GH - NASDAQ

Hello, everyone, and welcome to the Guardant Health Q3 2023 Earnings Call. My name is Thrisha, and I'll be your operator today. [Operator Instructions] I will now hand you over to your host Carrie Mendivil, Investor Relations from Guardant Health. Please go ahead, Carrie.

Thank you. Earlier today Guardant Health released financial results for the quarter ended September 30, 2023. Joining me today from Guardant are Helmy Eltoukhy, Co-CEO, and AmirAli Talasaz, Co-CEO and Mike Bell, Chief Financial Officer. Before we begin, I'd like to remind you that during this call, management will make 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. This call will also include a discussion of non-GAAP financial measures, which are adjusted to exclude certain specified items. Additional information regarding material risks and uncertainties as well as the reconciliation to the most directly comparable GAAP financial measures are available in the press release Guardant issued today as well as in our Form 10-K and other filings with the SEC. Guardant disclaims any intention or obligation to update or revise financial projections and forward-looking statements whether of new information, future events or otherwise. The information in this conference call is accurate only as of the live broadcast. With that, I'd like to turn the call over to Helmy.

Thanks, Carrie. Good afternoon and thank you for joining our third quarter 2023 earnings call. I will start off our call today with our top-line results for the third quarter and then go into more detail on our progress in therapy selection and MRD. I will then turn the call over to AmirAli for an update on screening. And finally, Mike will provide a more detailed look at our financials and outlook for the remainder of 2023. Starting on Slide 3. Guardant is a liquid biopsy leader in therapy selection with a strong pipeline of opportunities in MRD and screening. With our comprehensive suite of tests we are transforming patient lives across the continuum of care. In early September, we hosted our inaugural Investor Day where we shared our long-term vision for Guardant. I encourage anyone who wasn't able to attend our Investor Day to access the replay on the Investors section of our website. It was a great opportunity to reflect on how far we've come over the past decade and look ahead to where we are going. We are just scratching the surface of what we believe is a massive opportunity in front of us. Our commitment to patients has always been at the heart of what we do. We look forward to continuing to grow our reach to impact more patient lives across the globe. To demonstrate the impact of our tests, I will start our call off today by sharing patient story for our newest product, Shield. Earlier this year a woman in her late 50s visited her primary care physician. She was un-screened for colorectal cancer and was resistant to receiving a colonoscopy. Her physician proposed a Shield LDT test which was added to our annual blood work. The Shield test results reflected an abnormality which letter positioned to order a colonoscopy. Though she had been hesitant of a colonoscopy at her initial visit with this result of Shield she prioritized getting the procedure done. The colonoscopy determined that she had stage 2 colorectal cancer. She started receiving chemotherapy right away followed by surgery to remove a portion of her colon. After surgery and just a few months of treatment she was healthy again. With their cancer caught early she was able to participate in her son's wedding this past fall. This story is a powerful example of delivering on our commitment to increase colorectal screening compliance through the preference and ease of use in the physician's workflow. Serving this patient and the millions of others just like her who will face cancer this year is why we exist. The results we share today reflect the positive progress we are making in our mission to help as many of these patients as we can. Turning to top-line performance on Slide 4. We are pleased with our third quarter results with revenue growing another 22% this year to $143 million. This solid growth was driven by precision oncology revenue, which increased 31% in the quarter. We continue to see strength in our core therapy selection business with a number of tailwinds to drive growth over the long term. Turning to Slide 5. We delivered strong growth across precision oncology with a record number of combined tests during the quarter. Clinical test volume during the third quarter reached 43,900 tests, an increase of 35% from the prior-year quarter. Clinical growth was driven by strong contributions from our key products, supported by a robust commercial platform. For biopharma, we delivered 7,500 tests increasing 11% year-over-year. Turning to Slide 6. Looking more closely at some of the highlights from the third quarter. We continue to benefit from tailwinds seen earlier in the year with another quarter of solid year-over-year clinical volume growth across Guardant360 and TissueNext. Notably, nearly half of oncologists in the United States are now ordering a Guardant360 test every month which highlights the strength of our core therapy selection business. As is typical with new approvals following the Guardant360 CDx approval for ESR1 mutation-positive patients, we saw a spike in breast volumes in Q1 and Q2, fueled by pent-up demand. In Q3, we had worked through this backlog and therefore had sequentially less breast cancer tests in Q3 than in Q2. That said, we still had