All right. Good morning, everybody. Welcome and thank you for coming to the Perspective Therapeutics Analyst Day. We're really excited about this. It's an extraordinary journey for the team to bring us here. We appreciate everyone showing up in person. I do need to get this out of the way. Please read every word very, very carefully. We keep our filings current with the SEC. We encourage you to look there for any forward-looking statements that may or may not inadvertently show up. But we do keep everything on file. We will actually be making a version of the deck we're presenting today available at the end of today. So, feel free to take pictures of the slides as we go, but the material will also be available afterwards. So the agenda today, we're going to go through just some quick intros of the team, who we have here. We do want to talk about our pipeline. You know, we spend so much time innovating behind the scenes, and we get very few chances to talk about it because people always want to know what's happening on the clinical side. But this is a company with an extraordinary pipeline, and we really want to take the ability to sort of teach in for that, tell you what's going on, what's the groundbreaking science that we're investing in, and that we're developing as we really go through things. We do want to give you a clinical update, which will cover our existing programs and what we're doing in humans right now. We have, Dr. Richard Wahl here, to go through some of the concepts and his own experiences with the nuclear medicine field as it's grown, as it's moved forward. Dr. Wahl is enrolling patients in our current clinical trials. I think that says he so far supports what we're trying to do. That's probably a fair statement. Then I want to get into a corporate update and a manufacturing overview. We get an awful lot of questions that show up on a regular basis. I thought, let's at least do a teach-in for everyone to talk about what does that mean? How easy is it to actually roll these products forward, to distribute? Then if you'll forgive me, we'll do a little bit of what I call myth-busting. We've heard various issues that get raised out there by various people that we don't necessarily believe are true. We'll try and support a belief with fact and data. We really want to sort of, you know, you know, talk about that and the issues that we think are definitely out there. There will be Q&A at the very end, and so we'll pass around to Mike as well for that. Please, we encourage people to ask questions. But what gets me most excited about the job I have every day, apart from treating cancer patients, is actually waking up and getting to work with some terrific people. In the room right now, we have Dr. Frances Johnson and Dr. Michael Schultz, who are the two scientific founders of legacy Viewpoint Molecular Targeting. We have Dr. Markus Puhlmann, our Chief Medical Officer, who we pulled over from Seagen. We have Jonathan Hunt, our Chief Financial Officer. Amos Hedt is our Chief Business Strategy Officer. And also in the room, we just appointed Annie Cheng to head up our investor relations. And so we have a new sort of point of contact. If you want to get an answer eventually, send it to me. If you want it right away, send it to her. And she's super excited to have joined. You know, I will make one inflammatory comment on purpose. And so when I recruited Dr. Puhlmann, I said, the way to think about this is these are like ADCs, except they actually work. So very inflammatory statement for someone that ran a lot of the programs at some of the largest companies out there. But you'll see over this presentation why we really believe that. And the reason why we do have that kind of conviction in terms of what we're doing is that if we look at, you know, sort of across our platform, right, we have a whole platform of products. We've got these theranostics. We've got these sort of we have a combined elemental pair, so Lead-203 and Lead-212, that together allow you to do incredible discovery work, at a very low risk. But that's translated into more than just, you know, a lot of cool technology that's turned into, you know, clinical stage programs. We've got programs actively enrolling patients in a variety of settings, both compassionate use, first-line setting, second-line setting. We're pleased to announce that we're going into a combination setting as well. And really, it means that if we look at the data readouts that are coming, there's an awful lot of news flow, an awful lot of activity. And we've had great support from the street, about which we're really excited how we kind of transform these products and take them forward. So that slightly inflammatory comment about ADCs that actually work, right? For an ADC, you have to have it bind to the surface of the cell, be internalized, release a payload, and then the payload has to do something. And in our case, we simplified, take three steps out of there, right? Attach to the surface of the cell and then blow it up. And in this case, we use targeting peptides. So up until today, we would have said that peptides, or we think the best way to actually target, to target a tumor, especially without expressing on the cell surface, because they have this very, very rapid accumulation if you design it right. We do a great job at designing it right so it accumulates very, very quickly on tumor. And historically, you haven't really wanted to do antibodies with, with a shorter-lived isotope like ours until now. And we want to sort of dive into that a little bit further because that's a really interesting breakthrough. We're taking the best of all possible worlds. We do use a proprietary chelator. We file for composition of matter IP on this chelator, and we think this got a lot of advantages in clinic as well as in terms of from a biochemistry basis and a medicinal chemistry basis. In everything we do, we use proprietary composition of matter peptides. So we file our IP. Our, our earliest IP starts to run out in the late 2030s and now is extending out in the 2040s. We really like to innovate. And along the way, we've developed some pretty interesting enabling technologies. Hidden in plain sight all along in our corporate deck has been this image here. This is our third compound that's now coming into humans. This is a sarcoma that was in the animal's right shoulder. We love the fact that we can look at this tumor kidney ratio. By actually using Lead-203, the imaging isotope, we can actually do this amazing correlation and perfectly predict what will happen if that same animal gets Lead-212. So a lot of these things will come up, and we don't want to give our standard corporate presentation today, but really is to kind of put things in the back of your mind. We can do repeat images in animals, several animals in a row in the same model and compare our products against each other. And then when we get to humans, we feel a lot more confident that what we see on a biodistribution image will actually correlate into what that patient will receive with an alpha therapy if you swap around that molecule. So in terms of our platform, we're not going to talk about everything today. There are some highlights that we have here that we want to go through. And so we'll be doing a safety update on the VMT-α-NET program as well as on the melanoma program. We'll be showing first-in-human images of our, our clinical candidate for FAP. We're really excited about that. We do want to cover some of the technology background on our pre-targeting platform and also on our approach for prostate cancer imaging. Some of these fields seem a bit crowded. We are pretty adamant. We're only going to go into the space if we think it's we're going to be first or best. We'll explain to you why we think the unmet medical needs do exist in prostate and where we want to go with that. With that, I want to turn the microphone over to Dr. Michael Schultz. Mike. Wow, thanks, Thijs. As the mic—I guess the microphone is on. So I am absolutely super excited to be here and talk to you today. As Thijs mentioned, I'm here with one of the co-founders of the Viewpoint, a legacy Viewpoint company. So it's just a really exciting time for us. We've grown in measurable ways over the last, you know, couple of years. And really excited to have brought on Thijs and Markus and Jonathan and Amos Hedt to help us to lead this company forward. So, I guess I could sort of start off with a disclosure. I'm also a college professor, so that means I love to give lectures. And they asked me to try and keep this short. Many of you that are in the room today, we've gone through a lot of different things that we've been working on, right? So we've really focused on the chelator, why that's important, lead isotopes versus actinium, beta particles versus alpha particles. And so we spent a lot of time on that. And there's plenty of time for questions for that, for those kinds of issues. But today, we're going to talk a little bit more about, you know, the depth and breadth of the pipeline that we actually are bringing forward. So we're going to show you some examples of how for the, for the FAP-targeted peptide, for example, we'll show, you know, a little bit of the process for how do we do this? How do we go from, you know, millions of amino acid sequences to a clinically relevant radiopharmaceutical that has the potential to be transformative for cancer patients, right? So I'll go through that. We'll talk a little bit about this recently licensed PSMA-targeted ligand and why we think that it has advantages. As Thijs mentioned, we're always looking to be either first or best. So we do head-to-head comparisons with the other molecules that are out there to make sure that what we're going to introduce when we get to the clinic is going to be the best or it's going to be the first. And so, so I'm going to lead you through that. And then we're going to talk about, you know, over the last, you know, couple of years, we've talked, you know, incessantly about this idea about how peptides and peptide-like small molecules had, you know, some key advantages over monoclonal antibodies, for example, for radiopharmaceuticals. That has to do with circulating half-life and things like that that I'll talk about. But we're going to introduce a new platform that we've recently licensed from Stony Brook University that we think is a best-in-class platform for what we call pre-targeting. And so I'll talk a little bit more about that and try and answer what I believe are going to be some of your questions about why that's good. So, the first program that I'm going to talk about is this fibroblast activation protein alpha. This is a glycoprotein that is highly expressed in stromal cells in the tumor microenvironment. It's a protease that's on the cell surface that has functions in degrading peptides in the tumor microenvironment. Much of its signaling is not really that well known so far as in terms of, or there's lots of investigations that are going on right now to try and understand these stromal cells in the tumor microenvironment. What is the role that they really play in promoting, you know, the promoting the tumor microenvironment in favor of the cancer cells? And so is there a rationale for depleting these FAP-expressing stromal cells in the tumor microenvironment that you see here on this sort of illustration, right? And so it turns out that in some cancers, these are immune suppressive, right? So in other words, they're suppressing the immune system. And so depletion of those stromal cells in those situations, you know, can potentially allow us to be able to treat cancers more effectively. And so we're going to be delivering this alpha particle therapy to these cells that are highly expressing this FAP protein. And in order to do that, we had to develop a, you know, de novo peptide that would bind with high affinity, high avidity to, you know, to reach those cancer cells very quickly, wash out of the rest of the body. And so I'm going to go through some of that. The other thing to remember about this is that there are some cancers, sarcoma, for example, that express this on the cancer cells as well. So that would be sort of the double whammy, right? It would be we're going to be able to deplete the FAP-expressing stromal cells as well as the cancer cells in the tumor microenvironment. And I'll show you some examples of that here. What you see up here on the screen is the breadth of cancers that this, that this, you know, protein target is expressed in, in a high concentration. The thing that you notice here, though, is that these are all PET images of agents that are labeled in most cases with gallium-68 that have very fast washout from. So here at an hour post-administration of the radiopharmaceutical, you see what looks to be, you know, terrific diagnostic images. And in some cases, this diagnostic imaging is replacing, you know, the gold standard for cancer imaging in radio-labeled glucose, right? Fluorine-18-FDG. So this is the breadth and depth of the potential for this target. And so that sort of prompted us to look at this from a commercial perspective, right? So, you know, given the breadth of cancers that can be addressed with this agent, this is an article that was written by Jeremie Calais from UCLA, very respected nuclear medicine physician. And so the key point here is that what had been developed so far were these small molecules that wash out of the cancer microenvironment very quickly. So in order to turn this into a therapeutic, we've got to not only target the cancer very quickly, clear from the rest of the body, but also then be retained in the tumor microenvironment. So I'm going to step through kind of the development process to kind of give you an idea of how we arrive at a, you know, clinically relevant radiopharmaceutical. So I'm showing three images up here that were extracted from, you know, from this paper on, you know, this FAP alpha as a target for imaging that was done by the group from Heidelberg, the Kratochwil group. And so I'm singling these out just so you can see what the level of expression is that's shown in the bar graph on the right-hand side of that slide there, right? So, but we, I'm singling these out because the sarcoma, for example, as I mentioned, is a cancer in which the, you know, the FAP protein is expressed on the cell surface of the cancer cells as well as the stromal cells. And then this lung cancer and NETs are, you know, primarily, as far as we know, where the FAP is expressed on, in the stromal cells. But I'm going to show you some clinical examples of our new, FAP-targeted peptide, PSV359 for these three cancers. So I'm just sort of highlighting those as three important cancers, that we're going to be looking at