Guardant Health, Inc.

Hello everyone and welcome to the Gardend Health Q3 2023 earnings call. My name is Felicia and I'll be your operator today. Please make sure you... Your lines will be muted for the presentation part of the call. So if you want to ask a question, please make sure you press star followed by one on your telephone keypad. I will now hand you over to your host, Kari Mendeville, Investor Relations from Garden Health. Please go ahead, Kari.

Thank you. Earlier today, Garden Health released financial results for the quarter ended September 30th, 2023. Joining me today from Garden are Helmi Altuke, co-CEO, Amir Ali Talaza, 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 most directly comparable GAAP financial measures, are available in the press release GARDEN Issue today, as well as in our Form 10-K and other filings of the SEC. GARDEN disclaims any intention or obligation to update or revise financial projections and forward-looking statements, whether because 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 Helmi.

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 Amir Ali 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 three, Garden 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 gardens. I encourage anyone who wasn't able to attend our Investor Day to access the replay on the investor section of our website. It was a great opportunity to reflect on how far we have 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 test, I will start our call off today by sharing a patient story for our newest product, Shield. Earlier this year, a woman in her late 50s visited her primary care physician. She was unscreened for colorectal cancer and was resistant to receiving a colonoscopy. Her physician proposed a SHIELD LVT test, which was added to her annual blood work. The SHIELD test results reflected an abnormality, which led her physician to order a colonoscopy. Though she had been hesitant of a colonoscopy at her initial visit, with this result from SHIELD, she prioritized getting the procedure done. The colonoscopy determined that she had stage two 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 her 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 in slide four, 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 five, 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 six. Looking more closely at some of the highlights from the third quarter, we continue to benefit from tailwind seen earlier in the year with another quarter of solid year-over-year clinical volume growth across Garden360 and TissueNext. Notably, nearly half of oncologists in the United States are now ordering a GARDEN360 test every month, which highlights the strength of our core therapy selection business. As is typical with new approvals following the GARDEN360 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 contributions 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 test within Flatiron's OncoEMR. 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-thirds of all oncology practices in the country, and these integrations are expected to reduce oncologist 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 gained, we expect these partnerships to contribute to an uplift in ordering volume in 2024. We are also seeing growing contribution from MRD with another quarter of record volumes for garden 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's garden-powered laboratory was awarded an expression of interest by the NHS to launch CGP 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 GARDEN360 for clinical use in Japan. In early September, GARDEN360 CDX received regulatory approval in Japan as a companion diagnostic to HER2 for treatment of non-small-cell lung cancer patients with HER2 mutations. This follows the recent national reimbursement approval for Garden360 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 volume, we expect significant growth from these core markets over the next year. Moving on to slide seven. 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 Garden360 with ASPs now towards the upper end of the $2,650 to $2,700 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 Garden 360 LBT to a price of $5,000 as part of a rate-setting process for reimbursement under the Medicare Clinical Lab fee schedule next year. If finalized, this will be a major milestone for Gardens that will have a meaningful impact in our top and bottom lines. Mike will share more about the uplift we expect to see in our ASD shortly. We are also working to expand private pay 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 enacted 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 and MRD. We will continue to support efforts by the American Cancer Society and others to get these bills passed in more states to expand access to comprehensive biomarker testing through broadened private payer coverage. Lastly, we are continuing to make progress with reimbursements for Tissue Next and recently surpassed 200 million covered lives. For MRD, we also received coverage for garden reveals from the Geisinger Health Plan, providing coverage for more than half a million members. The test will be covered when used after surgery or curative treatment to inform physician decisions 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 reveals and additional reimbursement wins. Moving on to slide eight to discuss some recent data for review. In October, Pegasus interim data was released as a late-breaking abstract of the ESMO Congress. Pegasus is a de-escalation clinical utility study for post-surgical liquid biopsy-guided 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 result after surgery had their cancer relapse, despite initiation of adjuvant chemotherapy. In addition, only 10% of patients with a 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 suggest that a revealed blood test can provide a sensitive tool to help oncologists 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 Amir Ali to provide an update on our screening business.

