the products and product upgrades just during the last few handful of years.
We are proud of the accelerated introduction of new products and product upgrades since the last two years that we met in our last Investor Day. This progress, accelerated progress, is only a testament to the quality of the team that we have and their dedication, but also to the tech stack and the learning engine that we have built over all these years. Today, we are very excited to announce that we are expanding the Shield product offering to include multi-cancer detection results. This will be available nationally next month, in the month of October. We are very excited about the days ahead of us. Throughout the day, you're going to hear more about our strategy for this multi-cancer offering. As of the second quarter of 2025, we are roughly 2,300 people strong. Our team of scientists and engineers with over 295 MD PhDs is truly world-class.
We are very proud of them. Our commercial team is top-ranked in terms of share of voice with oncologists. You will hear more details about it from Chris today. On the right side, you see the results from an industry survey showing that 81% of employees rated Guardant as a great place to work. By the way, we have you know that this 81% is not a censor adjustment. It's a real number. Now, let me share a little bit about our commitment to execution. To recap, for 2025, the midpoint of our guidance, we expect revenue of approximately $920 million. That's 24% growth this year on top of a very strong base. Importantly, growth has not only been sustained but has accelerated. Since our last Investor Day, our 2-year compound annual growth rate has increased to 28%, underscoring the strength of execution across the entire portfolio.
This acceleration reflects disciplined operational performance, continued adoption in advanced cancer and MRD, expansion into new indications, and progress in early detection. Together, these drivers have created durable momentum. Mike will walk you through the financial details, but the takeaway here is clear. We set ambitious goals, and we have met or exceeded them through focused execution. More specifically, this next slide highlights what we've accomplished since our last Investor Day. Over the past two years, we have delivered on nearly everything we set out to achieve. In many cases, we've gone further. On the oncology side, we've made significant progress in therapy selection, migrating both our liquid and tissue tests to our Smart Platform, achieved increased reimbursement for Guardant360, and launched 15 apps on Guardant360 Liquid that have greatly accelerated growth.
In MRD, we've delivered important milestones, securing CMS reimbursement for colorectal cancer in the surveillance setting, reducing COGS by 50%, and submitting breast and IO indications to MALDX for Medicare reimbursement. In screening, we've established an entirely new category with Shield. We're on track for Shield to be one of the most successful diagnostic launches in history outside of COVID testing. This has been fueled by Shield's FDA approval with a primary label, NCCN guideline inclusion, and differentiated Medicare pricing. Taken together, this represents not only achievements against our plan but exceeding our own lofty expectations and key milestones. It demonstrates our ability to innovate, execute, and scale simultaneously while continuing to advance patient care. From the beginning, Guardant has been a blood-first company. Our platform was predicated on the idea that continuous improvement and compound innovation is key.
The key to this improvement is the learning from every sample that we sequence and every patient that we help. To this end, since launching commercially in advanced cancers in 2014, we've been building what is now, we believe, the largest blood-based biobank in the world. With acceleration oncology volumes and early traction of Shield in its first year, this biobank has grown to over 1 million patient samples, and it continues to expand rapidly. This resource is more than just a number. It represents a unique and durable competitive moat. Each patient sample contributes to a data set that improves the sensitivity of our tests, accelerates product development, and generates insight that no one else in the industry can replicate. As Shield adoption continues to massively scale, this biobank will only become more valuable, strengthening both our scientific leadership and our ability to deliver for patients.
From the start, we knew that data would be the key to expanding beyond late-stage cancer into earlier points of the patient journey. Each step upstream in cancer requires exponentially more data to identify weaker signals and molecular signatures. A critical breakthrough came with the introduction of our Smart Platform, the first of its kind AI-powered biochemistry platform for simultaneous high-performance genomic and epigenomic data generation. With Smart, every sample produces roughly 10x-100x more information than our earlier genomics-only assays. This has fundamentally changed the slope of our data curve. You can see that inflection point clearly in 2023 when Smart was introduced into our clinical portfolio. Over the last two years, strong growth in Guardant Reveal, the launch of 15 Smart apps on Guardant360 LDT, and the rapid uptake of Shield have driven what can only be described as a data explosion.
Today, our data treasury is expanding at a rate of about 1 PB per week. We have now crossed over 200 PB, and in the next couple of years, we'll reach 1 EB of data. I think it's hard to understand the scale of the data we are generating as a company. To put that in perspective, Guardant Health now generates more than 20x the data Visa does from global transaction activity. Visa processes roughly 1 billion transactions per week. We haven't stopped at genomics and epigenomics. We've layered in multimodal data sources and real-world evidence, making our database even richer, more comprehensive, and powerful for discovery and development of groundbreaking new applications. Through the application of the AI tools, we are leveraging this data treasure that we built together. This is helping us to bring powerful and pioneering new products for our patients to market faster than ever.
This integrated learning engine that we put together provides us higher resolution understanding of the biology of our technology and helps us to upgrade our current products and also build entirely new ones for the clinical business, helps us to find novel signatures for faster drug discovery, which is relevant to our biopharma services, and also helps us to learn about some data around our commercial engine and also helps with the decision support tools for the physician. Just as a reminder, all of our products across continuum of care: Guardant Reveal, Shield CRC, Shield M-Set, and the new apps that we have launched for Guardant360, all of them actually have been built based on this data and the insight that we have and the power of the AI on top of that data.
Now, with the explosion of the data that you heard earlier and the AI tools that we are using, we believe the rate of innovation at Guardant is just going to increase and increase. Effectively, all the product testament that we talked about earlier is a testament of this growth and acceleration of innovation and development. What our team has achieved during the last one decade has been extraordinary. We've taken liquid biopsy from just a bold idea a decade ago to a standard of care which is reshaping the way patients are getting managed today. We are not just building for the future. We are growing rapidly as we speak. Guardant is the leader in therapy selection, in tissue-free MRD, and blood-based CRC cancer screening, three of the biggest opportunities that exist in the healthcare industry.
Even as just exciting as what's in front of us, the more powerful applications are just beginning to unfold. The most profound impacts on patients are just about to come. Guardant is the leader in the liquid biopsy field today, and we are just getting started. If you look across history, transformative technologies rarely move in a straight line. They advance in successive S-curves, each breakthrough enabling the next wave of applications. We've seen this with electricity, which began by powering light bulbs, but quickly scaled to factories, transportation, and ultimately the digital age. We've seen it with semiconductors, where the first chips made basic computation possible, then unleashed personal computing, the internet, mobile, and now artificial intelligence. Each curve larger and more impactful than the one before. Guardant's journey has followed that same pattern. We've unlocked three S-curves already.
The first one, therapy selection, opening up a $10 billion market. Second, minimal residual disease, a $20 billion market. The third, cancer screening, a $50 billion market. Each step expanded both the utility of our platform and the scale of the opportunity. Now, as our technology grows in power and reach, it opens a door to the next S-curve, multi-disease screening. Shield is a foundation, but the vision is much broader. Routine blood testing that not only finds cancer but helps intercept many of the most serious diseases at their earliest and most treatable stages. In that future, a simple blood draw could become one of the most important tools in preventative medicine, helping physicians protect health and not just treat disease. This is the arc we are building towards, a succession of S-curves, each unlocking more value for patients, for physicians, and for society.
These are some of the topics we are going to cover today. You will learn about our Smart Platform more, which is fueling the best-of-breed innovation platform, this proprietary epigenomic tech stack that we built, combining it with multimodal data treasury, AI on top, which is fueling our growth. You're going to hear about the power of Infinity AI Learning Engine, which is really unlocking opportunities across the organization for us. We are going to talk about oncology business acceleration and how these smart apps are fueling the new wave of growth for therapy selection. We are going to cover MRD and the fact that we are the number one player in the tissue-free MRD. We talk about our industry-leading biopharma business and how it's strategically connected to everything that we do. We are going to talk about Shield as the winner in the blood-based screening field.
Shield has a blockbuster product, strong first-mover advantage, which is further increasing with what we are going to do in the field of multi-cancer detection expansion. Finally, Michael will update our financial outlook. With that, I would like to welcome Darya, our Chief Technology Officer, to come to the stage and talk about our technology and innovation engine. Darya.
Good morning. Two years ago, we spoke about the transformative potential of our technology to redefine liquid biopsy diagnostics. Today, I will show how that vision was actually transformed into reality. The Smart Platform now powers our products across the whole portfolio suite. With that, we've generated the data that now transforms our assay-driven innovation into data-driven innovation with Infinity AI, powering the next wave of advancement. Guardant has pioneered the field of liquid biopsy with genomics more than a decade ago, transforming precision oncology. Yet the biology of cancer is too complex to be explained by mutations alone. We're now leading the multimodal revolution. With epigenomics and genomics revealing underlying biology at unprecedented resolution, we're changing how clinical decisions are made to detect cancer, monitor cancer, and treat cancer.
Our Smart Platform is uniquely designed to capture both the genomic hardware, the mutations that define the structure of the tumor, and epigenomic software that determines how that structure actually functions. Think about genomics as the hardware components that exist, but without epigenomics, you're looking at CPUs without knowing what software is running on them. The epigenomic layer reveals that functional information or tumor phenotype. It tells us how the tumor works, how it integrates with the immune system, how it evolves under evolution with treatment, and many, many more insights. That combined view of epigenomics and genomics provides a more clear, more full picture of the system, where both tumor genotype and tumor phenotype are revealed from a single analysis. This leap in Guardant 's technology has opened multiple S-curves of growth, as you just heard from Helmy.
With genomics opening up therapy selection, epigenomics allowed us to detect tumors and quantify tumors at very low tumor fractions in circulation, unlocking early-stage disease, MRD, and screening. Powered by epigenomic data generated through that platform, we're now developing differentiating epigenomic capabilities that completely change what we can do in therapy selection. We've now reaccelerated that growth, and I'm excited about the commercial updates that you will hear from Chris that reflect on that. This is not a one-time advance. It's a flywheel of innovation that positions us to move into multi-disease screening in the future. How do we harvest the power of epigenomics with our Smart Platform? To have been assigned a class in epigenomics one more time. Imagine a genome-wide measurement system where methylation can be profiled across thousands of epigenomic regions, and the methylation intensity is measured for each one of them in every sample we test.
Here, the signals specific to colorectal cancer light up in specific regions of the genome at an intensity level that roughly corresponds to the tumor fraction. In lung cancer and breast cancer, these signals light up in alternate regions of the genome, in this case, for an example of a sample with lower tumor fraction. What is important is, as we collect more data points from more patients, as we profile more regions of the genome, we're getting this map with a higher and higher level of resolution, where we can now not only map these diseases, but also subtypes of diseases and more refined phenotypes of how that tumor works, as shown here for a triple-negative breast cancer as an example.
Given the richness of biology encoded with methylation, we can both detect and quantify tumors using the signal intensity and characterize them and predict how they would respond to therapies based on the locations where these signals light up in the genome. How was this possible to deliver? The efficient extraction of this rich signal really comes from a decade of compound innovation, where proprietary and patent-protected biochemistry allows us to deliver both genomic and epigenomic insights from a single pressure sample without loss of signal in either of these two compartments. To this day, it remains the only platform with this kind of capability. In our results to deliver best-in-class performance, we evaluated multiple methods available off the shelf, like bisulfite or newer enzymatic methods that deliver less lossy sample preps. Each time, we affirmed the superior capability of the Smart Platform.
The core of that advantage is in maintaining the highest signal-to-noise ratio. We're maintaining maximum signal in molecules and effectively depleting the background to both minimize noise and stretch the power of our sequencing dollars. In addition to best-in-class performance, we've always been committed to delivering that wealth of data in a cost-efficient way. We've redesigned our automation platform with continuous flow batch processing, reducing footprint, hands-on time, and turnaround time. This innovation will support our scale-up in screening and overall efficiency across future upgrades across our portfolio. We're thrilled that this was possible for an assay of extraordinary complexity. What has been exciting in the last two years is actually taking all of this and implementing within the suite of our products.
We brought up the Smart Platform across the whole continuum of care that we provide and jump-started the data generation engine that powers our newest capability that you will hear a lot about today. Our speed of execution in delivering these product upgrades was remarkable, largely thanks to a very dedicated team, but also driven by the significant acceleration we're seeing by deploying AI tools across all areas of product development. You will hear about Shield and Guardant Reveal in other sections, and I'll focus on therapy selection for a while. With our tissue launch, assay innovation delivered multimodal data capture across RNA, DNA, and methylation, returning maximum insights to the physicians. Moreover, we successfully developed that with minimum inputs, including challenging specimens with 92% less surface area and 40% less slides than are required for typical assays.
This is a critical differentiating feature for tissue NGS, where rates of QNS, quantity not sufficient, or failed results remain high at 10% - 20% due to the often scant amount of tissue material available. For Guardant360 Liquid, data-driven innovation unlocked entirely new capability. While liquid biopsies have been adopted widely for some time for genomic biomarkers, most phenotypic biomarkers that tell us how the tumor functions are only accessible through histology or direct analysis of the tissue, which means limitations of scant amount of material, high QNS rate, but most importantly, lack of ability to easily access that information longitudinally as the patient progresses. Guardant360 makes it possible now to read out this phenotypic information from a blood sample. This was made possible by the accumulation of a wealth of data that you heard about from AmirAli and Helmy . We've seen 1 million patient samples.
We're generating data at a scale close to 1 PB a week, and we continue to increase the information density associated with every patient. In 2025 alone, we expect to generate close to 250,000 epigenomic profiles across our products. Moreover, over 40% of our patients would be sampled longitudinally with multiple time points during their patient journey, which means our database is going to be enriched for longitudinal tumor evolution and therapy response patterns. This ecosystem, which Craig Eagle is going to talk about in the next section, enables our scientists to do discovery and validation of the novel multinodal signature at an unprecedented 1 million patient scale. We're at a point where data and science are converging to provide new insights from liquid testing. Molecular and real-world data with each patient defines a high-resolution map where patients sharing similar tumor characteristics cluster together.
As our database grows, we can map these patients with higher resolution and direct patients to the therapy with a higher likelihood of response. By integrating these diverse data sources and harnessing the power of Infinity AI against real-world datasets combined with genomic and molecular data to extract value from both structured and unstructured data, we've launched a suite of 15 new features and redefined how tumor phenotype can be accessed from blood. I will share a few of them now with you. We have initially launched features that recapitulate known phenotypes like tumor of origin and molecular tumor types like hormone receptor positive status in breast cancer. We're very excited about novel phenotypes that are currently in development and promise to identify more patients eligible for treatments or trials or to predict response to existing approved therapeutics and expand indications.
Let me start with an example that is available in the clinic today through Guardant360 Liquid test. While in some cases, tumor origin is known at the time of diagnosis, for too many patients, the disease has progressed too much, where that diagnostic workup requires a lot of time or is nearly impossible with current pathology workups. Yet knowing tumor origin obviously alters the treatment pathway significantly. With the Smart Platform, we train ML and AI models to differentiate methylation patterns observed in blood and provide confidence-ranked predictions of the tumor origin. These predictions, when made at high confidence, recapitulate the accuracy of analysis that can be afforded with tissue NGS using RNA. Another exciting future application of that is actually tracking secondary malignancies during surveillance of early-stage disease patients who have increased risk of secondary malignancies.
In technology, we're often focused on precise analytical development, but it's the stories of patients and providers like this one that help us get inspired as we continue this work. In this case, our medical field reported a conversation with a key opinion leader in GI cancer. For this patient, tissue NGS was quantity not sufficient, so no cancer-type prediction test could be used. IHC was inconclusive. Guardant360 came back 100% biliary. He said this was immensely helpful for him in selecting first-line treatment for this patient. The treating physician responded, "This is really good. The results truly make a difference for this patient. I want you to experience these things with us." At a finer resolution, it's not only tumor origin, but also a molecular subtype of the tumor that defines optimal treatment. For example, hormone receptor status in breast cancer.
It has been known for a very long time that these types are critical in putting the patient on the right treatment. It has also been known that as patients undergo treatments, their subtypes can change. Yet there are no tools today that allow you to follow that patient longitudinally and figure out when that transition happens. We've demonstrated with the Smart Platform the ability to match these molecular phenotypes to their epigenomic profiles and identify clusters of patients that map, for example, to HR positive status. Now, applying this capability to patient samples tested over time during treatment, we're able to offer longitudinal assessment of molecular types and let physicians identify the right treatment for the right patient at the right time. With Guardant360, this is now available today.