strong contribution from breast volume in the quarter, which increased significantly year-over-year and we expect to see continued growth in this indication. Our team remains focused on investing in our commercial infrastructure and providing the best customer experience. Last week we announced the integration of our CGP tests within Flatiron oncology EMR. With this underway, we are in the process of integrating the top three oncology EMR providers in the United States. These providers collectively represent approximately two third of all oncology practices in the country and these integrations are expected to reduce oncologists ordering time by 75%. Notably, by the end of the year, we expect to be fully integrated in over 400 accounts. In addition to the customer experience benefits and efficiencies gains, we expect these partnerships to contribute to an uplift in ordering volumes in 2024. We are also seeing growing contribution from MRD with another quarter of record volumes for Guardant Reveal. We are on track to upgrade Reveal with smart liquid biopsy by end of this year. As we shared at our Investor Day, we are expanding into other geographies and are seeing an increasing contribution from labs globally. This quarter we saw good momentum, particularly in Europe as the Royal Marsden Guardant powered Laboratory was awarded an expression of interest by the NHS to launch CDP for non-small cell lung cancer in England potentially making this technology accessible to thousands of patients across the country. We are also making good progress in Asia with the recent launches of our assays for biopharma use in China and of Guardant360 for clinical use in Japan. In early September Guardant360 CDx received regulatory approval in Japan as a companion diagnostic to ENHERTU for treatment of non-small cell lung cancer patients with HER2 mutations. This follows the recent national reimbursement approval for Guardant360 CDx in Japan, which became effective at the end of July. We are really excited about the opportunity in this market as Japan currently represents the largest expansion opportunity within our portfolio. While international revenue has historically been a relatively small portion of volumes, we expect significant growth from this core markets over the next year. Moving on to Slide 7. In the third quarter, we continue to see breakthroughs in payer coverage that provide tailwinds for our clinical business in the near term. Starting with therapy selection. We are starting to see the impact of the recent coverage wins for Guardant360 with ASP now towards the upper end of the $2650 to $2700 range. While this marks significant progress so far this year, our ASPs will increase meaningfully more throughout the next few months. In late September, CMS proposed to crosswalk Guardant360 LDT to a price of $5,000 as part of the rate-setting process for reimbursement under the Medicare Clinical Lab Fee Schedule next year. It finalized this will be a major milestone for Guardant. It will have a meaningful impact on our top and bottom line. Mike will share more about the uplift we expect to see in our ASP shortly. We are also working to expand private payer reimbursement with the ultimate goal of getting national biomarker testing coverage. We are seeing important inroads made here. To date 13 states, most recently California have enacted biomarker bills into law that require providers to cover biomarker testing. Collectively, these inactive bills cover nearly half the U.S. population. Two more Ohio and New York are pending. In many cases, these bills support private payer coverage for both therapy selection in MRD. We will continue to support efforts by the American Cancer Society and others to get these bills passed and more states expand access to comprehensive biomarker testing through broadening private payer coverage. Lastly, we are continuing to make progress with the reimbursement for TissueNext and recently surpassed 200 million covered lives. For MRD we also received coverage for Guardant Reveal from the Geisinger Health Plan providing coverage for more than 0.5 million members. The test will be covered when you use after surgery or curative treatment to inform physicians decision about adjuvant therapy and to monitor for disease progression recurrence or relapse. This builds on the previous coverage we received from Blue Cross and Blue Shield of Louisiana. We look forward to continuing to drive adoption of Reveal and additional reimbursement wins. Moving on to Slide 8 to discuss some recent data for Reveal. In October PEGASUS interim data was released as a late-breaking abstract at the ESMO Congress. PEGASUS is a de-escalation clinical utility study for post-surgical liquid biopsy guidance treatment of 135 Stage 3 and high-risk Stage 2 colorectal cancer patients. Initial results show that 34% of patients with a positive liquid biopsy results after surgery had their cancer relapse despite initiation of adjuvant chemotherapy. In addition, only 10% of patients with the negative result experienced a relapse. Approximately 40% of patients converted from ctDNA positive to ctDNA negative after treatment suggesting treatment efficacy of chemotherapy for some patients. These results are promising and suggests that our Reveal blood test do provide a sensitive tool to help oncologist make informed treatment decisions, that improve outcomes for their patients. We expect full readout of this study in 2024. With that I will now turn the call over to AmirAli to provide an update on our screening business.