today. So how do we go about this? You know, so we have a target. We know that it's highly expressed in cancer cells and in the stromal cells in the tumor microenvironment relative to, you know, normal cells. And so, you know, in the case of just to sort of contrast between VMT-01 for melanoma that we have in our pipeline and VMT-α-NET. So those are, those are peptides that targeted to G protein-coupled receptors. That's a specific type of cell surface receptor that generally has, you know, some kind of signaling pathway that it is regulating in some way. And, and so those types of G protein-coupled receptors normally have a native, what we call a native cognate ligand or a peptide hormone that binds to them natively. So that allows us to be able to start from what nature gives us, right? So we can start with that and we can, and generally those signaling peptides have circulating half-lives. Biologically, they're very, very short, right? So it could be on the order of minutes, not long enough for us to be able to manufacture the radiopharmaceutical, administer it to the patient, have it circulate in the body long enough so that we can accumulate the radiation dose where we want it to go and have the rest of the peptide, you know, clear through the renal system. But in this case, you know, there's no such known peptide hormone that we could start with. So the only way for us to do that, and it's also a small glycoprotein, which means that there's not a lot to work with, right? So peptides are excellent for this in that with, you know, with a sufficient length and design, we can make a peptide that is highly, not only highly selective, but also has high avidity so that it will bind very specifically with high affinity and excellent avidity to the target. And we do that by starting with what we call sort of a library-based approach. And I won't go into the great details of what phage display and those types of techniques really, really are. But the key thing here is that we start with, you know, for this, for example, we started with 900 million amino acid sequences that were panned to look for key sequences that we could really learn what is the key binding domain for this receptor. And we can, in this case, there were, you know, small molecule inhibitors that we could use to know that we were in the binding pocket. So the binding pocket is generally a molecular sequence in the protein of the cell surface receptor that gives us some complexity to be able to make for a very high binding affinity and specificity. And so we do that in a few steps, right? So there, you know, so first we're panning through, you know, 900 million amino acid sequences. And then in step two, we're starting to get to initial hits. That could be in the hundreds, right? So even then, you know, we'll go through another round of what we call affinity maturation, right? So affinity maturation is getting us down to just a few compounds. So now we've gotten, you know, the complexity of binding it with this very high affinity and specificity down by doing these, you know, these high throughput screenings to generate these hits. But the key thing that, you know, where the secret sauce really is, and some of that we can't really go through in great detail, is going from those first hits to these, you know, to these molecules. Right now, these hits might be sub-nanomolar affinity, right? But they have also, they've got to be stable in serum. They've got to be stable in blood. And they've got to be stable through the radiopharmaceutical manufacturing. And we also need to add a chelator and a linker so that we can, you know, add the radio metal to the product for the radiochemistry part. So this is where, you know, we spend quite a bit of time in this optimization using bioconjugate chemistry techniques and medicinal chemistry techniques that we've learned over the years we can use to improve on all those key metrics. This is kind of a picture of what that optimization kind of looks like, right? So on the far left-hand side of the screen, you're seeing a molecule that might have, you know, sub-nanomolar affinities, right? So a sub-nanomolar picomolar affinity, that's a very high affinity for this type of a molecule, right? But with making some, sometimes seemingly minor changes in the medicinal chemistry of the peptide, we can go from what you see a tumor to kidney ratio here that's somewhere around one. And then, you know, we're improving on the tumor targeting with the next generation of this, but we still have a little bit of kidney accumulation and retention that we're trying to minimize, right? So all the other organs and tissues that looks like this molecule is washing out of very quickly. And then if you see PSV359, right, you can see that now we've got the tumor targeting characteristics and the tumor to kidney ratio, tumor to all normal organs. What we think in competitive assays that we do against the other, you know, FAP-based compounds that we know of, so we can synthesize those and do comparisons in our laboratory. And so that we know that we believe based on what the data that we're looking at that we've got a best-in-class compound. And so, and what you'll see here is that what we predicted from what we knew about FAP alpha expression in tumor stroma and in sarcoma cells, that the tumor to kidney ratio would improve when we got into our human imaging. And so, with that, we're starting to step forward into, you know, the what I'll show in just a few minutes is that, you know, that worked out to be the case. So we'll show some human images. But I also wanted to kind of give you an idea about how we use imaging. You know, we talk about how Lead-203 imaging can be so valuable and important for us in the not only, you know, in the clinical setting for doing dosimetry, but also in the preclinical setting. So this, you know, these images help us to understand what is the very quickly, you know, what is this candidate worth taking forward? Do we need to do some more medicinal chemistry? And so I'm going to kind of step through those, you know, the same biodistributions, but by imaging here just so you can kind of get a picture of how we, you know, make that decision. This is the compound that we want to take forward. So here you can see this is very early on. And by the way, I should talk about, you know, very early on. So I'm stepping through a sequence of images that were collected over a period of, you know, somewhere in over a few months. So once we get through that first, you know, affinity maturation process, then we really have, you know, a team of people who, you know, we've been working together on this, you know, on these kinds of strategies for quite some time. And so we can move through that very quickly. And so here you can kind of see pretty nice tumor targeting here, you know, within 3 hours we see, you know, a pretty nice tumor accumulation. It's being excreted into the bladder. A little bit too high of kidney accumulation or retention there for our taste. I actually think that this might have been one of the images that I brought to Thijs, and he saw the tumor accumulation, and he said, "Wow, that looks great." And I said, "No, I don't think you understand. We're not finished with this yet." We brought him this image a little bit later. And he was thinking, "Yes, we've really got it now." And, but we said, "You know, I think that we have, you know, the team can look at this molecule, and there's a few more things that we can do to this." To really turn it into what is going to be, you know, a clinically relevant radiopharmaceutical that has great potential for cancer patient therapy. And these are the kinds of images that we got when we got to that state, right? So, at the same time, we're comparing this to lead candidates that are in the literature so that we're making sure that, you know, if we're not first here, we want to make sure that we're best, right? And so you can see, you know, the tumor to kidney ratio that we're achieving at 2 hours, then at 24 hours. So we know not only are we getting fast tumor accumulation, fast renal clearance, but we're also getting excellent retention in the tumor microenvironment for that therapeutic application that we're really after here. Now, the other thing that I, you know, that I just wanted to touch on is, you know, I, we talk about the Lead-203 versus Lead-212 and the idea that elementally matched, you know, peptide-based radiopharmaceuticals, you know, will behave identically in, you know, the, in a mammalian model in this case, and in humans. This allows us to make real dosimetric predictions about what's going to happen with the therapeutic, right? And this is becoming increasingly important. You know, recently in Sweden, for example, this became mandatory by law that you do some kind of dosimetric, you know, true theranostic scan of the patient and do patient dosimetry before you administer a radiopharmaceutical. This is, you know, chatter in the European Union and certainly in the United States. There's more and more, certainly, you know, more and more people who are talking about this idea of how important dosimetry can be. And from the very beginning in, you know, in our heads when we were thinking about this platform, we were thinking, you know, this will be, this is really forward-looking, right? Look out on the horizon and think about how patients and physicians are going to be looking for this kind of dosimetric information. At the time, it was very unique in oncology, right? To be able to get a picture of where the drug was in the body for an oncology drug was just, you know, you just administer the drug and you do the trial and you do the dose escalation. And if it works, it works, right? So this is really de-risking for new compounds when they go into the clinic, right? You can do some imaging for a relatively small amount of money and time and understand, is this drug going to be effective? So that led us to do, you know, some therapy studies. And we have 2 models here. In the upper right-hand side here, you see this 90-day, 100% survival, 80% complete responses. This is in a transfected sarcoma cell line. So recapitulating what we are expecting to see at, you know, for, for sarcoma patients that express the receptor on the cancer cells themselves, as well as, you know, here on the, on the bottom left-hand side here, you see this is a stromal model that we made by transfecting some cells with human FAP protein. So relatively low expression in the bottom left-hand corner. But certainly 90 days post-administration, 100%, you know, 100% survival. And then, you know, we had some excellent complete responses when we had the receptor expression on the cancer cells themselves. And this is just a comparison to Lutetium-177. We're not talking, we've talked a lot about alpha versus beta and the power of alpha particle therapy. And we'll see some of that today. But certainly against, you know, this, FAP-2286, peptide or, you know, FAPI-46, which is a small molecule, we're seeing, you know, just, definitely significant improvement in response and, and survivability. Speaking not only to the potential effectiveness, but also to the tolerability of the drug. And I should note that these are 40-day results. Generally, that means that's because the tumors were growing out of control, and they had to stop the study. So, so now we've led up to, you know, the sort of the, the process for how we go from, from, you know, de novo. We've got a cell surface receptor that we know is highly expressed in cancer cells. And we've been able to get to what we think is a clinically relevant candidate for, you know, both stromal expressing FAP tumor microenvironment, as well as, as tumor microenvironment that has, you know, FAP expression on both the cancer cells and the stromal cells, right? And so this tells you that there's a breadth of cancers that we can target with this agent. And so now I'm going to step through the first human images that, that we've shown for this asset. And it's, I have to say, it's really an exciting time for me. You know, this is, we, we've had success getting two agents into the, you know, into the clinical setting. Developed an organization around this that will help us to be able to deliver these therapies to cancer patients. We think that we can be transformative with this alpha particle radionuclide therapy. We believe that the Lead-203 can be really helpful for all of these agents moving forward. And so these are kind of some examples for how we can do that, right? So this first one here, this is a 16-year-old male patient who has osteosarcoma in the shoulder. You can kind of see this image here. And just a few things that I just want you to sort of notice while we're looking at this. First of all, this is 1 hour, 4 hours, and 24 hours post-administration. And remember that when we looked at the preclinical data, we were always looking for that, right? So we were looking for, let's see, fast tumor accumulation, rapid clearance of the residual dose. And then at, you know, the later time points, we want to see high retention of that agent in the tumor microenvironment. And so you can see that shoulder at the 18 hours post-administration looks terrific. And just take a look at, you know, the gold standard for, you know, for imaging of these patients in fluorine-18 FDG, and make a comparison between what you see in this image. And what we see in the tumor microenvironment, or the in the tumors for the whole body images. And you're seeing all of these characteristics that we were hoping for for this agent, as a SPECT agent, are, you know, telling us that it's got the right PK properties for treating these patients. Here's, some PET/CTs versus the FDG, the fluorine-18 FDG scan. This is really remarkable to see this kind of tumor conspicuity with a SPECT agent at 4 hours and 24 hours post-administration. We're definitely seeing excellent washouts. The background against the tumor is extremely low. It actually rivals, or, you know, in this case, it looks like it's an improvement on fluorine-18 FDG PET scanning for this. This is telling us, this is a remarkable image that tells us that this, to me, would be a patient who would, you know, be somebody that would be, you know, potentially benefit from this as a therapeutic. And since we have identical Pb-203 and Pb-212, we know that the biodistribution that we'd see with the therapeutic agent would be the same. Second patient in this case is a 71-year-old male. This, this is a patient with a GEP-NET, gastroenteropancreatic neuroendocrine tumor, that's metastasized here in the lungs. On the right-hand side here, you can see the FAP-2286. This is a peptide labeled, a similar size, that has been labeled with gallium-68. And you can see, once