Guardant Health, Inc. Q3 FY2021 Earnings Call

Hello and welcome to the Guardant Health Q3 2021 Earnings Call. My name is Alex and I will be coordinating the call today. I will now hand over to your host Carrie Mendivil from Investor Relations to begin. Over to you, Carrie.

Thank you. Earlier today, Guardant Health released financial results for the quarter ended September 30, 2021. If you have not received this news release or if you'd like to be added to the company's distribution list, please send an e-mail to investors@guardanthealth.com. Joining me today from Guardant are Helmy Eltoukhy, Co-CEO; AmirAli Talasaz, Co-CEO; and Mike Bell, Chief Financial Officer. Before we begin, I'd like to remind you that management will make statements during this call that are forward-looking statements within the meaning of federal securities laws. These statements involve material risks and uncertainties that could cause actual results or events to materially differ from those anticipated. Additional information regarding these risks and uncertainties appears in the section entitled Forward-Looking Statements in the press release Guardant issued today. For a more complete list and description, please see the Risk Factors section of the company's Annual Report on Form 10-K for the year ended December 31, 2020, and in its other filings with the Securities and Exchange Commission. This call will also include a discussion of certain financial measures that are not calculated in accordance with Generally Accepted Accounting Principles. Reconciliations to the most directly comparable GAAP financial measures may be found in today's earnings release submitted to the SEC. Except as required by law, Guardant disclaims any intention or obligation to update or revise any financial projections or forward-looking statements, whether because of new information, future events, or otherwise. This conference call contains time-sensitive information and is accurate only as of the live broadcast, November 4, 2021. With that, I'd like to turn the call over to Helmy.

