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2026.09.24 | TB | MedTech | Grail Galleri Pre-AdCom

原标题：Grail – Galleri Pre-AdCom Evaluation & Regulatory Approval Risks

#medtech

Third Bridge · 2026-09-24

Analyst-led • 10 Sep 2026

Companies: GH US, GRAL US, ABT US

Victoria Groner (VG) Lead Genetic Counselor & Project Manager at Memorial Sloan Kettering Cancer Center

Anjelique Soriano (AS) — Third Bridge Sector Analyst

Agenda

Key Insights

Introduction

AS: Welcome to Third Bridge's Interview entitled Grail – Galleri Pre-AdCom Evaluation & Regulatory Approval Risks. I'm Anjelique Soriano, and I'll be facilitating today's Interview with Ms Victoria Groner, Lead Genetic Counsellor and Project Manager at Memorial Sloan Kettering Cancer Center.

Victoria, before we start today's Interview, please state I agree or I disagree to the following statement: You understand the definition of material non-public information and agree not to disclose any such information, or any other information which is confidential, during this Interview.

VG [00:00:33]: I agree.

AS [00:00:35]: Could you begin with the brief introduction of your background?

VG [00:00:40]: My name is Victoria Groner. I'm a certified genetic counsellor by training. I work at Memorial Sloan Kettering as a Project Manager and Lead Genetic Counsellor for an NIH-funded research study, and I have a background in bioethics as well.

Questions

[00:01:04] How would you describe the current adoption level of Grail's Galleri test across academic medical centres vs community health practices?

VG [00:01:18]: My understanding is that the adoption is much higher in an academic medical centre where there are more resources available vs community health. Additionally, community health, my understanding as well is there can be a lot more variation in the resources of the patient population, too, and also in terms of insurance coverage. I don't think that there is as much adoption in a community health setting than there would be in an academic medical centre.

[00:01:59] Could you discuss the specific clinical and operational barriers that are keeping academic centres vs community health centres from ordering Galleri?

VG [00:02:11]: Yes. I think in community health centres, there is definitely a dearth of resources in terms of funding, and that means not just for technology, but also for people. If there aren't enough people available to recommend it or assist in the test interpretation and discussion, then they're less likely to order it. It's also an expensive test. Additionally, the follow-up burden may not be something that is able to be handled at a community health centre vs an academic medical centre, which might have more funding resources, patient populations with more insurance coverage and just higher resource in general.

[00:03:08] How does the lack of institutional NCCN [National Comprehensive Cancer Network] guideline inclusion directly restrict an academic centre's ability to build standard EHR [electronic health record] order sets for Grail's test?

VG [00:03:23]: Because it's not a recommended test, we are working with our patients, we as in, medical providers, not necessarily where I work. Sorry, I lost my train of thought there. Without it being approved, it's really hard to get insurance coverage. If it's not recommended by NCCN or by other greater governing bodies, we're just less likely to order it. Without it being approved, there's also not diagnostic or billing codes that can be associated with it, which prohibits us from building EHR order sets. From multiple levels, it's preventative.

[00:04:15] How are clinics practically integrating the Galleri blood test into their existing patient risk assessment and routine screening workflows?

VG [00:04:29]: Tell me if this is something that would be redacted, but we don't order it, we don't recommend it as a genetics provider. Is that okay to talk about my own?

AS [00:04:42]: At large within certain settings, do you see if they are usually integrated or not?

VG [00:04:54]: Honestly, no. From my understanding, it's more of a patient-directed screening test recommendation, privately sought out and paid for, or patients are asking for it vs it being something that we would recommend as a healthcare provider. Any time that I have ever encountered a patient who has had done Grail, it's been on their own volition.

AS [00:05:19]: How common is it for a patient to ask for the specific test? How often it is that patients come in aware of the various market offerings standardly?

VG [00:05:30]: I wouldn't say it's super frequent, but I definitely have had patients ask about it. It's not something that I would order for them for multiple reasons. Also, it's just not… I work more in the hereditary cancer space rather than cancer detection. I always recommend that my patients discuss it with their treating oncologist or their primary care provider, but I definitely had a number of patients ask me about it. It could also just have to do with the patient population that I work with. There tends to be a higher health literacy. People read about things and then they talk to me about it, but it's not…

[00:06:17] Are there any specific friction points during pretest counselling sessions that usually cause primaries to drop or avoid ordering the Galleri test?