again, we have the same kind of, you know, look at what you see and what you don't see on these whole body SPECT scans, right? So you definitely see tumor accumulation that's in the same places where you see it with the gold standard FDG PET. You generally don't expect a whole body planar scan like this to have the same kind of resolution. But you're seeing the PK properties is what I'd like you to focus on here. Because you're seeing that rapid clearance through the kidneys, you know, rapid tumor accumulation and high tumor retention of this agent telling us, once again, that this has the potential to be, you know, potentially transformative for this, for for patients that are seeing this kind of tumor accumulation and retention. This is another example of the just amazing tumor conspicuity that we're getting with what is generally accepted to be, you know, a lower resolution technology in humans for imaging and SPECT/CT at 4 hours and 18 hours post-administration. Fast tumor accumulation. Tremendous tumor to background ratio, you know, in comparison to, you know, the FAP-2286 that was done, you know, at, you know, 2 hours post-administration of the gallium, or 1 hour post-administration of the Gallium-68. You know, imaging of the SPECT/CT that's rivaling PET CT is telling us that we've got tremendous tumor targeting, excellent washout of this agent through the background. So this is a third patient. This patient, you can see, these are posterior views. So you can kind of see there's a lot of spinal column involvement here, which is, you know, recapitulated by the Gallium-68 FAP-2286. In this case, we're seeing the same kind of, you know, very low accumulation and retention of this agent in the kidneys, which is, you know, primarily. I say that a lot. It's primarily the dose limiting organ for peptide-based radiopharmaceuticals. But we're just really not seeing that kind of retention. And so these are some images, you know, a comparison, once again, to this gallium-68 FAPI-2286 PET scans. And you can just see the kind of tumor conspicuity that we get in the pelvis region for this. There's an extra tumor here that we're seeing on scan here. That's not necessarily that the other one is missing it. It's, it's, you know, things can kind of move around from one imaging scan to the next. But certainly, if there are lesions there that are expressing the tumor, we're seeing excellent tumor to background ratio here. So this is another look at that, some of those spinal lesions that I talked about at 4 hours and 18 hours post-administration, looking at, you know, the same region by gallium-68, FAP-2286, right? And once again, you're just seeing this incredible, tumor conspicuity with resolution that is, you know, rivaling, PET/CT in this case. And so that's just telling us that this is another sort of example of, you know, what might be a very inoperable tumor, right? You know, right next to the spinal column, very difficult to treat. Those are the kinds of situations where these targeted radiopharmaceuticals can have tremendous value for cancer patients. And we're we're really excited about the results that we're seeing with this FAP asset. So sort of wrapping up the, you know, the FAP alpha section of what I'm going to talk about today. So this is, as we mentioned, this is a, you know, this is a receptor that is highly expressed in, you know, a large number of cancers. I think the paper that I showed, the, you know, the images that I showed were something like 28 cancers that they had shown really positive accumulation and retention by Gallium-68. We have, you know, what I think that we're, you know, I really feel like we're living up to, you know, the mission and vision. with, you know, with this company right now, we've got a discovery team that is just really skilled in the art of, you know, the fundamentals behind the bioconjugate and medicinal chemistry that's necessary to take, you know, the hundreds and hundreds of binders that you can get in these high affinity screens, and turning them rapidly into, you know, clinically relevant radiopharmaceutical therapeutics. And so I hope that you think that the data that we showed today is something very special. So, moving on to prostate cancer. I'm not going to talk a lot about this, other than to say that the key fundamental here is that this is a relationship that we've built with the team at Mayo Clinic, who, you know, know and love and respect, and have worked with for quite some time on this radiopharmaceutical platforms. So the key point here is, and I'll show some data, is that, you know, we're looking to be 1st or best. Salivary gland accumulation and retention, and the xerostomia that goes along with that is a critical dose limiting toxic effect that is associated with certainly alpha particle therapies targeting the PSMA ligand. In this case, we're venturing into the PSMA case with a copper 64 imaging agent, you know, combined with this Lead-212 therapy agent. The key thing that we don't deviate from is that the imaging agent and the therapy agent are elementally identical in this case as well. And this also gives us some platform that we could explore the combination of alpha therapy and beta therapy in the same molecule with the same elementally identical isotopes. So, the data that really brought us to this, I mentioned that it was the, you know, salivary gland versus tumor accumulation and retention. We really feel like to go to the next level for these PSMA ligands, you have to be able to solve that problem for these patients. And so these data, you know, showed us, in comparison to, you know, a PSMA targeting ligand that is known in the space and in the clinic right now, that the tumor accumulation retention was higher. Salivary gland, and washout from the salivary gland was better, so, and significantly better. And so that there's going to be more on this PSMA targeting ligand. But we feel very strongly that what we've got here, based on the data that we've seen so far, is something that could be that will be better than what's out there. So, the last thing I'm going to talk about today is this idea of pre-targeting. So, pre-targeting, you know, is, the pre-targeting has been around for several decades, right? And it has great potential to utilize the best properties of antibodies and peptide-like small molecules, right? So in this case, I'm showing the why we like peptides for radiopharmaceutical therapy, right? So this is just, you know, they have very rapid accumulation and retention in the tumor, just like what we showed in all these images. And then they, you know, deliver, but they wash out of the rest of the body. Their biological half-life is very, very short, right? If we design them appropriately, then they'll, you know, they'll be retained in the tumor. And you'll deliver that Lead-212 radiation dose, high intensity dose, over a couple of days. The difficulty with antibodies from that perspective, and why we had spent so much time on peptides over the last few years, has to do with they have very slow blood clearance, right? So you need to have a very long-lived radionuclide, lutetium-177, Actinium-225. So that because it takes so long for them to accumulate in the tumor microenvironment that, you know, you're irradiating normal cells and healthy tissues along the way. And so that, you know, that led to, you know, higher off-target toxicity risk for the patient for antibodies as radiopharmaceuticals. This picture is, you know, one in that I just want you to look at just for a moment and just think about. This is an undisclosed antibody. This is unpublished data. We labeled this so we can modify this antibody with our chelator and label it with Lead-203, right? So if you look at, look at this, you know, the targeting specificity of the antibody, it's quite exquisite, isn't it? Right? And then if you can kind of see the blue, that's like residual antibody that's still circulating in the blood at 48 hours post-administration, right? That blue starts to go away by 120 hours, right? At 120 hours, we're starting to see that, you know, that the antibody that's in the blood is clearing away. All you're left with is this very specific and high intensity, tumor signal in this case, right? So that really begs the question, right? What what if there was a way for us to be able to combine what we know about these peptides and peptide-like small molecules, radioligands that clear very quickly, combine them with this kind of specificity? And what what comes out of that is what we call, this pretargeting approach. It's a 2-step approach. And so this picture kind of gives you an idea of how we might be able to do that, right? So this is a radio-labeled peptide. Joe O'Donoghue and the group at Memorial Sloan Kettering worked on this. And you can see on the far left-hand side how, you know, it the antibody, you know, in over the first 2 hours, it's just starting to accumulate. And then it's, you know, it's got a signal that's kind of all over the body out over, you know, 4 days. But then by 5 days, you start to see that it's cleared out of the rest of the body. And so if you were labeling this for imaging, was zirconium-89, I think, in this case, you know, that would allow you to be able to identify those tumors. But if you were labeling it with an isotope that was a therapeutic isotope, it would be irradiating normal. Excuse me, normal cells and tissues all that time, right? So what if we could take, you know, advantage of this? And the idea here is this 2-step approach. What we're looking for is a 2-step approach. In the past, there had been a 3-step approach that involved a clearing agent. And we won't go into great detail on that. But basically, you know, what if we had a chemical entity that we could label onto the antibody and inject it cold, right, with no radioactivity whatsoever. And let it accumulate. We know it's going to accumulate over time. And it accumulates in its target, just like we showed the image over 120 hours. We have this exquisite Lead-203 imaging, right? And then we wait, you know, some sort of lag time that could be, you know, a couple of days, 4 days. We learn about the, you know, the PK properties of the antibody over time. And then at some point, we administer a radioligand that has more peptide-like characteristics, right? So really fast clearing that has, you know, that's conjugated with a chemical entity that recognizes just that chemical entity that we, you know, conjugated to the antibody, right? So now you have a radioligand that is going to engage just with that target and no other. This is an example of how this can be done using what's known as a bispecific antibody, right? So we're looking. And remember, we're always looking out on the horizon for, you know, what's going to be the best for the patient radiobiologically and clinically. But at the same time, it has to be operationalized, right? So this is an engineered antibody that has specificity for the tumor. And it has specificity for the radioligand. So that's a process that has to be done for every single one of those antibodies. But the key thing here is that look at the kind of tumor conspicuity that you can get with this Gallium-68 image when you do this approach, right? It works. It works. The radioligand is administered. The bispecific antibody is already bound to the target. That ligand circulates through the blood. It recognizes that part of the antibody that is designed to recognize. And it binds and shows us this beautiful PET image that shows, you know, small lesions and, you know, in different areas of the body here. So, you know, it's, I guess, we call this sort of compelling proof. And this was published in 2021. And I should mention that this group, in France has been working on this approach and this bispecific antibody to this anti-CEA antibody for a very long time. But they're this. This is some terrific data that tells us that this this can really work. So. So I guess there's a long lecture on the different types of approaches that have been done here. But I just want to just focus on, you know, for the sake of time here, these are the things that we're really looking for, right? So the bispecific approach, I don't think, is a platform that could be used. What we're really looking for is something that is modular, right? So we can do this with any antibody, any antibody, any antibody fragment, right? So modularity, immunogenicity, right? So there's going to be a small amount of immunogenicity with these types of molecules. And that's something that we can manage. But, you know, it's it also, I think, another one that's really key here is stable, right? So there have been some approaches that have been that I've seen. There's this click chemistry approach. We've done that kind of chemistry before. It's always been a little bit concerned over the last few years, you know, why I've been studying this, that, you know, the click chemical approaches wouldn't be stable when it came down to operationalized scale. So in a mouse model, maybe in small clinical studies, you know, very well controlled could be done. But I didn't think it would scale. Certainly, there's, you know, hybridization approaches that I also think are along the same lines. And so, with that, you know, introducing what we've licensed from Stony Brook University, we've worked with several groups on this. We just published a paper with a group from MSKCC. So we've looked at this very closely. You know, in the end, I think that this cucurbituril as the host. This is named after the pumpkin, actually, for just looking like a pumpkin. So, highly stable in the in vivo and in, you know, different chemical conditions. So pH temperature, etc., for, you know, operational scale. And then, so this is the host, right? So this is going to be conjugated to the antibody. And we combine that with what you see on the top part of the screen here, which is this adamantane radioligand, right? So there's going to be a test on the synthetic chemistry that is going on at the top of this slide after the presentation today. But I guess the key point is that, you know, we'll be spending some time over, you know, in the development of this, operationalizing and optimizing that ligand. But this is the first data. We published this first at the WMIC meeting, or the World Molecular Imaging Conference, the last World Molecular Imaging Congress in Prague. So this tells us that what we've got here is a platform that really has great potential. So what you see here is tumor accumulation that's, you know, that's excellent 4 hours, 8 hours, 24 hours post-administration. We see it. We see an increase, very low accumulation and retention in other organs and tissues. So we'll be stepping through the optimization process for this. This is