Great. I'd like to get started. My name is Biren Amin. I'm the Managing Director here at Piper Sandler. I'd like to welcome everyone to the Piper Sandler Healthcare Conference. With us is our next company. We have Perspective Therapeutics and their CEO, Thijs Spoor. Welcome, Thijs. So maybe provide us an overview of, you know, the company's clearly involved in, you know, radioligand therapy and has a deep pipeline. Provide us with maybe an overview of the pipeline assets, next key catalysts for investors. Sure, no. Thank you. And thanks for having me here. At Perspective Therapeutics, we're really excited about a really deep pipeline. We have a sort of relentless focus on really developing innovative molecules. Everything we do is patent-protected, with very long, composition of matter patents that go out to the late 2030s and beyond. Our programs, if we're gonna innovate and develop a molecule and bring it into clinic, we know it has to differentiate on its pharmacokinetic, pharmacodynamic properties. We'd wanna design better drugs with better biodistribution. And I bring that up out of the gate 'cause that feels intuitive, but I think that's where a lot of people are learning as they go in the radio pharma space. We've just been doing it for so long, it feels intuitive. And so we always focus really on what does that biod look like. We have one program where we're actually looking at neuroendocrine tumors. We have another program looking at melanoma and a certain type of melanoma subset that expresses a receptor called MC1R. We have another program that's looking at a pan-tumor target called FAP alpha, which we think is really interesting, and then we have several other programs behind that using direct peptide targeting. We do have an approach that we're pioneering called pretargeting, which allows a combination of an antibody to kind of paint a tumor and then have a peptide go in and take it out, and there's other programs we're looking at as well. So we've been innovating in the field for quite a while. It basically, if we can find a really interesting way to get a radioactive isotope to a tumor and not to healthy tissue, we like it 'cause that's when we can actually deliver a pretty powerful punch. The lead pipeline program is the VMT-α-NET. Clearly, you're looking to differentiate versus market leader Lutathera. You know, how does it, what are the differentiating attributes of VMT-α-NET, as it relates to, you know, Lutathera, which is, you know, on the market today? It's a great question 'cause Lutathera really started off, and I'm not gonna call it the gold rush, but the wave of excitement into radiopharms. And initially, the initial work with using dotatate, targeting SSTR2 receptors was done with lutetium, chelated to DOTA, in that name embedded in that name. And there was some really interesting data that came out with a beta particle in the patients with those tumor types. And in patients where there are no viable options, where the standard care is somatostatin analog was about a 3% ORR, Lutathera was able to generate in the NETTER-1 study about a 14% ORR that made its way into the package insert. So to go from 3 to 14 is a big innovation for patients. If you have a PFS in those patients about two years, let's call it, that was really helpful to try and look at disease control, but in the world of if you're in the 86% of patients that's not there, that's not enough, right? Is there a room for innovation? Absolutely. There's a lot of room to innovate. That's prompted a lot of other competitors in the space. Other people with the SSTR2 type analogs going with either the same generic dotatate and either trying to change the dosing frequency with lutetium. In some cases, they may have gone and tried a different isotope like actinium. In our case, we went one step further and said, "Let's do the power of an alpha, but let's do not just another isotope, but let's do what we think is a more precise isotope with a safer profile based on the daughter tox and innovate on the peptide and the chelator and really change what's happening." So by switching away from DOTA to a proprietary chelator, you lower the charge of the peptide from being charged to neutral, and that changes biodistribution. So again, a recurring theme whenever I've talked to people about the radiopharmaceutical business is that biodistribution is key. If you've got a biodistribution that looks really favorable at one point in time, that's an imaging agent. If it looks favorable across the entire curve you know, sort of two to six half-lives of an isotope, that's a therapeutic agent. Got it, and so data were presented a few weeks ago at the NANETS meeting, Phase 1/2 data. Talk a little bit about what you saw in the first two dose cohorts, so this is data from the first two dose cohorts, and you know, so maybe provide an overview on, on the efficacy that you saw and what are next steps for the trial. Great. Yeah. So we were really happy with the data so far, and the reason why I say we were very happy was that we actually had really good initial results in what's a dose escalation study. So this is dose finding, and dose finding means just that. You're trying to figure out what works best, where is there a therapeutic window you can hit. In several cases in the radiopharma space, people didn't hit any therapeutic window. There were programs that had to be discontinued because the safety signals showed up well before any activity or efficacy signals showed up. In our case, we were really happy that eight out of nine patients at the first two levels, the very first levels that we tried in the U.S. in humans, we had disease control in eight out of nine. And so the very first thing is a patient with a neuroendocrine tumor. They're stable on their somatostatin analog. And then when the disease starts to progress, then the physician's saying, "I need another therapeutic option." And so out of the gate, eight out of nine, immediately we had disease control. The one that didn't had a non-SSTR2 expressing carcinoid that grew out of control. So not a surprise. It didn't express the receptor, and that tumor on its own, you know, had the patient continue to progress. When we looked at the safety profile, we had a very, very clean safety profile. Our safety monitoring committee recommended two things. One, to escalate to a higher dose