VG [00:06:29]: Can you explain more what you're asking by that question?

AS [00:06:32]: Yes. When, say, genetic counsellors are talking to patients, is there anything else aside from especially the price point that leads to primaries to avoid ordering the Galleri test?

VG [00:06:49]: Oh God, yes. You're asking what hesitancies providers have in ordering the test for patients?

AS [00:06:57]: Yes, exactly.

VG [00:06:59]: I have a lot of concerns with the test, and this is something that I've heard from colleagues as well. I think it provides a false sense of security for patients. The data have not shown that it's yet an approved recommendation for actually lowering cancer mortality in patients or morbidity. I don't think that there's enough data for me to endorse ordering it at this time because I don't feel confident with the results. I don't feel that the Grail test is sufficient for us to say, "That's completed your cancer screening. If nothing showed up on this, then I'm not worried about it."

I was looking at some of the information, and it looks like in the most recent trial, there was a high specificity, so low false positives, but a false positive is a lot easier to deal with than a false negative because if you have a false positive, and I have concerns about that as well, especially in terms of limited resources, the follow-up screenings, both in terms of the technology, insurance coverage as well as just manpower and bandwidth of health systems to handle false positive follow-up, but I'm even more concerned about there being what does not look like a high sensitivity, which would be the low… Therefore, we're looking for there to be a low false negative, meaning if you get a negative result, it really does mean that there wasn't anything detected. That's really what's important is screening as opposed to be, "Okay, we're screening this. If it's negative, then we trust that negative," and I don't trust that a negative from Grail is a negative.

[00:08:49] What are the top 1-2 drivers that push clinicians to order the Galleri?

VG [00:09:05]: I don't work with any providers that would consider it a go-to.

AS [00:09:14]: I know we'll probably talk about some other competing offerings later down the line, but are there any specific offerings that come to mind that take place or take precedence here?

VG [00:09:28]: Not in terms of multi-cancer early-stage detection blood tests, but really in terms of what the actual screening recommendations are for patients that have been built over years and years of data and outcomes research. I do think there is a significant need for a feasible blood cancer screening. I really do. I think it would be tremendously important, especially for cancers that it's very hard to screen for or that we don't yet have screening, like pancreas cancer, but I would never recommend that somebody do this instead of a mammogram or a colonoscopy or a Pap smear in general.

[00:10:13] Given that multi-cancer blood tests such as Galleri are usually seen to be more complementary rather than replacing standard single cancer screenings, what level of clinical evidence do physicians tend to require before routine ordering?

VG [00:10:36]: FDA approval and usually backed by a number of papers as well as a governing body of some sort. We would want the American Cancer Society, NCCN, radiologists to all back this type of screening. I think we would want to see that there actually is a major reduction in morbidity or mortality or a significant increase in detection at an earlier stage for us to adopt it into our screening, but I do agree it's more of a complementary thing and used… If it worked as it should, it would be a great thing to offer the general population vs high-risk patients because… It could be a great thing to offer high-risk patients as well. I can make arguments for it being important for either group. Ideally, it would be for everyone if it worked well.

AS [00:11:47]: What would make you more inclined to consider this test further? Given that we've discussed some of the drawbacks, in what specific instances would you feel more positive or keen to proceed with it?

VG [00:12:09]: If they've had really good outcomes for screening for cancers that are difficult to screen for, pancreas, ovarian cancer, anything that's internal and difficult to do, where screening either isn't available or is very invasive, that would be amazing. It would also be incredible, especially for patients who have high screening burdens because of their hereditary symptoms, like for somebody with a TP53 mutation who's doing multiple screenings every year, MRIs, invasive biopsies, things like that. It would be incredible for them to not have to do that, especially at younger ages or at older ages, once patients have lived through some of their hereditary risk and the screening burden is more for them as well, but I would love to see it backed by the NCCN as well. That would be great.

AS [00:13:08]: In the potential future if this test need to be paid for out of pocket, do you think that would likely cause a significant uptake?