Thanks, Helmy. Turning to Slide 9. We are continuing to make advancements with our Shield blood test as we pioneer a new category in the CRC screening market. We submitted our premarket approval application for Shield last March and are making steady progress with FDA review. We continue to expect FDA approval and the launch of Shield IVD in 2024. Most recently we concluded enrollment in our ECLIPSE clinical study. Collectively we enrolled over 45,000 patients and biobank these samples. This is a huge milestone and this biobank will really be a treasure for us for additional regulatory grade studies for future device upgrades. Turning to Slide 10. We are committed to innovation and continuous improvement cycles powered by efficient data generation. At our Investor Day in September, I shared some exciting new clinical data for the next-generation version of Shield. This data looks at the U.S.-based colonoscopy screening cohort of about 2,000 blinded cases collected prospectively from clinical sites and included screening negative adenomas and CRCs. Individuals from this cohort were tested with both version of the Shield tests. The version used in our PMA ECLIPSE study which we will refer to as the Shield V1 and the next generation version, which we will refer to as Shield V2. When we look at Shield V1 performance in this prospective cohort sensitivity was 84% with specificity of 90%. This was in line with the performance we saw from the same as an ECLIPSE cohort where sensitivity was 83% and specificity was 90%. With the upgraded algorithm in V2 overall performance improved to 91% sensitivity and 91% specificity in this new perspective cohort. Looking at only early-Stage 1 or 2, sensitivity was 88% compared to 76% using the V1 assay. CRC sensitivity in Stage 3 and 4 with blood test for a 100% and sensitivity in detecting advanced adenoma was similar. This data gives us confidence that the clinical sensitivity of Shield V2 will be higher than the current Shield V1. We plan to conduct a regulatory grade clinical study utilizing our already biobank samples that were collected during ECLIPSE study to assess the performance of Shield V2. Pending a successful readout we will submit a supplemental PMA with the potential for approval in 2025. Moving on to Slide 11. At the American College of Gastroenterology or ACG Annual Meeting in October, we presented some additional data about the real-world adherence rate with Shield and new insights from our health outcome models. In addition, Kaiser Permanente Center for Health Research presented data on their experience with Shield and the perception of blood-based testing for colorectal cancer screening from both patients and providers. The results of the randomized prospective trial were overwhelmingly positive for Shield. In this study, providers offer the Shield blood test to a randomized cohort of patients who have not completed the FIL test. Patients who were offered Shield we more than two times as likely to complete CRC screening, compared to the patients receiving usual care. In addition, the study found that the patient and provider surveyed were enthusiastic about the potential for blood-based CRC screening tests to increase compliance. Last month, we reached an important milestone with the first publication of blood-based CRC screening testing in Annals of Oncology. This study was run on an early prototype of what is now Shield and highlights how and accessible and convenient blood test helps to increase effectiveness of CRC screening. We have always had a vision for blood-based multi-cancer screening. We started with CRC as the first indication for Shield because of the established pathways for FDA approval and reimbursement, which allow for broad access. We are working to add lung cancer as a second indication, followed by an expansion into other cancers. We are continuing to make good progress in enrollment into our lung cancer screening trial and look forward to beginning enrollment for our interventional and MSET study next year. With that, I will now turn the call over to Mike for more detail on our financials.