some images that kind of give you an idea of the kind of tumor specificity that we can get with this approach in mice. This is a paper that was published by, or actually, this is unpublished data by the group at Stony Brook. So here you can see at, you know, the coronal and the maximum intensity projection at 24 hours post-administration that really shows the kind of tumor, you know, specificity that we can get with this approach. And so that kind of leads to the discussion of what this actually represents, right? So if you think about it. Just, you know, we have in the company. We in the discovery group. We have what we call target vigilance, right? So this is where we're always out. We're all out there. If we're interested in this space, thinking about what's the next target? What's going to be the one that's going to be the differentiator? If you think about antibodies and antibody drug conjugates that have been in the clinic, there are literally, I would say, there's probably thousands of them that have potential for this application. So this makes this a, you know, potentially something that could be transformative for radiopharmaceutical therapy for cancer. So with that, I will turn it over to Markus Puhlmann, who's going to talk a little bit more about our clinical programs to date. So thank you very much for your attention. So thank you very much, Mike. My name is Markus Puhlmann. I'm the Chief Medical Officer. I don't have Mike's problem. I'm a surgeon. I usually like to have it tight and concise. So I will do my best to talk a little bit more than usual. So I want to provide you with an update of our current clinical program. We have 2 compounds, as Mike already suggested, in the clinic. I would like to start with our VMT-α-NET program, which, of course, is for the neuroendocrine tumors. Now. The program initiated in late 2022 with a compassionate use program in India. At the same time, we also received a fast track designation through the FDA that did, obviously, several things. One, you have better access to the FDA to discuss your program and the clinical development. But also the FDA, at that time, provided us with some guidance. And the guidance was to really take the program and not go beyond or after Lutathera, but actually in the same space. So we are actually in a pre-PRT space with our NET program based on our fast track submission. We are also working together on an IIT with the University of Iowa. That study is situated in the post-Lutathera space and provides us with additional clinical information how our drug would actually fare in this post-Lutathera indication. And we may eventually choose to go into the space as well. Now. This is our compassionate use program. This is a study that was, as I said, initiated in 2022. And the investigators at that time weren't quite sure how to dose our drug because our own phase I hasn't started, or hadn't started at that time. So the investigators used a weight-based approach and came up with a dose of 2.9 millicurie per patient in average. We found that this was safe in a very heterogeneous population. The investigators enrolled patients pre and post-Lutathera, some with a really incredible amount of tumor. And what we learned really from this study so far is that a, it is safe. B, we do see responses. These results, this waterfall plot, is from our presentation from Fortis from last year's EANM in Vienna. We do see responses pre and post-Lutathera. So again, suggestive that the drug can be developed in both indications. Updates of these trials will be presented in a much more complete form during SNMMI this year in Toronto. I want to quickly remind you of our own trial design. This is our phase I study. The study is, of course, ongoing. We are enrolling patients with unresectable and metastatic SSTR2-positive tumors. They are, as I mentioned, PRT naive. We are using a Bayesian MTPI-2 methodology. That methodology does allow us to be very flexible. It also allows us to quite quickly hone in onto a very efficacious dose level, as well as the recommended phase II dose. We already knew, of course, from our Indian compassionate use experience that the first dose level should be safe. Hence, we only enrolled 2 subjects for the initial cohort 1. That cohort is now closed for enrollment. The SMC reviewed the safety data. I will briefly show you an excerpt of the safety table, or at least one safety table. And unanimously agreed to open to cohort 2. We have currently 2 subjects enrolled. We are planning for this particular cohort to enroll up to 8. All spots already have been taken. These additional patients are currently being screened and will be dosed subsequently in the next few weeks. This is an adverse events table about the treatment emergent adverse events so far in the program. Now, at the time of the cutoff, there were about 30 subjects treated. The 2nd subject of the cohort 2 was actually treated on the 14th of March. So hence, these data are not yet included. I would like to quickly run you through this. You can see in the first column is actually an incidence column. So you see the AEs listed according to the frequency. On the subsequent columns to the right, you see grade 2, 3, and 3 AEs. We have had one grade 3 AE in a subject with diarrhea. Diarrhea is very difficult to categorize. What is grade 1, 2, and 3? It's actually the frequency of the stools. That subject started initially with a grade 1, then developed the next day a grade 2, and the third day a grade 3, which is 7 stools and more. And then it resolved. So, the subject so this, the subject fully recuperated without intervention. If we look at the frequency of the AEs, we see that some patients develop some hair thinning, called alopecia. That could be, and we talked to quite a few KOLs, that could be actually an on-target effect. It seems that SSTR2 is expressed in the hair follicles. We also know from our experience in India that this is only temporary. So the hair will grow back. We also saw diarrhea. Oops, this was the wrong one. Can we yeah. We saw diarrhea, and nausea also with 3 patients developing it. And this is what makes this so important to have a look, actually, at these relatively early AEs. We have to administer the drug in conjunction with amino acids. Amino acids alone can cause nausea. And we have not stipulated in the protocol to use antiemetics. We advise our KOLs in the field to follow their normal Lutathera protocol, but some of these subjects may not have had enough antiemetics. So we have to we are working very closely together with the KOLs in the field. And this is something we may want to emphasize a little bit more. Then we see also some fatigue and lethargy, but otherwise, it's actually quite clean. One subject had an elevated amylase, which was, or which is, asymptomatic. This is something we are currently observing. There could be a variety of reasons why that lab value is elevated. All in all, this is, for me as a drug developer, a very encouraging picture, especially because we are already at the 5 millicurie level, albeit. It's an early look. In summary, what we can say at this moment in time. The study is open at 7 sites. We get a tremendous amount of interest from the field, including patients. Patients actually contact us and the physicians to get into the trial. I mentioned already we get, we have 6 patients currently in screening. And we have not seen any SAEs, no DLTs, and there were no discontinuations. We can say with confidence in the moment that the VMT-α-NET is tolerated well with no unexpected AEs. And of course we are continuing with the dose escalation as planned. I want to quickly switch gears, go to our Melanoma program. That program was initiated with an imaging study at the Mayo Clinic. We found out and tested actually the feasibility of patient selection using Lead-203. And VMT the there is a there is a typo. Should be VMT-01. That prompted us to develop, of course, our own phase I dose escalation study. We are in the process of submitting a fast track application. We already have submitted to the FDA also an ODD and orphan drug designation application as well. Another exciting part about this program, and we talk a little bit more in detail a little bit later on, is the option and the possibility to develop combination approaches for this indication. We're going to talk a little bit more, as I said, later on. Again. A quick reminder how our trial is designed. The patient population here is—are patients with unresectable and metastatic MC1R-positive melanoma. These patients must have been treated with standard of care for the first-line systemic therapy. Usually, this consists of checkpoint inhibitors, either in mono or in combination, or where appropriate with BRAF and MEK inhibitors, or a combination thereof. Again, we're using the MTPI-2 methodology. We enrolled and completed cohort 1 with 3 subjects. The SMC, again, unanimously, suggested to open cohort 2, where we have currently treated 2 subjects. Four are in the moment in screening. These subjects will be used also for dosimetry evaluations, as well. Here is the AE table with the treatment emergent adverse events for these 5 patients. We only see grade 1 and 2 AEs in the moment. The only grade 2 AE that actually was related is actually grade 2 of nausea. Otherwise, all other events were grade 1 that were deemed related. Nausea was the most frequent. Again, we probably have to work with the investigators to increase antiemetics during dose administration. We did see some lymphocyte count decreased, anemia, and hyponatremia in more than 1 patient. Again, these are apart from 1; these are all grade 1 AEs. Interestingly, there was 1 infusion site extravasation. This occurred in the line with the amino acids. And that resolved the day after. Again, a very manageable and benign AE profile so far, which bodes well for our next dose escalation cohorts. So, in conclusion, we have, for this particular site study, 8 sites in the moment active. Again, we see a lot of interest. There were no AEs, again, no SAEs, DLTs, or dose discontinuations. Okay. I want to quickly get a summary of both studies. So both programs, of course, have now their cohort 1 completed. We are currently with both programs in cohort 2. Except for 1 grade 3 diarrhea, all observed AEs were grade 1 and 2s. There were no DLTs. We are planning to actually provide an update about the safety and efficacy of these two cohorts in fall at the end of the third quarter. Okay. I want to switch gears a little bit. I want to stay with melanoma, but switch gears. I mentioned that we are very interested in combination approaches. I'm pretty sure you have seen the press release that came out this morning. It suggests that we went into a collaboration agreement with BMS, where BMS is supplying us with one of their checkpoint inhibitors, nivolumab or Opdivo. And this is, this is, in particular, for me, who has worked in this space, a very exciting event. We do know that checkpoint inhibitors have, in particular in melanoma, really revolutionized the therapeutic approach. The problem is that despite checkpoint inhibitors, we still see a lot of patients who are either unresponsive or eventually progress. If you then take biopsies from these patients, from the tumor lesions, you do see plenty of tumor infiltrating lymphocytes, but these are not active. They actually show signs of T-cell exhaustion. Now, we do know that ionizing radiation is very immunogenic and causes immunogenic cell death. The problem, of course, is if you look how, for example, external beam radiation affects the tumor microenvironment, one can quickly see that external beam may not be the proper tool to combine with radiation sorry with checkpoint inhibitors. I myself am guilty about this. We had plenty of trials where we tried to see whether we could elicit an abscopal effect. We were not successful. However, giving radiation systemically changes really the game. And we do know that alpha particles are particularly good in releasing really neoantigens into the tumor microenvironment. And hence, we actually postulated that, in particular, in our case, MC1R targeted alpha radionuclide might actually synergize with the existing standard of care, checkpoint inhibitors. And that actually can be seen and observed in the experiment on the right. And this is one of many experiments that our preclinical group, well, led by Mike Schultz, have conducted. This tumor model is in B16F10 checkpoint-resistant melanomas performed in actually an immune-competent murine mouse model. The interesting part here is that, as you can see, checkpoint inhibitors alone do not lead to any cures, what you would normally expect in this indication. These mice succumb quite quickly. The black interrupted line is controlled. The other interrupted lines are the various checkpoint inhibitors, either PD-1 alone or in combination PD-1 with CTLA-4. A single administration of VMT-01 has essentially a similar, if not slightly better, effect. But a single administration of VMT-01 in combination with either of the checkpoint inhibitor groups does something absolutely remarkable. It not only causes objective responses in these animals, but it also generates a tail. So it reinvigorates really the immune response and leads to a dramatic improvement in overall survival. The other important part here is that it doesn't really matter whether or not you just add VMT-01 to a PD-1 alone or to the combination. Now, we do know that CTLA-4 can be quite toxic. So we decided to opt in the moment just for a combination with the checkpoint inhibitor nivolumab. We have written an amendment that now includes several additional combinations or escalation steps for the combination, where we treat with nivolumab at 480 milligrams (this is the four-weekly dose level for up to two years) and test this combination initially at 3 millicurie, 5 millicurie, and then perhaps at the recommended two doses. Or maybe we go even lower. We'll have to see how the data will read out. These cohorts will start at the end of the second quarter. This is, I think, what I had. Thank you so much. Back to Thijs. Okay. Thanks, Markus. Yeah. See, Rich, if you want to sort of come up. You know, my next guest needs no introduction. So Dr. Wahl graduated from Mallinckrodt Institute of Radiology, WashU, back in the seventies in nuclear medicine. Went on a fabulous career. It was, had nuclear medicine at Hopkins and is now back at WashU, Mallinckrodt. I've been in the field for 30 years. And when I came out in the late 1990s as a nuclear pharmacist, Dr. Wahl was writing textbooks about nuclear medicine. So, if he hasn't seen it, it's probably not relevant in this field. So for this portion, we just want to do a little bit of an interactive discussion with Dr. Wahl and