Quanterix Corporation (QTRX) Earnings Call Transcript & Summary

So let me go first. Yes. Absolutely. So I think we have also the same view that in the future for the therapy to be -- to get broad adoption, it's going to be absolutely needed for there to be broad access. And broad access is going to be not just access to a major city where you have a medical center and you can get infusions. One, the therapy has to be able to be easily administered. And if we get to that stage, the need for broad-based testing, triaging and diagnostics is going to have to go to your -- where you're doing the blood testing, where you're doing the blood sampling. And that's 90% of the population today is close to where you can do a blood draw, but that's nowhere near where you have to be for a CSF or PET scan location. So I think that this does become broad-based. I think blood screening does become the first mode in addition with clinicians, workup of a patient for screening. And I think it does get there. And I think it's reasonable to say that, that happens in under 5 years.

Yes. So I'm pleased that my finance officer and myself just completed our 10-year planning a number of different business scenarios. But when we think about like how this market is going to be shaping up. We think about where we are today, which is diagnosis. There's a major unmet need in just properly diagnosing people with MCI in early dementia. And as we heard in earlier panels, the earlier one intervenes, the more effective these therapies are going to be. That's indication #1. Then what's going to have to follow is understanding how to use these markers in treatment monitoring and disease progression assessments. And so there's still some work to be done there. There's some incredibly early compelling data, and it is very -- both some of Quanterix' test and C2N's tests have been used in some of the pivotal studies that for both Lakenbi and Lilly, where some of our markets were able to show very nice correlations with amyloid PET resolution. But there's still more work to be done there. And then we think about the third indication, which is kind of that asymptomatic high-risk screening. The moment you start moving to the broader population and the involvement of primary care, I think that I come from the field of cardiology, and it's -- I personally think it's paternalistic to think that this will remain a very memory care-focused effort. It just isn't possible. There aren't enough neurologists and memory care specialists in the U.S. to be able to accommodate the bottlenecks. And so primary care will be absolutely fundamental to involvement in the patient care. And I think that, as we've seen from many other new modalities that are being incorporated into new standards of care that the primary care clinician plays an absolutely pivotal role in identifying that patient who needs to then go see a specialist or maybe go get some additional care that requires more sophisticated treatment techniques or other assessment methods. And so I think what you're going to see is us moving towards much better understanding of how these markers fit into each of these 3 indications, diagnosis, monitoring disease progression and then also identifying high-risk individuals. And I think that to just simply use the 1 key message, which we're adamant about is that these tests should not be looked at in isolation. They are not pure diagnostic tools. A diagnosis of Alzheimer's disease is made the same way that one would evaluate a patient who appears to have ongoing Ischemia. You have to look at all the data, and it will involve that cognitive evaluation. It will involve MRI. It will involve PET tracers to some degree, and it will involve blood testing. So I think that when you start looking at this in the context of a broader clinical care picture, it becomes transformative. And we do think that it will be a standard practice at some point with the primary care community.

Got it. Maybe we drill down into each of your companies and offerings. Maybe just talk about the importance of your Simoa platform, sort of the basis of your technology? And how you think Simoa and the advantages that it brings you can sort of unlock the opportunity in Alzheimer's diagnostics and neurology more broadly?

Yes. So the Simoa technology is really a single molecule array. And it uses basically a pair of antibodies to -- in a very sensitive way detect proteins that are very low in concentration. So if you were going to do a measurement, a very common protein in blood, you wouldn't use necessarily the Simoa platform. But if you're going to look at something that was rare or hard to measure in blood. That's where the Simoa platform offers a broad range of sensitivity. As I said, 2 to 3 orders of magnitude better detection than anything that's sort of immunoassay-based in the market. So the technology is not only been used in neuro, but that's been a key focus of the of Quanterix. And then the application in neuro is so compelling. At the end of the day, a lot of these proteins are misfolded or they're going to your CSF and they're going to your blood and you'll need something that is able to differentiate with all the other proteins that are out there. And that's why Simoa has been a key differentiator for us. And it's a lot of the hard-to-measure proteins. The tau proteins, but it's the phosphorylated tau that will use unique positions that are important. It's the neurofilament light, it's the -- looking at the axon, neuronal axon, it is looking at the astrocytes. So exquisite measurement of these proteins in blood requires just a much higher degree of sensitivity than what you could do with a typical immunoassay. And so we offer basically a sample-to-answer platform, it's called our HD-X platform where you can put sample in and you get results out. And then we have 2 bench top platforms where there's some more manual intervention, but they both offer that sort of sensitivity.

