All right, so we're going to go ahead and get started. I'm Stephen Willey, one of the Senior Biotech Analysts here at Stifel. I'm glad to have with us in the next session is the CEO of Perspective Therapeutics, Thijs Spoor. Thijs, any opening comments you want to make before we get into Q&A? And then maybe just a quick overview of the Perspective story and kind of how you view yourself within kind of the radiopharma space. Sure. Thanks, Stephen, and thanks, everyone, for coming in today, and Stifel for hosting us. So we're in the radiopharmaceutical space, all puns aside, the hottest sector, we think, in oncology right now. It's really a dynamic environment for radiopharms, especially for those of us that are able to actually really differentiate on drug development and how that relates to distribution. Radiopharmaceuticals give the opportunity for instant gratification. You can hammer that tumor right out of the gate and get an immediate impact on the tumor, on the tumor microenvironment, and have an immediate benefit to those patients if you get your design right. And we have the exquisite ability to actually design a drug, see what we treat, treat what we see. We can use actually the exact same molecule to actually see if a patient should or could respond to therapy. By innovating on innovative structures, composition of matter IP, we do it in a really, really exciting way. OK. So I think oncology, specifically in the last kind of few years, has been characterized by a lot of novel emerging modalities, whether it's next-gen antibody drug conjugates, T-cell engaging bispecifics, et cetera. Where do you see radiopharma kind of fitting into the overall oncology therapeutic landscape? So it's a great question because radiation has been used for decades now in treating cancer. And if you've seen some of our previous corporate stuff, we refer to the concept of treating cancer from the inside out. I think external beam has its limitations. If you know exactly where the tumor is, and if it's only one tumor, external beam can be great, surgery is great, identify the tumor, take it out. If you know what the tumor looks like on its surface, then that's where radiopharms and all targeted therapies actually get a lot more interesting. Targeted therapies means just that. If you know what it looks like, send the drug only to that tissue that's expressing a receptor. With your choice of targeted therapies, ADCs have done some really interesting things for looking at kind of releasing a payload with some sort of, I call it, deferred gratification. Whereas what's nice about radiopharms is you get instant gratification. It's a very unsubtle approach. It's going to smash that cell physically. It's going to damage it physically, acutely, and not require derivative downstream effects of toxin for release incorporation and some other sort of issues that way. But at the end of the day, cancer biology is so tricky. You need a lot of different things. There's very few cases where it's a one-size-fits-all or one approach is curative, except if it's really early and you can kind of cut something out discreetly. OK. So you're specifically focused on using Lead-212 as a therapeutic isotope. Can you maybe speak to some of the key differences of this relative to some of the other commonly used isotopes that we see out there, Lutetium, Actinium? And maybe kind of speak to that in terms of half-life, what you perceive the risk of off-target toxicity to be, and then also maybe on the supply and production cost side. And I guess maybe in that answer, you can frame how you believe those things potentially serve as advantages for you. Sure. So in theory, we're isotope agnostic. I think every radiopharm company says they are. We really are in love with Lead. And there's a whole bunch of reasons as to why we like that, and so no particular order. What's really interesting about Lead has got an elemental twin, Lead-203. So that means that the same composition of matter can be used to diagnose and to treat. Lead-203 is a gamma emitter. And so all it's going to do is provide you a location data over time of where the drugs go if injected into a patient. You can follow up the very next day in the patient with the Lead-212 version, which will then sort of deliver that metal to the tumor. When you think about the various isotopes that are out there, and I'll just zoom out, everyone's heard of Iodine-131, really interesting beta, but chemically difficult to work with. And free iodine will go to salivary and thyroid and other off-target issues. Delivering iodine directly to a tumor has had impact. There are some approved products that have been used. But the goal in nuclear chemistry and within nuclear pharmacy was how do we get a better isotope? And so lutetium came out as having some advantages of being a beta, similar half-life, and the ability to chelate it. Chelating means you can actually put it inside a metal cage and drag it and force that metal to get to a tumor without a risk of something called deiodination, meaning you don't just have a free release of the radioactive element, and the element is only dragged to the site of interest. Lutetium has had some great commercial success with Lutathera and Pluvicto. Lutetium has a longer half-life that allows for overnight distribution, and it's had some clear benefits. But the scientific community wanted more. And to try and get more, they said, well, let's go from beta to alpha. Betas are 1/8,000th the mass of an alpha. It takes about 1,500 betas to kill a cancer cell. It takes one alpha to kill a cancer cell. So Actinium was a way to really add a lot more power to that same payload. But it comes with some pretty interesting trade-offs that are perceived supply chain issues and perceived safety issues in the patient. So when we actually looked at getting into lead therapeutics, what we liked was that we could chelate lead. We had the elemental twin. And by having a shorter half-life, you then actually have the ability to have a really fast, hard punch. So hit the tumor hard and fast, and then disappear. And don't let anything interfere with the body's immune system coming in and trying to sort of recover and help that patient's body recover. There's a lot of important concepts in there. The other one that was initially not well understood and is getting a lot clearer in the scientific community is what do you do with the downstream effects? So you're going to have an isotope that's going to decay. It goes from a parent to a daughter. What happens to that daughter? If that daughter leads the way to another daughter, to another daughter, to another daughter, if all those daughters have off-target effects, you can then really lower your safety profile of your drug. What we're doing with this drug development is looking at overall therapeutic window. How do we get a safe drug that actually has a wide enough gap between its effective level and where it has safety issues? If you have to account into daughter kinetics as well, it gets really tricky. With actinium, you need to guarantee that all four daughters are staying in the tumor microenvironment or going somewhere that's safe. There's a lot of discussion and debate about that that we don't have time to cover here. But then you go a step further, which is really with actinium, how do you actually look at getting it into the manufacturer and into the patient? So when we look at isotopes across the board, can you get it? Can you turn it into a drug? Can the drug be safely given to a patient? And will all the daughters afterwards stay where you want them to be at tumor and not in other parts of the body? And so what's really great about lead-212 and the fact that we invented a proprietary chelator, it's a composition of matter on a chemical structure that holds that lead there and it holds its