really talk about where is this field going? Because for most people in this room, nuclear medicine and the radio pharma space is kind of new-ish. We're trying to, you know, teach and educate people about it. It's not new for us. And so that's why we wanted to really, sort of talk through some of these things about what are the trends in the radio pharma space and what's really exciting for someone that's in the field. And so, Rich, let me throw it over to you. Yeah. Well, I think the introduction basically told you that I'm really old. So, yeah. Don't have great expectations. All right. I've been around a long time. My interest in this field really came about when I was a medical student at Washington University in St. Louis and monoclonal antibodies were identified and I got interested in using those. I thought, if you could get these things to target in vivo, that would be really good. And if you attach radioactivity, you could diagnose and treat cancer. And that was, in fact, a reasonable hypothesis. But antibodies themselves, as we've heard, have significant challenges, as they're highly specific, but their long serum half-life makes it a bit of a problem in terms of their ability to deliver dose just to tumor, so because you have a lot of off-target effects. But I'd say the exciting things for me have been the use of peptides, low molecular weight compounds, which target to tumor more quickly, and which get around some of the blood toxicity. You probably noticed in some of the slides that were shown that hematological toxicity really wasn't high on the list, in terms of what we're seeing. And we know that for some of the established peptide drugs, it can occur, but not such an issue. So this whole concept of targeting two tumors has been attractive and reasonable and gradually growing. And I'd say, for me, the lower molecular weight compounds are exciting. And my knowing the limitations of monoclonal antibodies, I got particularly interested in what could we actually treat. And I got involved in well, lymphoma is very radiosensitive. And so early work that I was involved with was involving developing the drugs, Bexxar and Zevalin, which actually worked quite well, in radiosensitive tumors. And you see here, like, the early growth here in radiopharmaceutical therapy really was a lot of it was in lymphoma. But that has plateaued, even declined a little bit. And a lot of the other interest here is in prostate, hepatocellular with local regional therapies, and neuroendocrine. So, the field got going and then just really a lot of growth. Beta particles have been sort of the dominant way we've treated. I mean, I-131, which has been around for 80 years, treating thyroid cancer has been around for quite a while. It's it's well established. But other beta particle emitters have come into play. Lutetium-177, which is attached to several FDA-approved radiopharmaceuticals for prostate cancer and for neuroendocrine tumors. Lutetium-177 is like iodine, except it doesn't have these high-energy gamma rays that travel out and are radiation protection issues and which can irradiate normal tissues. So lutetium has real advantages. But lutetium has different disadvantages. One of the problems with beta emitters is that the beta particles, when they decay from a spot, they will travel some distance. Lutetium can go a couple of millimeters. Yttrium-90 can go a centimeter or more. So if you've got a highly heterogeneous necrotic tumor, those those are good characteristics. But for small tumors, it's very hard; those very energetic particles leave the tumor and they deposit their energy in normal tissue instead of in the tumor. And that's where these alpha particles are so attractive. They deposit the helium nucleus right very close to where the disintegration occurs. So they're very good at killing single cells or small clusters of cells. And it turns out I don't know if we're going to show all the data, but we've published. Others have published very hard to cure some tumors with Yttrium-90, very hard to cure some tumors with lutetium as a label. But you put an alpha particle emitter on, and you can cure those tumors in animal models because you can hit small tumor clusters. So a lot of interest in alphas, and it's just really taken off. This is, I point out, from a paper by George Sgouros in Nature Reviews. This ends at 2018. What's really happened, probably we don't have a big enough screen. We may have to go down on the trading floor to find one, that that would show the growth in some of these things. But, alphas have really been big. Radium, of course, was approved radium dichloride in a randomized trial for Xofigo. And I think that was approved in 2013, if I recall correctly. And, and and so there's a lot of interest with radium's approval and trying it in other things. But now, actinium has grown a lot. One of the problems, of course, with actinium, not a great supply. It's hard to get a hold of. And we don't really see lead on this curve, but lead is beginning to take off quite rapidly as well. You've heard about Lead-212, Lead-203. Pretty exciting. Probably more than you wanted to hear, but great excitement about the targeting molecules. The choice of the radionuclide really makes a difference. I guess I would say the other thing is if you can't get the therapeutic isotope, it may be great in principle, but in practice, you have to have access to the radiopharmaceuticals. Thank you. So as we look at the whole issue of alphas and betas, and you know I had a question even last week where someone said, "Well, I'm not convinced yet that alphas are better than betas in terms of treating, you know, a lot of the tumors that we're looking at." So we've previously shown some data with the, you know, untreated tumor on the top left, treating with lutetium on the top right, and then that same model treating with either a single dose alpha drug on the bottom left or 4 fractions on the bottom right. So, you know, recognize that we still want to see clinical data. Just like to get your thoughts about what does this tell you in terms of relative confidence for what could happen in patients. Yeah. And this is a little bit of what I was referring to. Obviously, treating tumors with vehicle in mice isn't very effective. So we see this is a very aggressive tumor. And using a pure beta emitter in this particular model, in repeated doses really wasn't able to achieve tumor control. By contrast, using an alpha emitter here, the bismuth, or, excuse me, Lead-212 VMT-α-NET, repeated fractionated doses, small doses, or a single large dose, really were able to achieve excellent tumor control and cure. And this is what I was referring to earlier. Sometimes with the more energetic beta emitters, you can't cure the tumors because you can't knock out all of the single tumor cells because the energy is being deposited too far away. I guess in a military sense, if your enemy is in a small boat coming up to your ship and you've got a cruise missile that you're going to fire, it may not be the right weapon for the particular engagement. So, the alphas are particularly well suited to hitting some of these, smaller tumor foci. And then the question is, you know, can they take your larger tumor foci? I think we've seen some of that data already. So but the choice of the particle emission makes a difference. And highly energetic betas have limitations. So I think it as was sort of mentioned, each, I think, will have a place. but it's increasingly recognized that the alphas have an important place. I mean, when we think about sort of designing these programs and products, and we think about the isotopes, you know, a lot of things come to us in terms of, in development. And things are either problems or they're expenses. And I think about this when I deal with my family. My daughter says, "Dad, I have a problem." It's like, if I can fix that with money, it's an expense. It's not a problem, right? But things that you can't fix with money are legit problems. And one of the things that we think about for availability of isotopes is that I think if we spend enough money, we can eventually supply most isotope logistic issues. But what we can't solve is something that happens afterwards. So you give the drug. It's going to do something. What happens next? There's a lot of chatter in the space about what happens with daughter isotopes in the decay. So we've talked a lot about, you know, sort of alpha and beta. Lead-212 will fire off a beta, and then immediately an alpha from the Bismuth-212. And that's kind of where that story ends. But with Actinium-225, it doesn't feel like it ends there. And so the question about daughters, we've had people say to us, "Well, there's some data presented last year that proves conclusively that the Actinium daughters are not a problem." I'd like to get your take on that. Yeah. And, you know, on that prior slide, I did want to point out what was really impressive with the alpha therapy was that it was possible to control the tumor with a single dose. So this idea that you need repeated, repeated, repeated doses isn't necessarily always going to be the way it's going to be. It might be that a single dose, the right dose, may be therapeutic in that animal model. This particular okay, yeah. Thank you for going back. You this lower left thing. So if a patient could come in and be like this mouse and get a single dose and be cured, there's huge economic implications because the workforce has been discussed as an issue. Who's going to do all the work? Where are the rooms? A single dose instead of four doses might be attractive. Something to think about. Sorry. But, next. So this one, daughters. I have a daughter as well. And sometimes I don't I don't know what she's up to, unfortunately. But she's with me right now. It's all good, I think. In any case, I think most of you know that Actinium-225 is incredibly interesting, but it has a complex decay scheme where there are four alpha particles emitted. And the times from when the decay occurs until when the radioactivity is actually gone can vary. But there's one in particular, Bismuth-213, that has something like a 46-minute half-life. And it's long enough that if the actinium decays, let's say it got to where it wanted to go, where let's say it gets to a tumor, can this stuff get loose? And 46 minutes, if it's loose for 46 minutes, you could potentially go some distance. So the question really has been, can you tell the early decay products, the early alphas from the late alphas? And this field is really early. These data aren't published, but there's been a couple of publications of the presentations, European Society of EANM and SNMMI in the past six months, where there have been presentations that use imaging to look at the different gamma photon energies that you can detect with a gamma camera. You can sort of tell the early decay alpha surrogate francium from the late decay alpha surrogate Bismuth-213. So they can be separated to some extent by imaging. One of the challenges with all this stuff is that the image quality is low. The counts are low. So you're dealing with sort of the fringe of detection technology. I think that adds a level of uncertainties to some of these determinations just because the methods are new and they're low count. So these are some data that are up. But basically, if Actinium-225 and Bismuth-213 are the same, the curves should look the same in terms of their height, the y-axis, and their shape sort of on the x-axis. And you see, though, that they don't look exactly the same. And I think you can see that these have the same y-axis. But here, this Bismuth-213, especially at early time points, is higher in some tissues, such as kidneys and liver, than the parent. So it's perhaps not surprising that when the Actinium-labeled compound is injected, there are some daughters already present, and they're migrating. And they will go to some of the other tissues, particularly the kidney with Bismuth, more than to normal tissues. So, my look at this data, and it's got a lot of uncertainty, is that what's been published is something like maybe 25% less dose in the tumor when measuring it with Bismuth than with francium. And when you look at the kidneys at early, if you look at some of the data, there may be 1.5x-2x more dose with Bismuth than francium. So it's complicated. But you know I think that there's little doubt that some Bismuth gets loose. It can move around. And then at a point, the question is, is a daughter really causing you trouble? And that's sometimes you have to wait. The clinical trials will give the relevant readout to those things. But these early imaging data have uncertainties, but they suggest they're not equivalent and that there is loss, particularly at early time points of Bismuth-213. And of course, what's injected early on, saying it over, clearly not identical at early time points. And I think not identical at later time points, though they're certainly correlated. So we think it's really interesting that people are doing the work, and we really support that. We like to put everything we can out there in the public forum and present and publish everything we do. As we look at where things are moving forward in terms of the space, one of the questions we also get asked a lot by investors and sell-side analysts is, how do we compare doses? And this whole concept of for an absolute dose. So if actinium is giving off 4 alpha particles and lead-212 is, you know, deriving 1 alpha particle, how do we think about that? How do we think about 200 microcuries versus 2 millicuries versus 200 millicuries of lutetium? If you can kind of help explain a little bit, what does that mean? And we're not trying to make everyone a health physicist during today's session today. Yeah. I've got to say that this term dose has been one of the doses used in a variety of ways. And I think it's a really bad term and can be very confusing. Sometimes the word dose refers to the mass of how much you put in. Like that's pretty typical in pharmacology. So what's the dose? The another thing is how many millicuries or how many gigabecquerels or how many, you know, kilobecquerels are injected. That's actually how many radioactive molecules are injected. And then perhaps I think most relevant to nuclear medicine physicians and to patient biology is how much energy is deposited, how much energy deposition occurs. And that's a dose. That's radiation absorbed dose. So dose can mean at least three different things. And it can be very confusing. I think the most relevant thing is radiation absorbed dose. And that can be calculated by dosimetry using imaging techniques. But a more relevant term, I think, is injected activity. So that's how many radioactive molecules would be injected. And basically, if