Got it. And Joel, one thing that I found was interesting was your proprietary algorithm that creates an amyloid probability score, ranging low intermediate to high, maybe talk through the specifics about how each patient is bucketed in the respective categories. And why this approach.

Great. No, great question. So the way we think about blood biomarkers is that as kind of Masoud indicated is that there's probably no single analyte that is going to be able to provide the picture -- complete picture that you need, right? So we already know what kind of the contribution and the importance of amyloid beta 42/40 is as an analyte that you can measure in plasma and it's extremely good at picking up early disease presence. But it has its own analytical liabilities like virtually any analyte that you're measuring. And so when you look at that as a stand-alone, we say, well, there's probably something we can do to make it even more robust. And that's where you start looking at different combination markers. What we do is with these algorithms. So we use high-resolution mass spectrometry. Mass spectrometry is a powerhouse for discovery and development applications. It is a very rapidly growing area of clinical diagnostics, and you see all the major instrument manufacturers that are developing mass spectrometry, working on moving some of their instruments into regulated clinical routine clinical use. But it is really the ideal standard for being able to use characterization, quantitations and looking at different analytes, i.e., the multiplexing capability of a mass spec. And the mass spec pretty much looks at a bunch of different analytes and it separates them by mass and charge. So if you have 2 molecules at different in subatomic weight difference, take pTau-231 and pTau-217. They have different ion charges, and they also have different subatomic weights. That's what the mass spec is designed to do. It can pick out those different species. And in fact, it can report out all these different species at one time. So what we do is we combine different markers that we think are important to the disease process. We combine them, we develop models based on a lot of data, and then we develop a parsimonious model that identifies whatever the outcome of interest is. So our first product, PrecivityAD and AD2 use what we call this amyloid probability score. And that is basically taking the 42/40 value plus ApoE proteotype plus age into an algorithm that we've extensively validated clinically that we know, based on the scale of 0 to 100, where that individual falls the certainty that they have amyloid pathology or not. And most of our correlation studies have been either with PET, which would be considered the reference standard in most cases, certainly according to the FDA and CSF. And so the PrecivityAD2 test represents yet another algorithm that incorporates Abeta 42/40 plus this pTau/non-pTau-217 ratio. And when you combine those two, you get a very powerful score that will tell you whether or not amyloid is present or not. We could theoretically do the exact same thing for looking at tau pathology. We could do something similar for looking at really the outcome of interest. And you've seen this applied in many different fields of medicine like oncology, Oncotype DX is a good example to predict certain risk of recurrence. So we think about the power of more than just the single analyte combined to really tell that a more complete and robust picture.

Got it. Masoud, you've talked already about the utility of pTau-217, particularly in the early diagnosis. You also have a LucentAD test, which includes pTau-181. Maybe talk about sort of the context of how important it is to have that early diagnosis, given what the therapies actually are treating. And in that context, pTau-217 versus 181 and sort of where you are in terms of emphasizing one or the other? It sounds like you're going to be combining them. But maybe just talk a little bit about that dynamic. I think there's a lot of confusion. Everyone here is all these biomarkers and wonder which one is going to win. But like I do think that there is a sort of a broad range of outcomes here. So maybe your expertise in that area would be helpful.