daughter. So the chelator we have leaks less than 2% of the bismuth daughter. DOTA, DOTAM, the generic chelators leak about 25%, 30%. You need to make sure that your isotope is on target and all daughters are on target as well, or you know where they've gone. There's a classic joke in nuclear medicine that says, you know, it's 11:00 P.M., do you know where your daughters are? And that's a reference to when you actually have that decay, if it breaks open from the chelator, those daughter metals have their own biochemistry and are going to do something different in the body and may give unintended consequences. And that's really what we're trying to solve for sort of across the board. OK. I know that you've also talked about being, I guess, isotope agnostic. I'm not sure if you're scaffold agnostic, but I know a lot of the work that you're doing now is primarily focused on using peptides as a targeting ligand. And this is kind of more in line with what we've seen from the radiopharm space, I think, because you can kind of use a peptide to get both rapid tumor penetration, but also excretion as well. But I guess the consequence of that rapid excretion is usually diminished target engagement. And so what are the implications of combining a peptide with a short circulating half-life to an isotope with a short half-life? And does that kind of create any unique challenges for you on the PK/PD front or impose any kind of limitations on the types of tumors that you can go after? So I'd actually flip it the other way. And I'd say this gives us actually unique advantages. And so whenever you're looking at your targeting vector and your isotope half-life, you want them to be aligned and to be able to be in sync with each other. If you've got a really long-lived isotope, you need to know everything about where that goes over its entire life. You need to be able to quantify where does every alpha emission go and what happens to the patient. The unique advantage of peptides, if they're the right peptides, is they have really, really rapid accumulation. Within sort of 30 to 45 minutes, you can get complete incorporation of or you can have that peptide leave the bloodstream and either get dumped into the kidney, bladder, or bind to tumor. If you have a targeting vector that takes days and days and days to accumulate, what's happening in those days and days and days? And if the entity is radioactive over the time, you're getting pretty broad systemic exposure to radioactivity and all of the sort of both the parent and the daughter decays. So if you're thinking about antibodies as a targeting vector for, call it a week to sort of finally have its specificity, if that's been radioactive the entire time, you run an extraordinary risk that then the patients can be exposed systemically throughout the whole circulatory system to these radioactive entities. Whereas if you can clear that out of blood within 30-45 minutes, you have the amazing ability to know exactly where the entity is and where it's not. When you think about your radioactive decays, you want to look at area under the curve. And it's really, what is the ultimate fate? How long does it stay in each compartment? So on the imaging side of radiopharms, there's less import as to what happens outside of your discrete imaging window. If it moves back and forth between compartments in the body, no one's really that concerned because these are gamma emissions that are fairly safe. If you have an alpha or beta emitter and it's moving between compartments in the body, there's a much increased chance that something bad can happen, or you're almost guaranteed to get off-target effects. So if you can bind that tumor quickly and have it stay there over its entire life, you can quantify exactly where those alphas are going, where all the damage goes. And so there's two different ways to think about. If you're going to target, have it give a hard, fast punch, have it only go to tumor. If it's not on tumor, have it eliminate from the body as fast and safely as possible. So you think that alignment between the shorter half-lives of a peptide and lead are actually very well suited for each other? I do, very much so, and so if you're going to give a long-lived isotope with a long-lived distribution parameter, that's going to be tricky. I wouldn't give lead overtly with an antibody because it won't have enough time to accumulate by the time it's going to sort of give off all its energy. OK. So I know that there's also maybe some dogma out there that suggests that the selection of the isotope should be informed by the target that you're going after. And so, for example, the short path length of an alpha particle is maybe better suited for those cancers that are characterized by high homogeneous target expression. Do you think that Lead-212 imposes, for whatever reason, any kind of constraints on the types of targets that you can go after? Lead-212 and the Bismuth-212 decay is actually a mixed alpha and beta emission. So if you want to sort of say it, we get the best of both worlds. Most of the energy is really coming from the alphas. And the ability of the alphas to be so neoantigenic on their decay and so violently destructive, and I'm using those words deliberately, because the alpha particle is smashing through and causing double-stranded DNA breaks. It's really playing havoc with that cell, presenting an awful lot of new antigens to the immune system to respond to. We think Lead-212 has some really, really clear advantages along that path. Betas have as a strength and weakness the fact that they travel about 200 cell lengths. If you've got a lot of accumulated sort of radioligand on a tumor, you're going to get a lot more dose to what's adjacent to it. If it's going in the bladder, you're going to get a lot of pelvic extra radiation. If you're going to the lung, you're going to get extra areas. What we've seen with very, very bulky disease, with the initial work we've done in compassionate use work, is that for bulky tumors and for diffuse tumors and metastatic disease, we're getting really, really compelling results with an alpha particle. We don't necessarily think we need to shift to a beta because the alphas have so much more potency. OK. You mentioned the proprietary chelator that you guys are using. How is that different maybe from some of the commercially available chelators, and why is that very well suited for the lead isotope? So I guess if we think about the overall premise, and it's a great question, because if you just ask in isolation, is one chelator better or worse? Is one isotope better or worse? Is one targeting vector better or worse? It really depends once they're all together. The analogy I give, it's like asking what school is best for your kid. And that's going to depend on your kid. And so if we think about the tumor we're going after, and you have to look at the iteration all through between the isotope, the targeting vector, the chelator, all these things together combined. Why we love our chelator with lead is that it puts a neutral charge onto the peptide. And from basic biochem, if you have a charged peptide, you're going to get kidney accumulation that's extraordinary to a neutrally charged peptide. So we like rapid kidney clearance. We want drug to only go to tumor and nowhere else. By actually changing and thoughtfully designing the entire molecule altogether, the targeting vector, the chelator, the isotope, all these things together, how they sum up, you want your best possible biodistribution. And if you can change any of those, what we found consistently is we get much better biodistribution with lead when we use our proprietary chelator. It helps with labeling. It helps with kidney clearance. It helps with binding affinity. And more importantly, it also helps by not allowing daughter decay leakage. OK. Maybe