Thanks, Elmi. Turning to slide nine, we are continuing to make advancements with our SHIELD blood tests 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 biobanked 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 looked at a 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 versions of the SHIELD test, the version used in our PMA Eclipse study, which we'll refer to as SHIELDv1, and the next-generation version, which we'll refer to as SHIELDv2. When we look at Shield V1's performance in this prospective cohort, sensitivity was 84% with specificity of 90%. This was in line with the performance we saw from the same assay in the 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 prospective 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 both tests were 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 a CLIP study to assess the performance of SHIELDv2. 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 their randomized prospective trial were overwhelmingly positive for SHIELD. In this study, providers offered a SHIELD blood test to a randomized cohort of patients who have not completed a TIT test. Patients who were offered SHIELD were more than two times as likely to complete CRC screening compared to the patients receiving usual care. In addition, This 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 tests in Annals of Oncology. This study was run on an early prototype of what is now SHIELD. and highlights how an 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 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 GARNA360 ASP on slide 12. As Helmi outlined, we're starting to see the positive impact on Garden360 ASP from commercial paid coverage wins and have recently received confirmed and proposed Medicare price increases to Garden360 LDT. In the third quarter, the Garden360 ASP again trended towards the upper end of the $2,650 to $2,700 range we saw in Q2. At the start of October, we were informed by MoldyX that the Medicare price for Gardner 360 LDT has been increased from $3,500 to a new gap-full rate of $3,967, effective October 1, 2023. Furthermore, in late September, CMS published its preliminary clinical lab fee schedule for 2024, which proposed that the Gardner 360 LDT price the crosswalk to Garden360 CDX. If this proposal is finalized, the Medicare price for Garden360 LDT will increase to $5,000 as of January 1, 2024. To put this price increase into context, Medicare Garden360 LDT tests represent between 10% to 15% of our total Garden360 volume. As a result, the impact of the Medicare price changes will be to increase the overall Garden 360 ASP to be between $2,700 and $2,750 in Q4 2023. And then if the CMS proposed crosswalk pricing is implemented to $2,850 to $2,900 from January 1, 2024. With the tailwinds we are 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 Gardner 360. 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 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 fell to 103.9 million, up 34% from 77.8 million for the prior year quarter. Third quarter clinical test volumes was 43,900, an increase of 35% from the same period of the prior year. GARDEN360 continues to be the main revenue driver with continued strong year-over-year growth. As Helen mentioned, following the GARDEN360 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 had therefore sequentially less breast cancer tests in Q3 than in Q2. That said, we still had strong contributions from breast volume in the quarter, which increased significantly year over year, and we expect to see continued growth in the syndication. Also note that the third quarter clinical revenue includes a payment of $3.6 billion received from Medicare related to a successful appeal of claims dated between 2018 and 2020. This was a one-time payment, and there are no other outstanding claims that have yet to go through this 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, blended clinical ASP will continue to be influenced by both the volume mix between GARLAND360 tissue next review and response, as well as the mix of overall clinical volume between the U.S. and international. Precision oncology revenue from biopharma testing in the third quarter totaled $29.5 million, up 22% from $24.2 million for the prior year quarter. Biopharma test volume is 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 of $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 a 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, For 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 bucking 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 were 199.0 million, a reduction of 22.5 million compared to 221.5 million in Q3 2022. Net loss was $86.1 million, or 73 cents 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 compared to a $200.5 million in the prior quarter. Non-GAAP net loss was $79.2 million, or 67 cents 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 with 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 entered 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 a runway to reach cash flow breakeven, which we are targeting in 2028. In addition, we're on track to achieve our targets of reaching cash flow breakeven in therapy selection by the end of this year, and of managing the annual screening cash burn to be approximately $200 million. We continue to expect that our annual cash burn for screening be approximately 200 million over the next five years now turning to our outlook for the full year 2023 on slide 15. we're raising our full year 2023 revenue guidance and now expect revenue to be in the range of 553 to 556 million dollars representing growth of approximately 23 to 24 percent compared to 2022. this compares to our previous expectations of 545 to 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 $250 million in 2023. Then 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 TissueNet and remain on track to achieve the remainder of our stated milestones. At this point, we will now open the call to questions.