Yes, absolutely. So I think that begins with some of the collaboration and work we're doing in the early clinical trials. And part of this is a lot of learning and seeing sort of results versus in actual real patient setting. So you do a clinical trial, you have a cohort of patients who are coming for that clinical trial and you're able to measure sort of results from that clinical trial with the various biomarkers. So a lot of times when we begin a trial, it's not in the early pre-trial days. It's not hey, this is the biomarker that we're going to go with. And that's it. It's looking at a panel of blood biomarkers and looking to see, hey, with this age, with this sort of contextual setting, with this patient setting, these are the biomarkers that are going to be most informative. Some are better adapted towards just general neurodegeneration and sort of large sort of proxies for brain health, and some are a lot more specific to specific pathologies and some are better for patient monitoring and then the combination of that. So this is part of a learning of where the biomarker is going to be important in the pathology and an inflection of that biomarker. In the case of amyloid pathology, tau has shown incredible correlation as mentioned earlier on the CSF and PET scans. And so detection of a patient early in the stage of Alzheimer's disease appears to be best indicated by the pTau series of phospho-related proteins and specifically pTau-217. And as we look at these different markers, when can you detect the pathology earliest in a patient, it appears through these clinical trials and a lot of publications that pTau-217 is able to catch that patient at a much earlier stage. And as we start to kind of look at the clinical trial data, they're coming from Leqembi and donanemab and some other trials, you start to see that the efficacy of the therapy is better when you identify a patient that's early in the cascade. And so we start to put those 2 together, 217 becomes a very important candidate for that identification. We have a pTau-181 test. When you look at the pTau-181 test, and the 217 test, 217 appears to be able to perform and identify patients earlier in the cascade. And so -- and we think it's going to become a very important marker on the LucentAD platform through our CAP CLIA laboratory for patients.

Got it. And Joel, a similar question for you. I mean, a very common question I get earlier when people are just looking at this as well, if the therapies are addressing amyloid beta buildup. Why aren't you just testing amyloid beta in your PrecivityAD was just that on the 42/40. But you've since added the pTau-217 ratio that you talked about earlier, so why did you make that switch? And what caused you to kind of add that in order to increase the sensitivity-specificity in the metrics rule around that test?

Yes. So similar to what Masoud was saying regarding each of these different analytes, every one of them kind of tell a different story. In fact, the phosphorylated forms of tau and there's many, many different forms. All tell a slightly different story. pTau-217 has some very unique properties as an amyloid that make it quite interesting to be able to track in this case, let's say, amyloid pathology. pTau-217 is not the most -- not likely to be the most robust marker for looking at tau pathology, which sounds a little bit like oxymoron because well, tau is in the nomenclature of pTau-217. But what we find is that this concept of integrating Abeta 42/40 with our phospho to non-phospho 217 value. We find that, again, each of them are slightly telling a different story. So we know that Abeta 42/40 with a really good assay that can measure 42/40, and 42/40 is very difficult to measure precisely and with high accuracy in plasma. And mass spectrometry has proven to be a pretty robust method for being able to look at that amyloid. We know that, that amyloid plays an important role in the earliest stages of disease. But as disease progresses and one gets closer to clinical onset of symptoms, that's where you start to see the pTau-217 signal intensify. pTau-181 does follow some of that similar behavior. In our experience using mass spectrometry, 217 is a far more robust amyloid than 181. And it relates a little bit to dynamic range and variability. And when you start thinking about across the entire spectrum of, let's say, amyloid pathology burden, if you will, the 217 does a nice job of tracking earlier stages of amyloid pathology plus later stages. But then the question is like, okay, so you've kind of -- collectively, the field has made great progress to identifying amyloid pathology, and you could make an argument for combining a few of these markers to get the best tools to properly identify amyloid pathology. But then there's the question like, well, what do you do about tau pathology? And so there's tau tracers that are being used today in clinical care, but not as much being said about what kind of blood testing can be used. And so there's a lot of great innovation occurring there. C2N is involved with some very interesting programs, and there will be some very exciting data presented at CTAD this year that talks more about the tau angle to the story. But I think, again, this concept of looking at different amyloids, knowing that each of them tell you something slightly differently about the disease will be important if you want to provide a more complete picture of the patient.