something has a really long half-life, it's going to be a and it stays in the body quite a while. You can't inject as much of it as something with a short half-life because the absorbed energy will be greater for the shorter half-life. Excuse me. Well, it has to be the injected activity would have to be greater to have a similar dose. So this comes down to then not just dose in terms of administered activity or administered mass or absorbed dose, but also dose rate. So the radiation absorbed dose, I mean, in external beam radiation, there's fractionated radiation, and then there's sort of hypofractionated. So high dose rate and low dose rate. And the rate at which the radioactivity the energy is deposited makes the difference. So this is why it gets a little confusing. So I think I'm overdosing you on this information. Sorry. But I mean, if and basically, if you have a shorter half-life, let's say, for sake of discussion, Lead-212, and the half-life is around 12 hours, roughly. So, about 75%-80% of the dose of the energy would be deposited within 24 hours. So most of the energy would be deposited fairly quickly. That, and I think that can be good. That can be very good if your targeting molecule gets to the tumor quickly and it gets out of the body very quickly. In fact, that's probably ideal. It also means radiation safety. It can be easier as well. But if you had that on an intact antibody, which the antibody takes 3-4 days to get to the tumor, then that's a very bad match. That's not a match made in heaven. That's a match made elsewhere. So longer half-life are probably more appropriate in general for longer-lived compounds. So actinium with a 10-day half-life, roughly, it takes 23 days or to deliver 80% of the energy radiation absorbed dose. So it's; they're really much different in terms of how the deposition is. If it all goes to the tumor and stays in the tumor and never leaves, then you've got a question of low dose rate better or high dose rate better. In general, from a radiobiology standpoint, high dose rates are more lethal per amount of energy deposited. But they're; they do differ substantially. And then I guess the longer something hangs around in the body, the greater the chance that you know daughters could get loose and they could go elsewhere. So that's also a risk. I mean, one thing with lead, I think it was briefly discussed, is that you only have a single alpha. So it goes there. You have a single alpha, and then it's done decaying. So you don't have that daughter problem in the same way. Thank you. So just thinking about the space, you know there's a lot of focus on certain you know tumor types, SSTR2, PSMA, and where is the field going with FAP and some of these things. So this is a pretty complex chart. We're not going to read through every word here. But really, as you think about the space, why has SSTR2 been interesting? Why is PSMA interesting? And where do you think some of the field can go? Well, yeah, this is a complicated chart, and I had to look at it pretty closely when you showed it to me before. I think it the somatostatin receptor, as was discussed, is really exciting because there has been natural ligands, which could be improved upon, which have shown really excellent results in a variety of trials, randomized trials, prolonging with higher progression-free survival. So that's been a proven credentialed target that's well understood. Yet in the trials, response rates of 18% are seen. So you've got anatomic responses. You've got 82% not responding potentially. So in some of the trials, the rates are higher. But there's a large number of patients who don't have a classic anatomic response. So nice thing about somatostatin receptors, well understood target, but still unmet need. We still have patients, many patients dying with progressive neuroendocrine tumors. PSMA, very exciting, VISION trial, which you're all familiar with. And you know how that's gone as long as you can produce and distribute the radiopharmaceutical, you know, and get it to patients who can benefit. But right now, you got 4 months improvement in progression, roughly 4 months in progression, well, in survival. 4 months is important, but we have a lot a lot of room to go beyond 4 months. So a huge good target, not a perfect target. Salivary glands are an issue. But lots of opportunity to do better, proven target. FAP, I think maybe we'll talk about it in a little bit, but very interesting target with its general expression, especially in some tumors where we don't have good targeting. More to be done because of short residence times. And others, this is where there's tremendous excitement, can you know basically, like ADCs, can radiopharmaceutical therapy work in every cancer? My hope over the last four decades has been, yes, we're not there yet, but there's still time. So with a lot of material to go through here, one of the things I would just want to touch on is this concept with xerostomia and PSMA. And what are you seeing in your clinic doesn't really matter. I'd had one physician tell me at a conference two years ago, xerostomia is not that big a deal. But I'd like to kind of get your perspective. Well, I guess salivary glands are really important. And I think one of my former trainees that's here in the room has done some work with actinium. And I think is familiar with how bad the salivary gland dysfunction can be. It's been this has been used more in Europe, but it can be devastating. There'll be patients who just cannot go on with the actinium-labeled PSMA in particular. That's a bit of an issue. It's a significant issue and can be debilitating. I'd say with the lutetium, it's less of an issue, but it's less of an issue. And I'd say that when the survival is so short, it may not be as problematic in clinical practice as it appears to be with some of the agents. But there's been a major focus on trying to reduce salivary gland uptake of the radiotracer selectively so you can keep tumor targeting and not hit the salivary gland. So it is a real issue. And I think it's been more of an issue in practice with alpha emitters such as actinium. Do you mind just walking people through just what does the scan show and what's the non-activity? Sorry. Yeah. This is about an hour after injection of a PSMA-11 ligand, so a small radioactive molecule. And I'll just point on this one. But this is early on. Later on, what happens is these are the organs of clearance. These bright things, black is uptake, high uptake. So it's a gray scale. These are tumors, these three things, nodal metastases, liver, spleen, excreted activity in the urine, salivary glands, thyroid. So what happens if you have later images or lutetium, these guys will clear, the urine will clear, but the salivary glands and the tumor can get similar radiation absorbed energy doses. And that's good for the tumor, but bad for the salivary glands. And some of the science here, I mean, dry mouth, but this I've not experienced it, but from those patients who have this, it can be just devastating in terms of not being able to generate saliva. And it really diminishes quality of life. But again, it's been more of an issue to date with alphas than betas. Great. And just looking at the for the sake of time, we'll move through a few things. Sorry. First question is, can you just sort of comment as an imaging person, what do you see on these images? And is this a compelling match pair, or is this, you know, if you can kind of walk through it? Yeah. As you can probably tell, I'm a university professor too. So like Dr. Schultz, I yeah, tend to go on. But FDGs are standard of care for imaging melanoma. And injected an hour later, high uptake in tumor foci. We see many of them. This remarkable image over here looks almost the same, but it's not FDG because it doesn't go to the brain. And it has really exceptional targeted to background uptake, higher uptake in terms of the target to background than the FDG. And it's exceptional targeting of many foci. So this is with the VMT-02 per the label. And can you comment on the brain at all in these images? Yeah. I'm sorry. There's nothing in the brain there. I mean, the blood brain barrier keeps it out. FDG goes to the brain. And so that certainly, that's how you can tell them apart. So you're going to do better in the head and neck and brain. We don't do well at imaging metastases of melanoma in the brain with FDG right now. So this, I mean, this if this worked diagnostically, it would be, I mean, if it were routinely at this good, it'd give definitely FDG a run for its money. But I think the real excitement, of course, is this would presumably predict the distribution of the therapeutic or radiopharmaceutical. And that degree of targeting is very promising. Great. I wanted to have your take as a clinician on what does it mean to do combination therapies? And having seen this data, what's your take? I think it's, you know, it's really hopeful that radiopharmaceuticals on their own can cure every cancer. That hasn't, unfortunately, been the case in general. We can make meaningful improvements. But combining therapies is common in oncology, and I think it will be common in radiopharmaceutical therapy. To me, this is impressive. This particular this green thing is the radiopharmaceutical alone. It's a nasty tumor. It kills very quickly. So there's an improvement here with the radiopharmaceutical therapy, but with two checkpoint inhibitors or one checkpoint inhibitor, considerably better outcomes. So I think this will need extensive investigation, but I think likely combinations well tolerated. You know, clearly, nivolumab is better tolerated than the combination of nivolumab and ipilimumab. So I think this is an exciting result. And it looks like those animals are cured at least through 60 days, which wasn't achievable with the checkpoint inhibitors alone or the radiopharmaceutical alone. So just for the sake of time, I'm going to think about the concept of FAP in terms of as an imaging agent and as a therapeutic target, recognizing they may be different. FDG is not a great therapy because it's going to hit every glucose-hungry cell in the body, which obviously would have you know incredible off-target effects. But you know just want to get your take on that. Yeah. Well, there's some diseases where we just don't do very well with FDG. We don't do well imaging pancreatic cancer. We don't do well mucinous adenocarcinoma of the colon are examples. So from an imaging standpoint, there's an opportunity from a therapeutic standpoint. We haven't had great targeting for those tumors as well with radiopharmaceuticals. So those are a couple of the important areas where I think there are big markets and big need. Pancreas is really a big problem right now, among others. Terrific. So for the sake of time, I'd like to thank Dr. Wahl for this partial Q&A. After the corporate update, we'll open up to open Q&A and then we'll let you ask your questions with us as well. Thank you, Dr. Wahl. So when we talk about the field and where it's going with you know where the alphas go, where the tumors go, one of the other questions we get is first, is it even possible to get the isotope what in the first place? And it doesn't matter if we have the best therapy ever, but if we can't actually get it, then that's going to cause a problem. And how do we make it and how do we go? So I want to just sort of level set the field a little bit on how do we actually deliver the product and how do we bring it to patients? Initially, when I first started in the field, nuclear pharmacies made radiopharmaceuticals. They would combine previously approved FDA kits, using laminar flow cabinet, and deliver that just in time, same day to patients, especially those within sort of you know 2-4-hour driving radius away from there. Not really that large facility, about 5,000 sq ft. And with sort of non-lead shielding, you know call it up to an inch of lead, you could actually shield the product from the operator and the operator from the product and actually distribute things pretty well, technetium 99m. Then back in the late 1990s, early 2000s, PET manufacturing kicked in. And this is a case where taking or taking oxygen-18, turning it into an element, fluorine-18, then combining that through heating and cooling into a new molecule FDG, that the FDA rightly said, that's not practice of pharmacy compounding. You're not mixing a cream and an ointment together. You're literally manufacturing a new compound. So we need a revised standard. That standard, though, doesn't necessarily apply to what you do for an ophthalmic drop or a long-lived agent. You can't do a two-week sterility test on a product that only exists for six hours. And so there's a lot of these issues that came in where at the end of the day, the agencies and industry are passionate about quality products safely on time. And so trying to manage all of those things together, there is a section of the regulations that's called Part 212. Part 212, if you hear us refer to it, relates to the standards that the FDA put in place in conjunction with the industry to have reasonable ways to apply GMP into this environment of short-lived isotopes. One step further than that is going into what's called Part 211. And Part 211 is what's now being really applied for manufacturing for therapeutics because, and for a whole host of reasons, these are much higher energy emitters. They last much longer. The PET manufacturing compounds, these have a 2-hour half-life. If something goes horribly wrong with a spill in that facility, just close the doors for a day and come back the next day and it's almost all entirely disappeared. Whereas if you've got something with a 10-hour half-life or a 10-day half-life, you can't just close the door and come back the next day and expect it to have disappeared. So there's a lot of other constraints that kick in. You do need more shielding. You need more infrastructure. You tend to have about sort of going up to a 15,000 sq ft facility. You do need to be absolutely militant and vigilant with line clearance, with all your protocols for how you actually operate the facility. And so if you go sort of from left to right on the slide in terms of regulation, the energies you're trying to shield, facility size, the complexity increases as you go forward. And there are different regulations that kick in. Practice of pharmacies for previously approved products that you're combining. There are some products approved in this fashion so that any one of the 400 or so nuclear pharmacies in the U.S. can make it on a daily basis. Part 212 allows, again, daily basis about 110 GMP facilities that produce these products. And they can distribute them same day. They do every day for about 3 million doses. Larger facility, thicker