Thanks, Carrie. Good afternoon and thank you for joining our third quarter 2021 earnings call. I'll start off today's call by highlighting our progress across oncology, as we continue to build on our strong foundation as a liquid biopsy leader. I will then turn the call over to AmirAli for an update on our screening program in colorectal cancer and our plans for expansion into multi-cancer screening. And finally, Mike will provide a more detailed look at our financials and our outlook for the remainder of 2021. Our mission at Guardant is to conquer cancer with data, fueled by a commitment to putting patients first. To this end, we are dedicated to bringing the absolute best products to market that will provide clinically actionable information to inform patient care. Before I provide an update on our progress, I would like to start the call off with a patient story. This past summer, a 64-year-old woman was diagnosed with colorectal cancer. Her oncologist ordered a Guardant360 CDx test, which identified her cancer as KRAS negative, indicating that she may respond to anti-EGFR therapy. With this information, she was enrolled in a clinical trial. As her treatment progressed, she began to experience worsening symptoms that led to uncertainty about whether or not she was responding to treatment from the clinical trial. Her oncologist ordered a Guardant360 Response test, which is the first commercially available blood-only liquid biopsy test that detects changes in circulating tumor DNA levels to provide an early indication of a patient's response to treatment. The test confirmed her cell-free tumor DNA levels were decreasing, meaning she was indeed responding to treatment and her symptoms were likely a side effect from the therapy. With this, her oncologist had the information he needed to continue treatment through the trial and the patient's symptoms have since improved. This story highlights how Guardant360 can provide powerful information across multiple stages of cancer care, from treatment selection with our Guardant360 CDx to early treatment response monitoring with Guardant360 Response. Today the Guardant360 product portfolio is increasingly providing oncologists with a set of comprehensive tools to unlock the full potential of precision oncology across the continuum of advanced cancer care. Now turning to our performance. We realized record revenue during the third quarter of approximately $95 million, growing 27% year-over-year. On our earnings call in early August, we shared that the resurgence of COVID-19 cases was impacting oncology office visits and sales force access, with our international business particularly impacted. While the environment didn't worsen, these impacts persisted through August and into September. Despite these continuing impacts from COVID, our team delivered strong clinical volumes of 22,806 tests, up 9% from the second quarter of this year and 35% compared to the prior year. I continue to be proud of how well our commercial team is executing in this environment and achieving healthy volumes and continued growth. Notably, approximately 60% of our volume in the quarter came from the community setting, which represents over 10% growth over the previous quarter. We have also continued our strong cadence of clinical evidence supporting Guardant360. In September, we shared new data at the IASLC World Conference in lung cancer that demonstrated advantages of using the Guardant360 liquid biopsy test for clinical decision-making in advanced lung cancer. Shortly after, we showed data at ESMO, highlighting molecular targets of importance, treatment resistance patterns, and advantages of the Guardant360 liquid biopsy test to help improve the management of advanced solid cancers. These studies add to the growing evidence demonstrating that Guardant360 is an easy and quick way to identify more patients with actionable biomarkers, allowing clinicians to start biomarker-informed treatments sooner as compared to tissue biopsy for comprehensive genomic profiling. Turning to recurrence monitoring. We are encouraged by the growing interest in early success of Guardant Reveal and are continuing to invest heavily in the vast opportunity ahead, while leveraging our existing channel with oncologists. We now have a full commercial channel dedicated to Reveal and have added over 50 employees to the team during the third quarter. Across our oncology portfolio, we have a commercial organization of more than 250 employees across sales, marketing, and medical affairs. We are making solid progress towards our multi-cancer goal with data on colorectal cancer as well as bladder, lung and breast indications. Similar to our approaches in therapy selection, we are investing in clinical studies across MRD to demonstrate the clinical utility of our test. To that end, in October, we initiated the ORACLE study to evaluate the performance of Guardant Reveal to predict recurrence across many early-stage cancers. Specifically, this is a 1,000-patient prospective observational multicenter study designed to evaluate the performance of Reveal to predict cancer recurrence after curative intent treatment across 11 solid tumor types. This study in combination with our existing studies would establish clinical evidence for Guardant Reveal across nearly 80% of all solid tumor cancers. The first patient was enrolled in early October. If successful, ORACLE will pave the path for reimbursement for Guardant Reveal across multiple cancer types, definitively establishing the blood-only approach for MRD and unlocking the $15 billion total addressable market for MRD across all tumor types. Moving on to biopharma. We saw a healthy rebound in our biopharma business with volume of 4,839 samples, up 32% from the second quarter and up 58% year-over-year. We are seeing growing interest with our biopharma partners for using Reveal in the adjuvant setting with non-CRC indications such as lung, bladder and breast. Our partners are seeing significant benefits with our blood-only tissue-agnostic approach and we look forward to growing usage of Reveal in the biopharma setting. In addition to increasing sample volumes, the number of customers we serve continues to grow. We now have more than 90 active biopharma partnerships with a healthy pipeline and we expect to have more than 100 partners by the end of the year. The breadth of our product offering, strong customer service, and clinical market leadership makes us an attractive partner. Outside of the United States, we continue to expand our presence in Europe through established partnerships with premier cancer organizations. We have partnered with the Royal Marsden, a leading specialist treatment hospital in London. This is similar to the previously announced Vall d'Hebron partnership in Spain, which establishes in-house liquid biopsy testing services running Guardant360 tests and sequencing on-site. This service is expected to become operational in 2022 and will be available for clinical research and clinical care providing industry-leading next-generation sequencing to private and self-paying patients with a plan for future expansion for National Health Service patients. In addition, we continue to make important progress with our JV in Asia, the Middle East and Africa. Specifically, in Japan, we are on track for PMDA approval of Guardant360 and launching our clinical laboratory outside of Tokyo by early next year. We are also making excellent progress in other countries in the region as well as growing clinical volumes with both pharma customers and oncology clinics. Accordingly, we have decided to exercise our call right to purchase the remaining 50% of our joint venture from SoftBank. We are working towards the future where all patients with cancer around the world have access to the latest innovations to inform treatment decisions and managed care for the best possible outcomes. This additional partnership in Europe and our redoubled commitment to our efforts in Asia, Africa, and the Middle East are important steps towards realizing that vision. Finally, before I turn the call over to AmirAli, I want to take a moment to welcome Myrtle Potter to our Board of Directors. Myrtle currently serves as Chief Executive Officer and Board member of Sumitovant Biopharma. Prior to Sumitovant, Myrtle served as the President of Commercial Operations at Genentech. Myrtle has previously served on the Boards of Amazon and Express Scripts, Medco Health Solutions, Everyday Health, among others. Her extensive knowledge and experience bringing world-class healthcare products to market will be invaluable as we scale our organization. As Guardant grows, I continue to be amazed by the incredible talent we are bringing on board, joining our efforts to bring the best products to market as we strive to provide patients across all stages of cancer with access to the latest advancements in precision oncology. I will now turn the call over to AmirAli to provide an update on screening.