Thank you. If you'd like to ask a question, please press star followed by one on your telephone keypad. Please note that in the interest of time, you are respectfully asked to limit your intervention to one question per person and one follow-up only. The first question we have comes from Tejas Seven from Morgan Stanley. Please go ahead.

Hey, guys. Good evening, and thanks for the time here. Helmy, Mike, thanks for the color on the G360 ASPs here. 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?

Yeah, I can take that. Yeah, what we've seen over the past 12, 18 months is slowly the weighting between LDT and CDX has sort of moved more towards the CDX. So 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 changing mix is the CDX approvals that we've been getting over the last 18 months or longer. So, yeah, I don't think that the price impact will change that much. And the second part of the question, Dave?

That was just on the private payer side of things.

Yeah. Now, I think we think that's also being positive. You know, 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 that will definitely help. But yeah, 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, yeah, potentially it could make the system, well, take some friction out of the system, make the pricing more transparent and could have a positive impact. So we've not baked that into our ASP projections yet. But so we'll see how that goes next year.

Got it. And then one quick follow up on Pegasus. I mean, can you help us contextualize the significance of that readout for us? Sounds like, you know, of that 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, you know, your physician conversation so far? And given that this was the older version of the assay, how do we read through the results to the commercially available versions?

Yeah, I know. So I think this is very positive in multiple aspects. The fact that this potentially highlights that you can spare patients these high toxicity adjuvant chemotherapies. And this is really a sort of target that the investigators 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, you know, I think it's really exciting. And so I think we're really looking forward to the full readout of this trial sometime in 2024. In terms of, you know, how this reads through onto the current version of Reveal and future versions, we see essentially improvements across the board in terms of sensitivity and specificity. Clearly, if you're using an even better assay than the one here, 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 assays.

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

Thank you, guys. Thanks for the questions. Mike, 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 finish 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.

Yeah, Dan. Yesterday we were still, you know, over 40% year-over-year clinical volume growth. And, yeah, for the full year, yeah, high 30s is sort of what the guidance implies. So, yeah, we're still very confident that we'll see, you know, a sequential uplift in Q4. And, yeah, very strong year-over-year for the full year.

Okay. And then, Amira Lee, You know, 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 anyways. 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.

Yeah, 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 years before. We expect that reviews start sometime in the middle of 24 to second half of 24 and then, you know, conclude with recommendation updates in 2026. Regarding Shield V1 and V2 and guideline inclusion, I continue to believe Shield V1 with the performances that we reported as long as we can get FDA approval for it, that hopefully we will. would get into the guidelines. And once SHIELD as a blood based colorectal cancer screening branded by SHIELD goes into the guidelines, future upgrades and updates to that test, it's going to be continued, you know, market as SHIELD. So I don't believe that we need to go through the cycle of USPSDF in order to get the benefit of the commercial payer coverage that Shield would have. So once the Shield we want goes through that process, all the future versions, as long as they're better than Shield, I expect them to be grandfathered in similar to what we experienced with other products, you know, 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.

Hey, guys. Congrats on a strong quarter. I guess the first one is for Helmi. It's encouraging to see Geisinger and Blue Cross Blue Shield Louisiana come on for 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. 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.