In our next challenge, we're embarking on increasing clinical sensitivity of the Smart Platform for traditional genomic biomarkers with the goal of identifying more patients eligible for treatment through this wealth of data. Despite the success of liquid biopsies, some classes of biomarkers are notoriously hard to detect, especially when tumor circulation levels are low. That results in obviously mistreatment opportunities and trial enrollment opportunities. We are discovering that many of these genomic drivers have associated methylation signatures that effectively allow us to rescue those opportunities by bringing methylation data into our algorithms. Let me show two case studies. In the first one, we validated ALK fusion. This biomarker is associated with an 80%+ response rate, and any missed opportunity here is a meaningful opportunity to impact somebody's life.
Using Infinity AI against a database of 200,000 individuals, profiled longitudinally and providing real-world evidence data into our databases, we identified methylation signatures and demonstrated that we can rescue 40% of these samples that were missed by genomic testing alone. In another example, we validated MET exon deletions. It is a biomarker that is widely profiled in early-stage clinical trials in a pancreatic cancer setting. Methylome surrogate signatures identified 2.4x more patients than genotyping alone. These features will meaningfully increase the utility of liquid biopsy and provide a clear advantage over genomic-only assays. Finally, our most exciting new applications are being developed to address the major gap in precision oncology, where existing biomarkers do not fully explain response or lack of response within the patient population. Richer information is needed to separate responders and non-responders.
With the data density increasing, as well as longitudinal follow-up maturing in our databases, our Infinity AI has uncovered methylation signatures separating the groups of responders and non-responders with a higher degree of precision than current biomarkers afford us the ability to do. We have demonstrated feasibility of these signatures across multiple biomarker classes and multiple cancer indications. I'm really excited for you to hear the story from Craig in a few minutes. If we pivot back to the practicalities of working with hundreds of petabytes of data that gave rise to these powerful signatures, we clearly need to be thinking in a forward-looking way as to how this data can be effectively assessed and analyzed.
Several years ago, Guardant Health has initiated and led a consortium to set the industry standards and protocols for working with distributed exabyte-scale data, engaging partnerships with experts in storage and file systems, as well as other research organizations working with massive-scale datasets. With this vision in place, put in several years ago, we're prepared to fully maximize the power of our data. In addition to this infrastructure, we've also invested to build our systems for integrated analysis of molecular profiles coming from our oncology patients tested with Guardant products and asymptomatic average risk screening individuals tested with Shield, all within the ecosystem of their clinical attributes and real-world evidence data. Craig will share some powerful examples of how this system was used to advance our validation in multi-cancer screening.
Beyond existing applications in oncology, we can now query patient cohorts of average risk asymptomatic individuals across more than 500 disease areas and associate their clinical history, comorbidities, and outcomes with the methylation signatures we observed in blood. This drives the future diagnostics that expand into multi-disease screening. With all of the excitement on the oncology side, I would like to also reflect on our progress in screening. We're encouraged by the recently released Shield TRCV2 performance data, which demonstrated 2x improvement on the analytical side that we talked about a while ago, and solid clinical performance with 62% sensitivity in stage one colorectal cancer. To consider this work in the context, when we locked our Shield TRC assays, we had access to approximately 10,000 epigenomic profiles, with V2 approximately 30,000. With M-Set development, we had access to close to 100,000 patient profiles informing our algorithmic backbones.
We estimate that by the end of this year, we'll generate 350,000 epigenomic profiles. We're committed to continue to deconvolve the complex biology associated with healthy background and early-stage disease and break the barrier of current best-in-class performance in the future. As we think about the future of blood-based diagnostics, we imagine a universe where more than safe DNA plays a role in unlocking new clinical applications or qualitatively changing the landscape of possibilities in oncology. If all diseases shed sufficient DNA, we're confident our platform will be able to capture that signal. However, for the ones that don't, we're very actively exploring additional novel biomarker classes that could be additive to our existing platform. Over the last few years, our research team evaluated over 25 different biomarker classes or measurement approaches.
Critically, our rich biobank and data bank and data interpretation power on top of that supports our ability to construct the right pilot and interpret the data we receive from our partners. While most of these pilots so far have not been able to add additional performance capability on top of our existing Smart Platform today, we've taken several into phase II and phase III evaluation and are continuing to actively pursue them. The team is ready to act quickly should any opportunity emerge from either our internal R&D effort or those external pilots. To summarize key takeaways, the Smart Platform now fuels our entire portfolio, delivering high clinical utility and performance.
By driving rich multimodal data acquisition with this platform, we created a data moat that now powers our Infinity AI Learning Engine for creating new waves of clinical applications and constructing the cancer navigation map at a higher resolution. We believe in the power of our biobank and our data bank to maintain leadership in early detection and expand into multi-disease screening. In short, assay-driven innovation created a data moat that now powers our data-driven Infinity AI Learning Engine that will serve the next growth curve. Thank you. With this, I'm happy to welcome Craig on stage. Hopefully.
Do you want a hand? Excuse me. There you go. Well done. Thank you, Darya, and hello, everybody. My name is Craig Eagle, and I'm the Chief Medical Officer at Guardant Health. The way we manage cancer is rapidly changing for the better. Building on the possibilities that our technology that Darya just shared could help drive to patients and better outcomes, I want to share some more examples of our excitement around how this technology can actually change the way we think about cancer and other diseases. Clinical data is a key component to usher in any new innovation and any new ways of treating cancer. I'll cover with you some of the key facts that we continue and consider around data and give examples of the value of our technology to various stakeholders, as well as sharing our data engine in more detail.
You will see in the entire presentation today key aspects of the results of our clinical research throughout the various sections. The clinical examples and data come from all aspects of our clinical research work. I'm delighted that we continue to be very focused and actively contributing to science that matters to patients and create a better understanding of the biology of diseases. One of the key strengths of Guardant is our learning engine on our data engine that spans across different data structures. Today, I will share a deeper dive on some of those aspects. Just to remind you that we continue to build our clinical data across the oncology care pathways. We now have over 1,200 publications and abstracts. Most importantly and most impactful are peer-reviewed journals, and now we have over 600 peer-reviewed publications highlighting our technology across a number of cancer types.
Starting in the top left of these peer-reviewed publications, we have partnered with more than 45 NCI-designated comprehensive cancer centers, which is a testament to the quality and the strength of our clinical research. 31 publications have been used to obtain Medicare coverage. More than 235 publications have patient outcomes involving targeted therapies. Finally, 46 publications are included in successful NCCN guideline submissions. I've shared with you the current status of our clinical publications, and that activity is ongoing around the globe. I would now like to share how we will expand our impact using data. As previously highlighted, we have a differentiated clinicogenomic and epigenomic database consisting of claims data, longitudinal data, and electronic medical records in combination with the results of our technology platforms.
The data engine is building on the approach that as each commercial sample is tested, we have a methodology and a process that has been running for some time now that allows us to capture clinical data from those patients. Our database, as shown on the right of the slide, now consists of a million unique tests and over 350,000 smart epigenomic profiles across over 100 tumor types. When combined with patient outcomes, it makes a powerful combination. Taking all this together and processing it through an analytical framework, in this case, our Infinity AI platform , you can very quickly and very efficiently produce clinical data and tackle key medical questions in areas of unmet medical need. In addition, we are partnering with select companies that focus similarly on using AI analytics and data to further strengthen our data engine.
This approach, you will see some examples shortly throughout the presentation, will increase the efficiency of relevant data being delivered to key stakeholders from the patient and the clinician to enable care decisions to regulatory bodies, pharma companies, and payers. This data engine and AI platform provide cancer and disease monitoring both at a research level and potentially at an individual personalized level, including monitoring their health journey. Now I'd like to share some examples of the outcomes of this data engine just to give you a flavor of the possibilities that are found. These are examples of the types of clinical data and outcomes that can be produced and how this could change the way we think about cancer, and were alluded to by Darya earlier.
Starting with lung cancer, an epigenomic signature can separate people that respond very well to immune oncology therapy versus those that have a poor prognosis and don't respond as well. Identifying these patients is beneficial for patient care and many stakeholders. On the left, I have shown the ability of the current biomarker, tumor mutational burden, or TMB, to assess therapy prognosis, with the blue line showing good prognosis group versus the poor group in the red. As you can see, the groups are relatively close, suggesting the biomarker does not distinguish these groups well. When you combine the traditional biomarker, TMB, with epigenomics from our Smart Platform liquid biopsy, you can see on the right side the combination better identifies the different groups with greater separation of the blue and red curve. This creates a very powerful clinical marker that identifies good versus poor responder groups.
By identifying these groups, it enables potentially better targeting of treatment to the people that already have a good outcome. It also identifies a group where more therapeutic research into the poor group would now be possible. This, of course, is particularly interesting for the stakeholders like pharma companies. This outcome and data is derived from our data engine. Next, an example from colorectal cancer. Using the same AI database engine, we can identify differential groups responding to a specific therapy, in this case, cetuximab, an anti-EGFR therapy. Currently, colon cancer treatment with cetuximab is based on which side of the colon the cancer is occurring. On the left, you get cetuximab. On the right, you don't get cetuximab. This sidedness of the biomarker determines the likely response to that therapy.
As you can imagine, that's a very biological, imprecise manner using cancer location to determine therapy, yet it is the only method available today. When you start using epigenetics, you can delve into the biology more deeply, and what we find actually is left versus right is not as straightforward as we think. Assessing the data from the database, we find these very distinct epigenetic markers that show those that respond to therapy well, as shown again in the blue line, and those that do not respond, as shown in the red line. Interestingly, approximately 70% of the favorable blue line have their colon cancer on the right side, creating an exciting opportunity to get precision therapy to patients using the epigenetics platform that by current guidelines, right-sided colon cancer, they would have missed out on this therapy.
Before I shift to screening, I just also can't resist the opportunity to share an example of our ongoing clinical trial work. I'm really excited to share that we are close to seeing the results from a trial, PEGASUS, that has been ongoing for several years. PEGASUS is a large prospective multicenter colorectal cancer chemotherapy de-escalation study. The study has 140 stage three and high-risk stage two colon cancer patients who normally all receive follow-on chemotherapy. In this study, using Guardant Reveal to evaluate the status of the colorectal cancer post-surgery, subjects could either be de-escalated from the usual chemotherapy or continue on standard treatment. This is one of the first prospective clinical utility studies with therapy adjustments using tissue-free MRD in colorectal cancer. The final results will be presented at ESMO next month, and I suggest you look out for that presentation and see the results of that study.
I want to switch back now, after breaking from the database, back to the database and focus on how this database helps in the screening area and demonstrate the power of the Infinity AI Learning Engine again with this clinicogenomic and epigenomic database. Screening requires extensive and large datasets to demonstrate the impact of the device performance and also the impact of screening. As a reminder, this is the outstanding performance for the Shield multi-cancer device and was presented earlier this year. Overall sensitivity of 75% at a specificity of 99%. The performance of the multi-cancer detection device was assessed through a case-controlled study run by the NCI, where they provided samples from people with cancer and non-cancer. We did not know which was which. Effectively, we were blinded to the clinical diagnosis. We analyzed the samples and returned the results to the NCI.
The NCI connected the Guardant test results with the clinical information, creating a rigorous assessment of our device performance by an independent expert institution, the NCI. These are the results you see here. Please note, this analysis includes both cancer positivity and cancer site of origin. The combination provides more information for doctors. Let me explain a little bit more about the cancer site of origin, or CSO. CSO is the next question in anyone with a positive multi-cancer detection test. Where does the cancer signal come from? Epigenetics is able to solve the cancer signal or cancer site of origin, or CSO. For example, the figure on the left is a person with a positive cancer signal without the ability to understand the cancer site of origin. The result is a nonspecific follow-up pathway.
This increases the likelihood of missing smaller tumors, as well as the potential to expand the diagnostic pathway or have unnecessary testing. Contrast this to the figure on the right. By returning CSO, tumor-specific diagnostic pathways can be used to provide more clear guidance for clinicians and patients and allow for more specific evaluation of the tumors of interest. Unnecessary follow-up on diagnostic testing from positive screening is reduced by CSO calling, as well as removing the need to explore the whole body to find the cancer. This creates a better outcome for patients. In the Vanguard study, the NCI designed nine specific pathways based on CSO readout as an example. Now I've shared the MC device performance, I want to share even further data derived from the AI database engine. If I can get the slide to vent, there we go. How does this relate to the data engine?
I'm excited to share the approach with this type of data. First, looking into our database, we identified the potential for multicancer detection data on nearly 10,000 individuals. When you think about it, the effort and cost to collecting 10,000 people in a study in a more traditional clinical trial manner compared to pulling data from a database, the impact is very different. Less effort, less time, more cost-efficient, and greater study numbers. In this case, the study was performed to assess Shield MCD device performance in the real-world setting in a very short time and very efficient manner. The protocol outline is on the left and included people sequentially enrolled over a defined time that had completed a Shield test, as this made available the breadth of the epigenomic data to run the Shield multicancer detection device. The endpoints were specificity and positive predictive value, or PPV.
Just to note, PPV is a measure of the likelihood of a positive result that it will actually show cancer. Clinical information and analysis was based on claims data. By using this approach to complement our clinical trial program, it has a potential to increase study sizes and study number by more than tenfold at a fraction of the usual resources. What were the results? I'm very excited to share the results from the study I described above. By using our database engine and running the protocol, we identified 9,251 people for inclusion in the study to assess the Shield MCD device in a real-world setting. You can see the Shield MCD performance as assessed by specificity was 99%. This aligns with the early assessment from the NCI protocol.
In addition, positive predictive value is 41%, meaning if the Shield MCD test is positive, there is a 41% chance that cancer will be present. This gives insight into the potential Shield MCD would have on a real-world population and insight into its potential impact through cancer detection. We are expecting the Infinity AI Learning Engine, with the addition of data derived from the Shield testing, to rapidly expand and unlock and even give us further potential, as you've recently heard. Just think, as everyone has a Shield test, it creates a significant inflection point for the potential to address focused areas of medical need beyond cancer. Let me share the Infinity AI Engine as we now are thinking about this asset. As previously mentioned on the left, we now have over 100 cancer types in our database and more than 1 million cancer patients tested.
On the right, with the launch of Shield TRC, there's already more than 500 diseases beyond cancer. We can take a similar approach to the Shield real-world data example by using epigenomic insights with clinical data. Equally exciting, as shown on the left, is the database for screening and other diseases. The Shield platform database is on track to rapidly exceed 1 million people. This shows some of the diseases that are currently in the database. There are several autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease like Crohn's disease, and as our understanding of the immune system increases, epigenetics has potential to contribute to improved diagnostics and clinical categories. There is also diabetes, several cardiovascular-related diseases, and similar to oncology today, we have the opportunity to explore the impact of epigenomic insights in these other disease areas.
With that, I'd like to call Helmy back to the stage after I do a summary slide. In summary, I just want to summarize that there is an innovative way of using genomics and epigenomics in cancer and health. We are building a one-of-a-kind database. I gave two examples of lung cancer and colon cancer using the database and how it can unlock greater precision through unique signatures to better identify responders and non-responders. In screening, the approach demonstrates the ability to perform a rapid and efficient analysis of Shield multicancer device in a real-world setting, with results aligning with the case-controlled NCI study. This is reassuring that we're on the right path for the Shield multicancer detection device.
Finally, when adding Shield epigenomics combined with patient outcome, the database engine becomes a major differentiator and gives the opportunity to explore the impact of epigenomics in diseases and health efficiently and rapidly, and in addition, over a period of time as regular testing and screening becomes incorporated in the database. Now, with that, I'd like to call Helmy to the stage. Thank you.
Cancer remains one of the most complex diseases to detect early and treat effectively, with outcomes often hinging on time and precision. The future is powered by our Smart Platform. At its core, the Smart Platform analyzes genome-wide methylation, the engine that powers endless possibilities. The data generated by the platform can be used to rapidly develop new apps that integrate methylation, genomic, and germline data from a single blood draw. Guardant's platform and products are already reshaping oncology treatment worldwide. With Guardant360 CDx as the first FDA-approved comprehensive liquid biopsy, supported by the deepest breadth of clinical validation, we are the leader in therapy selection. With one of the lowest sampling requirements, Guardant360 Tissue taps into multi-omic insights that deliver the most complete view of cancer today and in the future. Guardant Reveal is the leading tissue-free MRD test, backed by the largest clinical evidence base. With minimal sampling, I'm getting maximum insights. The Infinity Smart Liquid Biopsy platform integrates the data I need into one clear picture. That's a game changer for me and my patients. AI Learning Engine and Smart Platform powering our liquid biopsy platform, I detected a patient's cancer weeks earlier than with standard tests. That time meant everything. At Guardant Health, we're just getting started. More apps, more biomarkers, more ways to put the power of targeted treatment into the hands of clinicians everywhere. Powered by a large blood-based dataset, we're leveraging AI to unlock new answers in detection and treatment. Each test transforms how oncologists get to decisions faster. With more applications coming, the Smart Platform is scaling rapidly. It's the leading platform for the future of cancer care. The Smart Platform, only from Guardant Health.