Thanks, AmirAli. Starting with Guardant360 ASP on Slide 12. As Helmy outlined, we're starting to see the positive impact on Guardant360 ASP from commercial payer coverage wins that have recently received confirmed and proposed Medicare price increases to Guardant360 LDT. In the third quarter the Guardant360 ASP again trending towards the upper end of the $2650 to $2,700 range we saw in Q2. At the start of October, we were informed by MolDX the Medicare price for Guardant360 LDT has been increased from 3,500 to a new GAAP full rate of $3967 effective October 1, 2023. Furthermore, in late September, CMS published its preliminary Clinical Lab Fee Schedule for 2024 which proposed that the Guardant360 LDT price crosswalk Guardant360 CDx. This proposal is finalized Medicare price for Guardant360 LDT will increase to $5,000 as of January 1, 2024. To put this price increase into context. Medicare Guardant 360 LDT tests, represent between 10% to 15% of our total Guardant360 volume. As a result, the impact of the Medicare price changes will be to increase the overall Guardant360 ASP to be between $2700 and $2750 in Q4 2023. And then the CMS proposed crosswalk pricing is implemented $2,850 to $2,900 from January 1, 2024. With the tailwinds we're seeing on coverage and pricing. We are making very good progress towards the goal we stated at our recent Investor Day of ultimately realizing an ASP of over $3,000 for Guardant360. Now turning to our Q3 financial results on Slide 13. Total revenue for the third quarter of 2023 grew 22% to $143.0 million compared to $117.4 million in the prior year quarter. Total precision oncology testing revenue for the third quarter was $133.4 million, increasing 31% compared to $102.1 million in the prior year quarter. As in previous quarters. This increase was primarily driven by strong year-over-year growth in clinical and biopharma volumes. Precision oncology revenue from clinical tests in the third quarter totaled $103.9 million, up 34% from $77.8 million for the prior year quarter. Third quarter clinical test volume was 43,900 an increase of 35% from the same period of the prior year. Guardant360 continues to be the main revenue driver with continued strong year-over-year growth. As Helmy mentioned following the Guardant360 CDx approval for ESR1 mutation positive patients. We saw a spike in breast volumes in Q1 and Q2, fueled by pent-up demand. In Q3, we had worked through its backlog and therefore sequentially less breast cancer tests in Q3 than in Q2. That said, we still have strong contributions from breast volume in the quarter, which increased significantly year-over-year and we expect to see continued growth in this indication. Also note, that the third quarter. Clinical revenue includes the payment of $3.6 million received from Medicare related to a successful appeal claims data between 2018 and 2020. This was a one-time payment and there are no other outstanding claims that have yet to go through this, the appeal process. Excluding the $3.6 million payment, the blended clinical ASP was approximately $2,300. Which is consistent with the previous quarter and in line with our expectations. As a reminder, lending clinical ASP will continue to be influenced by both the volume mix between Guardant360 TissueNext and response, as well as the mix of overall clinical volume between the U.S. and International. Precision oncology revenue from biopharma tests in the third quarter. Total $29.5 million of 22% from $24.2 million for the prior year quarter. Biopharma test volume was strong with third quarter totaling approximately 7,500 tests up 11% from the prior year quarter. Biopharma ASP in the third quarter was approximately $3,900. Which was higher than both last quarter 3,700 and the prior year quarter at 3,600 due to the product mix. Development services and other revenue in the third quarter totaled $9.6 million down $5.7 million or 37% from the prior year quarter. As we communicated last quarter. This was anticipated and was primarily due to the timing and amount of milestones related to our partnership agreements and companion diagnostic collaboration projects with biopharma customers as well as the reduction in royalty revenue. Gross profit for the third quarter of 2023 was $85.4 million compared to a gross profit of $76.9 million in the same period of the prior year. Gross margin was 60% compared to 66% in the prior year quarter. So Precision Oncology, gross margin was 60% in the third quarter of 2023, which was slightly lower than 61% in Q3 2022. Primarily due to changes in the product mix. Development Services and other gross margin was 59% in the third quarter of 2023 compared to 93% in Q3 2022. The change in margin was primarily due to the cost of processing Shield LDT samples as part of our market development activities, for which we are currently booking minimal revenue. We continue to expect overall gross margins to be approximately 60% for the full year 2023. Operating expenses for the third quarter of 2023 are $199.0 million. A reduction of $22.5 million compared to $221.5 million in Q3 2022. Net loss was $86.1 million or $0.73 per share for the third quarter of 2023 compared to $162.0 million or $1.58 per share in the third quarter of 2022. The $75.9 million year-over-year reduction in net loss is primarily due to a $31.1 million year-over-year improvement in our loss from operations. A $29.9 million positive change in unrealized gains and losses recorded for our equity investment in Lunit and a $9.9 million increase in interest income. Moving on to non-GAAP financial measures. On Slide 14. Non-GAAP operating expenses were $177.3 million for the third quarter of 2023. A reduction of $23.2 million compare to a $200.5 million in the prior year quarter. Non-GAAP net loss was $79.2 million or $0.67 per share for the third quarter of 2023 compared to $120.8 million or $1.18 per share for the third quarter of 2022. Adjusted EBITDA was a loss of $79.7 million in the third quarter of 2023. Compared to a $112.8 million loss in the third quarter of 2022. Free cash flow for the third quarter of 2023 was negative $80.2 million, compared to negative $99.9 million in Q3 2022. We continue to make very good progress in managing our operating expenses and cash burn. And we remain on track to achieve our goal of lowering our full year operating expenses compared to 2022. As well as reducing our free cash flow to approximately negative $350 million for the full year. We ended the third quarter of 2023 with cash of approximately $1.2 billion. As we laid out at our recent Investor Day. We expect our current cash will provide the runway to reach cash flow breakeven, which we are targeting in 2028. In addition, we are on track to achieve our targets of reaching cash flow breakeven in therapy selection by the end of this year and look managing the annual screening cash burn to be approximately $200 million. We continue to expect that our annual cash burn screening will be approximately $20 million over the next five years. Now turning to our outlook for the full year 2023 on Slide 15. We are raising our full-year 2023 revenue guidance and now expect revenue to be in the range of $553 million to $556 million, representing growth of approximately 23% to 24% compared to 2022. This compare to our previous expectation of $545 million to $550 million. Additionally as just mentioned, we continue to expect 2023 operating expenses to be below full-year 2022 and free cash flow to improve to be approximately negative $350 million in 2023. Turning to Slide 17, our long-term vision is to transform cancer diagnostics through cutting-edge technology. A focus on high impact opportunities and consistent execution. In the third quarter, we achieved our goal of 200 million covered lives for TissueNext. And we remain on track to achieve the remainder of our stated milestones. At this point. We will now open the call to questions.

[Operator Instructions] The first question we have comes from Tejas Savant from Morgan Stanley. Please go ahead.

Hi guys, good evening, and thanks for the time here. Helmy Mike thanks for the color on the GD360 ASP. Just had a couple of quick follow-ups, as my opener. Where do you anticipate that LDT versus CDx mix settling out following the change and how should we think about the impact of the unique CPT code on the private payer side of things.

Yes, hi, Savant. I can take that. Yes what we've seen over the past 12 to 18 months is slowly the waiting between LDT and CDx has sort of moved more towards the CDx. So it's, I think it's fair to say that it's just over 50% on the CDx side. And so, we're not really anticipating that this change in pricing is really going to change that mix. What we've seen really driving the change in mix is the CDx approval is that we've been getting over the last 18 months or longer. So, I don't think the price impact will change will change that much. I'm sorry. Then the second part of the question Tejas on the unique code.