VG [00:13:19]: If it was paid for out of pocket or not?

AS [00:13:22]: If it was not paid for out of pocket.

VG [00:13:24]: I think that would… It would depend on the insurance coverage. It's good if it's being covered, but how is it being covered and for who, under what conditions? Is it being covered for patients where they are the best candidate? Maybe this is great for Medicare patients, just for example, but Medicare has really strict issues, reasons or coverage about things like that. While I think it would be good if it was covered by insurance for the patients, it may actually… If the insurance companies are not willing to cover it for broader indications or just in general, then it wouldn't be able to be implemented if we didn't have the support from the insurance companies.

[00:14:17] What specific trial endpoints would you consider to be non-negotiables for the consideration of a Galleri institutional roll-out?

VG [00:14:28]: For me, I would really want to see a high sensitivity. That is something that I'm really harping on. I really would want to see a very low false negative rate. That would be very, very important to me, probably the most important thing.

[00:14:42] How significantly does patient demand and baseline awareness ultimately drive a physician's decision to order the Grail test? From what you've observed so far, orders tend to be driven by patients requesting it directly. To what extent is current utilisation due to patient demand and baseline awareness?

VG [00:15:13]: My understanding is it's really coming from patients more so than it is from providers. I would be hard-pressed, I think, to find a provider that I work with that would want to order it because we just know it's not good enough. I'm not trying to rag on the technology. I think it's amazing. I think this is absolutely where we're headed. Doing early-stage cancer detection through blood test would be phenomenal. It's akin to what NIPT is in the prenatal world, where instead of having to do an invasive procedure like an amnio or a CVS, you can do a blood test and it looks for cell-free foetal DNA and you're able to analyse chromosome abnormalities and other variants that could have a significant impact on the foetus and then you do a confirmation test, but the sensitivity and specificity for NIPT are really high. Then you would follow up with a confirmatory diagnostic procedure, but again, it's that sensitivity, that low false negative that I would need to see to feel comfortable.

[00:16:32] An AdCom [Advisory Committee] panel plans to review Galleri's premarket approval application on 23 September 2026. How do you expect the panel to conduct its benefit-risk assessment following the missed primary endpoint in the NHS-Galleri trial?

VG [00:16:54]: The missed primary endpoint… There were some good findings from the NHS trial. They did see a reduction in stage 4 cancers, but their primary endpoint was a reduction in stage 3 and 4 cancers. They actually saw an increase in stage 3 cancers, but that's because they were detecting them. My understanding is detecting them earlier when they would have become stage 4 cancers. I do think that there are some promising findings, but for me, it's not enough for them to adopt this into clinical practice with a recommendation. I think that we would need to see more data. If I were sitting on the AdCom panel, would need to see more data before supporting this as something to be integrated into general healthcare.

[00:18:44] If the AdCom panel votes no or recommends strict labelling on Galleri, how significantly do you think that harms health system adoption, even if the FDA eventually grants approval?

VG [00:19:09]: I would love to be… Educated providers will understand that it is a preliminary rejection at this time, waiting for more data, but I do think that people like to read a headline and not the body of anything, both in actual written context, but just in general society. People want the short thing, which is, "Oh, they rejected it." It's like, "Okay, they rejected it because they just still need to see more data." I do think it's still promising, but I would worry that it would mar people's thoughts about the technology and the company even in the future. They'll be, "Oh, they rejected it. Why are they accepting it now?" The other thing I will say, however, contrary to what I just said, is that I don't know how much trust there is in the FDA at the moment and in our government. I don't know how that would impact people's interpretation of government recommendations.

[00:20:18] Given the panel's focus on transparent clear data, how likely is it that the FDA AdCom votes against recommending Galleri's approval, considering broader hesitancies?

VG [00:20:33]: They failed their endpoint. I don't know if they have enough to support it. I don't think they have enough of a leg to stand on to say, "Yes, you should still use this testing." We still don't have enough data to support it, and medicine is all about evidence-based medical recommendations, especially in cancer.

[00:20:56] How would you consider clinical trial specialists and genetic experts to reconcile the NHS Galleri trial's missed primary endpoint of a combined stage 3 and 4 reduction with its observed greater than 20% reduction in stage 4 cancers?