Okay, thanks, Craig, for detailing our clinical work. Now I'll dive deeper into the oncology business. Therapy selection market in the U.S. represents one of the largest opportunities in oncology, with roughly 1 million advanced cancer patients and a total addressable market of about $10 billion. Guardant is leading the market with a suite of groundbreaking products, Guardant360 CDx, which was the first FDA-approved liquid biopsy in the space, and our newer products in our Smart Platform, Guardant360 Liquid and Guardant360 Tissue, representing best-in-class tests giving oncologists a complete view of cancer and, more importantly, a differentiated toolbox to do more both across blood and tissue than anyone thought possible in the field. Together, these products have established Guardant Health as a clear leader in therapy selection, reshaping how advanced cancers are diagnosed and treated. Let's take a closer look at the portfolio.
Guardant360 CDx has a turnaround of under five days, and it really set the standard in the category with a series of firsts in the industry, including first FDA-approved liquid biopsy, and remains a workhorse of therapy selection in the space today. Guardant360 Liquid, our flagship CGP test and the most comprehensive liquid biopsy in the market, profiles over 740 genes with leading sensitivity. It's powered by our Smart Platform, integrates genome-wide methylation, and that powers over 15 smart apps today. Results are delivered on average in under seven days, which is also faster than any competitive product in the space. Guardant360 Tissue, our newest addition and the only true multimodal test in the tissue CGP space, brings together DNA, RNA, IHC, and genome-wide methylation all in one assay.
With innovations like AI-powered PD-L1 and smart-enabled methylation coverage, it is positioned to deliver the same wave of novel, first-in-class applications that drove the accelerating adoption we saw with Guardant360 Liquid. As we said before, we're the clear leader in liquid comprehensive genomic profiling. Here's how we see the market today. We see the market as about a $3 billion opportunity, with most patients receiving about one test in their lifetime today. At present, the market is still very much weighted towards tissue, although liquid testing plays a major role now. Looking ahead, we expect this opportunity to expand to about $10 billion, with the majority of that growth coming from liquid testing. The reason is simple.
Instead of a single liquid or tissue test per patient per lifetime, we believe that the standard of care is shifting towards four to five liquid tests per patient each year, a massive increase in testing opportunities. Trials like SERENA- 6 with testing of breast cancer patients for molecular progression tangibly demonstrate this exciting paradigm of frequent liquid CGP testing is very, very near. To state the obvious, this kind of frequency is only possible with liquid testing, faster, minimally invasive, and more scalable. As the power and clinical utility of Guardant360 Liquid increases through the integration of smart apps, our data mode, Infinity AI, new applications are unlocked that drive further adoption and further accelerate our share gains. Let's dive a little bit deeper in terms of how our Smart Platform works and how it's differentiated from other products in the field.
We have multiple layers of very rich information that is coming from each patient across genomics, epigenomics, transcriptomics, proteomics, and real-world evidence. We're able to marry the molecular data, such as genomic and epigenomic information, with real-world evidence, which includes the type of drugs the patients were on, types of adverse reactions, treatment outcomes, and so on, and combine that all together to see new patterns in the data, new diagnostic applications, and new predictive signatures with our Infinity AI Learning Engine. Ultimately, these novel discoveries are powering our ability to classify disease with much higher precision than has ever been done before. As a result, what you're seeing is the recent onslaught of our smart apps.
In a remarkably short time, our Infinity AI Learning Engine has powered the launch of 15 applications as part of our Guardant360 Smart Platform and will soon fuel the launch of many, many more applications, as Darya highlighted. Let me share an example of how this works more specifically. This is a circular tumor biology map that was introduced earlier by Darya. These are in every report that we have in Guardant360 Liquid. It's a unique visual language and sort of tumor biology framework that we've developed at Guardant. As we essentially collect more and more multimodal information from patients, we can dramatically increase the number of patients in our database. We're able to map this tumor biology in higher and higher resolution, basically seeing the specific nature of a single patient's disease in much more detail.
As shown here, as you move forward from left to right, you can see that we can map this breast cancer in increasing density. Basically, as we go from testing thousands of patients to tens of thousands of patients to hundreds of thousands of patients and eventually millions of patients, we're able to essentially map the subtypes and subtypes of subtypes. We call these, you know, these almost micro subtypes, we call them methyl tumor types. They're redefining how we classify cancer at a fundamental level. This allows us to pinpoint the particular nature of a particular tumor of a particular patient's disease and use that information to develop applications and predictions that are truly suited for that patient. This is what was imagined when the term precision oncology was coined many years ago, but is finally only coming to fruition with our Smart Platform.
In this sample, we can take this specific patient's methyl tumor type, run it through our Infinity AI Learning Engine against over 1 million patient samples and clinical real-world evidence to predict what outcomes for that particular disease may be with some of the available treatment options. This is what I mean by a data mode. This type of predictive power is only possible when you have hundreds of thousands of epigenomic data samples and treatment outcomes. Here are the outcomes here for that patient. This only gets better and better over time with each successive patient we help in the field. It's really exciting to see the power of this platform and where it's likely going to go. As Darya highlighted, our Smart Platform is unlocking a wave of new applications that are driving real excitement in the field.
I was at ASCO a few months ago, and it was really exciting to see just how engaged KOLs were, the clinicians were, in terms of some of these new applications that have never been possible before. Just at ASCO, we launched 11 of those apps in May, and we have dozens more in development that will roll out not just on Guardant360 Liquid, but on tissue as well as Reveal because they all share the same epigenomic backbone. What makes Smart powerful is that it turns a single blood or tissue test into far more actionable information. Each application builds towards what we see as a GPS for cancer care, guiding physicians with the right insights at every step of the patient journey. As you just saw, the Smart Platform has unlocked many new applications.
What's important is these aren't just interesting scientific advances, but they're positively impacting the growth trajectory of our business. With the introduction of Guardant360 and Smart, we've seen a clear acceleration in Guardant360 volumes. Over the past four consecutive quarters, volume growth has reaccelerated, some of the strongest growth we've seen in the Guardant360 franchise in years. This is a clear sign of excellent product-market fit, mirroring the adoption pattern we saw earlier with our biopharma customers when Smart was first introduced a year earlier. This is only the beginning. Looking ahead, we see two main dimensions of volume expansion in the U.S., in addition to continued market growth. One, continued share gains as Smart becomes even more powerful. Two, rapid growth as physicians expand the use of liquid biopsy beyond the first test toward repeat progression testing and monitoring.
Applications like tracking tumor evolution, both histologically and genomically, will make Guardant360 a routine part of care at each stage of the patient journey. Of course, a prime example of this is tracking tumor evolution through liquid biopsies, the SERENA- 6 trial sponsored by AstraZeneca, where Guardant360 was the enrolling assay. In this study, breast cancer patients were tested with Guardant360 three to four times per year to detect the emergence of ESR1 mutations. When those mutations were identified, patients were switched to a next-generation oral therapy before radiographic progression. This is a true paradigm shift. Instead of waiting for visible progression, physicians can now make proactive therapy changes based on molecular signals. While that trial focused on breast cancer with a prevalence of over 40,000 patients in the U.S., we believe the same model will likely become the new care standard across multiple tumor types over time.
We believe this will result in an MRD-like testing opportunity for liquid biopsy in the therapy selection space, and we look forward to the potential approval of Guardant360 as a companion diagnostic for the drug. Shifting gears a bit, today I'm really excited to share an important milestone for Guardant360 Liquid. We have recently officially submitted our PMA application to the FDA for Guardant360 Liquid, a critical next step on the path to FDA approval. This submission is more than a regulatory step. It positions Guardant360 Liquid to become our single flagship FDA-approved liquid biopsy for therapy selection, further catalyzing adoption, simplifying our portfolio, and strengthening our leadership position in the space. With FDA approval, we also unlock the potential for ADLT status for the expanded test, which will create a pathway to improved pricing.
This marks another important step in the Guardant360 journey, bringing the most comprehensive liquid biopsy on the market one step closer to full FDA approval and establishing it as the new standard for cancer care. Now let's take a step back and look at the full cancer care journey. Beyond therapy selection, there are two other critical patient segments in oncology where Guardant is making a huge impact. First is for early-stage patients, where detecting residual disease can guide treatment decisions, and for cancer survivors, where monitoring can help what we call provide those patients quantitative peace of mind for detecting recurrence earlier. These moments are just as critical for patients as therapy selection, and they represent yet another major frontier for liquid biopsy. If therapy selection is about guiding the right treatment today, the frontier of minimal residual disease, or MRD, is about ensuring the right outcomes for tomorrow.
The opportunity here is enormous. In the U.S. alone, there are roughly 18 million patients who are either early-stage cancer patients or cancer survivors. This translates into a total addressable market of about $20 billion. Guardant is a clear leader in tissue-free MRD, and Guardant Reveal is the leading tissue-free product in this space. This is one of the largest emerging opportunities in oncology, and we believe Guardant is uniquely positioned to lead it. Let's break down those 18 million patients and why a tissue-free solution is critical. First off, roughly 12 million individuals are more than five years out from surgery. For them, tissue is often impossible to obtain, which makes a blood-only approach essential. Furthermore, when tissue is available, tissue can be less relevant given tumor evolution and additional primaries. Accordingly, physicians often prefer the wider catchment a detection approach like a tissue-free approach can provide.
Additionally, even in the adjuvant setting, 10% - 30% of patients, especially in cancers like pancreatic or lung cancers, simply don't have usable tissue for a tumor-informed MRD test. This is why tissue-free is just not more convenient. It's actually the only way to serve a pretty significant part of the market. Despite the size of this opportunity, penetration is still under 3% across the industry. We really are just the beginning stages of this very exciting market opportunity. Let me share more about Guardant Reveal. Today, we believe it is the most advanced and highest-performing tissue-free MRD solution on the market, with market-leading sensitivity down to 50 parts per million. Built on a Smart Platform, Reveal delivers precise methylation-based tumor fraction quantitation, setting it apart from other approaches.
With an average turnaround time of about five days, it provides results faster than any other commercial solution on the market today, which can be critical in guiding meaningful clinical decisions. Over the last 18 months, we've made strong progress in operational execution to drive greater volume growth for Reveal without adding to overall cash burn. At the start of this year, we secured Medicare coverage for CRC surveillance at $1,644 per test. Since then, ASP has stepped up meaningfully, reaching about $600 - $700 per test in Q2 of 2025. We remain on track towards a $1,000 ASP target by 2028. We've also reduced the cost of goods by more than 50%, with 2025 COGS expected to be around $500 per test. The combination of higher ASP and lower COGS has moved Reveal into positive gross margin territory today.
Together, these exciting developments and improvements set up continued momentum for the Reveal franchise and support our broader path to profitability. Now let's take a look at a few highlights of the extensive clinical data that we are producing with Guardant Reveal. Earlier this year at the American Society for Clinical Oncology, we presented results of what we believe to be the largest MRD clinical study presented to date. The N0147 trial was a stage III colon cancer study that consisted of over 2,000 patients, and we saw that methylation-based tumor fraction from Guardant Reveal could accurately predict disease-free survival and related outcome measures much better than the standard of care. Furthermore, we're very excited for the additional clinical utility readouts, such as the upcoming readout from PEGASUS, which Craig Eagle highlighted earlier, in just a few weeks at ESMO 2025.
We also recently submitted a breast cancer data package to MolDX for Medicare reimbursement for Reveal. In this study, we saw 100% sensitivity for ER-positive, HER2-negative breast cancer. In another study, we saw 83% sensitivity in the surveillance setting for triple-negative breast cancer with very, very high specificity. Breast cancer is one of the largest indications in MRD, and we would point out that we are already experiencing very strong momentum with Reveal in the breast cancer setting. One of the biggest challenges in oncology today, though, is knowing in real time whether a therapy is actually working. For many classes of drugs, and especially for immunotherapies, clinicians often have to wait months to rely on scans that do not always tell the full story.
To this end, in the RADIOHEAD study of 521 patients, Reveal was validated in its use of identifying non-responders more than three months before disease progression and before it was visible by standard imaging. This was published in Cancer Research Communications and was recently submitted to MolDX for potential Medicare reimbursement. While this is an important step in our vision of liquid biopsy as a new care standard and therapeutic monitoring, immunotherapy is but one of many classes of therapies used in the field today. Traditional chemotherapy, for instance, is still used in over 60% of cancer patients, and still no MRD or monitoring tests have been validated with this class of therapy to date. This lack of progress in the field has even caused some to wonder if perhaps ctDNA cannot be used to monitor certain classes of drugs.
For this reason, we are excited to share we now have data showing Reveal can be used to monitor response across chemotherapy, CDK4/6 inhibitors, and of course, immunotherapy with validation of other therapeutic classes in progress. Indeed, by leveraging the epigenomic backbone of our Smart Platform, we can stratify responders from non-responders with precision across almost all the most commonly used therapeutic classes, all from a simple blood draw, tissue-free. To our knowledge, no other ctDNA monitoring tool has validated this broad scope of application across all major therapeutic classes and all solid tumors. We're also pleased to report that these results are being readied for publication and will be submitted to MolDX for reimbursement. With this exciting data and new capability in hand, I'm thrilled to announce that later this year we'll launch Guardant Reveal for therapy monitoring. This is more than just an extension of our MRD platform.
We believe it will set a new standard for how diseases are tracked and adaptively managed. Instead of waiting for radiographic scans, physicians will soon have a liquid scan, a simple blood test that delivers a real-time view of how patients are responding to treatment. When paired with Guardant360 Liquid, this becomes even more powerful. Together, they create a seamless system to treat, monitor, and retreat patients again across successive lines of therapy. We believe this launch represents the next major step in making liquid biopsy indispensable in everyday care. As we presented at the last Investor Day, we have tens of thousands of samples across multiple tumor types that we had banked for potential clinical validation of Guardant Reveal across dozens of indications. I'm proud to announce that we've made excellent progress around accessing those biobanks and have been diligently working on a number of these studies.
For 2026, we plan a 10x increase in Reveal data generation and expect this to result in over 20 publications, with many of these publications supporting additional Medicare reimbursement submissions. I'm very proud of our team that has done an amazing job in terms of securing relevant clinical studies, patient samples, and working with key clinical research collaborators to be able to increase the rate of generated data that will help cement Reveal's place as the leading tissue-free MRD platform for years to come. Diving more deeply into the specific studies and indications we have planned to support reimbursement, we were successful in achieving CRC surveillance earlier this year and recently submitted dossiers for breast and IL monitoring for Medicare coverage. We'll be submitting packages for chemo, CDK4/6 inhibitor monitoring as soon as those publications are out.
Not too far behind those, our studies will support indication expansion for Reveal in over five additional tumor types in both the adjuvant and surveillance settings. Now I want to shift gears a little bit once again. One of the biggest remaining challenges we see in tissue-informed MRD testing is sensitivity. In many tumor types, especially in low shedding tumor types, it's critical to detect cancer at ultra-low levels, well below 10 parts per million. The reality is that despite these bold claims, we believe that none of the available tissue-informed approaches used today can reliably reach that threshold on true clinical samples. In fact, most current exome and even whole genome assays plateau between 100 and 10 parts per million. That leaves a critical blind spot where cancer may be present, but today's tests simply can't see it.
Even at ASCO this year, many clinicians expressed the need for what they called ultrasensitive MRD tests. This is why we believe there is a clear need for a next-generation ultrasensitive tissue-informed MRD test that pushes sensitivity much, much further. Today, I'm thrilled to announce the next leap forward. We've been developing a new test internally, and it's ready to push the envelope of what's possible in MRD. We're introducing Guardant Reveal Ultra, a breakthrough that pushes tumor-informed sensitivity down to an unprecedented level, approaching one part per million. This new test opens the door to ultrasensitive applications in cancer care that until now were out of reach. Let me share a preview of how this technology works. Guardant Reveal Ultra is built on our Smart Platform and combines the best of both worlds, the best of our liquid and tissue technologies.