Got it. Masoud, we talked a little bit about screening. I wanted to reference one study that came out that I thought was really interesting and probably longer term in nature, but it kind of gives people an idea of where this can go. There was a study from researchers at Gutenberg and Lund University that use finger prick examples where they collected dried blood spot samples and ran measurements on your Simoa platform. And they found that for 217 NfL and GFAP, all corresponded really well to measurements of just a standard blood sample. So just in the context of sort of the future market, the potential for finger prick versus traditional blood draw, I mean, we're already getting huge advantages of blood draw versus a spinal tap. But if you can move to finger prick, like how realistic do you think this is? And maybe just talk about the potential for that?

Yes. It was a great super interesting study. And I think it goes to -- and one of the reasons why the study was even performed. It was just the simple need that, look, there's a lot of folks that are suffering from dementia and Alzheimer's disease and infrastructure and access are probably two of the most important things for therapy. Once there are a few therapies in the market that are pretty widely adopted, what about that access and infrastructure. And I think that blood is a big step forward. And then can you start to look at things in the dry blood spot. A physician-ordered dry blood spot test to be able to measure very small quantities of blood. And maybe that answers the question of, "hey, maybe you should come to the clinic." And maybe you should speak to your physician because of this test. And so I think that's the sort of next level of decentralization that we're paying a lot of attention to. It's still very early stages, still small sample numbers, but goes to speak as to the need for incredibly sensitive technology, whether it's mass spec or whether it's Simoa assay where you're able to get that sensitivity, very limited amount of material to be able to begin to just improve access to patients.

Got it. Why don't I pause here and see if there are any questions from the audience.

Thanks for [indiscernible]. It's been great. I'm curious, as you think about the future of testing, how you think when the primary care physician is kind of a touch point, how is the testing going to be integrated with conversation because I feel like this could be obviously a difficult conversation, especially if it becomes more widespread; two, do people want to be tested? They want to know. And three, if they do, the combination of drug -- potentially drug intervention as well as the lifestyle conversation. And I'm thinking in that part of the question, what's going on with the weight loss drugs, where we're seeing now that there's a plateau in terms of much getting lose. And people -- if you want to keep it off, you've got to kind of hit the gym or for lack of a better phrase. So this combination of drug medical intervention with lifestyle choices. So a lot there, but you've brought some really interesting concepts. So thank you.

I can give a little bit of feedback of what we're hearing today. So when we're talking to physicians, one of the first things that they come to us is that I'm getting a patient population or the folks coming in through my door that I would ordinarily not refer to a neurologist. And they're worried because of either a family history or memory or forgetfulness and this is a concern? And that's part of the desire of what I mentioned earlier is a tool, additional differential testing that in addition with the cognitive test would be able to determine whether the patient will be qualified for a therapy. And I think that's where a blood test becomes important. And so that sort as a stage of, hey, who do I rule out today? And what sort of discussion can I have along with the patient and their neurologists to begin to say, hey, does this make sense today at your age. Okay, you have a family history, maybe you should be coming back on this sort of interval for additional testing until something might come up either through a blood test or then eventually a PET test. So I think that, that demand is there, and that's at least what we're hearing. There's too few tools. I have to talk to this broad patient base and blood testing is going to be a very important one in the arsenal. And then sort of on the -- your other question on sort of the long-term sort of view. I think monitoring is important. Right now, very little is talking about monitoring. You get on to the therapy than what? What happens over a period of time, you have to go back on the therapy. A lot of these questions are unknown. And I think their blood plays a heavy, I think, leading role from a monitoring perspective.