the last kind of lead-related question, and then we'll jump into the pipeline. But the short half-life here also has some implications for production and distribution. So maybe you can talk a little bit about what the Perspective's process looks like right now. How do you think about scaling that process to meet commercial demand? And maybe what's the level of investment that will be needed to eventually get there? Sure. One of the things that we're trying to do is to change the nomenclature a little bit to talk about product shelf life versus half-life, and so with some of the relatively shorter-lived isotopes and drugs, you tend to have a shelf life of up to about 24 hours. With some of the "longer-lived" ones, you'll have a shelf life of up to 48 hours, so really talking about the challenges of either same-day or next-day logistics. In either case, you need to have that pretty close to just-in-time delivery no matter what it is. By thinking about those kinds of shelf lives, the shorter-lived ones lend themselves more to a distributed network, but if you look at publicly what Novartis has been doing, they're building a distributed network for their molecules as well. If you only built one site, you'd probably build it in Indianapolis by the FedEx Dangerous Goods hub. If you had the choice for multiple sites, you'd probably build something on the West Coast, the Midwest, and the East Coast. And that's what Novartis has publicly said they're doing as their US expansion. If you look at Perspective Therapeutics, through our filings now, we've announced we have a site on the West Coast, the Midwest, the East Coast, and also a site in Texas. And any modern supply chain theory says you're always better with a network than a single point of manufacture. Because a single point of manufacture can always be a single point of failure. So when we think about things, our team's got an incredibly broad experience of delivering just-in-time isotopes. We're used to products with half-lives of two to six hours, shelf lives of 12 to 24 hours. And so we know how to bring that product closer to the patient. And on the distribution side, we're not trying to bring drug to every doctor's office and CVS. We're trying to bring drug to every cancer care center. So it's a much easier problem to solve for logistically than it appears to be. How do you get coverage across the whole U.S.? OK. So on the pipeline side, I know that you're going to be presenting some incremental data for your SSTR2 peptide at a conference, I believe, later this week. Correct. So maybe you can just kind of give us a little bit of preview of what that presentation will look like in terms of what's incremental on the patient number front, what's incremental on the duration of follow-up front. Yeah. So coming up at the North American Neuroendocrine Tumor Society conference this week, we'll be presenting some of the initial snapshot of how patients are doing in the company-sponsored dose escalation study. We previously reported out from a dose escalation program, Melanoma, earlier this year. And we really loved the conclusions we drew from there. With the SSTR2 program that's reporting out at NANETS, there'll be two patients dosed at that 2.5 millicurie and seven patients dosed at the five millicurie levels. This is a dose escalation. So we'll be describing those patient demographics at that study. It's not just us, but the collaborators and investigators of the trial will be presenting their results in an oral poster presentation. And they'll be showing what happened to those patients up to a data cutoff time that obviously is sometime earlier than this week. So we'll learn how those patients look like, their demographics, and what's been seen on safety, activity, efficacy, those metrics. OK. I know the safety monitoring committee that oversees that trial gave you the green light to move to cohort three, which I think is 7.5 millicurie. I think you had indicated maybe in your earnings press release that initiation of enrollment into that cohort will occur after some kind of alignment with the agency. Is that just a boilerplate kind of update? Or is there something that you need to agree upon with FDA in order to start that cohort three enrollment? That's a great question. Because if we rewind the clock, what happened is we went to the FDA and asked for a fast-track designation in the post-Lutetium environment, so post-PRT. And they said no. We got a fast track in the pre-Lutetium space. And so to phrase differently, we asked for a post-second line, and they gave us a first-line instead. So that's a great thing for a regulator to do and say that they really are encouraged by what you've been doing. The caveat they gave us was that they said dose at the two and one-half, dose at the five millicurie levels, and then come see us after those first patients are in so that we can review with you and then work with you on the next steps. That's a great feedback to get from a regulator. We've dosed exactly in line with what they've allowed us to do. It was previously agreed and negotiated with them that we would have them review the data with us before advancing to higher doses or going to lower doses, wherever the data takes us. The safety monitoring committee was very excited. They advocated that we also enroll up to an additional 40 more patients at that 5 millicurie dose level. We're quite comfortable with the recommendations they've made for dose escalation. OK. What does the dosimetry data that you have tell you about the TI that's available to you here, and where do you think you might be able to safely push dose escalation to? So we'll have to follow the data, and we'll comment on it once the data comes out. The important thing with dosimetry is that dosimetry data is only valid in the patient that the dosimetry was done in. It's such a personalized assessment. Dosimetry means you actually looked at what's happening in the drug in that patient. And so patients will have different body weights, blood volumes, tumor burden, tumor load, tumor characteristics, renal function, renal clearance. And so any measurement of dosimetry is truly patient-specific for individual patient management decisions. And so we want to be very thoughtful about kind of how we review things. We do care a lot about dosimetry. It may help predict overall risk and overall potential risk for radiation load. But there's a lot that's ultra-personalized. So it'll be really important to see what's happening with safety, what's happening with measurements of activity of the drug. We want to find out if you have a safe and active drug, then you want to keep doing it through dose exploration, escalation, or de-escalation as needed. OK. And I think before you talked about how you can use the same element for both imaging and for treatment. And so I guess in the case of using a theranostic and a therapeutic, given that patient variability, you probably have a greater degree of confidence based upon that imaging data kind of what that treatment experience is going to look like. I think that's a really good word choice you used there, which is greater degree of confidence. Because if you're using different isotopes and different drugs to predict dosimetry, there's going to be inherently some risk of error. So a different metal, a different chelator, a different ligand will all have the risk of potentially different biodistributions. What's nice about our construct is that we use literally the same composition of matter, and so we can look at the in vivo fate of everything given to a patient, see what happens because Lead-203 has such a long half-life over two days to see if that patient the next day received our therapeutic drug, where exactly would those molecules go in the patient, and therefore what kind of impact would have for whatever