The result is a groundbreaking new MRD test with unprecedented sensitivity down to about one part per million, as shown in the figure on the right. Flexibility, Guardant Reveal Ultra is designed to fit seamlessly alongside the rest of our portfolio. Speed and ease of use, results delivered rapidly and reliably using our tissue CGP technology that can work with even challenging tissue specimens. We look forward to sharing more details about this exciting addition to our oncology portfolio soon. Now I'd like to share a patient story to give you a flavor of how our tests are working synergistically together. In April of 2022, a 54-year-old woman completed treatment for triple-negative breast cancer. Given her high-risk disease, she was under close surveillance for the next two years. During one of her follow-ups, PET imaging showed significant activity in her upper chest.
Given this patient's comorbidities, the risks were too high to move forward with a tissue biopsy without additional data, so our oncologist ordered a Guardant Reveal test. The test came back positive, signaling the recurrence of breast cancer, and was later confirmed to be recurrent triple-negative breast cancer. Given the recurrence, her physician was able to quickly order a Guardant360 test off of the same blood draw, just using our portal. Guardant Reveal promoter methylation of BRCA1, which no other test in the market can do today. Based on this information, her physician treated her with Talzena, a PARP inhibitor. Within three months, the patient was no longer showing radiographic evidence of disease. This case is a powerful reminder of how our tests aren't just identifying disease earlier. They work together seamlessly, actively reshaping treatment decisions and driving better outcomes for patients.
To summarize a few key takeaways in our oncology business, we're the number one player in CGP today with accelerating growth, and we're continuing to extend our leadership position based on groundbreaking innovation from our Smart Platform and best-in-class commercial execution. This Smart Platform and the growing data treasury, combined with Infinity AI, is allowing us to rapidly develop unprecedented new clinical applications. We are making great progress around Reveal in terms of multiple indications supporting MRD and monitoring applications, as well as a major inflection in data generation that will support even more submissions in the coming years. We are the number one player in tissue-free MRD and very excited to introduce Reveal Ultra as a best-in-class ultrasensitive tumor-informed MRD product. With that, I'll hand it over to Chris Freeman, our Chief Commercial Officer for Oncology.
Thank you, Helmy. Good morning. My name is Chris Freeman. As Helmy mentioned, I'm the Chief Commercial Officer supporting the oncology business. Today I'm going to talk about how we bring all these amazing novel technologies to the market and ultimately how we can impact and change how cancer patients are treated. Over the last few years, we've seen a rapid increase in demand across the oncology portfolio, particularly in the past 12 months since the introduction of our Smart Platform. Importantly, we've been able to translate that volume into revenue growth. I'm going to explain what we did commercially to accomplish that and what we have in store for the future. As Helmy mentioned, everything at Guardant is predicated on our best-in-class technology. We pride ourselves on having pioneered the liquid biopsy space and providing world-class lab operations.
That's resulted in industry-leading turnaround times across the portfolio, which is a key point of differentiation to physicians who are making urgent treatment decisions. We also take great pride in making these technologies available across the country to community oncologists. Since we last met, Guardant 's made dramatic improvements across our core products. First, we significantly expanded the genomic panels for both our liquid and tissue tests, covering all guideline-recommended biomarkers. Second, we expanded our portfolio to include peripheral testing capabilities such as RNA, IHC, germline, and that helps us accomplish our goal of providing a complete portfolio. Finally, as we've discussed today, we've begun to unlock the power of epigenomics and explore novel use cases that can only be realized through this technology. By now, you've seen this slide a few times, and that is intentional. This slide depicts our commercial strategy and highlights our greatest advantage.
Now that we've established Guardant 's best-in-class technology across the portfolio, commercially, we've invested considerable time and energy into connecting our tests in a way that optimizes patient insights. Cancer care is complicated, and we've worked with physicians to simplify the ordering process through ordering bundles, workflows, and digital tools. So far, we've seen a really positive reaction from customers who appreciate how these workflows align with treatment guidelines and their own standard of care practice. As a result of these efforts, today, the vast majority of U.S. oncologists regularly incorporate Guardant into their practice. In recent years, it's been exciting to see the rapid increase in the depth of ordering, not just across our individual product lines, but increasingly in combination through the mechanisms that I just described. How do we continue to scale? We scale by bringing world-class commercial infrastructure to the market.
At Guardant, we're able to amortize that investment across the entire suite of products. I'm going to spend a little bit of time talking about some of these topics, but suffice to say, Guardant is extremely well-established with our customers. Since we last met, we've expanded our EMR footprint to over 1,000 accounts. That's resulted in significantly more digital ordering, which allows us to take advantage of some of the testing bundles and workflows that I discussed. We continue to set the standard for turnaround time, and we've had significant managed care wins, particularly with major commercial payers. As you saw from Helmy and Darya, we have quite a bit to talk about with our customers regarding the latest data and use cases for our test. On an earlier slide, AmirAli showed a number of oncology launches.
Over the past two years, that translates to a new product launch or major upgrade every quarter. Our rate of innovation in oncology is breathtaking. Therefore, getting in front of doctors to educate on these innovations is critical. We've worked hard over the years to provide an elevated customer experience and, as a result, have earned unprecedented access in the diagnostic industry. This allows our team to provide updates on Guardant tests, coverage, and various partnership opportunities. Why does the Guardant Health team get so much time with doctors? The formula is fairly simple. When you combine world-class products with a world-class team, that leads to access. We've been able to convert that access into physician demand across the portfolio. Now that we've driven demand, the next step is to ensure that physicians can order our tests and that they're covered by payers.
I'm pleased to share the immense progress that's been made in establishing our digital footprint. Today, 2/3 of physicians can access Guardant Health tests through their health system EMR. Over half of our orders are received digitally. This represents our fastest growing segment with continued room for expansion. Earlier, I highlighted that our core products are covered for over 310 million Americans. Our work is not done. Guardant is committed to ensuring that all of our tests are available to patients who need them. In support of that goal, Guardant Health has helped drive legislation at the state level. In the past two years, 10 additional states have enacted biomarker legislation. Our team has been successful in states like Arizona, Louisiana, and California, in working with state insurance commissioners and patient advocacy groups to ensure that payers comply with these laws.
Once we've established demand and we've helped provide access to the tests, we need to ensure that we're paid appropriately for our services. I'm pleased to share that we've seen strong ASP improvements across the portfolio. For Guardant360, we've had the opportunity to leverage Medicare price increases. As I mentioned before, we've had significant commercial payer progress with Anthem, Aetna, United, and Humana now covering our tests. In addition to that, we've been able to increase the Medicare price for our tissue test. With the inclusion of RNA to Guardant360 Tissue, this provides additional opportunity for ASP increases. Finally, as Helmy mentioned, we've secured Guardant Reveal coverage for CRC surveillance and have a number of ongoing submissions that could potentially drive that ASP further. We're very excited about the progress that we've made in the U.S.
Now we're taking that same approach globally, where there remains significant opportunity and significant unmet need, especially as it pertains to CACS for cutting-edge CGP testing. Across Europe and Canada, we've made progress with national reimbursement. This has been achieved in large part because of our strategy in establishing public-private partnerships with key academic centers in country, most notably the Royal Marsden Lab in the U.K., which has led to recent NHS reimbursement for non-small cell lung and breast cancers. As you know, we also have PPP labs established in Spain with VIO and are anticipating Gemelli in Italy to come online later this year. Across Europe, in part because of these efforts, we've seen either the approval of new reimbursement policies or the acceleration of national coverage negotiations. Outside of Europe, we continue to make progress in the Middle East and in Japan.
In the Middle East, since we last spoke, we've struck a commercial partnership with HCMA. In Japan, Guardant360 is the only liquid biopsy test approved, and it has, as of just this week, 10 CDx approvals. I'm proud of the progress over the last few years, both in terms of driving demand across the portfolio and driving additional revenue. However, this is just the tip of the iceberg. On the therapy selection business, moving to the Smart Platform, we have the opportunity to leverage wave after wave of novel applications. Many of these applications will be unique to Guardant and help us to differentiate in this space. On the monitoring side, we're excited about the addition of an ultrasensitive tissue-informed MRD assay to complement our market-leading tissue-free Reveal test.
At the same time, we will continue to make commercial investments that make it easier for physicians to access our tests, inclusive of portal enhancements, continued EMR integrations, and enhanced workflows. We will continue to explore potential ASP runway with the ADLT opportunities Helmy just described. In summary, we have built an incredible product portfolio over the last decade, spanning the entire continuum of care. At the same time, we've built a world-class commercial team and infrastructure. As groundbreaking as the individual tests in our portfolio are, what's even more exciting is that all of these products share the same Smart Platform and how that provides a unique competitive advantage. All of our tests, from Shield to Reveal to Guardant360, work synergistically across the entire spectrum of cancer care. Data collected from one test is seamlessly mergeable with data from another.
It is effortless for an oncologist to reflex from Guardant Reveal to Guardant360 and back again, creating a truly differentiated platform experience. Because the technology foundation is shared, the clinical information that we can derive is also richer and richer as physicians use more of our tests per patient. This testing ecosystem and the insights it creates lead to a very sticky and unique experience. We look forward to sharing more as we continue to populate our testing ecosystem with clinical applications driven not just by a single product, but by the entire platform. With that, I will turn it over to Jamie to detail progress with our biopharma business. Thank you.
All right. Thank you, Chris, and good morning, everyone. My name is Jamie Boyle. I'm Senior Vice President of Business Development, leading our biopharma commercial business. I'm excited to share a deeper look at our business with the investor community today. Over the past three years, the launch of our Smart Platform has been a true game changer for our biopharma business, driving innovation, accelerating adoption, and fueling growth. Our biopharma business also serves as a key leading indicator for the clinical business. Because we work hand in hand with our partners at the earliest stages of drug development, we gain unique visibility into emerging biomarkers, new therapy areas, and testing needs long before they reach the clinic. In other words, success with biopharma today helps to seed tomorrow's clinical growth. This combination of performance and efficiency is a clear leader in the space, and we're just getting started.
To date, we've achieved tremendous growth by partnering with over 190 lifetime biopharma customers, including 19 of the top 20 companies, allowing us to tap into a total addressable market of more than $3 billion. Our team has consistently delivered outstanding results. We're not only generating significant revenue, outpacing many of our competitors, but we're also doing so with strong margins that put us firmly on the path to sustained profitability. The launch of our Smart Platform, coupled with our growing partnerships, has helped us to generate tremendous growth over the last few years. 2024 was a banner year for the business, with 30% growth, and 2025 is off to a great start. We have delivered record performance in Q2 of 2025, and we're extremely confident in double-digit growth this year and beyond.
As noted earlier, we've been offering our Smart Platform to biopharma for several years now, and over 50% of our volume is now being run on this platform. As Darya and Craig highlighted earlier, achieving true precision oncology cannot be achieved through genomics alone. A recent meta-analysis published in the Journal of the National Cancer Institute indicated a critical gap. While 60% of patients tested with NGS present with genomic alterations, only 15%- 25% ultimately receive a matched therapy. Therefore, many patients are still unserved, even after comprehensive testing. This is exactly why we are so energized about the potential of epigenomics. Powered by our Smart Platform, we believe epigenomics represents the next frontier, unlocking a wave of groundbreaking discoveries that can expand precision oncology to more patients than ever before. Biopharma companies need a partner that can help them move faster and achieve breakthroughs.
Our mission at Guardant is to help improve our partners' odds of advancing new therapies to market with our technology. There are several ways in which we can accelerate drug development with our best-in-class services. First, we have expertise in companion diagnostics with approvals across the U.S. and around the world. Second, as we've already mentioned, genomics alone is not sufficient for precision medicine. By providing genomic and epigenomic insights with our testing platform, we can fuel translational research and improve the likelihood of identifying and targeting the right patients. Finally, our Infinity AI Learning Engine, applied to our real-world and molecular data, can provide even deeper insights. I'll expand on each of these further in the coming slides. Expanding on our CDx track record, we are a leader in companion diagnostics with 22 approvals across the U.S., Japan, and Europe.
We have a strong pipeline of new approvals that are coming soon. In the first half of 2025, we've already submitted multiple sPMA submissions and continue to execute on new partnerships with key customers. As Helmy mentioned earlier, we're excited to share that we've recently submitted the PMA for a liquid assay on the Smart Platform. This milestone marks an important step forward, helping us to expand the biomarker landscape with our partners. It also represents a powerful catalyst for driving our clinical business, accelerating adoption, broadening our market opportunity, and strengthening our leadership position in precision oncology. To underscore our leadership in companion diagnostics, I'd like to highlight a powerful example. Guardant Health is proud to have partnered with AstraZeneca as the enrolling assay for the SERENA-6 study, which was recently presented at ASCO .
This builds on our leadership as the first FDA-approved companion diagnostics for ESR1 in breast cancer, which we received back in 2023. The study itself is practice-changing in many ways and reflects the innovative surveillance design pioneered by AstraZeneca to help reach more patients in the treatment class. This recognition not only reinforces the critical role of our CDx partnerships, but also demonstrates the trust that our partners place in us to help bring the next generation of targeted therapies to patients. We are not stopping there. Together with our partners, we are bringing novel utilization of ctDNA to other tumor types, expanding on the potential for breakthroughs that can transform care for thousands more patients worldwide. In order to further support global clinical studies and companion diagnostics, we launched our partnership with ADACON for biopharma testing in China about 18 months ago. Oncology testing in China is not simple.
Specimens cannot leave the country, and local labs may not have a consistent solution for China and rest of world testing. This partnership positions Guardant as a provider with a seamless solution for clinical trial testing and enables biopharma to extend their testing into China with the same technology partner. We've engaged with over 30 partners and have over 15 of those already under contract. As a result, we expect to grow significantly with volume expansion over the next few years. Finally, ADACON has established themselves as a credible and reliable partner, including successfully running multiple phase III prospective studies. Our growth in companion diagnostics is fueled by our commitment to advancing science. Through our technology, we help translational researchers unlock new drug development strategies with genomic and epigenomic biomarkers to help improve patient outcomes and also expand label opportunities.
Our current and future applications can offer multiple solutions, including a few of those that you see listed here: response prediction, enhanced patient identification, molecular tumor subtype identification, adverse event prediction, and quantification for MRD and monitoring. Historically, biopharma companies have had to navigate multiple partners to access this full range of solutions. However, today, by partnering with Guardant , they can access this full range of applications through a single platform. One example of an epigenomic application that our customers are keenly interested in is ctDNA monitoring for dose studies. Typically, optimizing dosing in a trial requires aggressive methods that may lead to patient toxicity.
As illustrated by the figure here, by using ctDNA clearance as a surrogate marker and identifying a point of ctDNA clearance with minimal dose, this publication with Amgen showed how epigenomic tumor fraction could be used as a proxy to provide faster and safer dose optimization. Additionally, we are expanding our partnerships in new ways that provide even greater value. This year, we were pleased to announce a strategic collaboration with Pfizer aimed at using our platform across Pfizer's oncology portfolio. This includes using our assays in clinical studies around the world, evaluating the clinical utility of methylation applications, and partnering on the development and commercialization of new therapies. Another way that we are deepening partnerships is through the expanded use of our data. As you heard discussed earlier by Craig and Darya , we are using our data in new ways, including unlocking the potential of multimodal biomarkers.
By applying AI to our massive genomic and epigenomic database, we can identify patterns and features that would otherwise remain hidden. Using this multi-dimensional approach to identify biomarkers can allow our partners to tailor their drug and biomarker from multiple angles along the drug discovery journey, including early stage, clinical development, and trial design and launch. Essentially, our platform enables better precision. As we look to 2026 and beyond, there are several growth drivers for our business. First, by unlocking epigenomic applications with our Smart Platform combined with AI, we are creating new paths for drug development and future revenue streams. Second, the addition of ultrasensitive MRD, as discussed earlier, will position us to accelerate and expand share in these markets. Third, the expansion of our Smart Platform to tissue testing creates an opportunity with biopharma beyond liquid, strengthening us as a comprehensive precision oncology partner.