to the seven and a half millicuries. And the other is to do up to an additional 40 more patients at the five millicuries level. And that sparked an incredible amount of interest two weeks ago at the North American Neuroendocrine Tumor Society meeting then. We had a lot of physician engagement immediately after that meeting because they saw very, very strong disease control in the patients that were out there. They saw a very clean safety profile. If you count the response rate so far, I'd argue we're already on track or on par with where Lutathera is in the package insert. The ability to dose higher, which we should do, means we think we can actually really improve what we see. We'd previously agreed with the FDA that this would be a dose escalation study, and we initially asked for a fast-track designation second line, so post-Lutathera. The FDA came back to us and said, "No. You guys get a fast-track first line, so instead of Lutathera." And that was really compelling with the one proviso or caveat that we meet with them after the first few patients in the five millicurie level. We're exactly on track with what the FDA has asked us to do. The safety monitoring committee has recommended going higher dosing. We would like to. We need that agreement with the FDA first before we can actually go into a higher dosing cohort. Would you have to meet with the FDA, or is there written correspondence that's sent into the FDA for their blessing for the next dose cohort? I mean, it's a great way to just sort of reframe that, you know, behind the scenes how the sausage gets made. Yeah. It's written correspondence. We send in what we're seeing, with everything we've learned about the program so far as per their request. Their responses can either be written or meeting-based or hybrid or whatever. Once there's a back and forth that both parties are comfortable with, we'll communicate that to the street, and it's really in the FDA's hands. In some cases, they'll wait 30 days and give a letter. Some cases, they'll wait 30 days and have a meeting. In some cases, it's much shorter. It's really in their hands, but it's an interaction. And so once you get the green light, you would start to dose the next dose cohort. Correct. Of patients. Yeah. And so could we expect data back half of next year from that cohort? We'll see when those patients start enrolling. I don't wanna give guidance until we can actually start enrolling. But we are currently enrolling in a Cohort 2B, which is at that five millicuries level, and it's open for enrollment. A lot of investigator interest. We'll be disclosing kind of enrollment rates at the beginning of next year in terms of how that's looking. It's safe to say there's a lot of physician interest, a lot of patient interest in actually getting into these programs. Even from the patients that you've presented data on from cohort two, you still have additional follow-up that you can do, right? Correct. So there's a few patients that would still require, I think, a fourth cycle of treatment. Yeah. Correct. Yeah. So those patients that, the data that was presented at NANETS showed the results post-third cycle for all the patients there. Those patients are still in the study, and they're being followed up further. So there'll be a later assessment of the post-fourth dose, you know, sort of post-fourth cycle. What does that assessment look like? And that's usually it's a combination of, of, molecular and anatomic imaging, sort of PET CT scan that then helps you learn about what's happening with that patient. Across the board in every other SSTR2 radio pharma trial, it's taken, post-fourth dose or even four months after the fourth dose to look at all responses to, to show up. And so it's, it's reasonable to expect that as these patients continue their, their journey, that the data will change. You know, how do these data compare to the data that were generated in India through, like, I think this was the first IIT study that evaluated this compound? Can you talk about maybe, you know, compare and contrast the data sets and the trial designs in terms of dosing, patient-based weights across the two geographies, and what the key learnings were? Yeah. So to contextualize it, let me just first sort of point to the Sanofi partnered program, dotamtate with lead-212, which is human experience with lead-212. That program, from everything we've seen in the literature, did not show a lot of activity at the 52 microcurie per kilo dose level but did show activity at the 67 microcuries per kilogram level. So their RP2D, from everything we've seen published, it appears that they were not interested in going higher or they couldn't. It appeared like they were DLT. So that 67 microcuries per kilo is the RP2D for that lead-based program. Dr. Sen in India, when she came to us under compassionate use, we had acute need for patients to be treated. She could not access the other isotopes, lutetium or actinium. She had patients with a clear medical need. This is a compassionate use study that she was directing, and asked for our support to in compassionate use. Out of abundance of caution, some of her patients are very, very small. She has patients that are 40 or 50 kilos, that she sees on a regular basis. So she opted to do a weight-based dosing in line with the Sanofi partnered program, so at that 67 microcuries per kilo level. She reported out responses that were quite rapid, in her study and very, very encouraging and supportive that things can be done safely at that dose level for her patients. So learnings from there are pretty clear. When she's dosing at 67, she was getting a very clean profile, no Grade 3 AEs except for two anemia patients who had previously come in anemic into the study. And she wasn't seeing anything major from a safety side, and she was encouraged by efficacy. When we looked at the weight-based equivalent with our patients in the U.S., we only had one patient that was over that, really, that number. This is a smaller patient, 81-year-old lady. And she had a partial response. So she had a very rapid response and encouraged people to look at the spider plots from that study to see what are the implications. And it's small n's still, but it appears that you need to dose higher and get above that 67 threshold. We don't know what that RP2D looks like with our drug. We don't know where the