Thanks, Helmy. At Guardant, we always believe that a blood-based screening test during wellness checkups has the potential to guard us against cancer. Blood-based screening is simple, reduces the need for patients to follow through, is much easier to integrate into health system workflows, expands accessibility to underserved communities, and would likely improve compliance with screening tests. That said, the complexities of malignant disease, the imperfect nature of screening tests, and the morbidity associated with follow-on diagnostics mean that early detection does not intrinsically confer positive net health benefits. The net health benefit of early detection versus potential harm from unnecessary screening and follow-on diagnostic procedures varies for different cancer types. For instance, a large study showed that while it was possible to find ovarian cancer early, the long-term outcomes sadly were no different for cancers detected early versus later, at least based on the current interventions. In some hematologic malignancies, such as chronic lymphocytic leukemia, early chemotherapy confers no survival benefit to patients diagnosed in the early stages and may introduce significant psychological and even financial distress for a condition in which no treatment is required. Some investigators have applied blood-based screening even low-sensitivity tests in a one-size-fits-all approach regardless of cancer type with the presumption that early detection is always positive. In contrast, at Guardant Health, our focus is to develop a highly accurate blood test to screen for cancer types where early detection can offer a clear net population health benefit. We started our screening program with colorectal cancer, where the patient compliance rate to screening remains stubbornly at 66% in a disease where screening reduces the risk of death by 62%. In addition, we believe that developing a highly sensitive blood test was feasible, and the regulatory approval and reimbursement pathways were clear. We launched ECLIPSE, our prospective registrational study, in November of 2019 and made excellent progress over the past 24 months, amidst the backdrop of a global pandemic and its impact on overall colonoscopy screening procedures. I'm so proud of our team, who have worked tirelessly to continue patient enrollment and have kept us on track to hit our original timeline set back in 2019. We expect to hit our target patient enrollment in the coming weeks. Shortly after target enrollment is achieved, we are planning to start running the collected samples in our lab while we continue to collect colonoscopy reports and centralized pathology report of disease cases in parallel. We expect to have the trial readouts in mid-2022. Through ECLIPSE, our team has developed core competencies running a large registrational study and I believe this expertise will prove invaluable as we move on to additional cancer types. We are also making great progress building our commercial infrastructure to launch our screening product and are on track to launch the LDT version of our CRC screening assay in the first half of 2022. We expect to launch the IVD version of the assay in 2023, pending successful FDA review and approval. Recently our collaborators at Samsung Medical Center presented updated data at the American College of Gastroenterology Annual Scientific Meeting. This was a retrospective study that used biobank samples from individuals with non-CRC where 37% of individuals were asymptomatic. In this study, researchers evaluated the performance of our tests in an expanded cohort of 699 patients with non-CRC and found the test achieved an overall sensitivity of 96% with 94% specificity. In patients with Stage I and II CRC, the test offered 93% overall sensitivity. Additionally, our test identified 90% of patients with asymptomatic Stage I or II CRC. Now, looking beyond CRC through our opportunity with multi-cancer screening. Our focus is to develop blood-based screening for cancers where lives can be saved. Our differentiated core technology platform, which leverages combined analysis of genomic, methylation, and fragmentomic signatures within cell-free DNA, has the potential to detect many cancers at their earliest stages. We have developed a new generation of our high-sensitivity sequencing assay for evaluation of cell-free DNA across multiple tumor types. This new assay uses a custom targeted 16-megabase panel to enrich cell-free DNA across a set of highly informative regions in order to detect the presence of tumor-derived signals, while maintaining low sequencing costs per sample. In addition, we also utilize epigenomic signatures to evaluate tissue of origin or TOO of cancer. We evaluated the performance of the assay in a pilot study using a biobank cohort of 191 treatment-naive lung cancer patients and 1,576 cancer-free individuals. The assay demonstrated high sensitivity for detecting lung cancer cases for both early and late-stage disease, while maintaining 95% specificity. Our sensitivity of detecting Stage I and II cancers was 78% and further increased to 93% in late-stage patients, Stages III and IV. Importantly, we observed even higher performance with sensitivity of 95% for Stage I/II in lung squamous cell carcinoma cases, which is a more aggressive form of lung cancer frequently found in smokers. To evaluate the accuracy of tissue of origin prediction, we have developed a classification model distinguishing lung cancer patients from patients with colorectal and breast cancers. Overall, the model identifies the tissue of origin for 90% of detected non-cancer patients. We are thrilled by our progress in lung cancer screening. Lung cancer is the leading cause of cancer-related death in the United States. The evidence-based screening guidelines recommend annual lung cancer screening for high-risk individuals. However, the screening compliance study demonstrates growth underutilization as only around 14% of people eligible for screening are up-to-date with screening recommendations. We believe lung cancer is a great clinical indication candidate for our screening tests. To validate the performance of our assay in a lung cancer screening cohort, we have designed a new prospective registrational study called Shield. Shield is a single-arm clinical validation study designed to provide regulatory-grade evidence for the accuracy of our blood-based assay in individuals between the ages of 50 to 80, who undergo standard of care screening for lung cancer using low-dose CT scanning. As per USPSTF recommendations, all subjects enrolled in Shield will be high-risk for lung cancer and either current or former smokers. We are targeting enrollment of nearly 10,000 individuals. We expect to begin enrollment in December of 2021, and to complete enrollment within 36 months. We believe the promise of blood-based cancer screening is quickly becoming a reality and we see a brighter future for humanity by improving population health. A successful readout of our ECLIPSE trial will open up a $20 billion screening opportunity in colorectal cancer, and Shield along with other future studies will open up opportunities in lung and additional cancer types, paving the way toward a total addressable screening market of more than $50 billion. I am confident about our strategy in developing blood-based tests for the screening market, not just in CRC, but also in multi-cancer screening. With that, I will now turn the call over to Mike for more details of our financials and outlook for the remainder of 2021.