That was just on the private payer side of things.

Now I think we think that's also be a positive. What we've sort of talked about with that increase in ASP is purely the Medicare impact. And so I think there's potential additional improvements to the ASP, one from Medicare Advantage. And so, we think that will definitely help. But yes, having a unique CPT code, it's going to make the processing simpler for the private payers. They'll have a Medicare list price to match against what they're paying as well. And so we think potentially, it could make the system. Well, take some friction out of the system, make the pricing more transparent than could have a positive impact. So, we've not baked that into our ASP projections yet, so we'll see how that goes next year.

Got it. And then one quick follow-up on PEGASUS. Helmy, can you help us contextualize the significance of that readout for us? It sounds like of that -- so 10% of patients who experienced a relapse in the study, is that level sufficiently low enough to get physicians comfortable with de-escalation following a negative MRD result just based upon your physician conversations so far. And given that this was the older version of the assay, how do we read through the results to the commercially available version?

Yes. No. So I think this is very positive in multiple aspects. The fact that this potentially highlights that you can spare patients these high toxicity as adjuvant chemotherapies. And this is really a sort of target that the investigator said that they felt would move the standard of care for those patients forward. And the fact that we met the sort of interim endpoints and I think is really exciting. And so I think we're really looking forward to the full readout of this trial sometime in 2024. In terms of how this reads through to current version of Reveal and future versions, we see essentially improvements across the board in terms of sensitivity and specificity. And so clearly, if you're using an even better assay than when you are the results should be even better. So, we think this bodes very well in terms of being able to translate these results to our future versions of assay.

Thank you. We will take our next question from Dan Arias from Stifel. Please go ahead.

Here we go. Thanks for the question Mike, on just the clinical volumes for the quarter and for the year, 44,000 or so for the quarter, which I think is up about 1% sequentially. Do you still think you finished the year with high 30s or low 40s growth as a target for 2023? That does imply a step-up in 4Q. So just checking to see what the right way to model the full year is?

Yes, Dan. I think year-to-date, we're still over 40% year-over-year on clinical volume growth. And yes, for the full year, yes, high 30s is sort of what the guidance implies. So yes, we're still very confident that we'll see a sequential uplift in Q4 and very strong year-over-year for the full year.

Okay. And then AmirAli, on Shield, as we close in on the end of the year here, wondering if you just -- you might be willing to dial in your working assumption on a commercial launch time for 2024. And then just kind of expanding on some of your comments that you made at the Investor Day. It sounds like the USPSTF data review process could start next year for parts of the process anyway. Can you just add some color to the thought around having the likelihood of V2 get a look from the USPSTF as a part of that cycle? And then what that might mean if that doesn't happen and you have V1 being considered by the USPSTF, but V2 being the assay that presumably you feel better about going to market with?

Yes, sure. So in terms of the review cycle, as I mentioned in the prepared remarks, we continue to see good progress, steady progress in the review cycle and continue to expect approval and launch of Shield IVD in 2024. Regarding the cycles for USPSTF Yes, for 26 guideline inclusion, typically, they start the data review a couple of years before. We expect that review start sometime in the middle of '24 to second half of '24 and then conclude with a recommendation updates in 2026. Regarding Shield V1 and V2 guideline inclusion, I continue to believe Shield. We won with the performances that we reported as long as we can get FDA approval for it, that hopefully, we would get into the guidelines. And once Shield as a blood-based colorectal cancer screening branded by Shield goes into guidelines, future upgrades and updates to that test it's going to continued market as Shield. So I don't believe that we need to go through the cycle of USPSTF in order to get the benefit of the commercial payer coverage that Shield would have. So once the Shield V1 goes through that process, all the future versions as long as they are better than Shield, I expect them to be grandfathered in similar to what we experienced with other products that we upgraded them and the coverage policies continue to stay in place.

The next question comes from Mark Massaro from BTIG. Please go ahead.

Hi guys. Congrats on a strong quarter. I guess the first one is for Helmy. It's encouraging to see Geisinger and Blue Cross Blue Shield Louisiana come on for a Reveal MRD. I'm curious what other types of conversations are you having with other payers? I know that MRD is not yet included in NCCN guidelines. So I'd be curious to hear your thoughts on when you think MRD testing can be included in NCCN guidelines and how those conversations with other payers are trending at this time?