Yeah, great question. Thanks, Mark. I would say that, you know, 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, you know, 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 a tailwind catalyst in terms of getting us to coverage sooner rather than later. I think that's why I highlighted that now over half the US population is covered in uh that has one of these biomarker bills and we obviously have new york and ohio and hopefully some other states down the pike 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 these state biomarker bills you essentially have a really nice glide 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. NCCM 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 tissue next 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 US 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 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.

Yeah, and on the volumes, without breaking down into specific numbers, but both Reveal and Tissue Next. year-over-year growth was, were both very strong. You know, 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. Tissue next, very close to 100% year-over-year. you know, good in the quarter, a very strong year today. And so, again, I think we're looking at closing the year out strong on both Reveal and Tissue next.

Our next question comes from Puneet Sudha from Learing Partners. Please go ahead.

Yeah, hi. I'm early. And, Elvie, thanks for taking the questions. Maybe just on, you know, Shield V2, can you just confirm if the biobanked 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'll follow up.

Yeah, so the short answer is yes. You know, 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 analyzed from that first 24,000. And we have 20,000 plus more patients untouched, blinded, CRCs untouched, blinded, advanced, and almost the same in our biobank.

David Miller- Got it. Okay. Thanks for that. And then David Miller- Just maybe one quick follow up for you. I merely. I mean, anything, any feedback from FDA you pointed that, you know, the conversation is David Miller- Going well there, but I just wanted to see if there any updates on that front, you pointed out, but about 2024 approval still just wanted to get a sense of, you know, if you have any sort of guideposts in terms of

know earlier versus later or sort of first half versus first quarter anything you can provide there would be super helpful yeah as i mentioned point we are continuing to make uh steady progress uh still we are under review we are not done with it and it's uh 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 it continues to be the same. And the agency have been very collaborative with very collegial kind of attitude toward our application. They understand the 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 Mixon from Canaccord Genuity. Please go ahead.

Perfect. Hey, guys. Thanks for taking the questions. Mike, question three, Mike. Given this G360 ASP trend benefiting from multiple tailwinds with Medicare pricing, could you maybe just estimate, I guess, or tell us if it's possible that G360 ASP could you know, increased to some level by the end of 24. Look at the average revenue per test approach, maybe like 3,500 by that point. And then also, Mike, just a question on, like, cash flow as we think about getting to pretty given 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? You know, in other words, how much of an investment is there to advance that strategy, like, given that return so far, that kind of, like, mid-teens revenue number? Thanks. Thanks.

Yeah, Kyle, on the Garden360 ASPs, yeah, no, I mean, we've seen really good traction both on the Medicare side. You know, we have to wait for the finalization of clinical lab fee schedule yet. But, you know, if that comes through, we'll be closing on 2,900 at the start of next year. As I just mentioned on the call earlier, you know, there are potential Other tailwinds, you know, we could see Medicare Advantage come through. We could see that also help with private payer payments for Garden360 LDT. So I think, yeah, we've seen good traction. We set out on our investor day, what was it, eight weeks ago, that we wanted to get to a target of 3,000. So I think at the moment we're feeling very confident. we can get north of 3,000, definitely in the five-year timeline we set 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 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. course you know the key for us and we're managing the volumes to try and stay manage the cash burn and yeah the key for us going forward is really to get additional reimbursement and you know we've talked about CRC surveillance and then other indications so that's what we're really focused on with with MRD and at the same time managing the managing the burn okay that was fantastic Mike thanks so much for that and then I merely want 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 being a second-line, third-line test? I'm just wondering if you discussed that with the FDA at all, or maybe that's included in your opinions in this PMA submission.

Yeah, just to clarify, I think the mid-24 timeline that I mentioned was connected to the potential time USPSCF 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 Nefron Research. Please go ahead.

Thank you. Good afternoon. For Helmi, I have 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, you know, the bonds 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.