Thanks, AmirAli. Total revenue for the third quarter of 2021 was $94.8 million, up 27% from $74.6 million in the prior year quarter. This increase was primarily driven by strong growth in both clinical and biopharma sample volumes. Total precision oncology testing revenue for the third quarter was a record high of $79.3 million, with a growth of 31% compared to $60.4 million in the prior year quarter. Precision oncology revenue from clinical tests in the third quarter was $61.3 million or 27% from $48.3 million for the prior year quarter. Third-party clinical test volume was 22,806, which is an increase of 35% from the prior year quarter. Blended clinical ASP for the third quarter of 2021 was $2,689, which was above our estimate due to an improvement in ASP for Guardant360 CDx, where the team has done an excellent job ensuring payers were well prepared for the new ADLT code and efficiently processed claims. We are seeing solid traction for our new clinical products Reveal, TissueNext, and Response, and we expect their volumes to continue to increase with time. However, we don't expect these new products to significantly contribute to revenue until we receive Medicare and private payer reimbursement. Therefore, whilst we expect Guardant360 LDT and CDx ASPs to continue at similar levels, we expect the blended clinical ASP will be impacted as we make reimbursement of the new products. Precision oncology revenue from biopharma samples in the third quarter totaled $17.9 million, up 49% from $12.0 million for the prior year quarter. Biopharma volume was strong with third quarter samples totaling 4,839, up 58% from the prior year quarter. We are very pleased with the healthy rebound and we are still on track for low double-digit volume growth for 2021. Biopharma sample ASP was approximately $3,700, down 5% from approximately $3,900 in the prior year period, but improved from the second quarter of 2021 due to the OMNI and Guardant360 mix. Development services and other revenue in the third quarter totaled $15.5 million, up 9% from the prior year quarter. While we are continuing to see strong overall demand for development services, several projects have recently been completed or are soon to be completed and we expect some near-term lumpiness in this revenue line related to the timing of project milestones and other contractual arrangements. As a result, we expect that our development services and other revenue may be sequentially lower in the fourth quarter. And as new projects take time to ramp up, this is likely to persist into next year. Gross profit for the third quarter of 2021 was $64.0 million compared to gross profit of $53.4 million in the same period of the prior year. Gross margin was in line with our expectations and in the third quarter it was 67%, compared to 68% in the second quarter of 2021, and 72% in the prior year quarter. Operating expenses for the third quarter of 2021 were $171.3 million, an increase of 34% compared to $127.6 million in the third quarter of 2020. Non-GAAP operating expenses exclude stock-based compensation and related prior payroll tax payments acquisition-related expenses amortization of intangible assets, and changes in fair value of contingent consideration. Non-GAAP operating expenses for the third quarter of 2021 were $135.1 million, an 88% increase from $71.8 million in the prior year quarter. 2021 has been a year of significant investments, and we expect operating expenses to continue to accelerate for the remainder of the year, as we invest in our LUNAR program, ECLIPSE study, and other development activities and in our screening business as we prepare for the planned launch of the LDT version of our CRC screening assay in the first half of 2022. Net loss was $107.5 million or $1.06 per share for the third quarter of 2021, compared to $77.7 million or $0.78 per share in the third quarter of 2020. Non-GAAP net loss was $70.5 million or $0.70 per share for the third quarter of 2021 compared to $15.4 million or $0.15 per share for the third quarter of 2020. Adjusted EBITDA was a loss of $65.2 million in the third quarter of 2021 compared to a $14.1 million loss in the third quarter of 2020. We define adjusted EBITDA as non-GAAP net loss adjusted for interest, income tax, depreciation, amortization, and other income and expense. We ended the third quarter of 2021 with $1.7 billion in cash equivalents and marketable securities. As Helmy mentioned on November 1, 2021, we elected to exercise our call right to purchase the 50% of the Guardant Health EMEA joint venture shares that we do not currently own. As a result, we have initiated the process stipulated in the joint venture agreement to determine the purchase price, which at a minimum will be an amount that yields a 20% internal rate of return on the $41 million capital invested by SoftBank in May 2018. We currently fully consolidate the joint venture business in our financial statements. As such, the effect of exercising the call right will be to adjust the fair value of the redeemable non-controlling interest liability in our balance sheet to be equal to the purchase price of 50% of the joint venture and to reflect that adjustment on the income statement. As we exercised the call right on November 1, there was no impact to the fair value of $59.4 million as of September 30, 2021. We expect to complete the purchase before the end of the second quarter of 2022. Now turning to our revenue outlook for the full year 2021. We continue to expect revenue to be between $360 million and $370 million representing growth of approximately 27% over 2020 at the midpoint. We experienced some COVID-related impact to clinical volumes during the third quarter with respect to field sales access to oncologists and tightened restrictions internationally. We saw a recovery in September and into October as compared to a relatively weaker August but continue to see an impact on oncology office visits and sales force access in the US and across our global business. While we expect clinical volumes to grow compared to this quarter, we continue to be cautious given the uncertainty around the impacts of COVID-19. Despite this, we are expecting quarterly clinical volumes to finish the year strongly and grow approximately 14% year-over-year in the fourth quarter of this year. We have made great strides this year as we continue to broaden our oncology product portfolio and expand our reach into this cancer screening market. We are aggressively pursuing the best opportunities ahead and we are confident that we will be a leader in cancer across the continuum of care. At this point, we will open up the call for questions.

Thank you. Our first question today comes from Puneet Souda from SVB Leerink. Puneet, your line is now open.