Yes. Great question. Mark. I would say that, obviously, with 360 CDx, we have over 300 million covered lives. And so we have a very strong managed care team that has relationships with many of the plans out there. And so, I think those conversations are ongoing. We're continuing to make very good progress, I think, with many plans. And I would say that the state biomarker bills are certainly tailwind catalyst in terms of getting us to coverage sooner rather than later. I think that's why I highlighted that now over half of the U.S. population is covered in a state that has one of these biomarker bills, and we obviously have New York and Ohio and hopefully some other states down the pipe. And so, we see this as a very important structural change in terms of how cancer tests are reimbursed that if you have Medicare and you have the state biomarker bills, you actually have a really nice light path in many states towards full coverage, which is really going to upend what we think about cancer diagnostics in the entire industry for years to come. So this is a very big move. And one that bodes well for MRD and potentially for other tests that we bring to market in the cancer biomarker testing space. NCCN guidelines, I think utility data is what's typically required. I think PEGASUS will be a sort of positive piece of evidence that further bolsters the case for MRD testing. But there may need to be some additional readouts from the clinical utility perspective before we see guidelines change.

Excellent. And then my second question, the clinical volume growth of 35% was strong in the quarter. Is there any way you could break out the volume growth from either TissueNext or Reveal and then as we're thinking about 2024, I would love to get your latest thoughts on to what extent the integration with the EMR providers can help accelerate ordering either from 360 reveal or other tests?

Let me start with the second half. The first one, this is typically a huge uplift when you are able to integrate digitally with providers in terms of how they practice medicine and how they order their battery of tests and procedures and being able to really go a long way this year and hopefully next year in terms of integrating with most of the U.S. oncology market. We think is going to be an additional growth driver. We're doing things at the large group practice level, account levels, as we said, we'll have over 400 accounts integrated this year. And so, there's going to be a lot of top-down work that we're embarking on, especially in the community type centers that we think will allow us to essentially embark on the next stage of growth, not just for the 360, but for all our oncology products.

Yes. And on the volumes without breaking down into specific numbers, but both Reveal and TissueNext next year-over-year growth were both very strong. I think in previous quarters, like in previous quarter, Q2, both were year-over-year growth was over 100%. maybe both a bit slightly lower than the 100% year-over-year growth in Q3. But year-to-date Reveal is still well over 100% year-over-year growth. TissueNext very close to of 2% year-over-year. So good in the quarter, a very strong year-to-date. So again, I think we're looking at closing the year out strong on both Reveal and TissueNext.

Our next question comes from Puneet Souda from Leerink Partners. Please go ahead.

Maybe just on Shield V2. Can you just confirm if the biobank samples that you have are untouched and sort of unutilized in any of the trials so far that you can actually use them in the pivotal trial for the Shield V2 and get that submitted. Maybe just a clarification there first, and then I have a follow-up?

Yes. So the short answer is yes. More details, we have enrolled about 45,000 about 24,000 of them have been used in the first study through the CRCs that we analyze from that first 24,000, and we have 20,000 plus more patient on touch blinded - CRC's on touch blinded asset in almost the same in our biobank.

Got it. Okay. And then just maybe one quick follow-up for you, AmirAli. I mean anything -- any feedback from FDA, you pointed that the conversation is going well there, but I just wanted to see if there are any updates on that front. You pointed out about 2024 approvals still. Just wanted to get a sense of if you have any sort of guidepost in terms of earlier versus later or sort of first half versus first quarter. Anything you can provide there would be super helpful?

Yes. As I mentioned it, we are continuing to make steady progress. Still we are under review. We are not done with it. And it's very hard to predict the exact timing of it. But the confidence level is very, very high. That would be in 2024, as we expected at the time that we submitted the PMA, so continues to be the same. And the agency have been very collaborative with very collegial kind of attitude toward our application. They understand value of blood-based cancer screening, colorectal cancer screening. So we are pleased with the review cycle so far. We see how it goes.

Thank you. Our next question comes from Kyle Mikson from Canaccord Genuity. Please go ahead.

Perfect. Hi guys. Thanks for taking the questions. My question for you, Mike. Given this G360 ASP trend benefiting from the multiple tailwinds with Medicare pricing, could you maybe just estimate, I guess, tell us if it's possible that G360 ASP could increase to some level by the end of '24. Look at the average revenue per test approach, maybe like 300 by that point. And then also, Mike, just a question on like cash flow as we think about getting to breakeven by the end of this year and then kind of going forward, how dilutive to cash flow generation is MRD and reveal like right now, in other words, how much of an investment there to advance that strategy like given that return so for that kind of mid-teens revenue number?