VG [00:21:13]: I think that they probably will need to do another trial and rework what their endpoints are to really show where the most significant benefit is for people using this. That would be my thoughts.

[00:21:35] Biologically, why do you think Galleri's blood-based ctDNA [circulating tumour DNA] sensitivity is so much lower for early-stage 1 and 2 cancers compared to stage 4 tumours?

VG [00:21:47]: Yes. The smaller the tumour, the less shedding essentially. The blood test is looking for cell-free DNA or cell-free tumour DNA that's circulating in the bloodstream. The bigger the tumour or the more tumours you have and the more developed it is, the more cell-free tumour DNA is available for you to analyse. You just have to have a really, not sensitive in the low false-negative way, but sensitive in an easily touched way. You need to have enough material to be able to call something positive. You need to be able to get enough in the blood draw to be able to do any type of analysis.

[00:22:51] Do you think the argument holds that the UK NHS trial's 12-month follow-up was generally too short to show Galleri's true screening benefit?

VG [00:23:02]: It was a three-year trial. They did a check-in at 12 months each time. That was my understanding. It was over a couple of years, but every 12 months…

AS [00:23:16]: Yes, 12-month follow-up. I wasn't sure if you thought maybe…

VG [00:23:19]: I don't think the 12-month follow-up is too short. Cancer screening is all based on an annual or more cadence. I don't think that 12 months is too short, but I do think that had this trial kept going for a couple of more years, maybe we would have seen better results because I think it was only over two or three years.

AS [00:23:51]: Do you think Grail's decision to extend data collection by 6-12 months plays a big role in potentially altering the regulatory interpretation of the NHS Galleri study?

VG [00:24:04]: I don't know. 6-12 months isn't that much longer. I would think they would need to do it for another couple of years.

[00:24:10] How do the full PATHFINDER 2 trial results, which were presented at ASCO [American Society of Clinical Oncology], complement or address the limitations observed in Grail's NHS Galleri study?

VG [00:24:23]: I wasn't at ASCO, so I don't know exactly what they talked about. I did read about it. I do think that it is… They haven't published all of the findings yet, is my understanding. They reported about missing the endpoint earlier this year, and then they gave some of the data at ASCO. What was the question about whether… How that will influence anything? Sorry, can you repeat that?

AS [00:24:54]: Do you think the PATHFINDER 2 results presented at ASCO would complement or address the limitations observed within the Grail NHS Galleri study?

VG [00:25:08]: They talked about it. They talked about the limitations and everything. I think that they did. They are being upfront about what the data is showing because if you do dig into the data, yes, they missed their primary endpoint, but there are some good findings as well. I don't feel that the medical community is anti-Grail and Galleri. I think that we just want it to work well so that when we're actually discussing it in the clinic with our patients and discussing results, it actually provides valuable information for them. You're confident doing that as a sole implementation.

[00:25:55] Does PATHFINDER 2's roughly 60% PPV [positive predictive value] give regulators enough confidence on false positives despite the UK trial failure?

VG [00:26:05]: 60% positive predictive value. It's not bad, like I said, but it's still not enough for me to use it without other screening.

[00:26:31] Do you think the FDA AdCom will help evaluate the potential risk of overdiagnosing indolent non-aggressive cancers against the clinical benefit of detecting early-stage aggressive tumours with Galleri?

VG [00:26:46]: Do I think the panel is going to talk about that?

AS [00:26:50]: Do you think it would help assess the potential risk of overdiagnosing?

VG [00:26:57]: I'm just worried about overdiagnosing and more worried about missing a cancer, but I do think that, for a patient perspective, if you're going to diagnose any sort of… Anything that should have a follow-up or finding, that's good. Specifically, if we are able to diagnose early stage, that would be amazing. I think that outweighs the drawbacks of diagnosing non-aggressive findings.

[00:27:39] In the event the FDA grants premarket approval, how significant is immediate commercial payer coverage for Grail while awaiting formal Medicare reimbursement?

VG [00:27:51]: Oh, it would need to happen immediately. It would be really important. If it's still not covered by insurance companies, but it's now an offering, then I can't see there being significant uptake with people paying out of pocket.