Yes. I guess one other thing I would add -- I agree with all those points. But one other point I think that is actually going to be quite disruptive to the field is as you -- some of you may be aware, the National Institute of Aging, along with Alzheimer's Association came out with a revised context for diagnosing Alzheimer's disease. And they're almost completely flipping the narrative for how you arrive at an Alzheimer's diagnosis and they're turning it into a biological staging process. So that biological staging to me sounds a lot like kind of the playbook in oncology, where you -- it will turn out that if these turn into practice. Right now, these are draft guidance. But that document basically said that a person with MCI, which is mild cognitive impairment, theoretically, the earliest stages of cognitive impairment when they present to the clinician actually a Stage III Alzheimer's disease. So if I'm a patient, the moment some of this stuff starts getting discussed and becomes part of a much more common vocabulary in discussion with the advent of new therapies and new approaches, blood testing being more accessible. As a patient, I'm thinking, how can I get to stage 1? Because we all know that treating heart failure in stage 1 is much easier than treating heart failure in stage 3. And the same -- I think the same thing is for cancer, same application applies. So by turning it away from a little bit, there's clearly emotion attached to the clinical diagnosis, but the ability to provide it more in a biological construct, and getting patients to understand that this is just -- this is a biological marker that we now have approaches, whether it's lifestyle or treatments, and there are a number of really innovative preventive strategies that are being tested in large randomized clinical studies, you're going to see, I think, a major movement towards earlier stage assessment. And I think that -- that starts at the top with the KOLs and some of the advocacy saying that it's really not enough to simply say that one has cognitive impairment and dementia, if you will. Not pathological description and classification of where that patient is in the disease spectrum becomes a much more kind of intellectual approach to thinking about the disease, and I think will lead to better outcomes longer term.

We're almost out of time, but I would love to keep this going for a while longer, but I do have one last question that we discussed. [indiscernible], which is a monitoring [ market ]. We can talk about therapy selection market. I know a lot of it depends on dematumab label and things like that. But in the monitoring market, it was interesting in an earlier panel, they talked about you're going to be doing multiple PETs every 6 months or something like that. And that just struck me as one very big burden on the system, high cost, not enough capacity. Maybe talk about what you think the potential is for the monitoring market? And do we need a foresee mechanism to get blood into that protocol after going through maybe a period of time of there being just a flood of PETs needed if this therapy -- these therapies prove to be pretty popular.

Yes. Matt, I think that's absolutely really important, and it's really beginning. So if you look at the Leqembi label, there are quite a few blood biomarkers that were used in monitoring patients over the 79-week period. And I think that's going to extend. There's a lot that's unknown. And as you say, PET, maybe a good -- let's take a look at results in the beginning and maybe do PET towards the end, but that regular PET scan is just completely non-feasible, and I think blood there, everything we've been talking about today has been sort of that screen or the test or the [indiscernible] diagnostic, but that period of time where you're doing that monitoring is going to require multiple blood testing. And then after you're done with a therapy, you continue to do PET. It just -- it doesn't make sense. I think this where blood plays a big and probably a leading role.

Yes. I guess I would just add that clearly important application, I would say that to be able to start talking about blood biomarkers in the context of treatment monitoring, that requires very careful attention to the data and understanding I mean earlier discussions, talking about the need to have evidence driving decision-making for the best patient safety and outcomes. That's clearly going to be the need for the adoption of blood biomarkers into clinical care for treatment monitoring because just 1 simple analysis of how we think about PET and how we should think about plasma and CSF biomarkers, PET represents a cumulative exposure of pathology that you're visualizing at a single point in time. When you're looking at blood or CSF, you're actually talking about soluble markers that are part of a dynamic exchange process. And so you can imagine that while we were involved in the Clarity AD study and the Phase II Leqembi study as well as the TRAILBLAZER-2 study, and they use some of our markers. And at a group level, you get some beautiful correlations as PET -- amyloid PET resolves, you see changes in biomarkers. That's great. But I think there's a lot more that we want to do as a field and need to do as a field to really be able to think about how we're going to incorporate those tools into routine clinical care because the patient's life depends on it, right? We want to make sure that these patients have -- there's good evidence supporting our decisions for how we're going to start titrating and changing therapies.

Great. With that, why don't we conclude, I think you guys have been great and shed a lot of light on what I think is one of the clearest value propositions in diagnostics and where it's such an early stage. I think it's really exciting time to talk about it. So Masoud, Joel, thank you very much.

Thank you, Matt.

Thank you.