Finally, our growth in CDx partnerships will expand as we enable new biomarker discoveries and testing paradigms. In summary, we introduced our Smart Platform to biopharma three years ago, transforming the industry and providing a major catalyst of growth for Guardant Health. With paradigm-changing companion diagnostics, the biopharma business serves as a key leading indicator of our clinical business. Additionally, the Smart Platform is a catalyst for transformative partnerships, supporting biopharma across every stage of clinical development and empowering smarter and faster decisions. We can enable biopharma to identify novel biomarkers and customize drug development with our growing epigenomic database combined with AI-driven insights. Our biopharma business has achieved many firsts in the industry, and we are focused on shaping a healthier future for patients worldwide with our partners. Thank you. I think I'm turning it back over to Zarak.
Thanks, Jamie. We're going to take a 15-minute break, everybody. Jump into screen.
is a game-changing blood test recently approved by the FDA for colorectal cancer screening. Coming up on CBS Mornings, a potential game changer in the fight against cancer. The FDA just approved a new way to detect colon cancer in its early stages. A lot of people don't want to do those stool tests, so now we have a simple blood test. Shield received the first national guideline recommendation for screening. A couple of weeks after I had my blood drawn and the test was sent out, I received this text message with a link for my results. We have been expanding access across the country. You can take a blood test with your doctor to be screened for colorectal cancer. Sheila has won major awards, recognizing the platform's innovation. We're live on the air, connecting Guardant Health with audiences nationwide. Did you hear about Shield, that test for colon cancer? No, what? Just a blood test. No sh. Exactly. I don't have to spend time doing all that other stuff? Nope. No sh. Bring it back. No sh. Shield is for people 45 plus at average risk, not high risk, for colon cancer. Ask your doctor if Shield is right for you. For a more pleasant way to screen, ask about Shield. Craig, you might have heard of Shield. This was the first FDA-approved blood test for colorectal cancer screening, approved in 2024. It's a big deal. Today, James is here to spread the word about the importance of colorectal cancer screening. There are a lot of options out there. I teamed up with Shield by Guardant Health. Beyond CRC, the Shield MCD device has been granted breakthrough device designation by the U.S. FDA, recognizing its potential to offer a more effective approach to cancer screening. Based on its strong overall performance, the National Cancer Institute recently selected Shield MCD for its landmark Vanguard study. We're not stopping there. Today, we are officially announcing the expansion of Shield to include multi-cancer detection. At the same time, we're launching a data collection effort reaching hundreds of thousands of patients to better understand the clinical impact of this breakthrough technology. With Guardant's innovation, we're continuing to open the door to transform millions more lives.
Okay, we're on. Welcome back, everyone. It's hard to beat the exciting presentation that we had before the break, but I'm excited to actually do a deeper dive on our screening business and the future of cancer that we are envisioning. For years, we envisioned a world that everybody would have access to a blood test, a simple blood test to screen for cancer during annual checkups. Those days are not far away. From the very beginning, we built Shield as a multi-cancer detection platform, a platform that can detect and catch many cancers at the early stage when they are more treatable. With that vision in mind, we built this technology stack. We chose CRC as the first indication for Shield because of the attractive balance that exists in the CRC market to meet a big unmet need of filling the gap in improving CRC screening rate.
Also, a field, a cancer type, screening for a cancer type that has a clearly established pathway for regulatory approval and reimbursement to make sure at the end, patients at scale would get access to this life-saving technology. Let me first focus on CRC. We are going to talk about multi-cancer detection after. Our pivotal study has shown that we have market-leading performance for blood-based testing of 83% sensitivity in detecting colorectal cancer at 90% specificity, which was published earlier in New England Journal of Medicine. The promise of this blood test for colorectal cancer screening has been to offer a more pleasant, convenient option and a new choice option for patients and physicians to have access to. Shield got FDA approval as a primary screening option last year, and right after that, we launched it just over a year ago.
What we are seeing in the marketplace is over and over, the physicians are enthusiastically using Shield, ordering it, and when they order it, patients complete the test. The adherence rate or the completion rate of Shield blood tests continues to be more than 90%. In practice, what we are seeing today with the Shield volume that we are running, 90% of the patients who've been tested are the patients who had no history of CRC screening during the last five years, which is a clear signal that our targeting is working, as at this time we are targeting an unscreened patient population. In fact, those unscreened patient populations are getting screened with Shield. We have completed several studies now, some randomized with health systems, major networks, in terms of how Shield is really helping them to increase the overall screening rate.
For example, in one large health system, the screening rate was just over 45% after many attempts of using different modalities over a few years to increase the rate of screening. Once Shield was added as a new choice in the menu, the rate of screening went up by 2x to almost 90%. Interestingly, in another study shown in the right bottom, for the individuals who were overdue for screening, when the Shield was established as a choice for those patients, among other modalities, Shield was a test of choice for 65% of those patients versus 35% of the time for the other modalities combined, colonoscopy and stool tests. We are very excited with these results as the near-term validation of the potential long-term opportunity that really Shield has to improve screening rate and really to capture a very meaningful market share of CRC screening in years to come.
We are very pleased with where we are standing with guidelines at this time. In late May, early June, we were very encouraged to see that the National Comprehensive Cancer Network, or NCCN, updated its CRC screening guidelines to include Shield. As you know, NCCN is the voice of oncologists and arguably the most respected body in the oncology field. This first national guideline inclusion gives us additional confidence that Shield will be added to other national screening guidelines in the future. We continue to expect inclusion in the American Cancer Society guideline later this year, which would set the stage for the commercial coverage in over 10 states. We are confident about guideline inclusion by the U.S. Preventive Services Task Force, or USPSTF. Based on the latest development from HHS as it relates to USPSTF, we are not counting on it till late 2027 or early 2028.
This USPSTF guideline inclusion and incorporation into the quality matrix as managed by NCQA is an important catalyst for widespread commercial adoption of Shield. It is interesting that given the uncertainty around USPSTF timing and future, several stakeholders are aligning to encourage action by HHS on quality measures, leveraging alternative guideline bodies like NCCN and ACS. While we wait for USPSTF, we continue to build our base business in the currently reimbursable opportunity for CRC screening, which is massive on its own. Here is the snapshot of our outlook for Shield revenue for 2025. As a reminder, we are not updating our 2025 guidance at this time till our next earnings call. We are currently expecting $55 million- $60 million in Shield revenue this year. This will mark this launch as the most successful diagnostic launch outside COVID testing.
We are on track to exit the year with over 250 reps fully deployed in the field. At a steady state, we continue to have the plan of having 600 - 700 reps promoting Shield by the end of 2028. We continue to anticipate being the market leader in blood-based CRC screening with over $500 million in Shield revenues in 2028. Earlier today, we announced an exciting strategic collaboration with Quest Diagnostics to expand and accelerate access to Shield broadly in the United States. Quest provider clients will be able to order Shield tests and receive results directly through the Quest Diagnostics Connectivity System. This system is used by approximately 650,000 clinicians and hospital accounts. For the blood draw, the patient can go through the Quest 2,000 patient service centers and 6,000 in-office phlebotomy.
In addition, the Quest national sales team will proactively educate primary care physicians and OB-GYNs about Shield, accelerating the awareness among Quest ordering providers about the value of the Shield. We expect Shield to be available for physician orders through the Quest system in the first quarter of 2026. We will continue to process all Shield tests at Guardant and control client services, billing, and reimbursement operations. We would not expect any ASP or gross margin impact as a result of this partnership. Moving beyond CRC, as presented by our team earlier, at Guardant, we have access to a treasure of database across the continuum of care. We leverage the vast epigenomic data that we have captured in this company in CGP, MRD, and Shield screening, and combine it with the clinical data and AI tools.
We are pleased with the progress that we are making in our pipeline based on that data treasury. We are incredibly excited with our announcement earlier today about the expansion of Shield to include multi-cancer detection. How would that work? In order for a patient to get access to Shield multi-cancer results, their physician will need to opt in to receive the multi-cancer report. The patient will need to authorize the release of medical records to Guardant Health. We piloted this workflow in several accounts recently, and we got overwhelmingly positive feedback and reception from the physicians and very strong participation by patients to opt in and also opt in to authorize the release of their medical records. What happens then?
With the launch of this initiative, we are going to have an established scalable platform for clinical generation on one side, which enables assessment of the utilization of M-set testing and M-set results in patient care. We also provide a new avenue to expand patient access to multi-cancer detection, bringing this important innovation to broader patients who are getting tested by Shield CRC today. This nationwide initiative is expected to reach hundreds of thousands of participants, making it one of the most expansive prospective evidence generation initiatives in the early cancer detection field. Now, with this expansion of Shield to include M-set results and patient authorization to release their medical record to get access to those results, we are going to be positioned to even better grow our data moat.
This EMR data is of high quality and can be used as a source of truth for regulatory-grade data since it gives us the details of patient cancer journeys that we would not be able to get access to otherwise. Consider a protocol like this on the left. People who are going through this journey, we can look at the M-set results finding, is it positive and negative, and look at different endpoints in terms of device performance, safety of the device, cancer state shift, and the impact and the value of the interventions which are going to be used on those patients. This data engine, this high-resolution data engine, would help us to power the next generation of Shield M-set development and technology improvement to go to other cancers and to go from just cancers to many other diseases step by step.
As a reminder, Shield M-set as a standalone test has FDA breakthrough device designation and has been selected by the National Cancer Institute for use in its landmark Vanguard study. We now expect this Shield commercial scale and the amount of data that we are going to capture from the medical records would put us in a very strong position to build this high-quality regulatory-grade evidence about the performance and the utility of this test. While we are focused on cancer and many things that you guys are hearing today are about just oncology, Shield is a platform that can go well beyond cancer. As you heard earlier from our team, we have already accumulated a robust data set of epigenomic signatures in hundreds of diseases in asymptomatic individuals. I'm excited about the strength of the pipeline that we are building. I'm excited about the vast opportunities which are ahead of us. Now, let me turn the presentation to Stephen to talk about our commercial operation strategy for screening. Stephen.
Good morning. I'm Stephen Murphy, Senior Vice President of Marketing for Screening, which is our Shield product. It's been about a year ago since we launched Shield, and we brought the first broadly accepted and distributed CRC test in the marketplace out. At that moment, it was kind of like a watershed moment, not just for Guardant Health, but for the industry overall. For decades, it's been very difficult to get movement in adherence in CRC screening. The numbers have stayed stubbornly low for a long time. Shield now becomes a new tool for doctors to use to try to increase those adherence rates. As you saw from the Mary Lee slides, it's working. We're hitting the unscreened, and the product is out there. It works because Shield is the more pleasant way to screen for colon cancer.
It provides a modality that makes it easy for people who have been reluctant to get screened to want to get screened. Since we've brought that forward, we've hit a significant number of milestones, as you can see up on the screen. We've built a vast commercial field force. We've gotten coverage by Medicare. We've gotten ADLT status on our pricing. We've gotten, in our first set of guidelines, built a huge phlebotomy network. Just terrific progress, even within one year. There we go. What's happened in that last year? Within this growth, we've seen consistent double-digit rate increases in test volume, including in our most recent quarter. The revenue has grown significantly, both as a percentage and in absolute dollars. We unlocked a milestone that was terrific. We became gross margin positive within the first 12 months. That was not haphazard.
We made a number of decisions to help drive to that, including a very disciplined focus on reimbursable lives, some smart scaling decisions, and we got some pretty terrific pricing because of our ADLT rate. What that confirms is that the decisions that we went into our commercial model are working. We're seeing the benefits come through within already our first few quarters of performance. We're just getting started. We're in the very early stages of approaching this market. The opportunity, this is just the CRC screening market, but the opportunity here is enormous. $50 billion in the colorectal cancer screening market. Of that 120 million individuals, 54 million of them are unscreened. This is the group that we've been making some great headway with within our first 12 months. The scale of this highlights two things. One, the magnitude of the problem that we're trying to solve.
Two, the opportunity that we have at Guardant Health to deliver value in this marketplace. What is our approach and how are we going to go out and make a big impact in this market? Three things primarily, and it's very straightforward. We are going to leverage the strong value proposition of Shield. Shield is the more pleasant way to screen for colon cancer today. We also have the highest performance of any blood test. We have the industry's strongest adherence rates. With our expanded indications into Medicare, we now bring broad access to another product for coast to coast for Americans, which includes CSO capabilities, which Craig spoke about earlier today. Additionally, within our sales and marketing funnel, we are prioritizing reimbursable lives up and down throughout that funnel. That is supported by a very scalable infrastructure as we grow.
Finally, we use very bold messaging to stand out in a crowded marketplace. You saw one of our ads in the video that just went up. There's another one that's running out in the hallway as well. As we go out to capture this demand, the scaling has gone pretty quickly throughout the last year. We're on track right now to have a field force of more than 250 by the end of this year. That is deployed again against reimbursable lives to make sure that the revenue is flowing in strongly. We expect that growth to continue in the coming years. To support adherence, we've built a national network of 40,000 phlebotomists. This is very important, again, because one of the core value propositions of Shield is the ease at which you can go into your doctor's office and get a blood draw.
Making sure that we've got that full network strengthens the overall value, makes it very simple for the patient to go in and get the draw. I think one of the things that we announced earlier was our deal with Path Group. This is in addition to Quest . Path Group brings us the ability to reach another 250 health systems in 25 states. It's another accelerator in our ability to reach more doctors and more patients. We are integrating across the nation's largest EMR systems. This gets us directly into those electronic systems that doctors and health staff members use every single day. Getting into that workflow is a key part of ensuring that we make it easy for patients to get Shield as quickly as possible. We're live in Athena Health, eClinicalWorks, and Epic.
This is on top of the portal that we already have, and then our Quest partnership, as well as our Path Group partnership. It brings multiple options for HCPs to be able to order Shield. We're using some very bold messaging. I think the headline here speaks for itself. It highlights a core aspect of our value proposition. This is opening doors for us and getting us into the conversation. We take this kind of core concept of a campaign, and we distribute it across a number of the sales materials that we have as well. We're finding that it works. This does, in fact, open doors for us. We don't focus it in any one particular area, but we distribute it kind of across the spectrum of the funnel to drive awareness, improve education, and hit at the point of sale.
We've got TV spots, which we've already talked about, digital ads, direct mail, an influencer campaign, which we recently announced in August. These are designed to drive awareness, become top of mind, but most importantly, at the point of decision, when the doctor and the patient are having the conversation about what screening modalities do you want, we want to ensure that Shield is part of that conversation. In March, we achieved the ADLT designation for Shield. This ensures premium pricing and margin stability for us for the coming years. We're already seeing the benefits of this. We're getting a number of the leading payers in the industry. We're getting reimbursements from them. As Mike Bell will show you later, the ASPs, I think, have been very strong with Shield, something that we've been very happy about.
On the expense side, we are developing a next-generation operating model with our goal to, again, continue to drive long-term profitability for the Shield product. We're applying AI-supported initiatives and evolving our service process to lay the groundwork for a strong, efficient commercial infrastructure. This operational model, coupled with the Smart Platform, will enable continued innovation while maintaining our efficiency. What does that mean? We talked about the demand. We talked about our approach going to get it. We talked about the strong pricing that we get on the revenue side and our approach to scaling. Overall, the fundamentals of Shield are very, very strong. In fact, as Mike Bell will showcase shortly, we expect Shield to reach breakeven in under five years post-launch. This is an exceptionally rapid pace in our industry.
To summarize, in just one year, we've gone from a groundbreaking launch to a nationally recognized, rapidly growing commercial business. We've proven the clinical value. We've built a coast-to-coast infrastructure, expanded our offering to include M-set, and we've laid the foundation for sustainable growth through positive product economics. We've just begun. Shield is not only transforming how colorectal cancer screening is delivered, but cancer screening more broadly. With that, I'll turn it over to Mike Bell, our CFO.
Thanks, Stephen. Good morning, everyone. Great to see everybody here. I'm now going to walk through how everything we've talked about this morning relates to our financials and specifically how it's going to accelerate our revenue growth and our path to profitability. Before I jump into the longer-term financial targets, I just want to remind you all that we're not providing color on the third quarter at this presentation. We'll update our outlook for 2025 when we do our Q3 results on our next earnings call. I want to take a moment to remind you of the 2025 full-year outlook that we provided at our last Q2 earnings. We're driving very strong top-line performance across all our business lines and expect total revenue to be $915 million- $925 million this year, which represents year-over-year growth of 24% - 25%.