Hi Helmy. AmirAli, thank you for addressing the questions. First, regarding ECLIPSE, I wanted to confirm the status of enrollment compared to the collection of samples and the completion of colonoscopy. You mentioned that enrollment will conclude in the next few weeks. Is there any reason you would consider increasing the trial enrollment at this point? I ask this because there are currently two colorectal cancer screening trials that have had to increase their enrollment to over 20,000 patients and extend their timelines. I just want to confirm that there is no need to expand based on your current observations. Additionally, will your enrollment remain at 13,000 considering the events rate you’ve been experiencing?

Yes. Thank you, Puneet for your questions. So as you may know actually these studies are powered based on the number of CRC that basically we need to identify in these prospective registrational studies. And as we elaborated in our last earnings call, when we increased the target enrollment from 10,000 to about 13,000, that was based on some of the intermediate readouts of the CRC incidents that we've seen so far for patients that have finished their colonoscopy and we have the colonoscopy reports and their CRC were confirmed. And based on all the data that we've seen, we felt comfortable that actually we need to increase enrollment target from 10,000 to 13,000. And since then, our prevalence in CRC incidents remain the same. So we believe based on all the information we have right now we feel very comfortable that 13,000 is the right target enrollment for us. I cannot obviously comment about other companies' trials, but probably actually maybe what's getting experienced is maybe how well the sites have been selected for the trials and what's the expected prevalence of CRC in different locations, different geography. I think there are a number of factors there that potentially help Guardant. As you may remember during the early days of COVID, in fact, we doubled down on our screening study instead of slowing it down. And during those days, in fact, we went and secured some additional high-throughput, high-prevalence sites in our study. But, I know well our data that we are seeing at Guardant and definitely I cannot comment about other trials out there.

That's great. No, they're very helpful. For my follow-up, I understand it's still early to discuss reimbursement for the SHIELD trial or the SHIELD assay once it concludes. However, could you please share your thoughts on the potential pricing for this assay? Also, what are the regulatory and guideline inclusion pathways necessary to bring this screening test to market? Thank you.

Yes. We have extensively studied lung screening over the past few years. The criteria we use for selecting our next end indication includes factors like biology, technology, reimbursement pathways, and regulatory pathways. We believe lung screening is an excellent candidate for us, though not the only one. As we progress with this program and our initiatives, we will keep you updated. Based on our conversations and research, we have a clear understanding of what needs to be done to successfully navigate the FDA review and Medicare review processes. As we make more progress, we will certainly keep you informed.

Thank you, Puneet. Our next question comes from Brian Weinstein from William Blair. Brian, your line is now open.

Great. Thank you so much and thanks for taking the questions, guys. Good afternoon. AmirAli, you've kind of talked about this in the past but given the recent data a couple of weeks ago from ESG, I just wanted to go back into the concept of the representation of sensitivity in that trial versus what we should be thinking about relative to your bar for ECLIPSE, not the bar for the FDA, but kind of where you think things are going to come in relative to degradation in the pivotal versus the case control. So how representative do you think that case control study really was when thinking about what we should be thinking about relative to ECLIPSE? Hopefully that made sense.

Certainly. ECLIPSE is one type of study, and other biomarker analyses could effectively demonstrate the performance we expect to see in ECLIPSE. We do not need to conduct a prospective two-year study for sample collection of ECLIPSE. Since 2019, we have been working to mitigate risks associated with our technology by evaluating cohorts that closely resemble the screening population for ECLIPSE. The most similar group, although not identical, consists of asymptomatic patients with early-stage colorectal cancer where we have been showcasing our assay's performance. We acknowledge the limitations of that data, which is why we are very excited and optimistic about our assay's performance. However, it's important to remember that the results from ECLIPSE will ultimately stand on their own, and we are only a few months away from obtaining that data. Thus far, all indications have given us confidence, but we will need to see the final outcomes from ECLIPSE once we analyze that cohort.

Okay. Great. And then, as a follow-up we've been monitoring the job posting sites and you guys are clearly building an organization in advance of the launch of that product as an LDT next year. Can you just give us any idea about the type of sales force that you're looking to have here? Be it size, be it qualifications, where you're going to be getting people from? Any kind of information on that I think would be helpful. Thank you.

Yeah. Absolutely, so we are very excited about actually 2022. It's going to be a year for us that, we're going to go after a bunch of market shaping activities. Really our goal is to do the right investment so that once we have FDA approval in 2023, we can maximize the market adoption at that time. And we are building our sales channel accordingly to meet the objectives that we have in this market-shaping phase of our commercial base. It ranges from engagement with a bunch of high-value stakeholders that can basically help set the right framework for blood-based screening to be used in a proper way in health systems and also a bunch of early adopters on the PCP side. Also, we are going to engage heavily with key health systems and try to get a bunch of engagements when we are really on the post-LDT validation of our tests to really intake rates the blood-based screening assay into the procedures, workflows, and systems that these health care systems have. So that would be our activity in 2022. We are making appropriate investments through our sizable commercial channel to really go after those opportunities for us.