tissues they touch. OK. So you talked about how the NANETS presentation will be the company-sponsored part of this. I know that there's an investigator-initiated trial with this drug occurring in India. Maybe you can just talk about what you think some of the key takeaways are from that IST data that we've seen to date and maybe how extrapolatable that safety data is to the five millicurie dose that we're going to be getting later this week. Yeah. So we have several investigator-initiated programs ongoing, one in Iowa, the India program, and some collaborators in Europe as well. The data that came out from our Indian collaborators in the investigator-initiated environment looked at a mixture of pre-Lutetium and post-Lutetium patients. These are patients with a different body weight. And so we want to try and learn as much as we can. We're really focused on quality and safety. We want to know everything about these products and programs and anything that may show up. So we do look at things very, very carefully and closely. The patients that were treated in India were, as I said, quite small, and they used a weight-based dosing. We're using a fixed-dose dosing in the U.S.. So there's inherently going to be differences as well as where those patients are with their disease journey. So we think every bit of data is informative. We like seeing the images. We like understanding what's happening in patients. And in any dose escalation approach, we're trying to find out what are these therapeutic limits that we can approach and dosing limits. And so if we think about maximum tolerated dose, it's safe to assume that, for example, in various package inserts, you see that tends to drift towards that maximum tolerated dose. We're in dose escalation right now. So we really want to identify and learn what happens with these drugs in patients. OK. How do you think about the RLT competitive landscape in this tumor type right now? I mean, the competitive density around this target SSTR2, it's pretty high. It's certainly not as high as PSMA. But I think there's 10-plus programs in various stages of development. I think Ratio and Novartis announced some kind of collaboration this morning. How do you think about best establishing differentiation within this space around this target? So with this target, we're looking at therapeutic window. And we really want to get as broad a therapeutic window as possible. This meaning that if for any given efficacy profile, the drug should be safer or flipped around, for any given safety profile, the drug should be a lot more effective. I think the package insert for Lutathera implies a 13% ORR at a defined safety threshold that Novartis is comfortable with. And I think across the field, everyone thinks that we can do better. And so they're trying on a few different metrics. It's an interesting tumor type because it is mostly a homogeneous expression of that SSTR2. And it's a well-understood one. But really, the differentiation where we're applying a novel approach is a novel composition of matter with different biodistribution than what's more commonly used with DOTA or DOTAM. OK. The Melanoma asset, I think you mentioned that we saw some data from that program. I think it was about a month ago. So that data kind of suggested that there might be maybe a bell-shaped dose response curve here. So maybe you can kind of just walk us through that data and some of the biology that you think might explain what's happening here. When we think about a bell-shaped curve versus a straight kind of dose response curve, bell-shaped implies that you're going to get increasing response up to a certain level. Then if you keep going higher, then you don't plateau, but you sort of fall off for a variety of reasons. In the melanoma environment, we're looking at immunostimulatory implications on the body to really drive the therapeutic response. The immune system is a really highly calibrated, intricate system in each patient that's individualized that is also compromised in patients with metastatic melanoma. You've got very fragile immune systems that you're trying to support by giving just enough energy into the tumor to allow the immune system to be stimulated, but not so much energy into that overall animal or human that you actually overwhelm the immune system and the disease goes unchecked. In so many patients that are in late-stage disease, the immune system's constantly at war. That's why checkpoint inhibitors get used so frequently and have been so effective. But they tend to fall off after a period of time. So in the patients that we actually assessed recently, these are patients that the median average number of prior therapies was five, including two checkpoint inhibitors. These patients had failed everything they'd been seeing. Their expected progression-free survival and best possible standard of care would be in that 2 and 1/2 to 4 and 1/2 month range. And at a 3 millicurie dose level, we had those patients doing incredibly well at 9, 11, 13 months post. And one of those patients turned into a partial response. Whereas going at higher levels, it felt like something was happening with the immune system, and it wasn't able to actually then compensate for the disease. And at higher doses, the patients didn't do as well. Where I don't think we got enough sort of credit for is the fact that all three patients at three millicuries are doing incredibly well. They're not living the life that they thought they would have when they came into the trial. Patients progressing, metastatic melanoma, expected PFS of a few months. And that a year out, those patients are doing extremely well. That tells us there's a clear signal. And what's really nice about this bell-shaped dose response curve is that supported by the preclinical work that we've done as well. It's always helpful as drug developers when the preclinical biology and the human results align because it means that as far as you can tell, a lot of your theses are intact. OK. So maybe you can just talk about what are the next steps for this program and when might we expect to hear about another update? Yeah. So we've seen extraordinary synergies in the melanoma mouse model for going into overt combinations with immune checkpoint inhibitors. We have a deal with Bristol Myers Squibb to use Opdivo to avoid stacking of safety issues, you always lower down, so that three millicurie dose where we established a clear safety and efficacy profile, we're lowering that down to 1 and 1/2, and we're actively enrolling patients there. We're also going to be enrolling patients in a monotherapy environment as well to learn more at a few different dose levels, and so next year, we'd hope to tell people about how the patients are doing in that combination environment. Again, a combination of a checkpoint inhibitor plus an incredibly neoantigenic alpha emitter on the animal level is giving extraordinary results that are more than just synergistic. They're incredibly sort of phenomenal results that the NCI has given us additional grants to pursue and study further. OK. Maybe just last question because I think we're over time. But can you just speak to cash runway, what that allows you to execute on here over the course of the next however many months? Sure. So from our last quarterly filing, our cash balance showed $262 million. That gives us runway disclosed until mid-2026. That includes dose escalation and dose expansion on our two lead programs. That also includes dose escalation in our next clinical program, our FAP asset, as well as what we've guided towards building out new manufacturing sites on the West Coast, Midwest, and Texas. And so all those things are captured in that guidance. All right. So we're going to go ahead and get started. I'm Stephen Willey, one of the senior biotech analysts here at Stifel. I'm