Our oncology business is on track to deliver 20% revenue growth, biopharma and data mid-teens growth. In the first full year of the Shield launch, we're expecting screening revenues to be between $55 million- $60 million. We're making significant improvements to our gross margins across all of our products. That's increasing our blended gross margin from 62% last year to 63% - 64% this year. We're continuing to tightly manage operating expenses, which is helping us reduce cash burn for the third year in a row. Looking deeper into our revenue growth over the last few years, we're really pleased that since our last investor day in September 2023, we've seen a significant uptick in revenue growth, which has been driven by multiple factors. Guardant360 Liquid volume has accelerated four successive quarters since we launched the first Smart apps just over 12 months ago.
ASPs have improved across all our oncology products. Our biopharma and data businesses performed incredibly well over the last two years. We're delivering increasing revenue contribution from our successful Shield launch. Looking forward, we are expecting all of our businesses, oncology, biopharma, screening, to contribute positively to our revenue growth over the next three years. In fact, given the strength that we've seen in the last couple of years, particularly with ASPs, Guardant360 Liquid volume, and our biopharma business, we're now increasing our 2028 revenue target to $2.2 billion, which represents a CAGR of approximately 34% between 2025 and 2028. Over the next few slides, I'm going to break out this growth across each of our different revenue lines. Firstly, oncology. We've seen strong acceleration of oncology volume in 2025, with the year-over-year volume growth on track to exceed 27%.
Looking at the multiple growth drivers across the oncology products, we're confident that we'll continue to see volume growth at similar levels over the next three years. For Guardant360 Liquid, the continued rollout and adoption of smart apps will be the key growth driver, as will repeat progression testing and monitoring opportunities. For Guardant360 Tissue, we're already starting to gain traction with our recent upgrades. With our best-in-class test, we feel well positioned to start to grow our market share in tissue CGP. For Reveal, indication expansion and increased commercial focus are going to enable Reveal to continue to be our fastest growing oncology product. As Helmy announced earlier, our new Reveal Ultra test is going to allow us to enter the tissue-informed market with another best-in-class product.
On the ASP front, we've made great progress since our last Investor Day, reaching our 2028 targets for Guardant360 Liquid and Tissue, roughly three years ahead of schedule. As a result, we're updating our 2028 ASP targets. We believe we can continue to expand commercial coverage for Guardant360, which will lead to an ASP of $3,300 by 2028. For Guardant360 Tissue, we believe we can increase the ASP by 50% to $3,000 by increasing commercial coverage, improving the pull-through of Medicare Advantage reimbursement, and by expanding reimbursement for the tissue RNA test that we launched last quarter. For Reveal, we've made very good progress with ASPs over the last couple of years. We're still confident that we'll achieve our $1,000 ASP target in 2028. That's going to be driven by Medicare coverage for additional cancer types and by expanding commercial reimbursement. Finally, we're pursuing ADLT status for Reveal.
We intend to pursue ADLT for Guardant360 Liquid and Guardant360 Tissue. If we're able to obtain ADLT status for any of these oncology products, it's going to be upside to these targets. Putting oncology volume growth and ASP expansion together, this gives us a lot of confidence we can continue to grow this business with a CAGR of approximately 30% over the next three years and achieve oncology revenue of approximately $1.4 billion in 2028. Moving on to biopharma and data. As Jamie outlined, this has been an incredibly strong business over the last two years. We continue to believe it can deliver double-digit growth each year between now and 2028, which would result in revenue increasing from approximately $200 million in 2025 to approximately $300 million in 2028.
As well as generating strong gross margins and positive free cash flow, our biopharma business provides significant value from the biopharma partnerships that help fuel our product innovation, the companion diagnostic approvals that drive clinical volume growth, and the global footprint that supports our international expansion. Finally, our data business bolsters our Infinity AI capabilities. Now moving on to screening. At our last Investor Day, we gave screening targets that were based on a set of assumptions that are listed here. We're really pleased that two years later, we're tracking to or ahead of nearly all of these assumptions. We achieved FDA approval in 2024, as expected, albeit with an advisory panel thrown into the mix. We achieved a first-line FDA label, where our base case assumption was second line.
We gained ADLT status that was expected, but at a rate of $1,495, which was higher than our previous assumption of $920. As a result, our 2028 ASP target has increased from $500 to approximately $700. We assumed Shield would be a single cancer test in the period up to 2028, but as we've announced today, we've expanded beyond CRC to multi-cancer. Finally, the one assumption we'll miss is the timing of USPSTF guidelines. We originally expected Shield to be included in those guidelines in 2026, but given the delay to the start of the USPSTF review, we're now assuming guidelines are going to come in 2027 or 2028. Regardless of the change of the timing of USPSTF, we're now even more confident that we can achieve the screening target that we set at our last Investor Day, which was to generate more than $500 million revenue in 2028.
Summarizing our total revenue target again, with all the growth drivers across all the areas of the business, we're increasing the 2028 revenue target to $2.2 billion, which represents a CAGR of approximately 34% between 2025 and 2028. Now I'm going to go down the P&L. First of all, turning to gross margins. We've made great progress reducing testing costs over the last 12 months. Both Reveal and Shield COGS have been reduced dramatically from over $1,000 in the middle of 2024 to now below $500 in Q2 of 2025. Looking forward, COGS will continue to reduce across all our portfolio, as well as the positive impact we'll get from the volume increases with many ongoing COGS reduction initiatives. For Guardant360, we've already begun the transition to NovaSeq X.
This will complete sometime next year, and it'll initially offset any increases in the sequencing costs due to the expansion of the Smart Platform. Over time, this transition is going to lead to an overall reduction in Guardant360 COGS. For Guardant360 Tissue, we focused on operational efficiencies and leveraging the lab infrastructure we've built for liquid. For Shield, we're implementing workflow efficiencies similar to those we recently made with Guardant Reveal, and we're investing heavily in automation. When these changes have gone through FDA review, they'll lead to significant step-downs in Shield COGS. That's going to help us get to our target of $200 COGS in 2028. Finally, we're planning to implement the same automation for Shield into our MRD lab and further reduce Guardant Reveal COGS.
With these COGS reduction initiatives and our new ASP targets, we believe that we can continue to improve the blended gross margin, and we're targeting a range of 65% - 70% in 2028. Since our last Investor Day, we believe that we've successfully balanced tight cost control while still making significant investments in both innovation and commercial expansion. We've reduced R&D spend, and at the same time, we've successfully launched innovations such as Smart Platform and major tissue upgrades. We've completed the ECLIPSE study and gained FDA approval for Shield. We've developed a multi-cancer screening test and an ultrasensitive tissue-informed MRD test. We've kept our G&A spend flat, leveraging the infrastructure while expanding the complexity and scale of our business. We've strategically invested in the sales and marketing line to support growth across oncology and biopharma, as well as successfully launching Shield and building out our screening PCP sales channel.
Looking forward, we intend to continue to be thoughtful and strategic on how we allocate capital, how we maximize leverage across the business, and how we build out our commercial capabilities. One major area of focus for us is AI efficiencies. We're already utilizing AI across many functions. For some, such as software and technology, we've been at the cutting edge of AI for many years and can continue to get better and better. There are many high-volume, high-touch functions, such as reimbursement and client services, where we've now started leveraging AI. We see a clear pathway to significant reductions in cost per transaction as we scale the business. We're also very excited about the opportunity to start to integrate AI into our sales processes. We see this as something that will give us significant efficiencies and cost savings as we build out our commercial capabilities in screening.
Across the G&A lines, we're starting to implement AI solutions in finance, legal, and HR and have many ongoing initiatives to maximize AI efficiencies where possible. Finally, although we all love Zarak, maybe one day there's a moment where you guys are calling him up and you're going to be answered by an AI agent that sounds exactly like him. Maybe that's a few years down the line. We'll see. Okay, now turning to cash and the path to profitability. We've made good progress over the last few years on our commitment to reduce our free cash flow burn every year. This year, we're on track to bring our cash burn down to between $225 million and $235 million. Going forward, we intend to continue to reduce our cash burn each year.
Furthermore, given our improved revenue and gross margin targets, we're bringing forward our timeline to break even by 12 months, from our previous target of the end of 2028 to our new target of Q4 2027. To help understand our path to profitability, and because different parts of the business are at different stages of maturity, it's useful to talk about cash flow specifically for screening and cash flow for the rest of Guardant , excluding screening. Screening is still in its scaling phase. It's in the early days of the Shield launch, and we're building our commercial infrastructure to maximize our first-mover advantage. We'll continue to increase our sales and marketing spend and to reinvest all of our gross profit from Shield during 2025 and 2026. As a result, we're expecting a screening burn of approximately $200 million in both 2025 and 2026.
However, we expect to reach an inflection point in screening during 2027 as the gross margins will start to drop to the bottom line and start to rapidly reduce the screening burn. As Stephen outlined earlier, we plan that screening will reach cash flow breakeven when the Shield revenue run rate is between $600 million and $800 million. For the rest of Guardant , so that's excluding screening, we're well on track to reach cash flow breakeven by the end of this year. From 2026 onwards, the rest of Guardant Health, excluding screening, is going to generate increasing levels of positive free cash flow each year. We know how critical it is to reach company-wide breakeven and to begin to generate sustainable, profitable revenue growth. We have every confidence we can get there sooner than we previously planned.
Summarizing the financials, firstly, we're executing ahead of the financial plan that we laid out at the last Investor Day. We're increasing our 2028 revenue target to $2.2 billion. We're targeting gross margin expansion across all our products. We're balancing investment in commercial expansion and innovation with maximizing efficiencies, AI, and leverage. Finally, we brought forward our free cash flow breakeven guidance by 12 months. Thank you. I'll now hand over to Helmy and AmirAli to wrap up.
As we wrap up, let me leave you with a few highlights here. We've built a world-class innovation platform with Smart and Infinity AI , and it's accelerating the pace of science and product development. Our oncology business is growing faster than ever, with Smart apps fueling therapy selection and Reveal leading the way in tissue-free MRD. Our biopharma partnerships remain strong and are helping to accelerate drug development for our partners in new ways. Shield is proving to be a blockbuster in blood-based screening, with multi-cancer detection on its way. The message is clear. Guardant has the science, the data, and execution to keep leading. We're proud of how far we've come, but even more excited about where we're going.
Maybe just actually highlighting one more time the new announcements that we had today. Increasing 2028 revenue target from $2 billion to $2.2 billion, accelerating company-wide breakeven to Q4 2027, 12 months ahead of previous guidance. Submitted Guardant360 Liquid PMA to FDA. Launching Guardant Reveal for therapy monitoring in Q4 of this year. Increasing Guardant Reveal clinical data generation by 10x in 2026 and expectation of having more than 20 publications in 2026. Tissue-informed Guardant Reveal Ultra with sensitivity down to 1 ppm. Expanding Shield to include multi-cancer detection findings. Initiation of a large-scale study of real-world data for Shield multi-cancer detection. Finally, strategic collaboration with Quest Diagnostics to expand nationwide access to Shield. We are here for one reason: conquering cancer with data, to give patients more time with what matters most for them.
Whether through MRD peace of mind, whether through Shield early cancer detection, whether by just simply turning results hours earlier, every moment we save allows patients to have more time for life's precious moments. Our success proves our approach works. We believe we are just getting started. I guess now you're going to see the beginning video, right? Yes. We are not going to read through the whole thing one more time. Beginning video.
When we founded Guardant Health, the idea of detecting cancer with just a blood draw sounded impossible. We got it done faster than imagined, pioneering the liquid biopsy category and launching breakthrough after breakthrough, with products spanning the entire cancer patient journey, from the first blood test to detect cancer in its earliest stages to monitoring that brings peace of mind to cancer survivors, to tests that give doctors deep insights to tailor treatments in real time. Our AI-powered Smart Platform has accelerated our pace of innovation, allowing us to help more patients earlier in their cancer journey. It is activating Guardant's next waves of growth. We've already helped over 1 million patients, but it is just the beginning. We are expanding into multi-cancer early detection, unlocking the opportunity to impact millions more lives. We have other diseases in our sights. This is our purpose: to help every person live a longer and healthier life. Guardant Health. Speakers, please return to the stage to commence the Q&A portion of the day.
Okay, guys, we're going to start the Q&A for about 45 minutes. Going to take questions on mostly an ad hoc basis. There's going to be a strong preference for anyone that's wearing their socks from the 2023 Investor Day. Dave, Mark, Mark Massaro, good. I lost your hair. Yeah, I know. Yeah, Kelly and Carrie in the audience, they're going to be running the mics around. Maybe we'll start. Let's do that. Are you ready, Mark? Okay, go for it.
Hey, guys, congratulations on a good Analyst Day and increasing the targets. I wanted to start with the assumptions on the Shield. With respect to the fact that you're increasing your ASP from $500 to $700, why $700? You're obviously tracking ahead of that now. I also wanted to ask a question about, with Quest coming on and you have other positive momentum going on in Shield, why did you choose to maintain the Shield revenue target when there's some other? I guess implied is perhaps lower volume assumptions. Can you walk me through any changes?
I'll take that. Yeah, I mean, firstly, with the ASP. Currently, our ASP is over $900. Stephen talked through how at the moment, we're really focused on reimbursable lives. This is where we're getting reimbursed by Medicare, Medicare Advantage. We know that as we go forward and we start to get into ACS guidelines, USPSTF guidelines, we will be opening up the market to patients below 65. While we're very confident that we'll get strong reimbursement from those commercial payers, it's going to take time. For a while, I think there's going to be some commercial volume that's getting paid, maybe at a zero as it takes time for those patients to come on board or a bit lower. When we look at this, we're really pleased that the ASP is going to be higher than our previous target. We think $700 is a good future-looking target for 2028 when we're sort of in that transition of just adding on more and more commercial payments. I don't know, AmirAli, if you want to talk about the volume.
In terms of volume, we wanted to actually reconfirm our long-term guidance almost without the impact of USPSTF. If it happens, it would be upside if it would happen sooner. We don't want to get too ahead of our skis. We are very pleased with the way the launch has gone so far and excited about our rep productivity. We are also very excited about this commercial and channel part and distribution partnerships that we are doing. We didn't take that into account in terms of the upside till we learn more in terms of how the impact of that would be. The potential could be vast, step by step though.
Hi guys, Danny Aries from Stifel. I guess question maybe for Darya. I wanted to ask a little bit about AI. It seems pretty clear that that's going to be an important part of what you guys do well going forward. How much of what you have working for you is due to sort of a commercial offering, something that's accessible to your customers, sorry, your competitors, versus something that's developed in-house? Essentially, to what extent would AI be sort of a secret sauce for you versus other oncology organizations that can take a service offering and do something similar?
Thank you. I think it's a landscape that includes multiple options here. There's definitely internal development effort that's looking at how we can maximize the value of the data and the analysis inside using pretty complex multi-parameter, multi-billion parameter type models. We have seen initial baby steps in that direction. We're usually very careful with data and interpretation of that data in the context of multi-parameter models. We want biology to guide a lot of that. We're seeing the ability to use higher complexity models now that we've developed a database that stands for itself in terms of being able to service these multi-parameter models. We're looking at both partnering with others in developing some of these models and internal development effort to materialize that value. Time will tell exactly which paths prove to be more successful.
Yeah, maybe [audio distortion]
Hey, thanks guys, and excellent presentations by the team. One of the key questions, or one of the key points here is simply the ease of use of a blood test. You clearly highlighted that there's a DTC campaign ongoing. I just want to understand, can you talk a little bit about the focus on DTC? How much spend, how are you thinking about that into the next year? The number of reps, which are 250 by year end, how can they expand to catch that as that DTC campaign? We have obviously seen successful examples in colorectal cancer screening space with DTC. I just wanted to understand that point. Maybe AmirAli, I would love to get a high-level point.
I would say a simple question is really that investors want to get a better understanding is, given everything that you're seeing so far with the adoption of this assay, how should we think about the penetration of blood screening in the 120 million population in the U.S.?
Maybe I start some high level. I ask Stephen Murphy to talk more details about the DTC question. I end about where I think the terminal value of blood-based screening would be. Right now, actually, we are obviously very excited with how this launch is going. Our main focus has been our campaigns toward the healthcare physicians, the HCP front, more than consumers. We are doing some piloting programs, like with some of the ads that you guys have seen. We are aggressively investing on building the distribution channel on the Salesforce side. Maybe I give it to Stephen to tell more about some of the.
Yeah, I think on DTC advertising, there's a couple of things that outcomes that you look for. Who can drive in and convince their doctor to start offering Shield? And then who goes into an office where Shield is already offered? Part of what we need to do is make sure that we've built the pyramid where you've got the HCP advertising driving HCPs to join and offer Shield alongside that consumer. It'll build up kind of together. We lean a little bit more onto the HCP side today because that's a better optimization of the spend when you see it overall.