Okay. Thank you, Brian. Our next question is from Derik De Bruin from Bank of America. Derik, your line is now open.

Hi. Good afternoon. My first question is about the international expansion. You're making significant progress in Spain and the U.K., especially with the joint venture purchase. How should we evaluate the current volumes of liquid biopsy tests using LUNAR-2 in these markets? Additionally, what are your thoughts on utilization changes moving forward? When do you anticipate that international revenues will become substantial?

I think Derik, thanks for the question. A lot of what you're seeing is we're laying the groundwork for what we believe are the critical inflection points for OUS volume which is specifically public reimbursement in each country. We believe that the approach that we're taking, partnering with some of the leading institutions and thought leaders in each region, can accelerate that progress towards that goal. We're seeing fantastic traction with the studies that we're doing, with the volumes that we're doing in key academic centers in the EU-five and lots of Latin America, and certainly with our joint venture in Japan and many other countries in the region. But I think you're going to see more of that as we really turn our focus from being a largely US clinical volume-driven company to one that really has global leadership in this space.

And speaking of clinical volumes, can you discuss what the contribution was from Reveal this quarter?

Yeah, it's Mike here. We're not breaking out the volumes between the different products now. And as we get more products, there's going to be more impact from those new large products. But, I think we've been really pleased with Reveal from the start of the launch back in February. So it's going as well as better than we expected. So we're really pleased with that. But yes we're not breaking out those volumes at the moment.

Thank you.

Thank you, Derik. Our next question is from Jack Meehan from Nephron. Jack, your line is now open.

Thank you. Good afternoon. I wanted to dig in a little bit more on the recent data at ACG. Just comparing that versus the data set that was presented at ASCO and I think it was a similar group. The sensitivity improved from 91% to 95%. Just curious if you could just elaborate on what drove the performance improvement? Was it just related to the incremental samples that were included? Have you made any performance improvements to the test? Again, just trying to think about how this translates to the prospective data.

Yes, sure. Actually, the cohort that got presented at ACG by our partners in Samsung Medical Center was an expanded cohort that some of the earlier data got submitted earlier in the year and was presented in ASCO as a single biggest cohort data that basically got published so far by one of our partners. In terms of what are the factors that went into the performance improvements, I look at all these numbers as basically being in the same ballpark from my perspective. Definitely the cohort size was expanded. And one thing that we have in our assay although our assay is the same, on the algorithm side everything is based on training and learning. So definitely over time when we generate more and more data, an historical data just softens performance is going to get improved over time, just that's the nature of learning-based systems. But all those kind of improvements would be really at best marginal. So I don't expect like even from now until at the time we run ECLIPSE, we're going to see a significant jump in the performance. But over time, as more data is generated and fit into our algorithm, definitely the training is based on more samples representing all kind of smaller cell populations. In theory, you can expect maybe performance gets a little better slightly but very marginally from my perspective.

Got it. And as a follow-up, there were some headlines in the quarter around M&A. I was curious if you could just weigh in on your thoughts around continuing to forge ahead with the organic strategy versus maybe the benefits of doing something in terms of more of a big deal?

Yeah. No thanks for the question. We have an extensive team we've built around corporate development. We obviously have a lot of cash in the bank. And I think we'd like to use it for something that makes sense, potentially. But as you mentioned our bar is very high. We're very excited about the organic opportunities we have, about our pipeline, about the progress we're making. We've launched a whole host of products over the last 12 months into the market and have obviously some pretty breakthrough products planned for the coming quarters and years. The bar is understandably very high. But at the same time, we're open to anything that can enhance our technology platform, that can enhance our commercial channel, that can enhance our data offerings. We're always going to be focused on those things that make sense for the long term that continue to really bolster and enhance our growth prospects and so we're not really going to compromise on that.

Thank you.

Thank you, Jack. Our next question comes from Matt Sykes from Goldman Sachs. Matt, your line is now open.

Thanks for taking my questions, everybody. I just have one question and a follow-up. I'll do it all in one go. But just on OpEx maybe for you Mike, obviously, a step-up year-over-year and sequentially. And you guys talked about where some of that is going in terms of the commercial capabilities. I'm just wondering in terms of trends that you can kind of call out in terms of what we should expect as an elevated level of CapEx. I know Mike you said it will likely continue through this year. But as we enter into this year was anything pulled forward or accelerated in that aspect? And then secondarily on that can you kind of talk about the labor cost component as a portion of that OpEx increase if that's material if at all? Thanks.

Yes. First of all, I want to clarify that nothing has really been expedited. Everything we've done this year regarding our operating expenses has been carefully planned. Throughout the year, we've aimed to expand the oncology commercial team, which is now over 250 people, more than doubling in the past year. As we approach the end of this year and move into next year, we'll start to expand our commercial team for screening in preparation for the launch of our LDT. So, the commercial expansion has been the main factor contributing to our operating expense increase this year and will continue to do so next year. Research and development has also significantly contributed to our growing expenses. We have ongoing studies like ECLIPSE, and we've recently announced the start of the ORACLE and SHIELD studies, which will also factor into next year's expenses. We're consistently innovating and developing new products, having launched three new products this year, and we anticipate that research and development spending will continue to support these efforts next year. Regarding personnel, while I won't go into specific percentages, we have indeed seen an increase. As I mentioned, we are adding more personnel on the commercial side, both in oncology and screening, which indicates growth and investment in our workforce. We're also expanding the infrastructure of our business, which is another key reason for the increase in our operating expenses.