glad to have with us in the next session is the CEO of Perspective Therapeutics, Thijs Spoor. Thijs, any opening comments you want to make before we get into Q&A? And then maybe just a quick overview of the Perspective story and kind of how you view yourself within kind of the radiopharma space. Sure. Thanks, Stephen. And thanks, everyone, for coming in today and Stifel for hosting us. So we're in the radiopharmaceutical space, all puns aside, the hottest sector, we think, in oncology right now. It's really a dynamic environment for radiopharms, especially for those of us that are able to actually really differentiate on drug development and how that relates to distribution. Radiopharmaceuticals give the opportunity for instant gratification. You can hammer that tumor right out of the gate and get an immediate impact on the tumor, on the tumor microenvironment, and have an immediate benefit to those patients if you get your design right. And we have the exquisite ability to actually design a drug, see what we treat, treat what we see. We can use actually the exact same molecule to actually see if a patient should or could respond to therapy. By innovating on innovative structures, composition of matter, IP, we do it in a really, really exciting way. OK. So I think oncology, specifically in the last kind of few years, has been characterized by a lot of novel emerging modalities, whether it's next-gen antibody drug conjugates, T-cell engaging bispecifics, et cetera. Where do you see radiopharma kind of fitting into the overall oncology therapeutic landscape? So it's a great question because radiation has been used for decades now in treating cancer. And if you've seen some of our previous corporate stuff, we refer to the concept of treating cancer from the inside out. I think external beam has its limitations. If you know exactly where the tumor is and if it's only one tumor, external beam can be great. Surgery is great. Identify the tumor, take it out. If you know what the tumor looks like on its surface, then that's where radiopharms and all targeted therapies actually get a lot more interesting. Targeted therapies means just that. If you know what it looks like, send the drug only to that tissue that's expressing a receptor. And then with your choice of targeted therapies, ADCs have done some really interesting things for looking at kind of releasing a payload with some sort of, I call it, deferred gratification. Whereas what's nice about radiopharms is you get instant gratification. It's a very unsubtle approach. It's going to smash that cell physically. It's going to damage it physically, acutely, and not require derivative downstream effects of toxin for release incorporation and some other sort of issues that way. But at the end of the day, cancer biology is so tricky. You need a lot of different things. There's very few cases where it's a one-size-fits-all or one approach is curative, except if it's really early and you can kind of cut something out discreetly. OK. So you're specifically focused on using Lead-212 as a therapeutic isotope. Can you maybe speak to some of the key differences of this relative to some of the other commonly used isotopes that we see out there, Lutetium, Actinium? And maybe kind of speak to that in terms of half-life, what you perceive the risk of off-target toxicity to be, and then also maybe on the supply and production cost side. And I guess maybe in that answer, you can frame how you believe those things potentially serve as advantages for you. Sure. So in theory, we're isotope agnostic. I think every radiopharm company says they are. We really are in love with lead, and there's a whole bunch of reasons as to why we like that, and so no particular order. What's really interesting about lead has got an elemental twin, Lead-203. So that means that the same composition of matter can be used to diagnose and to treat. Lead-203 is a gamma emitter, and so all it's going to do is provide you a location data over time of where the drugs go if injected into a patient. You can follow up the very next day in the patient with the Lead-212 version, which will then sort of deliver that metal to the tumor. When you think about the various isotopes that are out there, and I'll just zoom out, everyone's heard of iodine-131, really interesting beta, but chemically difficult to work with, and free iodine will go to salivary and thyroid and other off-target issues. Delivering iodine directly to a tumor has had impact. There are some approved products that have been used, but the goal in nuclear chemistry and within nuclear pharmacy was how do we get a better isotope, and so lutetium came out as having some advantages of being a beta, similar half-life, and the ability to chelate it. Chelating means you can actually put it inside a metal cage and drag it and force that metal to get to a tumor without a risk of something called deiodination, meaning you don't just get a free release of the radioactive element, and the element is only dragged to the site of interest. Lutetium has had some great commercial success with Lutathera and Pluvicto. Lutetium has a longer half-life that allows for overnight distribution. And it's had some clear benefits. But the scientific community wanted more. And to try and get more, they said, well, let's go from beta to alpha. Betas are 1/8,000th the mass of an alpha. It takes about 1,500 betas to kill a cancer cell. It takes one alpha to kill a cancer cell. So Actinium was a way to really add a lot more power to that same payload. But it comes with some pretty interesting trade-offs that are perceived supply chain issues and perceived safety issues in the patient. So when we actually looked at getting into lead therapeutics, what we liked was that we could chelate lead. We had the elemental twin. And by having a shorter half-life, you then actually have the ability to have a really fast, hard punch. So hit the tumor hard and fast and then disappear. And don't let anything interfere with the body's immune system coming in and trying to sort of recover and help that patient's body recover. There's a lot of important concepts in there. The other one that was initially not well understood and is getting a lot clearer in the scientific community is what do you do with the downstream effects? So you're going to have an isotope that's going to decay. It goes from a parent to a daughter. What happens to that daughter? And if that daughter leads the way to another daughter, to another daughter, to another daughter, if all those daughters have off-target effects, you can then really lower your safety profile of your drug. And so what we're doing with this drug development is looking at overall therapeutic window. How do we get a safe drug that actually has a wide enough gap between its effective level and where it has safety issues? And if you have to account into daughter kinetics as well, it gets really tricky. And so with actinium, you need to guarantee that all four daughters are staying in the tumor microenvironment or going somewhere that's safe. And there's a lot of discussion and debate about that that we don't have time to cover here. But then you go a step further, which is really with Actinium, how do you actually look at getting it into the manufacturer and into the patient? So when we look at isotopes across the board, can you get it? Can you turn it into a drug? Can the drug be safely given to a patient? And will all the daughters afterwards stay where you want them to be at tumor and not in other parts of the body? And so what's really great about Lead-212 and the fact that we invented a proprietary chelator, it's a composition of matter on a chemical structure that holds that Lead there and it holds its daughter. So the chelator we have leaks less than 2% of the Bismuth daughter. DOTA, DOTAM, the generic