There are some actually interesting technologies these days that years back did not exist. Sometimes you can go and target the consumers within the practices that you have channels or their active orders of Shield today and specifically target those patients in your DTC campaigns, which brings a lot of efficiency in some of the pilot programs that we are doing. Maybe now talking about long term, the way we think about Shield value. When you look at the CRC market, when there are more than 50 million people unscreened, when there were other modalities for a decade or two decades out there, and still all these patients are unscreened.
When I showed some data earlier during the presentation, when Shield was introduced in some large health systems, which had campaigns like Care Gap campaigns, and they are dealing with this level of unscreening, the screening rate went up to almost 90%. That gives us a lot of actually validation of the potential long-term opportunity that Shield has in terms of the overall market share of CRC screening. In another study I showed, 65%.
Of the patients who are overdue for a screening, are picking Shield versus 35% all other modalities combined. Sometimes I get the sense people are getting confused that they look at it almost like a therapeutics kind of mindset, that maybe this is which line of kind of thinking it is for a patient, and then the opportunity gets smaller and smaller versus this 54 million unscreened patient population, which is the biggest piece of pie, which is completely untapped. I think over time we see what happens with the rest of modalities. Definitely, we believe the best in class test is colonoscopy, and this is for CRC. Just fast forward, envision a blood test that can look at different cancer types, different diseases. I think many people would like to get that test even beyond CRC screening in terms of the values of such tests.
Maybe let's see what's on Doug Schenkel s mind from Wolfe.
Okay, thanks everybody. This was a really fun and informative day. Thank you for all the information and all the effort that went into this. Where's Helmy? Helmy, I'm going to start with you real quick. It seems like you didn't include a lot of sources of upside to your ASP expectations. When I think about ADLT status and Guardant360 Liquid, seeing, you know, where you guys are priced relative to some of the new competitors in tissue, the possibility of Reveal ADLT seems like the error bars skew a lot to the upside there. Either you, Helmy, or you, Mike, any chance you'd be willing to quantify how much you think you've kind of left on the table as a potential source of upside there? I don't want to leave you out, AmirAli, so I'll have one quick feedback follow-up there.
You're not incorrect, maybe. Yeah, I mean, it's, so first of all, yeah, the ASPs that we laid out don't include any ADLT upsides. If we were to achieve those for any of the products, and again, we said we're pursuing Reveal now, and we intend to pursue it for Guardant360 Liquid and Tissue, obviously that would be an upside. We know, for example, with Reveal, our cash pay price is $3,500. Current reimbursement is $1,644. We would have a nice upside there. With respect to Guardant360 Liquid and Tissue, obviously that's going to depend on where the price is. Yeah, I mean, we would hope for upside. I don't think we want to sit here and say exactly what that would be. We think the ASP targets that we set out today are very strong ASPs anyway. They're going to improve our gross margins. Anything on top of that is going to be a very nice upside.
All right, I won't push on quantification, but that's enough for us, I think, to do some math. Thank you for that. AmirAli, blood's easier than stool in colonoscopy. Have you seen data that suggest, as we just think about, as a community trying to get the overall compliance rates, I mean, recognizing CRC screening percentages have been stubbornly low. Do you have data that suggests adding M-SED to CRC actually gets compliance higher for overall CRC, meaning blood will help alone, but just adding M-SED, do you think that gets people to basically say, okay, I'm going to get screened?
We are not counting on that, obviously. The reason we are expanding Shield to have this MCD finding is additional value that we can offer to the patients. Just imagine actually when we are getting patients tested for CRC and we are seeing the sign the patient looks like have ovarian cancer, at least with some post-test probability now. It would have tremendous value for patients if they are open to it and physicians open to it to get access to that potentially life-impacting information. That's the way we look at it. We are going with that vision of even multi-cancer, multi-disease to offer more value on the table for patients.
Kelly, let's see if maybe there's an investor on the side of the room that has a question. We tried today. Okay, that's fine. Yeah, maybe Dave Westernberg . Piper.
Thank you for taking the question. I'm going to stick with Shield a little bit, expansion on what Massaro was asking. First, I want to talk about the V2 version because the overall sensitivity only went up by 1%, but I would argue the performance was much better because of the stage one. You actually had a skew towards stage one that you kind of didn't talk about. Can you talk about the performance there? How fast can we be switching to that assay? Secondly, you answered a lot with Mark's question, but on that $500 million in revenue in 2028, that is a pretty steep ramp. Do you see a step function change in revenue growth as new indications hit? I just want a clarification. I think you said U.S. Preventive Services is not necessary. Can you clarify if you did say that? I thought you did. What's the ASP assumption kind of ramp as we get to 2028? Thank you.
Okay, so I'm pretty sure I'm going to forget some sections of that question. Maybe about V2, I say something and then I pass it to Darya to add. V2, stage one performance improved. You know, we knew it had 2x higher analytical sensitivity and that's why stage one kind of moved. The rest of it, I think, is just a matter of sometimes the cohort that you deal with, right? We take it as a small win, 83% - 84%. I think it tells us we are on the right path and we'll see over time for additional data, additional insight, or other multimodal that the team is working, what we can do. Darya, do you want to add anything?
I don't know.
Okay. The second one about maybe USPSTF and $500 million. A USPSTF and quality score inclusion is a big catalyst for the widespread adoption, no question about that. We wanted to make sure just based on what we are seeing and the delay, although there are actually some good alignment between different stakeholders, and if you're interested, maybe we can talk about that. In terms of what can be done with the process, we wanted not to count on it till late 2027, early 2028. Once it's late 2027, early 2028, till the commercial payers start to adopt it and payer coverages start to change effectively in this LRP window that we are talking about in 2028, we are not counting on it in terms of any material contribution. That's the way we thought about this revenue and we are, based on what we are seeing, confident we can exceed that $500 million target that we mentioned before. I forgot already the rest.
Yeah, I mean, I think it... Oh, you mean with the addition of multi-cancer? Yeah, I mean, we're just really focused on the reimbursement that we get from CRC. We've not built into the model any incremental reimbursement from adding any other cancers. Maybe down the line, you know, when this has gone through an FDA, multi-cancer has gone through an FDA approval, there may be some opportunities then. I think we feel that with the $1,495 that we get now and the strong gross margins, that's enabling us to still be able to offer that multi-cancer report. You know, we're not seeking additional reimbursement for that.
Maybe Patrick Donnelly from Citi. Sorry.
Thanks. Yeah, Patrick Donnelly from Citi. Maybe AmirAli, just on the Shield piece, obviously a lot of market moves over the last month or so. Has the exact Freenome combination changed your view at all in terms of the level of investment necessary? I think Mike talked about reinvesting all the gross profit proceeds over the next couple of years, just in terms of continuing to build that moat while you guys have the market to yourself. Obviously, the timeline shifted around a little bit. Just curious if that changed your perspective at all, both on the investment side and then just the competitive landscape.
On one side, we are reaching our competition. There's a block in the process they're going through. It's good for a marketplace sometimes to have multiple players to open up the market faster. We thought actually maybe the field could be potentially a three-player field. Now, it looks like maybe at most it would be a two-player for many years and we see how it goes. We believe this level of investment that we are doing in Shield is more than adequate to go after this opportunity very aggressively. This kind of a spend that we are talking about, it's been in place now, I don't know, maybe over a year and a half now, two years almost. We are continuing to have that mentality. I don't think we are underinvesting.
This is such a big opportunity that it would not be wise to underinvest when we have such a long lead time. I think it's an adequate level of investment and we are aggressively growing our commercial infrastructure. When you think about where we would be by the end of 2026, our own channel, partner channels that we just talked about, three of them during the last couple of weeks, it's a solid footing. When you think about EMRs, we are building those ourselves. Now through this Quest partnership, we have access. That one connection with Quest Diagnostics is going to be connected to 650,000 ordering physicians. We probably saved a decade of work there through this partnership. A very reasonable cost, in fact, for us.
There's a lot of good brand equity of Shield that gives us a lot of opportunities to access that we didn't even envision two years ago. Many people want to be around the table with us, which is very fortunate. We are very pleased and more confident than ever about the prospect of this brand.
Kelly Hans has a question from Federation.
Microphone since we have people on the internet.
If you want to reach the 100 million men who haven't been tested for CRC, the easiest way to get there is to add one ad in the Super Bowl for every man who watches it. Their revenues just went through the roof. Just a thought. Very expensive, though.
Thank you for sharing your vision. It's definitely something we thought about, but yes, step by step.
Let's try Bill Banello, please. Sorry, Kelly.
Thanks. I have a sort of two-part question on M-SED. The first is just want to make sure I'm understanding how this is going to actually play out. Somebody comes in, they're getting a Shield test for colorectal cancer, they're a Medicare patient, it's reimbursed. Your assumption is that as long as the doctor has also ordered the multi-cancer test and the patient has done the authorization that you asked for, then you can provide the multi-cancer result without charging separately for that. It will just be incorporated into... You'll still be able to charge the Medicare fee and provide the multi-cancer result.
It's pretty simple, right? It's the same test. It's a single test. It's not two tests. It's just a single test. When the patients are getting tested for Shield CRC, doctors can have the option of opting in for this M-SED findings. As long as the patient is willing to sign a form of authorization of release of medical record, there's an exchange of value, and actually then we would release the M-SED findings to them. We've wanted to be very thoughtful about this, and we decided to pilot it in a few accounts just to see, you know, is there something we are missing? It sounds kind of very obvious, very straightforward, very simple pathway. The feedback we got from physicians and patients has been very overwhelmingly positive. We said, okay, it looks like it's working, and let's go and scale it up.
The exchange of value is what allows you to...
We are actually doing the data collection for our clinical trial for the M-SED trial, right? We need that data in terms of generating the evidence for this breakthrough device. I think it's a huge value that we need to get in terms of evidence generation and potential value for patient and physician. We are excited to put it out there and see at the broad scale what would be the reception of patients to participate in that data collection initiative that we are talking about.
Sure. The second follow-up on it is, obviously we're seeing some real success with, you know, Grail out there. Will this only be available if you're going in and getting a colorectal cancer screening test, or are you going to make the M-SED test available in some other way to people who would, you know, maybe pay out of pocket but want to, you know, want to be screened for multiple cancers?
Step by step, right now we are thinking to just add this M-SED findings based on the pathway I mentioned to the patients who are getting tested for Shield that we have in the marketplace today. We evaluate, like, you know, we had this kind of really belief at Guardant that we are doing all this hard work building breakthrough innovative technologies. We wanna make sure people get broad access to this kind of innovative technologies versus just maybe a pathway that would be suitable for the most affluent people who can pay such a big out-of-pay cost. I'm impressed and very pleased that our peers in other companies have built that market for affluent. I give them a good kudos.
We wanted to make sure we really democratize that and make sure that people can have the right level of access to that test if they wanna participate and if the physician is open to get that information. That's a pathway that we are pursuing.
Random number generator says Brennan .
Thanks, Rock. Dan Brennan from TD Cowen. Maybe one for Mike and then one for Helmy. Mike, the 65 to 70% gross margin target for 2028, did you talk about what that translates into, excuse me, for operating margins? I know you talked about cash flow. I'm just being interested in that. I know the last target, obviously two years ago, you set out to 2028. I'm just wondering, even if we look beyond 2028, kind of how does operating leverage unfold for the business? B, just, you know, maybe a multi-part just on MRD. You threw a lot of information at us. The Ultra, kind of when will we get an update on that? Any color, any early data? The PEGASUS de-escalation reported ESMO. I know you reported out some data on this already, but how important could that be? Monitoring, you spent a lot of time on monitoring for MRD. I'm just wondering where that really fits in because it's not very clean versus other MRD players. Thank you.
Yeah, I'll start. No, I mean, we didn't talk about operating margins. We focus in on the gross margins. We know we can improve those across all of the products. We're focusing really on getting to, you know, cash flow breakeven. We're really pleased we brought that forward. I think from an operating margins and then getting positive, obviously once we start to generate, you know, positive cash flow, we're probably in the area of getting positive operating margins. Looking forward beyond 2028, I think, you know, we would then expect to be generating positive operating margins. I think our focus at the moment, we're absolutely laser focused on getting to this breakeven point and then starting to get into cash flow positive territory. Maybe the next Investor Day, we'll talk about operating margins and we'll look further out than 2028.
I guess maybe I'll let Craig talk about PEGASUS in terms of the importance of that and then I'll take the other two.
Yeah, PEGASUS, of course, is a utility study. Using a tissue-free MRD, basically it allows a decision about follow-on therapy. This is really the first time that we're going to show that utility decision and the impact that has. Obviously, we're all hoping that creates a benefit, in other words, de-escalating those that don't need it and those that do. The results we'll be seeing in October, basically next month. Very important study as we move from measuring the device to actually now the device changing therapy.
Yeah, in terms of Reveal Ultra, we're really excited about kind of what we're seeing in terms of early data from that platform. We're seeing, you know, obviously in major cancer types, you know, lung, breast, colorectal, really good performance in terms of limits of detection, ability to really detect things at levels that really are sort of beyond kind of what has been in the published literature right now. It's kind of a really cool way of, you know, how we use our platform, both the genomics and epigenomics and so on, to be able to get to such low levels of disease. Obviously, we're keeping some things close to the chest right now, but we'll obviously release, you know, more data as time goes on. It's something that we think the other piece about it that I think is exciting is that it really works synergistically with Guardant360 Liquid, with tissue, and so on. It's really a nice puzzle piece that fits in with all our other tests in the portfolio.
It's not just something that's shoehorned in like you see in some portfolios. We think it's really going to sort of create a really kind of a nice platform for physicians, basically, in terms of any scenario, any cancer type, rare cancers that may not shed very much. You'll be able to see this, I think, with very high sensitivity and very high specificity. The nice thing about a lot of our cohorts is that we have tissue for a lot of these things, so we can develop clinical data very, very quickly. In terms of monitoring for Reveal for therapy selection, IO has been something that we've had, other companies have had in the therapy selection space. IO is only one small segment. It's a large segment, but still not the majority of how patients are monitored.
When you think about successive lines of therapy in terms of first line, second line, and so on, our vision for liquid biopsy since day one has been this idea of adaptively managing disease over time. To do that, you have to take measurement points across essentially disease ebbs and flows. To do that, you have to be able to monitor really all classes of therapies. Chemo has been one that has frankly been challenging, I think, for ctDNA monitoring. There are some effects that can happen on chemotherapy, a lot of tissue that can be released, collateral damage, and so on. The fact that we've now validated the platform for chemo, I think, is really exciting.
It really, I think, is a major step towards this vision of essentially really becoming a surrogate or this kind of liquid scan to the sort of CT scans that are used as table stakes in the space right now. To be able to go in and say, use Guardant360 here and Reveal in the intervening periods and then switch back to 360, and the fact that we can do that without sending another sample in when you reflex from one to another, I think, really gives us a competitive advantage in terms of how these products work together. That's why I might have spent a lot of time on that because we think it's something that's going to catalyze further adoption in the therapy selection space as we bring Reveal into therapy selection for monitoring.
Let's see what Dan Leonard has up his sleeve, and then Jack and Danny Brennan, you just earned yourself two demerits for the seven-part question.
All right, thanks, Eric. Nothing up my sleeve, I promise. Helmy, I have a question about SERENA-6. You talked about that multiple times. Can you give us a flavor of what the pipeline of SERENA-6 like trials looks like in the biopharma landscape? Also, how do you balance your enthusiasm for that trial and that application with trials like SERENA-4? Even Roche on Monday had data from their SERD that could be used in all comers. Thank you.
Yeah, I don't know. Jamie, do you want to?
Yeah, maybe I'll start. I think there was a lot of enthusiasm and excitement with our biopharma customers after the readout at the American Society for Clinical Oncology. I think that's been a catalyst for more conversations about innovative trial designs that would enable, you know, surveillance-like approaches. I think we have nothing really to announce at this point. I think those conversations and opportunities are progressing. We think it'll be a great catalyst for more opportunities like that in the future.
Yeah, I would say like into a lot of other trials where anything where there's a resistance mutation that is emerging in a population, which is basically almost all targeted therapies, you know, have that sort of phenomenon. Things like prostate cancer with androgen receptor-like resistance, you know, there are similar trials that are shaping up there. This is not an isolated sort of incidence in terms of breast cancer and this type of monitoring. I have no doubt that this is going to be the future of all of cancer care, being able to monitor patients, switch therapies aggressively once you see molecular progression there in that patient population. In terms of like, you know, whether it goes to all comers or not, that's the risk with every trial and every drug. We know that there are patients that don't respond to these therapies.