Great. Thanks very much. I'll hop back in queue.

Thank you, Matt. Our next question comes from Patrick Donnelly from Citi. Patrick, your line is now open.

Helmy maybe one for you just on the volume side. It sounds like September and October recovered pretty nicely from August. I think you're talking about a 40% volume increase in Q4. Can you just talk about the cadence as we went through the quarter? And even in October your confidence level things are stable to obviously pointing up here as we enter into 2022? Just trying to get comfortable with the volume piece. It sounds like you guys are a little more confident relative to last quarter certainly.

Yes. No, thanks for the question. Yes, I think the good news was some of the early learning signs we saw in the last call kind of dissipated or at least stabilized, and it seems like there's been a sort of new normal out there with Delta, obviously, is still a concern but not really causing any kind of increased closures or increases of restricted access. It's sort of still restricted, still not like it was pre-COVID. But the good news is it's not getting worse. We just have seen great traction with our sales teams with our products and so on. So we are hopeful this means good momentum going into 2022.

Okay. That's helpful. And then on SHIELD, might be one for Mike. I apologize if I missed it but do you guys break out what you think the study will cost? I know you talked about 10,000 patients, maybe three years enrollment. But if you could just talk about the cost side would be helpful. Thank you.

Yes. No, we don't break out the cost of individual studies. But obviously, this is a multiyear study with a large number of patients. So it will be a sizable amount spread over the next few years and in similar level to ECLIPSE. But yes, we're not breaking out each individual study and giving those costs.

Understood. Thank you.

Thank you, Patrick. Our next question is from Julia Qin from JPMorgan. Julia, your line is now open.

Hi, good afternoon. Just a follow-up on Reveal. I know you're not ready to quantify the volume contribution in a quarter. But just qualitatively is Reveal uptake so far mainly within biopharma users, or are you seeing equal traction for clinical customers? And are you still expecting LCD coverage by year-end?

Yes, Helmy do the last piece. Yes, I think we're – that's still our expectation as it pertains to reimbursement. I would say for volume, we're seeing good traction on both sides. We're seeing clinical volumes really grow nicely. And on the same thing, on the biopharma side we're seeing the platform and the tests really, I think resonates with a lot of our pharma customers. And obviously, as we continue to grow our user base and customer base on the biopharma side, we see ample opportunities ahead for good traction for all of our products including Reveal.

Got it. And then on the M&A front just dovetailing on a previous question. I know you didn't really rule out the potential to grow your sales channel inorganically. But just thinking about your priorities like how important is it for you guys to acquire a channel in the community oncology setting at this point in time versus building it out organically during this time period where you're waiting for guidelines and reimbursement to fall in place?

I mean, I think we broke out our growth in the community setting, I think in the prepared remarks. We're growing faster in the community than we are in academic. That's really the area of most success for us. It's something we're very, very confident about. You can see the great performance we had in Q3. Heading into Q4, we believe on the clinical side. So we're very confident about that. Like I said, I think in the previous question, when we think about different M&A opportunities potentially, it's not about the short-term or what's happening in the business now but or what it means for the business three to five years from now. But yes, right now we're very confident with both the mix of products we have, our offering and the success we're having in our commercial channel.

Thank you, Julia. Our next question comes from Tejas Savant from Morgan Stanley. Tejas, your line is now open.

Hi, everyone. This is Edmund on behalf of Tejas. Thank you for taking my question. I have a couple of inquiries about biopharma volume. The volume trends seem to be quite strong, but could you provide a comparison of your current sample volumes to the levels before the pandemic? Also, how is your backlog of work looking as we approach 2022?

Yes, it's Mike here. I think we're sort of recovering now from the depths of the pandemic impact. I think we're back to levels where we were before that. And as we forecast going out towards the end of the year, I think we just see that rebound getting stronger and stronger. So now that's very positive for us. I think volume back above the pre-pandemic levels.

And in terms of backlog of work heading into next year can you give some color on what that looks like?

Backlog of work. I mean we don't generally break out a dollar value of backlog of work. But I think on the biopharma side, there's definitely a backlog. And we look at the pipeline and we look at going into 2022. So, I think we look at that as being a continued strong volume coming out of Q4 into Q1. But specifically breaking that out and giving a number, we don't generally do that.

No, that's helpful. And then a follow-up for you Mike. On the mix skew you saw in terms of volume shifting away from OMNI. I'm not sure if you explained this but what drove that? It seems to be normalizing. But just trying to understand what happened here and if it's going to be something we should be looking out for in the future?

Could you repeat the question from the start? I missed the first please.