chelators leak about 25%, 30%. And so you need to make sure that your isotope is on target and all daughters are on target as well, or you know where they've gone. There's a classic joke in nuclear medicine that says, you know, it's 11:00 P.M., do you know where your daughters are? And that's a reference to when you actually have a decay, if it breaks open from the chelator, those daughter metals have their own biochemistry and are going to do something different in the body and may give unintended consequences. And that's really what we're trying to solve for sort of across the board. OK. So I know that you've talked about being, I guess, isotope agnostic. I'm not sure if you're scaffold agnostic, but I know a lot of the work that you're doing now is primarily focused on using peptides as a targeting ligand. And this is kind of more in line with what we've seen from the radiopharm space, I think, because you can kind of use a peptide to get both rapid tumor penetration, but also excretion as well. But I guess the consequence of that rapid excretion is usually diminished target engagement. And so what are the implications of combining a peptide with a short circulating half-life to an isotope with a short half-life? And does that kind of create any unique challenges for you on the PK/PD front or impose any kind of limitations on the types of tumors that you can go after? So I'd actually flip it the other way. And I'd say this gives us actually unique advantages. And so whenever you're looking at your targeting vector and your isotope half-life, you want them to be aligned and to be able to be in sync with each other. If you've got a really long-lived isotope, you need to know everything about where that goes over its entire life. You need to be able to quantify where does every alpha emission go and what happens to the patient. The unique advantage of peptides, if they're the right peptides, is they have really, really rapid accumulation. Within sort of 30-45 minutes, you can get complete incorporation of, or you can have that peptide leave the bloodstream and either get dumped into the kidney, bladder, or bind to tumor. If you have a targeting vector that takes days and days and days to accumulate, what's happening in those days and days and days? And if the entity is radioactive over the time, you're getting pretty broad systemic exposure to radioactivity and all of the sort of both the parent and the daughter decays. So if you're thinking about antibodies as a targeting vector for, call it a week to sort of finally have its specificity, if that's been radioactive the entire time, you run an extraordinary risk that then the patients can be exposed systemically throughout the whole circulatory system to these radioactive entities. Whereas if you can clear that out of blood within 30-45 minutes, you have the amazing ability to know exactly where the entity is and where it's not. When you think about your radioactive decays, you want to look at area under the curve. And it's really, what is the ultimate fate? How long does it stay in each compartment? So on the imaging side of radiopharms, there's less importance as to what happens outside of your discrete imaging window. If it moves back and forth between compartments in the body, no one's really that concerned because these are gamma emissions that are fairly safe. If you have an alpha or beta emitter and it's moving between compartments in the body, there's a much increased chance that something bad can happen, or you're almost guaranteed to get off-target effects. So if you can bind that tumor quickly and have it stay there over its entire life, you can quantify exactly where those alphas are going, where all the damage goes. And so there's two different ways to think about. If you're going to target, have it give a hard, fast punch, have it only go to tumor. If it's not on tumor, have it eliminate from the body as fast and safely as possible. So you think that alignment between the shorter half-lives of a peptide and lead are actually very well suited for each other? I do, very much so. And so if you're going to give a long-lived isotope with a long-lived distribution parameter, that's going to be tricky. I wouldn't give lead overtly with an antibody because it won't have enough time to accumulate by the time it's going to sort of give off all its energy. OK. So I know that there's also maybe some dogma out there that suggests that the selection of the isotope should be informed by the target that you're going after. And so, for example, the short path length of an alpha particle is maybe better suited for those cancers that are characterized by high homogeneous target expression. Do you think that Lead-212 imposes, for whatever reason, any kind of constraints on the types of targets that you can go after? So Lead-212 and the Bismuth-212 decay is actually a mixed alpha and beta emission. So if you want to sort of say it, we get the best of both worlds. Most of the energy is really coming from the alphas. And the ability of the alphas to be so neoantigenic on their decay and so violently destructive, and I'm using those words deliberately, because the alpha particle is smashing through and causing double-stranded DNA breaks. It's really playing havoc with that cell, presenting an awful lot of new antigens to the immune system to respond to. We think Lead-212 has some really, really clear advantages along that path. Betas have as a strength and weakness the fact that they travel about 200 cell lengths. And so if you've got a lot of accumulated sort of radioligand on a tumor, you're going to get a lot more dose to what's adjacent to it. So if it's going in the bladder, you're going to get a lot of pelvic extra radiation. If you're going to the lung, you're going to get extra areas. What we've seen with very, very bulky disease with the initial work we've done in compassionate use work is that for bulky tumors and for diffuse tumors and metastatic disease, we're getting really, really compelling results with an alpha particle. And that we don't necessarily think we need to shift to a beta because the alphas have so much more potency. OK. You mentioned the proprietary chelator that you guys are using. How is that different maybe from some of the commercially available chelators? And why is that very well suited for the lead isotope? So I guess if we think about the overall premise, and it's a great question, because if you just ask in isolation, is one chelator better or worse? Is one isotope better or worse? Is one targeting vector better or worse? It really depends once they're all together. The analogy I give, it's like asking what school is best for your kid. And that's going to depend on your kid. And so if we think about the tumor we're going after, and you have to look at the interplay throughout between the isotope, the targeting vector, the chelator, all these things together combined. Why we love our chelator with lead is that it puts a neutral charge onto the peptide. And from basic biochem, if you have a charged peptide, you're going to get kidney accumulation that's extraordinary to a neutrally charged peptide. So we like rapid kidney clearance. We want drug to only go to tumor and nowhere else. By actually changing and thoughtfully designing the entire molecule altogether, the targeting vector, the chelator, the isotope, all these things together, how they sum up, you want your best possible biodistribution, and if you can change any of those, what we found consistently is we get much better biodistribution with lead when we use our proprietary chelator. It helps with labeling. It helps with kidney clearance. It helps with binding affinity. And more importantly, it also helps by not allowing daughter decay leakage. OK. Maybe the last kind of lead-related question, and we'll jump into the