Yes. Kyle, on Guardant360 ASPs. Yes, I mean we've seen really good traction, both on the Medicare side. We have to wait for the finalization of clinical lab fee schedule yet. But if that comes through, we'll be closing down on 2,900 at the start of next year. And as I just mentioned on the call earlier, there are potential other tailwinds, we could see Medicare Advantage come through. We could see that also helped with private payer payments for Guardant360 LDT. So I think we've seen good traction. We set out on our Investor Day, it was 8 weeks ago then we wanted to get to a target of 3,000. So I think at the moment, we're feeling very confident we can get we get north of 3,000. Definitely in the five-year time line we said on the Investor Day, but I think probably we're trending towards that a little bit earlier than we would have anticipated and exactly where we can go. I think we'll have to see how these tailwinds roll out. But again, we're confident. And then on MRD. I think we've broken it out before, probably the net investment on the MRD, if you take into account the cost of processing the test this year the research and development efforts that are going into it and the data development efforts as well as the sales and marketing costs, probably a net investment of around $100 million this year, give or take. And we see that likely continuing into at least 2024. Of course, the key for us, and we're managing the volumes to try and stay manage the cash burn and yes, the key for us going forward is really to get additional reimbursement. And we've talked about CRC surveillance and then other indications. So that's what we're really focused on with and at the same time, managing the burn.

Okay. That was fantastic. Mike, thanks so much for that. And then AmirAli one on screening for you. The approval seems pretty likely. I think you mentioned like mid-24% around there for Shield. What's the latest thinking there for you on the label that you ultimately attain, like second-line, third-line test. Just wondering if you discussed that with the FDA at all or maybe that's included in the -- in your opinion in this PMA submission?

Yes, just to clarify, I think the mid-'24 time line that I mentioned was connected to the potential time that USPSTF review cycle in terms of some of the early data research would start based on our understanding of the process. In terms of label, we haven't got to the label negotiation yet so far, there's been some conversation with agency about this matter. And I think so far, so good, but we'll see when we go to the official like label negotiation phase what happens.

Thank you. We will move on to the next questioner, Jack Meehan from Nephron Research. Please go ahead.

Thank you. Good afternoon. For Helmy. A couple of questions on the G360 volumes. First is with breast cancer. This dynamic you called out. I was curious, do you think this sequentially continues to taper in 4Q? Or is that bolus normalized at this point? And second, volumes are obviously pretty strong. I was just curious with the dynamic backdrop we're seeing, are you seeing any changes in market share versus tissue or other liquid players? Thanks.

Yes. No. As I said, there was a sort of warehousing effect that happened where you had this pent-up demand for everyone that wanted to get on the drug. And so we had a huge jump up and we believe we've completely worked through that bolus. And now we're just continuing on a very nice trajectory. And I want to highlight that we're still extremely elevated levels of breast cancer testing than we were a year ago. I think year-over-year, we're over 100% growth. And so we're very excited in terms of where we are with breast cancer. And I think now on kind of the right trajectory here, now that we've worked our way through that bolus. Yes, in terms of sort of competition, I think we're seeing a lot of the kind of same dynamics play out, ebbs and flows, the usual suspects out there. But we continue to be the leader - undisputed leader in terms of liquid biopsy, especially in therapy selection. So we're just chugging away. And obviously, as we said, we have all these catalysts coming up in terms of really working at a really much closer level with a lot of the important oncology practices around either through EMR or other sort of center-wide arrangement. And so, we're very excited about what this sort of next phase bodes for Guardant360 testing and Reveal testing.

Great. And one question for Mike. With the pricing improvement for G360 that you're seeing. I was curious if there's any flag you're willing to put in the ground for cash burn in 2024? Just with the trajectory you're on with that improvement? What's a good landing spot for next year?

I mean I think if you look at our Investor Day slides, we said this year was a year of reduction of cash burn. Next year will be to -- we said over the next five years, we expect the cash burn to come down each year. Although I want to sort of -- cut that because it is a year of launch within screening. We're still making investments on MRD. We will definitely see therapy selection flip to generating positive cash flow. So I think it will be a little bit lower than this year, but not too much lower because, again, we need to invest in the launch. But yes, just to reiterate, we'll end the year with $1 billion in cash, and we still see that as being able to get us through to cash flow breakeven in the five-year time line we pointed out at the Investor Day.

Thank you. Our next question comes from Dan Brennan from TD Cowen. Please go ahead.

Hi, thanks for - thanks for the questions. Congrats on the quarter. Maybe the first one just on Reveal. Could you just kind of walk us through the road map forward in terms of how we should think about filing for expanded coverage both in CRC and then also be interested to hear about what expectations should be for the upcoming data at San Antonio Breast and how that could play into your Medicare filing plans in breast?

Yes. So as we speak, we're putting, I think, some of the Kosmos data for colon cancer, getting it ready for publication and so hopefully, once that's published, that is something that would really make up the majority of our submission to MolDx for the expanded surveillance CRC indication. As we speak, we're seeing a lot of, I think, good breast cancer data internally. We've also made a lot of good progress on lung cancer as well. And so we're hopeful that -- we'll be able to have something out there certainly, hopefully published sometime in '24 and have that submitted as well to MolDx. So we think - we're laser-focused on breast, colon and lung cancers. We have obviously multiple other cancers in the pipeline as well, but we think those 3 indications would get us really a long ways of the way we need to be to have a reasonably reimbursed product for Reveal.