[00:28:09] If the FDA approves Galleri, how do you anticipate commercial health plans to handle coverage while waiting for the Medicare REACH study to finish in 2030?

VG [00:28:28]: I'm not an insurance company employee. From an overall perspective, if the data is good for the Galleri test, it would benefit insurance companies to approve it because the earlier you catch cancer, the easier it is to treat, the less long-term follow-up, the less invasive procedures, the less treatment that you need. That means that insurance companies are paying less. Obviously, that is their goal. They don't want to pay money. We know that they want to pay as little as possible because they want to make money. If it's preventative in the way that… Not preventative, but early-stage diagnostic to avoid further spending down the road, then it would benefit them, but if it's not actually going to be making a significant difference beyond what they're already paying for, then I can't imagine them approving it either because they'd say, "We're already paying the mammograms, colonoscopies and all these other screening." I have issues with the Medicare reimbursement. I deal with it all the time in genetic testing. Genetic testing is one of the most preventative things that you can do, and insurance companies don't always want to pay for it.

[00:29:53] When a patient receives a positive Grail Galleri result, what diagnostic follow-up pathway is usually triggered to locate the cancer signal origin?

VG [00:30:07]: It would depend on what the results were, but I would assume there would be a diagnostic follow-up, which is usually a biopsy.

[00:30:20] When a Galleri test returns positive, are there specific bottlenecks that delay the diagnostic hand-off between PCPs [primary care providers] and oncologists?

VG [00:30:30]: Oh, yes. If their PCP is the one ordering it and then they aren't part of a medical system where there's oncologists, health systems don't always like to work with each other. If a patient then has to go to a hospital system or cancer or oncology practices, first off, finding one, making sure they take their insurance, registering them as a new patient. I know just as a human in this era, waiting a long time for appointments, there's limited resources, limited surgeons, pathologists, technologies. I could definitely see if it's not… Yes.

[00:31:18] When follow-up imaging fails to confirm a positive Galleri signal, how long does full diagnostic resolution take and who typically absorbs the out-of-pocket costs when insurance denies coverage here?

VG [00:31:32]: You're saying if the diagnostic testing is negative?

AS [00:31:39]: If it fails to confirm a positive test.

VG [00:31:45]: Usually, it's the patients who have to deal with that out-of-pocket burden. That's what they sign away when they sign up for a health system.

AS [00:32:02]: When it appears negative, about how long does full diagnostic resolution usually take?

VG [00:32:10]: It really depends on what is necessary. If they can get an appointment quickly and biopsies happen in pathology, people usually get results relatively quickly, but that all depends on how soon they can get an appointment to do any type of biopsy or additional testing.

AS [00:32:27]: Do primary care clinics handle cases differently where Galleri returns a positive cancer signal, but initial imaging potentially comes back clean across all recommended sites?

VG [00:32:43]: I can't necessarily speak to what primary care providers are doing. That's not my area of… I haven't worked with primary care providers.

[00:32:54] When insurance denies coverage for unguided diagnostic follow-ups after a positive Galleri test, what's the average out-of-pocket cost that the patient is usually left with? How much uncompensated cost does the health system tend to absorb?

VG [00:33:12]: Gosh, it can be thousands and thousands of dollars if you're having a biopsy done and then a pathology reading as well. I don't necessarily know how much the health systems are compensating for it. I know that sometimes there are policies where it's saying, "We think you need this. If your insurance company flat out denies it, we'll absorb the cost," but a lot of times, people are still paying a significant out-of-pocket cost even if their insurance company does approve it. Most of the time, it's these patients who are saddled with large bills when their insurance companies deny recommended…

AS [00:33:58]: Sorry, was the last thing you were saying?

VG [00:34:00]: Just when insurance companies deny what's recommended by medical providers, which happens all the time, it's patients who are stuck with the burden.

[00:34:10] Grail claims that Galleri reduces the cost of diagnosing cancer by approximately 65% by pointing directly to the tissue of origin. How do clinicians and health systems currently view this claim against the actual cost of false positive diagnostic work-ups?

VG [00:34:32]: Yes, that's an interesting claim. It's like pointing to the tissue of origin, but then to do the follow-up, it's a moot. It evens out in a way, I would guess.