Sorry about that on the volume mix skewing away from OMNI in the second quarter that seems to have normalized a bit this quarter but I was just wondering what was the underlying driver for that?

No. I mean that generally it changes every quarter. If you look at our average selling price on the biopharma side, it does fluctuate from quarter to quarter. Obviously, it depends on what has been processed and what samples we receive for that quarter. So yes, we had a shift this quarter compared to last, leaning more towards OMNI. But there's no definitive driver causing that change. There's no real trend to observe. I think it just fluctuates on a quarterly basis.

Got it. Thank you very much.

Thank you, Tejas. Our next question comes from David Westenberg from Guggenheim Securities. David, your line is now open.

Hi, thank you for taking the question. So I wanted to focus on the community oncologists. You highlighted the growth there. Are there any initiatives there that you want to highlight? And then as we look to the next three to five years what do you think the magnitude of growth is going to be in the community oncologists versus the academic setting? And that's all the questions I have.

When considering the market segmentation, it's often perceived that around 80% is within the community. Currently, our mix is actually over 60% community, indicating significant growth potential in that area, which we are prioritizing. There are several reasons for our success there. We needed a critical mass to effectively address the distributed nature of the community setting, which led us to significantly expand our commercial team in the past year, particularly with the launch of Reveal. It's not only about the commercial team; our medical affairs team plays a crucial role as well, particularly with genomic specialists and medical partners who assist in interpreting results and providing feedback on test reports. We've made early investments in this area and continue to do so. Additionally, our service offering aims to deliver an excellent customer service experience, creating a white-glove service that integrates our portfolio with the offices we work with, and we remain dedicated to this approach. As we expand our product range, these offerings will increasingly complement one another, making us more relevant in the community setting. Blood testing simplifies the delivery of precision medicine and care, minimizing the logistical challenges associated with tissue testing and facilitating collaboration with various medical professionals who may not be on-site. This empowers community oncologists and supports patients' desire to stay close to home.

Thank you, David. Our next question comes from Lu Li from Wells Fargo. Lu, your line is now open.

Thank you for taking my question. And I think just one question. Can you please frame like the early impact of the Guardant Response on the volumes over sell? And then also expectation for 2022?

Well, again, I think like for Reveal and TissueNext, all of the products that we launched this year, we're really pleased with how they've been received and how they've been utilized. Again, the volume that we're seeing we're very pleased with and it's in line with our expectations. But again, we have this now multi-products on the clinical side and we're not breaking out the volumes. But obviously, the main growth driver for us continues to be Guardant360, LDT and CDx. And from a revenue perspective, the vast majority of our revenue is seen from those two sort of fully reimbursed products.

Got it. Makes sense. And just maybe just final questions on, how do you thinking about the market share at this point, any impact from competition from other players? Just wanted to get a sense about how you're thinking about the market dynamic? Thank you.

Yes. That's a great question. In terms of all the metrics we track, we believe it's never really been in a better position than we have now. We continue to make great progress. We think we have great performance from a share of voice perspective. We continue to invest not just in our products but on our commercial offering and commercial channel as well. We feel very good in all the areas that we compete today and we're going to continue to invest more as we continue to have success.

Thank you, Lu. Our final question comes from Dan Arias from Stifel. Dan, your line is now open.

Hi, everyone. This is Daniel Macek filling in for Dan Arias. I just want to clarify something. I believe I heard that the ECLIPSE readout is anticipated in the first half of the year, and I want to confirm that. If that's the case, is there a chance it could be available even sooner? Also, Mike, regarding ASPs, while you expect the blended average to be lower with new products, do you think the issues with private payers and the new ADLT code have mostly been resolved? I know you mentioned your teams are addressing this, so I'm trying to understand if this will be less of a concern moving forward. Thank you.

Okay. This is AmirAli. I'm starting our first question. We expect to reach our target enrollment for ECLIPSE in the next few weeks. We're almost done, so it will be soon. We anticipate the data readouts to occur in mid-2022, around the middle of next year, and then I'll hand it over to Mike.

Yes. And yes on the ASPs, I mean, yes firstly with LDT and CDx actually we had very, very strong ASPs this quarter. I think we've guided to $2,600 and it was getting closer to $2,700. Basically, our blended ASP was $2,689, so really strong. Yes to the ADLT issues, I would say, they're pretty much pushed through now and the team has done a great job in actually getting payers prepared for that code. We've seen a lot less friction in the system than we thought that we would see. Strong ASP. I think as we go into the end of the year and we sort of flagged that in the remarks earlier as our newer products start to gain traction, we'll see some impact on that overall blended ASP. While we see LDT and CDx rates above the $2,600 level probably at the blended level, we'll start to see that overall come down a little bit each quarter. It will take time to get full reimbursement from Medicare and private payers before we pass on the uplift, but the message is for CDx and LDT those issues are pushed through with very strong ASPs.

Okay. Appreciate it guys. Thanks.

Thank you, Dan. That concludes the Q&A session for today. Thank you for all joining today's call. You may now disconnect.