pipeline, but the short half-life here also has some implications for production and distribution. So maybe you can talk a little bit about what the Perspective process looks like right now. How do you think about scaling that process to meet commercial demand? And maybe what's the level of investment that will be needed to eventually get there? Sure. One of the things that we're trying to do is to change the nomenclature a little bit to talk about product shelf life versus half-life. And so with some of the relatively shorter-lived isotopes and drugs, you tend to have a shelf life of up to about 24 hours. With some of the "longer-lived" ones, you'll have a shelf life of up to 48 hours. So really talking about the challenges of either same-day or next-day logistics. In either case, you need to have that just-in-time delivery no matter what it is. By thinking about those kinds of shelf lives, the shorter-lived ones lend themselves more to a distributed network. But if you look at publicly what Novartis has been doing, they're building a distributed network for their molecules as well. If you only built one site, you'd probably build it in like Indianapolis by the FedEx Dangerous Goods hub. If you had the choice for multiple sites, you'd probably build something on the West Coast, the Midwest, and the East Coast, and that's what Novartis has publicly said they're doing as their US expansion. If you look at Perspective Therapeutics, through our filings now, we've announced we have a site on the West Coast, the Midwest, the East Coast, and also a site in Texas. And any modern supply chain theory says you're always better with a network than a single point of manufacture, but that single point of manufacture can always be a single point of failure, so when we think about things, our team's got an incredibly broad experience of delivering just-in-time isotopes. We're used to products with half-lives of two to six hours, shelf lives of 12 to 24 hours, and on the distribution side, we're not trying to bring drug to every doctor's office and CVS. We're trying to bring drug to every cancer care center, so it's a much easier problem to solve for logistically than it appears to be: how do you get coverage across the whole U.S.. OK. So, on the pipeline side, I know that you're going to be presenting some incremental data for your SSTR2 peptide at a conference, I believe, later this week. Correct. So maybe you can just kind of give us a little bit of preview of what that presentation will look like in terms of what's incremental on the patient number front, what's incremental on the duration of follow-up front. Yeah. So coming up at the North American Neuroendocrine Tumor Society conference this week, we'll be presenting some of the initial snapshot of how patients are doing the company-sponsored dose escalation study. We previously reported out from a dose escalation program, Melanoma, earlier this year. And we really love the conclusions we drew from there. With the SSTR2 program that's reporting out at NANETS, there'll be two patients dosed at that 2.5 millicurie and seven patients dosed at the 5 millicurie levels. This is a dose escalation. So we'll be describing those patient demographics at that study. It's not just us, but the collaborators and investigators of the trial will be presenting their results in an oral poster presentation. And they'll be showing what happened to those patients up to a data cutoff time that obviously is sometime earlier than this week. So we'll learn how those patients look like, their demographics, and what's been seen on safety, activity, efficacy, those metrics. OK. I know the safety monitoring committee that oversees that trial gave you the green light to move to cohort three, which I think is 7.5 microcurie. I think you had indicated maybe in your earnings press release that initiation of enrollment into that cohort will occur after some kind of alignment with the agency. Is that just a boilerplate kind of update, or is there something that you need to agree upon with FDA in order to start that cohort three enrollment? That's a great question. Because if we rewind the clock, what happened was we went to the FDA and asked for a fast-track designation in the post-SSTR environment, so post PRRT, they said no. We got a fast track in the pre-SSTR sort of the SSTR space, so to phrase differently, we asked for a post-second line, and they gave us a first line instead, so that's a great thing for a regulator to do and say that they really are encouraged by what you've been doing. The caveat they gave us was that they said dose at the two and one-half, dose at the five millicurie levels, and then come see us after those first patients are in so that we can review with you and then work with you on the next steps. That's a great feedback to get from a regulator. So we've dosed exactly in line with what they've allowed us to do. It was previously agreed and negotiated with them that we would have them review the data with us before advancing to higher doses or going to lower doses, wherever the data takes us. The safety monitoring committee was very excited. They advocated that we also enroll up to an additional 40 more patients at that 5 millicurie dose level. And we're quite comfortable with the recommendations they've made for dose escalation. OK. What does the dosimetry data that you have tell you about the TI that's available to you here, and where do you think you might be able to safely push dose escalation to? We'll have to follow the data, and we'll comment on it once the data comes out. The important thing with dosimetry is that dosimetry data is only valid in the patient that the dosimetry was done in. It's such a personalized assessment. Dosimetry means you actually looked at what's happening in the drug in that patient. Patients will have different body weights, blood volumes, tumor burden, tumor load, tumor characteristics, renal function, renal clearance. Any measurement of dosimetry is truly patient-specific for individual patient management decisions. We want to be very thoughtful about kind of how we review things. We do care a lot about dosimetry. It may help predict overall risk and overall potential risk for radiation load. There's a lot that's ultra-personalized. It'd be really important to see what's happening with safety, what's happening with measurements of activity of the drug. We want to find out if you have a safe and active drug, then you want to keep doing it through dose exploration, escalation, or de-escalation as needed. OK. And I think before you talked about how you can use the same element for both imaging and for treatment. And so I guess in the case of using a theranostic and a therapeutic, given that patient variability, you probably have a greater degree of confidence based upon that imaging data, kind of what that treatment experience is going to look like. I think that's a really good word choice to use there, which is greater degree of confidence. Because if you're using different isotopes and different drugs to predict dosimetry, there's going to be inherently some risk of error. So a different metal, a different chelator, a different ligand will all have the risk of potentially different biodistributions. What's nice about our construct is that we use literally the same composition of matter. And so we can look at the in vivo fate of everything given to a patient, see what happens because Lead-203 has such a long half-life over two days, to see if that patient the next day received our therapeutic drug, where exactly would those molecules go in the patient, and therefore what kind of impact would have for whatever tissues they touch. OK. So you talked about how the NANETS presentation will be the company-sponsored part of this. I know that there's an investigator-initiated trial with this drug