[00:34:54] How do genetic counsellors come into play with regards to managing the anxiety loop when a patient tests positive on Galleri, but all follow-up scans come back clean?

VG [00:35:09]: As a genetic counsellor, we're not necessarily ordering Galleri specifically because, like I said, we're focused on more of the hereditary cancer, but I do talk with my patients about it because as a genetic counsellor, we are creating this safe space to really discuss what's going on in their medical life. Obviously, these are patients who might have cancer or have cancer and are very concerned about it. I definitely think even for a patient… Also, the health literacy is really, I find, declining. For a patient who has a false positive that then additional follow-up imaging or diagnostic procedures don't confirm a diagnosis, if I were a patient and didn't have a medical background, I'd be, "Maybe they missed something." If you get any type of positive finding, you're going to be concerned. It's definitely something. Patients also talk to me about things like Grail or, this isn't the same thing, but the idea of a Prenuvo, which is the full body scans. I want to know as much as possible, I want to know as much as possible, and they think that it's just going to give them good information, but that's not the case. There's a lot of rabbit holes that you can go down. It doesn't actually provide technical peace of mind. These are all things that I would discuss with patients who were considering doing this test.

AS [00:36:50]: How serious is the risk of false negatives at large?

VG [00:36:58]: I was trying to find the sensitivity values online, but I do think that there's a significant concern for a false negative. That would be the data that I would want to see the most, what's your rate of false negatives here because that's the biggest problem. Isn't this supposed to detect cancer? If you're not detecting cancer, then you're not doing your job.

[00:37:22] When a patient undergoes a long and stressful diagnostic work-up following an unconfirmed Galleri test result, do you find that the experience reduces their willingness to return for routine standard screenings?

VG [00:37:35]: I'm sure it would, yes. Especially, if it's not a positive experience, a diagnostic odyssey, the burden of screening, especially if they had significant financial responsibility, their insurance company wasn't paying for it, then I would absolutely understand and think that they would be deterred to continue to do anything like that. They certainly… Couldn't imagine them wanting to do Galleri again.

[00:38:06] What specific post-market clinical utility data will insurance plans likely require before agreeing to cover the costs of downstream work-ups for Galleri's false positives?

VG [00:38:18]: What will the insurance companies want to see so that they think this is actually valid? I think that they would need to see probably post-market data showing a tremendous decrease in morbidity, not necessarily mortality because health insurance companies don't have to pay anything if your patient dies, but more so morbidity and aggression of disease to show that it really is reducing… It is being caught at earlier stages. That means that in the long run, by doing this, by paying for Galleri and any of the follow-up downstream diagnostic pieces, that they will save a lot of money because it is going to catch cancer earlier.

[00:39:10] Are there any specific protocols that genetic counsellors usually follow when a patient with a false positive result requests a repeat blood draw, say, six months later?

VG [00:39:23]: For genetic testing?

AS [00:39:25]: Yes.

VG [00:39:35]: Genetic testing is different, and the false positive and the false negative rates are tremendously low because it's almost 99.9 sensitive and specific to the germline genetic testing that we do. There's always a possibility, mostly it's because of human error. We talk to them about confirmatory testing. Usually, it has to be paid for out-of-pocket because insurance companies won't cover it again.

[00:40:05] Regarding switching friction in the competitive landscape, how do health systems and physicians evaluate Galleri's multi-cancer performance profile relative to single-cancer liquid biopsy screening tests, such as Guardant Health's FDA-approved Shield test for colorectal cancer?

VG [00:40:28]: I think that it would be great to have one blood draw that could look at a bunch of different cancers, but the individual liquid biopsy tests are more targeted, so to speak, but we still don't order Shield here, but Guardant is not a bad technology.

[00:41:00] How much does Guardant Shield's FDA approval and Medicare coverage in colon cancer hurt Grail's multi-cancer value proposition?

VG [00:41:09]: I don't think it hurts it. I think there is some precedent to have insurance coverage for liquid biopsy. I think it probably would help because multi-cancer, they just pay for one test instead of individuals.

AS [00:41:30]: Would you consider it to be more so complementary to each other?

VG [00:41:36]: Not necessarily complementary, but I think that the approval sets a precedent that is supportive hypothetically for Galleri's approval and insurance coverage.