shielding. And now it's been the growth of the therapeutics. So again, when we talk about expenses and problems, people say, well, isn't it a problem to manufacture these compounds in the therapeutic environment? My answer is no. It's an expense. We need to invest in the facilities, get them up to speed, and they are being built and being rolled out. For Perspective Therapeutics, we believe in both building and partnering. We have our own facility that's making product in Iowa that's distributing for our clinical trials in the Midwest. We just announced recently we purchased a facility in Somerset, New Jersey. The intention of that is to use certain products for the East Coast of the U.S. for distribution. Some of the longer-lived agents for imaging, for example, can then be flown out of that facility across the U.S. We do rely heavily on partners, the CDMOs that have established themselves. There are four competing commercial chains of CDMOs that regularly are producing product and are investing in infrastructure to produce product. Most of these can be upgraded for Lead-212 commercial production in the same way that they're being upgraded for actinium production as well. We actually think it's important with so many products coming out, and again, it's not a veiled brag alert. This is a brag. Our products keep doing really well, and we keep having to find ways to kind of increase our capacity and roll things out. The nice thing is that we can do some of that ourselves and some of that with partners as they get rolled out. What does this facility look like? From the outside, it looks like a standard industrial building, but you go inside and you've got these massive bits of equipment. These are designed to be cleanable, but they're also being designed to shield. Inside these doors, you've got 4 inches of 4 inches thick of lead that can actually go and use to be shielded the internal environment. You've got an 8-inch-thick piece of lead paint glass. All these things, again, to design are designed to protect the operator from the product they're trying to distribute and put out. It takes a year or two to build these sites. They have to be able to handle 70,000 tons of lead. And so incredible sort of reinforced floors and a lot of infrastructure, but once you build it, it lasts for quite a while. The facility that we purchased from Lantheus was previously used for I-131 for Azedra. And we knew going into there that a facility that could handle I-131 could just as easily handle Lead-212 and provide us with sort of three operating suites that we can actually use to kind of create product on a daily basis as we go forward. We've also heard various people say that centralized production is truly the only way to go. I would argue that any modern distribution theory, any modern supply chain theory, says a distributed network is always better than a single point of failure, a single point of distribution. That's just as important for radiopharms as it is for any other product you can think of. Multiple points of manufacture, if you look at these sort of population density heat maps of the U.S., you see kind of how do you distribute a product, especially with a short distribution radius. So if you can, you know, send a person in a car eight hours in one direction, plot out how far can they go in a day, and then the next day they drive back. That's good for clinical trials, but it's not good for full-scale commercial. That's really where we're trying to move in the field and move things up. The nice thing about a network, there is no single point of failure. As Novartis has learned last year, they need to have more than one point of failure as well, or one point of potential failure. So across the industry, we're all investing in multiple manufacturing distribution facilities that can roll things out. There's, you know, I'd like to say there's nothing new under the sun. So, you know, we're not reinventing anything for Lead-212 distribution. There are facilities and networks that have been designed historically to actually roll out products like this. When I first got into the field in PET in the late 1990s, there were a few academic sites, and then the FDA kicked in and said, well, we need to regulate what's happening on a commercial basis for distribution. In 2004, we dug into the archives and pulled out, this is a distribution map of FDG facilities that could supply product across the U.S., and there's 41 of them back in 2004. In 2014, there were 78, and they started to fill in because we're not actually trying to get doses to every patient in the U.S. We're trying to get doses to every cancer center in the U.S. It's a different logistical challenge. We're not trying to get it to a CVS. We're trying to get it to a cancer care center. And if you focus on that, your actual distribution becomes a lot easier. If you look at what happened this year, we've got about 101 GMP commercial sites. In fact, every day in Seattle, they make FDG and fly it to Alaska. So if you're a cancer patient in Alaska, you do get an FDG scan, but it's flown into you. So a combination of air and ground, you can actually cover the U.S. very, very well, and there are multiple competing commercial networks that do provide this. The nice thing about these facilities is an awful lot of them have the ability to retool, scale up, modify what they have in order to allow for the Part 211 compliance and not the 212 compliance. And so there's a lot of misnomers out there, but what do you need? And the answer is, we need to make sure the investments are there to deliver a safe, effective product to people and really roll it forward. So in this map, we've identified you know the two sites that we now currently own and what they can cover with during a clinical trial phase. As we get to commercial, we need to fill in. We're going to rely on our CDMO partners and our own facilities to provide product across the US. You can probably tell where our major, you know, sort of areas of interest are and really rolling things out. But again, you start to overlap. And as soon as you start to get overlap, that means you get network effect. And what's really exciting here is that we're getting so much demand on the clinical side. Dr. Puhlmann is screaming at me saying, I need more manufacturing sites up because I got so many patients. Well, we only have so many patients we can roll in the trial anyways. So it's always this tension of really figuring out if we can only put eight patients into a trial, we're not going to open up eight manufacturing sites and 120 clinical sites. We're trying to adjust real-time for what we're doing. One of the other things we hear is that Lead-212 is hard to get. And just to what rather than oversimplifying the process, the easiest, cheapest, most effective way to ever make an isotope is called doing nothing. Take a bunch of precursor and do nothing. Wait one day, it turns into something else. And if you do that regularly, I guess medicine's called watchful waiting, which is another code for doing nothing. But if you just wait, it will turn into the next element. And so we can supply and stockpile Thorium-228 and keep this on hand. The 2-year half-life means we need quarterly you know distribution of Thorium-228. If we do nothing, it turns into Radium-224 that we can purify and separate. And we can ship that then to the CDMO sites. Once it reaches the site, if we do nothing and just wait a day, we can get daily production of Lead-212. So doing nothing involves, you do have to do some purification separation. But if we calculate the number of doses that we need, for example, we need 100,000 finished doses per year of Lead-212, we can start with a 10-curie stockpile of Thorium-228. If you have it sitting there, all you have to do is just wait. Every 2 weeks, you can pull off your Radium-224. Every day, you can pull off your Lead-212. So we do have a lot of resiliency in the supply chain that we think is quite a luxury for us. And it comes down to how we actually pull it off. The separation is very straightforward. It's a chromatography column. And so if you load your isotope then onto that column and you wash through any new element that's been produced that if we did nothing, just sat there, it grew in, we can wash it off every day or wash it off every two weeks. And so these washes are obviously done in a controlled GMP environment. You validate everything that you've put in, everything you've pulled out. And there's a lot of rigor that goes around purifying and proving what you have. But we have the luxury of not requiring massive capital equipment to actually go and move things forward. In contrast, and again, I'm not trying to, I'm just trying to put a spotlight on what happens. So if you're trying to make Lutetium-177, you do need a reactor. There are a few different ways you can actually produce it. And depending on your starting material, you're either going to start with Ytterbium-176 or Lutetium-176. And again, you're trying to think through exotic isotopes and parents and slightly unstable precursors. So you have to find a way to make an exotic precursor and then irradiate that and produce your product. You can do this. It's a fairly capital-intensive manufacturing that happens and needs to happen for just-in-time supplies. And you do run a risk of global shortages. Again, this isn't a problem. This is an expense. This can get fixed with a lot more money in terms of increasing the capacity. The same thing with Actinium-225. We encourage people to look at some articles that were published recently by Richard Zimmermann. And if you need the, you know, any of these articles, we can, you know, talk to Annie. We can point you towards them. But there are many, many ways to actually make Actinium-225. But the common theme is that a lot of them require a lot of capital equipment. So we're not in the business of investing in massive capital equipment. We're in the business of developing drugs. And we like a very elegant Lead-212 solution. You can do gamma irradiation to make Actinium-225. You can do proton irradiation. You can do direct production through spallation. So a lot of really cool things for nuclear chemists. But at the end of the day, there are many, many ways to get there. It requires an awful lot of money and really intense bits of capital equipment. So that's one of the things there. We're thankful we don't have to worry about that because if we take a generator or a bunch of Thorium-228 and do nothing, it naturally just turns into the element that we're looking for. There's, if we kind of move forward here, we can actually then stockpile. And again, we really want to say, we have lined a site on an awful lot of Thorium-228. We've identified 6 sources around the world. We know the Department of Energy keeps quite a bit on hand. It is a waste product from other manufacturing processes and from mining things. We've tried getting people to pay us to take their waste from them, but they're not buying that one. We have to procure the Thorium-228 on its own. But we can stockpile it. And that's what gets so interesting about really taking risk out of the supply chain. There is a question that the daughters from Actinium-225 don't redistribute. I don't think that's been proven by anything so far that we've seen. I think if Actinium-225 stays in the tumor and microenvironment, it's going to kill off and damage the TILs and impair the ability of the body to repair itself. If it does redistribute and move around the body, you then have a risk of actually going to other tissues. And so at Perspective Therapeutics, we don't like this issue of daughter toxicity. We think that, yes, there are some slight convenience factors that Actinium-225 has, but we feel that the trade-off for patient safety is absolutely worth it. We will always take patient safety over convenience. If we look at you know what's happened with the formulations, again, there's problems with how you actually manage the stability of your formulation. A pure Actinium-225 labeled conjugate, if you just do nothing, will actually turn into spontaneously into a whole bunch of other isotopes that then have each of their own biodistribution. And so there's nothing you can do with this solution that you're trying to inject into a patient. If you try and filter it or chelate or do something special to just pull off all the daughters, you then have a new drug product. And so there's a lot of challenges to actually produce a product where you don't know if the daughters will have an impact. So we like the fact that it's a very pure pure decay chain. We also know that every time that Actinium-225 releases an alpha particle, that it breaks every chemical known chemical bond. It will always jump out of the chelator, and the daughters will always be free-flowing in the patient with the chance of redistribution. Some of them may stay in the tumor microenvironment. Some of them may leave. But a 46-minute window for something like sodium, any biochemistry person will tell you that's going to start moving around the body with its own biochemistry. The other thing in terms of, as we think about dose rate, you know and sort of what happens, if we look at days post-injection here, which actually corresponds to half-lives, so how much of the activity curve goes in here? And so if we look at some of the imaging studies we've seen with actinium and its daughters, that's all done within the first week, but that's only you know less than 50% of the energy is even sort of gone at that point. At the 10-day half-life, you need to think about what's happened with everything over the entire series. 