occurring in India. Maybe you can just talk about what you think some of the key takeaways are from that IST data that we've seen to date, and maybe how extrapolatable that safety data is to the 5 millicurie dose that we're going to be getting later this week. Yeah. So we have several investigator-initiated programs ongoing, one in Iowa, the India program, and some collaborators in Europe as well. The data that came out from our Indian collaborators in the investigator-initiated environment looked at a mixture of pre-Lutathera and post-Lutathera patients. These are patients with a different body weight. And so we want to try and learn as much as we can. We're really focused on quality and safety. We want to know everything about these products and programs and anything that may show up. So we do look at things very, very carefully and closely. The patients that were treated in India were, as I said, quite small, and they used a weight-based dosing. We're using a fixed-dose dosing in the U.S.. So there's inherently going to be differences as well as where those patients are with their disease journey. So we think every bit of data is informative. We like seeing the images. We like understanding what's happening in patients. And in any dose escalation approach, we're trying to find out what are these therapeutic limits that we can approach and dosing limits. And so if we think about maximum tolerated dose, it's safe to assume that, for example, in various package inserts, you see that tends to drift towards that maximum tolerated dose. We're in dose escalation right now. So we really want to identify and learn what happens with these drugs in patients. OK. How do you think about the RLP competitive landscape in this tumor type right now? I mean, the competitive density around this target SSTR2, it's pretty high. It's certainly not as high as PSMA. But I think there's 10-plus programs in various stages of development. I think Ratio and Novartis announced some kind of collaboration this morning. How do you think about best establishing differentiation within this space around this target? So with this target, we're looking at therapeutic window. And we really want to get as broad a therapeutic window as possible. This meaning that if for any given efficacy profile, the drug should be safer or flipped around, for any given safety profile, the drug should be a lot more effective. I think the package insert for Lutathera implies a 13% ORR at a defined safety threshold that Novartis is comfortable with. And I think across the field, everyone thinks that we can do better. And so they're trying on a few different metrics. It's an interesting tumor type because it is mostly a homogeneous expression of that SSTR2. And it's a well-understood one. But really, the differentiation where we're applying a novel approach is a novel composition of matter with different biodistribution than what's more commonly used with DOTA or DOTAM. OK. The Melanoma asset, I think you mentioned that we saw some data from that program. I think it was about a month ago. So that data kind of suggested that there might be maybe a bell-shaped dose-response curve here. So maybe you can kind of just walk us through that data and some of the biology that you think might explain what's happening here. So when we think about a bell-shaped curve versus a straight kind of dose response curve, bell-shaped implies that you're going to get increasing response up to a certain level. And then if you keep going higher, then you don't plateau, but you sort of fall off for a variety of reasons. In the melanoma environment, we're looking at immunostimulatory implications on the body to really drive the therapeutic response. And the immune system is a really highly calibrated, intricate system in each patient that's individualized that is also compromised in patients with metastatic melanoma. And so you've got very fragile immune systems that you're trying to support by giving just enough energy into the tumor to allow the immune system to be stimulated, but not so much energy into that overall animal or human that you actually overwhelm the immune system and the disease goes unchecked. In so many patients that are in late-stage disease, the immune system's constantly at war. That's why checkpoint inhibitors get used so frequently and have been so effective. But they tend to fall off after a period of time. So in the patients that we actually assessed recently, these are patients that the median average number of prior therapies was five, including two checkpoint inhibitors. These patients had failed everything they'd been seeing. Their expected progression-free survival and best possible standard of care would be in that two and one-half to four and one-half month range. And at a three millicurie dose level, we had those patients doing incredibly well at nine, 11, 13 months post. And one of those patients turned into a partial response. Whereas going at higher levels, it felt like something was happening with the immune system, and it wasn't able to actually then compensate for the disease. And at higher doses, the patients didn't do as well. Where I don't think we got enough sort of credit for is the fact that all three patients at 3 millicuries are doing incredibly well. They're not living the life that they thought they would have when they came into the trial. Patients progressing, metastatic melanoma, expected PFS of a few months, and that a year out, those patients are doing extremely well. That tells us there's a clear signal. And what's really nice about this bell-shaped dose response curve is that supported by the preclinical work that we've done as well. It's always helpful as drug developers when the preclinical biology and the human results align, because it means that as far as you can tell, a lot of your theses are intact. OK. So maybe you can just talk about what are the next steps for this program and when might we expect to hear about another update? Yeah. So we've seen extraordinary synergies in the melanoma mouse model for going into overt combinations with immune checkpoint inhibitors. We have a deal with Bristol Myers Squibb to use Opdivo. And so we're now enrolling patients in an overt combination study. So patients will receive both our drug and the BMS drug. Anytime you go into combination, to avoid stacking of safety issues, you always lower down. So that three millicurie dose, where we established a clear safety and efficacy profile, we're lowering that down to one and one-half. And we're actively enrolling patients there. We're also going to be enrolling patients in a monotherapy environment as well to learn more at a few different dose levels. And so next year, we'd hope to tell people about how the patients are doing in that combination environment. Again, a combination of a checkpoint inhibitor plus an incredibly neoantigenic alpha emitter on the animal level is giving extraordinary results that are more than just synergistic. They're incredibly sort of phenomenal results that the NCI has given us additional grants to pursue and study further. OK. Maybe just last question, because I think we're over time, but can you just speak to cash runway, what that allows you to execute on here over the course of the next however many months? Sure, so from our last quarterly filing, our cash balance showed $262 million. That gives us runway disclosed until mid-2026. That includes dose escalation and dose expansion on our two lead programs. That also includes dose escalation in our next clinical program, our FAP asset, as well as what we've guided towards building out new manufacturing sites on the West Coast, Midwest, and Texas, and so all those things are captured in that guidance. All right. Thijs, appreciate the time. Thank you very much. Thanks, Stephen. Appreciate you all. Thanks everyone.