AS [00:41:57]: How do clinicians weigh Guardant Shield's about 83% sensitivity for colorectal cancer against Galleri's lower overall sensitivity?

VG [00:42:10]: You said a 60% sensitivity for Galleri vs 83% for Guardant. That's a significant difference to me. I would need to calculate the PPVs and stuff, but…

[00:42:27] How do physicians weigh ordering a single-cancer test with guaranteed Medicare coverage against a multi-cancer test that carries out-of-pocket financial risk for the patient?

VG [00:42:40]: Yes. I don't order the test, but I can speak about it hypothetically.

AS [00:42:44]: Go ahead, that would be great.

VG [00:42:49]: I would have a conversation. Hypothetically, I don't think the data is good enough for me to support ordering a multi-cancer test that would be out-of-pocket costs. I'd rather order something that's approved by insurance. Yes, it's specific for one cancer, but it's much better data, and it's still decreasing the invasive screening for patients. A colonoscopy is quite invasive.

AS [00:43:22]: With Congress passing Medicare MCED [multi-cancer early detection] coverage legislation authorising CMS [Centers for Medicare & Medicaid Services] coverage starting in 2028 and 2029 once approved, how critical is Grail's first-mover advantage against competitors such as Guardant, Exact Sciences and Abbott?

VG [00:44:01]: I honestly don't know if I can… I see what you're talking about. Yes, they got it. They should take advantage of being early to the scene. That's all I have to say.

[00:44:23] Do you think the first-mover advantage would hypothetically change physician and genetic counsellor sentiment?

VG [00:44:34]: Yes, I do. I'll give you an example. The first major genetic testing company to bring genetic testing as a commercial laboratory is Myriad. Myriad is still regarded as one of the most reputable labs. Part of the reason is because it was the first one and they have the most data and they have the most brand recognition. What you hear about first is helpful. That being said, there is all of this data and information, but I do think… Again, I don't think that there's a negative opinion towards Grail or Galleri. It's just not good enough yet, but I would be thrilled if it were.

[00:45:27] How do Galleri's clinical datasets compare head-to-head against multi-cancer pipelines from Exact and Guardant Health? Does Galleri's 99% specificity rate give Grail an actual competitive advantage against lower-cost liquid biopsy peers?

VG [00:45:49]: I don't know about the clinical datasets for Guardant or Exact Sciences, so I can't necessarily speak to that, but 99% specificity is very high. Again, without comparing that against the sensitivity, it's not… Yes, I don't know what else to say there? Sorry.

AS [00:46:21]: Basically, the specificity doesn't hold up as strong as the sensitivity at large?

VG [00:46:28]: Yes.

[00:46:31] What would you say are the main friction points for healthcare systems or self-insured employers when considering adding Grail's Galleri test or switching liquid biopsy screening vendors?

VG [00:46:43]: The main friction points. I would say the follow-up burden and downstream burden. Do we have enough bandwidth, both for technology and for the people at the hospital systems to take care of the follow-up that would be necessary? It's screening. It's not diagnostics. You have to do diagnostic follow-up for everything that's detected. Do we have enough people to really discuss this information, the results, properly consent, etc?

[00:47:23] How hard would you say it is admin-wise for a health system to switch its routine cancer screening vendor once it's integrated into its EHR system?

VG [00:47:32]: It's really hard. It's really hard. There's a lot of administrative… It definitely would require significant input from the EHR team in terms of financial resources, time, etc, and also in terms of restructuring the workflows if they're different as well as training and education for all of the providers who would be discussing this. It's definitely not an easy switch. It would be very carefully considered, and there would be major initiatives in order to support the proper transition, that would take a lot of bandwidth, and resources, financial, time, etc.

[00:48:18] Does the lack of a standardised EHR system across different liquid biopsy platforms ultimately impact the provider's willingness to offer multiple competing blood tests alongside Galleri?

VG [00:48:32]: Because it's not all standardised in the EHR?

AS [00:48:36]: Yes.

VG [00:48:38]: Sure, yes, providers (ph 48.39) are lazy. We want to do the easiest thing, especially when you're constantly encouraged to just have a higher patient volume, higher patient volume, higher patient volume. You're going to do the thing that makes the most sense and is the most seamless in your practice for sure.