Yeah, no, as I said, there was this 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 believe we've completely worked through that bolus and now we're just continuing on a very nice trajectory and yeah i want to highlight that we're still at extremely elevated levels of breast cancer testing uh 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 uh that uh Yeah, in terms of sort of competition, I think we're seeing a lot of the same dynamics play out, ebbs and flows of 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 a really much closer level with a lot of the important oncology practices around, either through EMR or other sort of center-wide arrangements. And so we're very excited about what this sort of next phase bodes for GARDEN360 testing and ervial 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?

You know, I mean, I think if you look at our Invest Today slides, you know, we said this year was a year of reduction of cash burn. Next year will be to, you know, we said over the next five years, we expect the cash burn to come down each year. Although I want to sort of caveat that because it is a year of launch within screening. We're still making investments on an MRB. You know, we will definitely see therapy selection flip to generating a positive cash flow. So I think it will be, you know, a little bit lower than this year. but not too much lower because, again, we need to invest in the launch. But, yeah, just to reiterate, you know, we'll end the year with a billion in cash, and we still see that as being able to get us through to a cash flow break even in the five-year timeline we pointed out at the investment day.

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

Hey, thanks to the questions. Congrats on the quarter. Maybe the first one just on reveal. Could you just kind of walk us through the roadmap 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 and Brest and how that could play into your Medicare filing plans in Brest?

Yeah, so, you know, as we speak, we're putting, I think, some of the COSMOS 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 MALDx 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 MoldeX. And so we think, you know, we're later focused on breast, colon, and lung cancers. We have obviously multiple other cancers in the pipeline as well. We think those three indications look at 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 and Brest, that'll be a piece of the larger filing package, Helmi, for Brest?

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

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

Hey, guys. Thanks for taking questions. Help me maybe just on kind of the core business. You know, it sounded like breast, yeah, the backlog had some benefit from the pent-up demand early in the year, normalized a bit in pre-Q. 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 we'll be curious just a little more on the moving pieces there and the right way to think about that going forward.

Yeah, I think now we're sort of at, normalized rates, and now it's just a matter of getting additional patients tested. You know, 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, you know, our, I think, very large increase in volume of breast testing, that a lot of patients are still being tested by tissue or by, you know, other methods to to try to assess ESR1. And it's very important that physicians know that it's very unlikely to detect ESR1 mutations, since they're often emergent mutations or distance mutations, through an 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. Obviously, in the other cancer types, you know, 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, yeah, we're continuing to see, I think, that there 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?

Yeah, we're very excited to move to that platform. Obviously, it has even better performance than where we are now from a sensitivity and specificity point of view. But, you know, 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, you know, is the cancer there or not, but what's happening with the cancer, 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 features, it'll 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 Derek DeGruyne from Bank of America. Please go ahead.

Hi. Thanks for taking my question. Two questions first. Just 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 V1 and V2? Just trying to get my head around that. And then second question would be, any comments on volumes that you're thinking about for 2024? You still expecting something in the 30% growth rate for next year? Thanks.

So for shield-return advanced adenoma, yes, we didn't see improvements on AA side. And from that data, it's not very clear exactly how we should read into it. You know, it could have multiple reasons, including the level of shedding of these advanced adenoma signals are still lower than our level of detection. So, you know, even with improved, detection limits that we have that we can effectively detect, like, 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 insights would tell us more about what's maybe next for us to get into at least some higher grade advanced adenomas over time.

Our final question and call comes from Alex Novak from Craig Halem. 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's FDA approval regarding initial rollout sales team, primary call points, and just what to expect for 2024?

Yeah, 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're promoting and doing some of the market development for SHIELD even as a lab-developed test. But we are going to go through that expansion in near future.

Great. And just as a follow-up, also regarding SHIELD, So what other 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 LVT is in the market, like, you know, Many, many thousands of samples have been processed from over 1000 plus accounts and Those teams are in place. It's just matter of scaling and some of the fixed cost is already there. It's just level based on The number of people that we are going to 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.

Thank you. With that, we have reached the end of the conference call. Thank you all for attending. You may now disconnect your lines. Thank you.