Right now, ESR-1 may be an imprecise sort of tool when we think about genomics. We know that there are more precise tools like with our Smart Platform and epigenomics actually seeing those patients in either population that respond or not. I think that may be a stop in the way whether SERENA-4, you know, reads out and is positive or negative. It doesn't change the underlying biology that there are patients that respond and patients that don't respond to drugs. Those that respond will eventually form resistance mutations and will, you know, unfortunately need monitoring and a successive line of therapy. I always bet on biology and where it's going. We have no doubt whether it takes one year, two years, three years, that that's where space is headed.
Thank you. I wanted to add another MRD part to Dan's question, which is maybe for Mike, within the 2028 target, how much revenue is embedded for MRD sales? Maybe for Helmy, as you look out, you introduced Reveal Ultra. What do you think the mix looks like between tumor-informed versus tissue-free? Do you think one is going to be larger than the other when we get out there? Thanks.
I can start then. Of course, you know, we're not breaking out within the oncology, the different revenue lines. I think it's fair to say with all the opportunity that we talked about with Guardant Reveal, the expansion to other indications with therapy monitoring, with Guardant Reveal Ultra, we do, we envisage that by 2028, it's going to be a material part of our overall revenue without putting a specific number. We feel, I think some other thing, it's our fastest growing oncology product from a volume perspective. We think that's going to continue. Again, as a proportion of the oncology revenue, it's going to increase over the next three years. Hopefully that answers without giving some specifics. It's going to be a big driver for us to have this 30% CAGR over the next three years of oncology.
I would maybe sort of answer that question by pointing to therapy selection in some ways where tissue, you know, until now has been the majority of the market. There's no doubt in my mind over the next five to ten years, liquid will be the majority as patients are tested multiple times, as you get to patients that are not as accessible and sort of easily tested with tissue. I think the same phenomenon will happen on MRD side where, certainly now tumor-informed, tissue-informed is the majority of the market. We see tissue-free eventually becoming really probably the biggest part of the market if we fast forward ten years from now. That being said, we're excited about both products. I think there's some exciting features of the product we have that'll allow us to answer that question more clearly once we launch it.
Maybe let's try Casey from JP Morgan.
Great. Thank you for taking my questions and for hosting us today. Can you just elaborate on the USPSTF push out? What's the new timeline for Shield data generation and ultimately submission for USPSTF? Any sort of color on the data you plan to share with them? Just as a follow-up, you mentioned that you're seeing strong traction from Medicare Advantage payers for Shield even without USPSTF. Can you just elaborate on what's driving payment there? Thank you.
Yeah, in terms of data generation for USPSTF, we have everything you needed. We don't, we are not waiting for any other study, any additional evidence. We have multiple papers, multiple studies, a couple of randomized studies, our NEJM paper, FDF. We have more than historically was needed for guideline inclusion. They have to start the process and start reviewing the evidence for it. Maybe I'd use this opportunity and introduce you guys to our Senior Vice President of Public Affairs. Maybe she can share with you some of the latest that we are hearing on Task Force and some of the activities there that could be interesting.
Hi, Jen Higgins. Nice to talk to you guys. A couple of positive things about the Task Force is that over the past five years, we've worked really actively in Washington to kind of figure out what's happening with colorectal cancer. Obviously, the tremendous advancements in the space, not just from Guardant Health, but from other companies. I think one of the positive things for us has been the fact that we aren't the only ones wondering where the CRC recommendation is, which is a positive. About 60,000 patients across the country, as well as numerous stakeholder groups in and outside of the CRC community, have not only encouraged the last administration, but this administration to take a closer look and move faster to at least move forward with the recommendation. Now, that's no guarantee, but at least it shows there's strong momentum to see and break this loose.
We know how important this is in terms of the context of how it's tied to timing for a lot of different factors for our business and others. One of the things that we are looking at is making sure that we're doing two things. One, working closely on a strategy to engage around quality metrics because we know that there is momentum in the likelihood of a delay for the Task Force. We have the ability to engage to say what are other guideline bodies that NCQA and CMS could work together to evaluate around. Benchmarking to USPSTF is difficult if USPSTF has not yet taken action. The potential for something like ACS or NCCN guidelines to be a reference point for quality metrics, we believe, is a potential catalyst for this in the absence of a recommendation from the Task Force.
I think the second point too is that from our standpoint on a government affairs front, a lot of the work that you've seen Guardant and other companies do with respect to state legislative efforts is important. As we anticipate ACS guideline inclusion, there are 10 states where we can move forward quickly in those states. If you look beyond that, there are a number of other states that have coverage mandates for CRC screening that are linked to USPSTF or frankly not linked to anything at all specific to guidelines. We've worked actively in a few states like Florida and Louisiana to move the process forward to expand those guideline recommendations to include not only USPSTF, but also ACS and NCCN, right? There's a positive momentum there.
I think finally on the Task Force, there are a number of states that are linked to the Task Force that we could also tie back to legislation and link them to ACS. We have a strategy to employ to help to expand the number of states where we would have potential coverage in 2026 and 2027, as well as an effort to recognize that the delay in the Task Force does not inhibit our ability to move forward with a quality metric strategy. In fact, it probably creates a catalyst for faster action from NCQA and CMS. The timeline, again, cannot control the U.S. government, but we are having great dialogue with this administration about the importance of CRC and moving forward on that recommendation as quickly as possible to support innovation as well as patient access.
Exciting signals, but we are not counting on any of that. Just set there.
I was going to say, Jen is really kind of a secret weapon of ours in this space. I look forward to you guys maybe spending some time with her at lunch.
Thank you guys for putting this day together. You, Craig, you have an enriched database for cancer signatures. How do you go about figuring out epigenetic signatures for other diseases as you think about expanding into beyond cancer?
Yeah, one of the things we think about obviously is our medical need first, making sure that there's an area we need to define a patient population. If you think about it, different diseases have our expression of protein, which is the expression of the epigenome. By identifying where there's differences, we can actually pick, then we can look through our database to see if there's epigenetic signatures that are different or epigenetic expressions different. That links into that outcome and that unmet medical need that we talk about. That's sort of how we start from the top end to come down.
Got it. Thank you for that, Craig. AmirAli, some of the MCDs are annual, like lung cancers and breast cancers. Probably a three-year timeline isn't suitable for them. As you think about self-pay annual MCDs that are available in the market today, how do you see Shield with MCD option play out? Have you heard any feedback from physicians on those testing frequency?
I think over time, when you want to think about it very long term, and as I mentioned, we're envisioning a blood test that would be used for annual checkup for multi-cancer detection, even potentially multi-disease detection. We have to go at it step by step, especially for us that we want to go after the vast majority of this market, regular people that if out-of-pocket is just more than nominal, they cannot utilize those services versus most affluent patients. For that one, we have to go step by step, generate evidence, maybe get regulatory approval for other indications. That is why our lung cancer screening indication, we are excited about it, and it would be a strategic indication for us for Shield. We have a pathway for it, but it is going to take a few years. Right now, this is what we can offer to the patient. I think it is going to be a great potential for us to build that database, clinical evidence for potential submission to even agency with that data and for a patient to get access to that data on a trial annual basis, step by step.
Let's do rapid fire. Andrew Cooper, Ray J, Kyle, and Mason. Thanks.
Perfect. Thank you. Maybe first just, Mike, for you. Glad to see the free cash flow pulled forward. It sounds like you kind of specifically called out some inflection in Shield there in 2027 and into 2028. Previously, you had tied the ramp in the sales force to USPSTF timeline. Is that a little bit decoupled now? Are you still ramping at the same pace, or has there been any change to the plan there?
I mean, we're still ramping at a relatively same pace. I think, you know, last Investor Day, when we assumed those guidelines were coming earlier, you know, we gave a similar number of sales reps by 2028, the 600- 700. Yeah, I mean, the pace will continue at a similar level. Again, you know, there's the Medicare population, the over 65, it's a huge field for us to mine, and we've been very, very successful. I think, yeah, that ramp is going to continue similar to what we previously assumed.
Maybe add a couple of additional statements. As Mike mentioned, you know, this pricing of ADLT we didn't imagine before. COGS of Shield is reducing faster than our original expectations. We are generating more gross profit. Something which is very fantastically happening on the commercial, which was way more than what I thought, is this targeting is really working. The payer mix has been shifted very dramatically toward the reimbursable cases. When we are reinvesting that gross profit, like by the end of this year, more than 250, we thought maybe we were going to be 150 by the end of this year. Just imagine, we are not talking about next year, but just imagine how many sales reps we can have by the end of next year. It's very, very exciting.
Perfect. One quick follow-up just on MRD, following on to, I think, one Jack asked. What have you seen from the marketplace that makes you feel like Ultra is the right product at the right time? It sounds like kind of true ultra-sensitive is really what you were highlighting. I would love the thoughts on how that fits into the landscape with what everybody else has talked about. Thank you.
Yeah, no, I was at ASCO this year, and you can hear many of the talks. We're talking about, you know, some of these tests are just not sensitive enough. Need things that are more sensitive that are, you know, get to this sort of ultra-sensitive level of MRD detection, especially in, you know, rare cancers, certain metastases potentially don't shed as much. Especially in some of those, like, I think about de-escalation studies where you really want to make sure that you can spare the patient from chemotherapy. We saw that, you know, I think that maybe there wasn't as much progress as we expected, maybe in the field in terms of tumor-informed and sensitivity. Obviously, we have a lot of research we're doing inside the company, and we saw there was a potential, I think, unmet need that we could address with a sort of ultra-sensitive approach.
I mean, these technologies that only look at, you know, tens or hundreds or even a couple thousand mutations are not, you know, probably where the sensitivity needs to be to be able to get to the levels we're talking about with our technology.
Thanks, Kyle Mixon from Canaccord Genuity. Just on M-SET, just clarifying, AmirAli, how many cancers you'll be adding? Is it just lung, for example? What's the timeline and the pathway, let's say, to FDA submission and approval? If these other tests get reimbursement for $500, like that's in the kind of ongoing legislation, how could this test that's at that higher price, much higher price point, compete?
Yeah, so right now, actually, we are targeting 10 cancers. Between 10 cancers, like one of them is breast, the other one is prostate, that, you know, it's kind of, you know, performance, these are low shedders stuff. That's why we are highlighting the eight other cancer types in terms of performance, but it's a panel of 10 cancers right now. In terms of that legislation, actually, it's pretty interesting. It would be, I think, a tiny positive for us, but there's so much limitation with it, like price cap in some aspects of it. We see what the latest is going to be, but the latest I heard from the team is now maybe it's just coming for patients at age 65 and just 65, and then every year it's going to go upward, age 68 and just 68, I forgot which one.
Effectively, it's going to take 10 years to even have a coverage of 65 - 75, right? Versus the pathway that we have enables us potential access for patients much, much faster, and as a result, much bigger opportunity. In terms of FDA submission, we need to see really in real world what fraction of the patients would participate in this kind of clinical data generation initiative. We are expecting to generate data from a few hundred thousand patients. Once we have that, I think we are sitting on a statistically powered study to align with FDA to review that evidence. I don't know, Craig, if you wanna add anything.
No, I agree.
Perfect. Just a quick one on the push into the $300 billion multi-disease screening markets. Is that totally going to be organic using, I guess, like if you're in the AI, or is that going to be, you know, are you open to acquisition, let's say, as well?
Sorry, I missed the question. Do we do it organically or do we acquire companies or technology? We're exploring both options as we move forward. At the moment, the focus is organically. That's where we're focused. I think that's the underappreciated aspect of what we built here, that it's an architecture because it's blood, it allows us to go well beyond just cancer. I mean, when you think about genomics, it was really confined to rare disease, infectious disease, and cancer because that actually changes the genome. Almost every disease impacts the epigenome. This chemistry allows us to transform this huge blood biobank we have and this sort of data acquisition through blood that we have as a company into a vehicle that allows us to essentially rinse and repeat the same process we did for cancer for every other disease potentially that we can see.
We're seeing really exciting signals, I would say, for many other diseases, inflammatory diseases, and liver diseases, and so on. We think that it's underappreciated in terms of where we can go versus, let's say, a tissue company or a stool company or something. It's very hard to go into multiple diseases when you're limited by the specimen collection that you have.
I'm not going to add, I mean, at the end of the day, you think about a disease like rheumatoid arthritis. Two rheumatoid arthritis patients have different outcomes to their treatment. They have different response to disease. The disease can be worse for some one week, not for another, plateaus, stable. That's all epigenetics. Everything that happens in that patient, that's why I'm saying you start with a clinical piece. With the data we're building through our Shield and collection through screening, we have to screen rheumatoid patients.
What we've got to do now is say, okay, these rheumatoid patients respond once the therapy is stable. These rheumatoid patients respond, and three weeks later, they're relapsing and don't respond to therapy. That's epigenetics. You just start to look in the epigenetics, and you can start to pick these patients out. That's what we want to achieve with cancer as well. We want to pick out the patients that respond to therapy and those that don't. Respond to therapy, substitute rheumatoid, substitute Crohn's disease, etcetera, etcetera. The model's the same. Epigenetics is whatever you see can be explained through epigenetics. We just don't know what it is at the moment until we get the data, basically.
Let's try Mason and then Brandon.
Thank you. Maybe on the MRD opportunity, specifically, those 12 million patients that are five years out plus or five plus years out from surgery. Could you just talk about your access to them today? What proportion of them are still routinely seeing their oncologists? What has to happen to really unlock utilization there?
Yeah, it's, I don't know, Chris.
I mean, I think it depends on the tumor type, how often the follow-up is going to be. I think that that's something where patient activation is probably going to be part of the commercial strategy. Because to your point, if a patient is not going into the office, then the testing is not going to take place. I think to AmirAli's comment earlier, as more entrants come into any given market, and in this case, MRD, it elevates the collective voice around that new technology. At this point, I think Helmy showed it's less than 3% of the collective market is penetrated, which suggests a combination of low awareness, obviously data generation, which we're working on, and to some extent, which we're looking to solve with Ultra, that the current solutions do not deliver what the market needs. As those forces, I think, come to bear, and as the MRD market matures, that in and of itself is going to lead to additional patient awareness, which over time is going to activate that prevalent population.
I'll just add that we have programs with many advocacy groups in terms of survivorship campaigns and so on, where we can sort of activate them. Obviously, over time, the primary care channel is going to be a very important avenue for us to be able to essentially get to those survivors that are further out. That's why I think it's really important when you think about the overall MRD opportunity, especially at scale, that frankly you have a primary care channel and sales force to be able to access all of it.
Yeah, last question, Brandon, please.
Hey, Brandon at Wells. Thanks for squeezing me in. Two questions on Shield. The free cash flow breakeven range of $600 million - $800 million, it's a pretty wide range. What are the variables there? What are you leaving cushion for? If you're doing $500 million with 700 reps, surely that's not the endpoint. How do you think about rep productivity long term? Could it approach the incumbent over time?
I think the main driver of that range, and we think that's a good range, is going to be the ASP. Just a little bit of the, you know, we talked about before, the mix between Medicare and Medicare Advantage and how quickly we can ramp up the commercial reimbursement. It's going to depend on that mix because that's going to have a little impact on our overall gross margins. I think from the OpEx side, we know what we'll spend on our research and development. It's going to be relatively flat over the next few years. We've laid out our plan to expand on the field sales team. The main variable that's going to drive that is ASP and the gross margin. Did you want...
Yeah, in terms of opportunity per rep, this is still even at that $500 million, like we talked about, it's just 2% market penetration in this unscreened patient population. At that level, we are going to have the right breadth of commercial infrastructure in place. We don't need to significantly increase from that point. It's just going to be over time the reps would become more and more productive. We are seeing something pretty interesting in the accounts which are tenure for the reps that are tenure. Even today, higher depth of ordering of Shield in those accounts is giving us some very interesting revenue per rep in those accounts, which when you just kind of extrapolate, you get to some kind of very crazy numbers. We are one year into it. We have to see how this thing would kind of evolve over time. Definitely, $500 million is still just, again, less than 2% market penetration.
With each guideline inclusion, the rep performance will get stronger and stronger.
That's right.
On that note, stop the hour. Thank you guys for coming out.
Thank you.