[00:48:57] Given that the vendor switching rate is very low from my understanding, are there any other switching frictions you think are important to discuss, or is there anything else driving stickiness across specific vendors?

VG [00:49:17]: You tell me if this is not something that's discussed, but I work in a system where we do most of our things internally, and we have a lot more control over what's being done. We have our own labs. We develop our own technologies. That could be done exactly how you want it, and you don't have to pay more for it to incorporate it from an outside vendor.

[00:49:46] Following the FDA AdCom review, what are the operational and commercial milestones that you think Grail ultimately needs to achieve over the next 12-24 months to support Galleri's post-approval deployment?

VG [00:50:01]: I think that they need to publish their data, show the positives and then there would need to be major educational rollout, I think, for them to show why it would be valuable for payers and hospital systems to integrate the test.

[00:50:32] How realistic are broader market expectations for rapid sales acceleration immediately following potential FDA approval? In other words, if FDA approval is granted, will that automatically translate into high sales velocity?

VG [00:50:50]: No, definitely not. I can't imagine that being the case. There would be so many other… It would (ph 50.58), "Oh, it's approved, let's incorporate it." Health systems are… There's a lot of bureaucracy. There's a lot of red tape. It would be a huge undertaking to incorporate it into clinical practice as well as if it's not approved by insurance companies, it would be very hard-pressed for it to be something that we would recommend. We all work and live within the system that exists in this country. We are trying to work with it instead of against it for our patients because we don't want to make their lives any harder than they are, especially if they have cancer diagnosis.

[00:51:35] How do you expect commercial payers to evaluate Galleri's pricing stability during the interim period before Medicare policy takes effect around 2028 or 2029?

VG [00:51:59]: I don't know. I feel like they're not going to want to pay for it. There would need to be major negotiations with Galleri to have it adopted by a health insurance company. I do think that if one of them were to adopt it, that might set up a domino effect, but especially without the Medicare reimbursement studies, then it's hard because so much of our other reimbursement is based on that.

[00:52:33] How significantly do you think post-market study or registry commitments will impact clinical workflows and operating overhead, thinking about Grail's 50,000-patient REACH Galleri-Medicare study that's running through 2030?

VG [00:52:49]: What about that study?

AS [00:52:50]: How significantly could post-market study or registry commitments impact clinical workflows and operating overhead?

VG [00:53:10]: Because those would be patients who would be getting it at health systems here. I don't know. I definitely think it will increase overhead and operational overhead for sure. Ideally, those studies are taking place at places where Galleri is already being offered, where it's already integrated into the workflow. Like I said, it's not something that we really are doing much at my organisation, and so I can't necessarily speak any further on it.

[00:53:44] Beyond increasing sensitivity, what clinical utility metrics would Grail need to demonstrate within these ongoing registries to ensure a smooth transition from initial premarket approval to broad commercial payer coverage?

VG [00:54:04]: I definitely want to see a decrease in later-stage cancers. That would be incredible to see. If there's a potential to identify stage 1 and 2, that would be phenomenal. That's really where a huge difference could be made because sometimes those are still in a curable stage.

[00:54:26] Does participating in large post-market registries, such as REACH-Galleri, make a health system more likely to expand routine commercial ordering across its affiliated primary care clinics?

VG [00:54:38]: Yes, I feel like if it's already part of their system and they're partnering with it, that they want to support what they've invested in and encourage it. If they've already decided it's something that works for their system, they should expand it beyond that.

[00:54:52] Beyond FDA approval, what would you consider to be the biggest execution risk that could cause Grail to lose market share over the next 3-5 years?

VG [00:55:02]: Competition, other companies developing similar technology.

AS [00:55:10]: Are there any players that come to mind here?

VG [00:55:14]: Guardant, Exact Sciences. I know that there's some other smaller companies that are growing in this space as well in the liquid biopsy and early cancer stage detection through blood screening.

AS [00:55:31]: Is there anything else you'd like to highlight or discuss about Grail?

VG [00:55:40]: No.

AS [00:55:42]: Awesome. Thanks so much. This was a really great call. I appreciate you for taking the time.

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