And with the data at San Antonio Breast, that will be a piece of the larger filing package, Helmy for breast?

Yes. I mean we continue to have data we had data at ESMO that was a very compelling in breast. I think we'll have some additional data in San Antonio. But we have some other studies as well that may make up the bulk of the submission. So yes, we have sort of multiple shots on goal. I won't be reliant on this one study.

Thank you. Our next question comes from Patrick Donnelly from Citi. Please go ahead.

Hi guys. Thanks for the question. Help me maybe just on kind of the core business. It sounded like breast, had the backlog had some benefit from the pent-up demand early in the year, normalized a bit in 3Q. Can you just talk about, I guess, the trends you're seeing there? It sounds like maybe the backlog you had you worked through and now it's just kind of executing on the healthy backdrop, but I would be curious just a little more on the moving pieces there and the right way to think about that going forward?

Yes. I think now we're sort of at normalized rates. And now it's just a matter of getting additional patients tested. One thing -- we see a lot of room to grow even for ESR1 and for breast cancer testing, we're seeing data out there that despite our, I think, very large increase in volume of breast testing, and a lot of patients are still being tested by tissue or by other methods to try to assess ESR1. It's very important that physicians know that -- it's very unlikely to detect ESR1 mutation since there are often emergent mutations or distance mutations through our archival tissue biopsy. And so there's obviously, more work to do, but that is a, I think, opportunity for us to continue to increase volumes, I think, considerably. And obviously, in the other cancer types outside of lung and breast I think there's still a lot more room to grow. So CGP, I think, is still not top of mind for many patients. And yes, we're continuing to see, I think, that can be considerable growth for years to come.

Okay. That's helpful. And then maybe just another quick one on Reveal. It sounds like smart liquid biopsy upgrade is on track for the end of the year. Can you just talk through, I guess, the impact there, what we should be thinking as that rolls out?

Yes. We're very excited to move to that platform, obviously, as even better performance than where we are now from a sensitivity and specificity point of view, but I think more so, the types of capabilities that assay will be able to provide in terms of not just telling the sort of the what in terms of as the cancer there or not. But what's happening with the cancer or where is the cancer. And so while the transition initially may be somewhat invisible or very low impact, we think, over time, as we start layering in these new futures, it will be really exciting in terms of where the MRD space goes and really using this tool as a sort of blood-based equivalent of a CT scan. I think it's going to be really exciting for the oncology space.

Thank you. The next question comes from Derik De Bruin from Bank of America. Please go ahead.

Hi. Thanks for taking my questions. Two questions. First, just on the -- going back to V2 on Shield, can you explain why the AA detection didn't go up even though the sensitivity increased pretty significantly between B1 and B2. But just wanting to get my head around that. And then second question would be, any comments on volumes that you're thinking about for 2024 and you still expecting something in the 30s percent growth rate for next year?

So for Shield, we trying to advance that anomaly, we didn't see improvements on AA side and from that data, it's not very clear exactly how we should read into it. It could have multiple reasons, including the level of shedding of these advanced adenomas signals are still lower than our level of detection. So we -- even with improved detection limits that we have that we can effectively take at least 2x lower levels of tumor in blood, that's not good enough to detect any material amount of advanced adenomas. That could be the reason or it could be like maybe just the biomarkers of advanced adenomas for detection, are different than the current epigenomic and genomic panel that we have that we are detecting CRC with. So still, that's an area that we are looking into. We are doing research. And as we generate more data as we generate more insights, those data and insight would tell us more about what's maybe next for us to get into at least some higher-grade advanced adenomas over time.

Thank you. Our final question call comes from Alex Nowak from Craig-Hallum. Please go ahead.

Hi. Good afternoon, everyone. This is [Albert Hu] on for Alex. Can you please outline a bit more on the sales strategy after Shield FDA approval regarding initial sales team, primary call points and just what to expect for 2024?

Yes. As we outlined in our Investor Day, we are going to expand actually our commercial team, and we are going to have about 100 people, 100, 150 people on the commercial side all in. The call point would be primary care physicians and right now, we have a small sales team in the field that they are promoting and doing some of the market development for Shield even as a lab develop test, but we're going to go through that expansion in near future.

Great. And just as a follow-up also regarding Shield, so what are the back office activities or work reimbursement personnel, customer service, et cetera, do you need to bring - do you need to have ready to bring the test online and get ready for day one of the FDA approval?

So we have some of those teams already in place because, again, Shield LDT is in the market like many, many thousands of samples have been processed from over 1,000-plus accounts and those teams are in place. It's just a matter of scaling and some of the fixed cost is already there. It's just based on the number of people that we are kind of hire in the field, we need to staff up some other personnel on the client services side, for instance. So all this is already in our commercial plan projections for 2024, and all this is included in the statement that we had that the contribution loss from screening next year would continue to be about approximately $200 million. All those are embedded there.