10 half-lives of Lead-212 is 3 or 4 days. So it does make a big difference for when do you need to worry about the patient, when do you need to worry about the patient's bio-waste, when do you need to worry about how the patient's being treated in a hospital. In Europe, for example, they do want to segregate all bio-waste for 10 half-lives. And so the amount of volume that bio-waste created in a patient with Actinium-225 is quite extraordinary, and the hospitals do have to hold that completely until decay. So again, 100 days for every single patient's worth of bed linens, urine, stool, everything has to be kept and segregated. So if things get successful, we like the ability to outpatient real-time, short-acting half-life agents make it more convenient for a patient, but clinically, hit the tumor hard and fast and then disappear. And that's really what we like about where some of these shorter lived agents are going. These slides will be posted later on. So just for the sake of time, as a general corporate update, we're really excited about where we've come, and we're even more excited about where we're going. In 2023, we were able to close this merger between Viewpoint Molecular and Isoray. We've completed dosing of interim results in a compassionate use program. We initiated phase I studies for VMT-α-NET and VMT-01 in melanoma, two different drugs, each with composition of matter IP. We filed a new composition of matter for our FAP asset. We're really excited to show those images today, not just in a human seeing where it goes, but you also know that the image you saw is going to perfectly predict where the Lead-212 energy should go. And so if you can actually have a very, very clean way to target new kinds of tumors, and with our other press release this morning, doing that in some cases in conjunction with checkpoint inhibitors, you really get transformational oncology. And that's really where we're trying to go as a company. We did announce a strategic partnership with Lantheus. They invested cash into us. We bought a facility from them. They have some rights to negotiate on our programs. They're a terrific partner to deal with. They're the largest player in the imaging space, and they know how to run CDMO networks. I think they have about 55 contract CDMOs that make PET agents for them on a regular basis in the 212 environment. We do expect to complete the divestiture of our brachytherapy business unit. That should be closing in this half. We also expect then our VMT-α-NET compassionate use data to be coming out in June. Not our data, but the investigator, Dr. Sen, has told us she intends to present the whole data set at the SNMMI conference. For those that watch carefully, the abstracts for that will probably drop in May. We're really looking forward to seeing what that looks like. That's more of a real-world evidence environment that we think you know does tell us an awful lot about what we could expect. We're also going to expect, we've tried to be as transparent as we can. We do actually. We showed, we think, some very strong safety data this morning. This is where we are to date. We're not seeing anything showing up that's causing concern for safety for either program. But we will be talking about safety and efficacy in the third quarter of this year. So an awful lot here. Really appreciate everyone's attention, but I want to make sure you have a chance to ask questions as well. So with that, I'll open the floor to any questions out there. And we have some mics moving around. So let's start over there. Yep, start at the front here. Hey, Robert Burns, H.C. Wainwright. Three from me. So you know the preclinical you'd showed, the preclinical data you showed for 359 was generated in the HT1080 model. And I know the 2286 data that you compared it to was done in the HEK-FAP cell lines. So I was curious if you evaluated 359 in HEK-FAP so we could do a more apples-to-apples comparison to 2286 and more importantly, PNT6555. So that's a really good question. Highly technical. So the difficulty in doing that is that the HEK293s that they used for that study, it's a you know, it's a single clone. So the ability for us to be able to do true head-to-head against that in the preclinical setting is really tough for us to do. We would have to have access to that exact clone. Okay. Just Just given the time, I'll give you one question at a time first. So it's sort of Ted with a question at the back. So I had a couple too, but one from Michael. I really appreciated how you were showing the importance of imaging during discovery. That was to graphically see that really, you know, illustrates how you're able to do that. My question was really on with this optimization for linker chelator. Do you always use the same chelator? And then are the modifications really more on the linker side? And are they different linkers or are they different lengths? How do you maybe tell us just a little bit more about the components? Sure. So first off, thank you for, you know, for the comment about the imaging. Second, I would say that, you know, there's lots of complexity in linker chemistry that can be explored. And we've found, you know, if you look at the compositions of matter, we've found these PEG linkers to be particularly effective. In some cases, addition to the chelator alone can have a big impact on the PK properties of the molecule, binding, internalization, and things like that. But there's lots of complexity to explore in linker chemistry. One, yeah, the key thing about the chelator that differentiates it is not only, you know, faster radiolabeling with Lead-212, more stable Lead-212, but also the key there is stability of the Bismuth daughter in the Lead-212 Bismuth decay series. So that gives you, you know, gives you better confidence that you're going to deliver radiation to the tumor microenvironment. Is there any question there? Hey, it's Michael Schmidt with Guggenheim. Just a high-level question on the tumor-to-kidney ratio. I was just wondering how you think about that for Lead-212 versus other radioisotopes. What's the flexibility there in terms of the safety concerns? I think that no one will dispute the fact that alphas or betas hitting a tumor is what we want. Alphas and betas hitting healthy tissue is unwanted. We really need to get this best as we can. What's extraordinary about the FAP images, for example, is you saw only tumor and almost nothing else. On the neuroendocrine side, we've tuned things and we can show you some preclinical work that shows by tweaking what we're trying to do, unlike DOTA and DOTAM and DOTATOC, we're not at a 1:1 tumor-kidney ratio. We go up to more like 8:1 or 10:1 in animals, right? Animals, as we know, you know, they don't pay and they're not grateful and they don't scale the same way. We have to do the work in humans and see how it pans out. You want. Thank you for hosting us and thank you, congratulations on the collaboration with Bristol Myers on adding the PD-1 to the melanoma program. So I guess it's a two-part question. Number one, how about adding PD-1 to neuroendocrine tumor? And number two, how about adding CTLA-4 to melanoma program because we know that works? Very good question. So first of all, I think we all agree melanoma is a model disease really for immune checkpoint inhibition. And as such, you know, we're going in the moment into the melanoma indication to really try to understand, does the principle, you know, can we actually provide proof of principle in this indication? If we see and can actually replicate what we are demonstrating in the animals, if we see this in humans, then obviously it will open up a whole slew of new indications where we can go, you know, if you look, for example, nivolumab or the pembrolizumab PI, you see, I don't know, over 20 indications in the moment. I think 26 indications for pembrolizumab. These are all potential targets you could actually go into. Not only that, you know, obviously neuroendocrine could be a potential next one, but they also, you know, in the moment already report that potentially you can make a cold tumor. You can actually transfer or transform a cold tumor into a hot tumor potentially with a targeted ready pharmaceutical. So that, again, would open up a tremendous amount of new opportunities. So the answer is yes, we would be interested in expanding the place. Regarding your second question, CTLA-4, of course, is a little bit more toxic. And we've seen it doesn't really make a difference, at least in the animal models, whether you combine it just with PD-1 alone. Whether this all translates into the human space, we don't know yet. Yeah. Good. Sorry, Justin. Thanks. Justin Walsh with Jones Trading. I've heard a lot of the folks who are going after FAP with beta therapeutics playing up the crossfire effect, given that it sort of preferentially will target the stromal cells. So just curious about your thoughts on that? So that's a great question. And so first off, you know, thanks to our colleagues from India for, you know, the opportunity to be able to do these first images that show us the kind of accumulation and retention that we get in the tumor microenvironment. Great group, Ishita Sen and her team there. There's, you know, there is some rationale for the idea of, you know, the stromal cells being distant from the cancer cells in the tumor microenvironment, that if that was the case, that, you know, maybe a longer-range beta might have a better chance at reaching the tumor. But we don't really know that to be the case, first of all. So in some cases, from doing immunohistochemistry, for example, we can see where the stromal cells are actually, you know, intercalated into the cancer cells in the tumor microenvironment. So if you have stromal cells that are adjacent to the cancer cells, you'll see the same kind of effect. So there's more to learn there. There's certainly some argument for longer range if the stromal cells are far away. But I think there's more research that needs to get done for us to be able to know that for certain. Great question. Question here. Hi, this is Kaveri from BTIG. Thanks for taking my question. I guess my question is on the checkpoint inhibitor combination. How are you thinking about the effect of radiopharmaceutical on immune cells, including the infiltrating T cells? And because of that, what kind of regimen you're thinking of, your dosing strategy, will you be using checkpoint inhibitors kind of subsequently or you plan to use them together? Very insightful, the question. So let me take it a little bit back. Obviously, we do know that, you know, not all alphas, at least our hypothesis is that not all alphas are being treated equal, certainly in the tumor microenvironment. In order to really have an immune-stimulating effect, I think the ideal radionuclides that you want is something that goes in, releases a lot of these neoantigens, and then essentially dissipates. Because then the immune system moves in, the APCs take up all the neoantigens, stimulate the effector T cells, which then either do their job locally at the tumor site or then move into the local lymph node and then propagate as well. So you do want to have basically a very short-acting alpha. And I think Lead-212 may actually be a perfect alpha emitter for this case. What was your second question? Just wanted to get some sense on the strategy. Are you planning to? Yes. Yeah. Sorry. Yeah. It has been shown that ideally you go in first with an alpha or a radiopharmaceutical and then you add the checkpoint inhibitor. And that's what we are planning to do as well. We're going to have a staggered approach for the first cycle. Obviously, once you have checkpoint inhibitors in the system with a long circulating half-life, they have a 22-26-day half-life for pembrolizumab and nivolumab, then it doesn't really matter because you always have a circulating level for subsequent doses. So for the first dosing cycle, we will have a staggered approach. Sorry. Question, Jeff. Just a question on your pretargeting approach, which I think is really promising for mitigating some of the issues around monoclonals in the long circulation half-life. But then the question becomes, how is a radiopharmaceutical then differentiated from an ADC? So can you speak to sort of how you think about maybe target selection or are there aspects strategically opposite the ADC field? There's a lot to unpack there, but a really great question. I think that, you know, the basic difference between the pretargeting approach and an ADC is the ADC, you know, has the warhead conjugated to the antibody. It has to circulate through the body. You know, it has to get that drug inside the cell with a concentration that, you know, can mediate the effect that is intended, you know, whether it's a cytotoxic or it's, you know, an inhibitor. The difference here is that we let the antibody circle around cold with, you know, no real biological or pharmacological effect. And then we can send the radiation in very quickly. And the mechanism of action is different as we, you know, as we talked about earlier today. It's radiation deposited. When it's alpha particle radiation deposited in that cancer cell where the antibody is, then it's going to have a high probability of success in lethal toxicity. And maybe to add to your question, Jeff, ADCs show a lot of systemic toxicities, unfortunately, because to a certain degree, you know, if you bind the toxophore too stably, basically, onto the antibody, it diminishes the activity. So you do want to have a little bit dissociation, hopefully in the tumor microenvironment, to have a really optimal dosing effect. So you do see systemic toxicities with the ADCs, whereas with the pretargeting, I think we have a system where we probably can eliminate a lot of this systemic toxicity upfront. And that's really the exciting part for me. Sorry, one question there. Then we'll have to shut it down. Otherwise, I'll get kicked out of here. Yeah. Thank you. I really appreciated the discussion on the dose. And I'm wondering how well, from the Lead-203, you can predict the absorbed dose, like in grays in the tumor, and how you think that might compare to Actinium or Lutetium? Lots to unpack there also. But I think the key thing about Lead-203 is that it has a, you know, nuclear half-life that's long enough so that you can take multiple images of the, you know, the drug in the tumor microenvironment and other organs over time. That gives you the ability to be able to, you know, the area under the theoretical area under the curve that we showed on some of these slides, that Lead-203 allows you to do that with an elementally identical agent. So it's about as ideal as you can get from making those kinds of predictions about what's going to happen with Lead-212. And if you look at our paper recently, now with the group from, you know, our colleagues from Technical University Dresden, we showed that not only can we do that before patient imaging with lead-203, develop a dosimetry plan, but we can also image the lead-212 directly, you know, with pretty high efficiency using, you know, standard SPECT/CT imaging. And so that gives us this post-therapy dose ability to confirm what we thought when we made the predictions based on lead-203. So it's a nice example of this, you know, elementally identical isotope pair for answering those kinds of questions. Super helpful. Thank you. I want to thank everyone. We wanted to do an Analyst Day in lieu of an investor, you know, sort of earnings call. I think earnings are less relevant in our space right now. So as relevant, we'll come out and host Analyst Day and Analyst calls and follow up that way. We're pretty accessible. So please reach out for further questions. We can go further. I want to thank the NYC for hosting us and Dr. Wahl for coming in and speaking as well. We'll be around after us for questions as well. But thank you again for coming.