DLTs will show up. But everything about the preclinical and the human data says dose higher. And as soon as the FDA gives us the go-ahead, we'll expect to dose higher. Got it. And then I guess from a safety standpoint, can you talk about the safety profile that's emerged across the first two dose cohorts, impact on the kidney? What type of clearance have you seen from the renal system, as it relates to the VMT-α-NET program? So there's important to think about these dose-limiting toxicities and the safety concern and areas of interest. Obviously, everything's important, right? We care about safety no matter what tissue type it's in. We wanna learn everything about the patient. There are concerns about kidney exposure from a long-term chronic potential. And so that, you know, we look at creatinine clearance. We look at acute markers. We didn't see any across every program out there. You need to wait longer to see is there any sort of, you know, chronic issue that's kidney-driven. We did look at some dosimetry in some patients, and we publicly showed those curves. That dosimetry tumor-kidney ratio is relevant only in the patient that it's done in because you'll see it's very noisy. Each patient has different renal function, different tumor sink conditions, different biology. You really wanna look to see your calculated limits in those patients. Are they reasonable? You do look very carefully at all the other safety metrics. We only had one grade three event in that study. It was a patient who had a grade three diarrhea, which was one day only, and resolved itself on its own. Across the safety thresholds that we've seen on everything that we can assess, it looks to be a very, very clean program and one that oncologists really wanna develop further. You know, you mentioned, you know, clearly a lot of interest within academia. So you're running an IIT or there is an IIT study, I guess, in Iowa. What's the objective of that trial? When do we get data from that study? Iowa is taking a different approach. They are currently studying the drug in post-lutetium patients. These are patients that neuroendocrine tumors that would've been controlled under somatostatin analog. When it started to escape, they would've been dosed with Lutathera. After some kind of response to that, they're living their lives again, but then the tumors are progressing again. Those patients are coming into a study. Iowa's taking a different approach. They're looking at a dosimetry-based dosing and more specifically kidney-based dosing. They are imaging a patient ahead of time with a lead-203 version of the drug. The luxury of using lead as an isotope is you can use the 212 variant, which will give rise to an alpha, or you can use the lead-203 version, which is a pure gamma and gives very, very good images. And you can look over the 24- and 48-hour window where exactly does the drug go? Every single organ, over various time points and look at tumor-kidney ratios and those metrics. And what the investigators in Iowa are saying is, "Well, let's solve for a calculated theoretical kidney dose." And independent of what that physical amount administered is, and they're allowed to do that. And they've dosed initially, some patients. One patient had, sort of 6.6 millicuries times two. They presented that data last year at the SNMMI Nuclear Medicine meeting, and that data showed very encouraging tumor reduction in very large disease. And so they are increasing their dosing two doses only, calculated to solve for a very precise kidney dose. So again, a different way of thinking about it. There's many ways to dose. You can do an absolute dose. You can do weight-based dosing, body surface area, blood volume, tumor volume, tumor load, kidney volume, kidney function. And so you rather we wanna have things that are reasonable, and especially with the broad therapeutic window, that we think can be developed in, in clinically feasible programs. And so, when would they present? Sorry. Yeah. Their patients are coming in under their own volition. This is an investigator-initiated study. They have updated the fact that they are enrolling patients, and they tend to present at reasonable medical conferences that are more nuclear medicine-focused. And so if they prove out, on a kidney-based dosing, is that something that the company would evaluate or think about? We're looking at everything to really figure out what's the safest way to treat patients. They're treating patients post-Lutathera, and so that's not where our current investigator-initiated, our current company-sponsored trial is. But there are all kinds of patients with acute needs, right? And that really we think that lead is a viable alternative to either actinium with lutetium or more lutetium post-lutetium. Got it. Okay. And so you've got a second pipeline program, MC1R. Tell us a little bit about that. You had data also, earlier this year from that program. So what are next steps, after you saw the phase one two data, and have presented that? Yeah. So in our melanoma program, we've done some dose-finding work. And dose-finding means just that. You're gonna go up or down depending on what you're trying to see what does the therapeutic window look like. There are two possible ways that we've established where it makes sense to treat melanoma patients, either in a monotherapy environment or in a combination setting with a checkpoint inhibitor. The animal data is really, really clear. If we go into combination with a checkpoint inhibitor, it's incredibly additive. And so we saw mice where we had complete disease control and couldn't even get tumor again on a rechallenge with injected with new tumors. We did not see that in the mono setting. The monotherapy in the mouse model showed efficacy but nowhere near as close as if in the combination setting. So the first thing we wanna do is establish monotherapy safety and efficacy so that getting into combination, we can disaggregate the effects. So we were thrilled with the results we saw. We got very clean safety profile in those melanoma patients that we dosed. Patients at three millicuries had an expected PFS of two and a half to four and a half months with best possible standard of care. And at the 9, 11, 13-month marks, they're doing very, very well. So a tripling in PFS is really meaningful in those patients in that mono setting. But we're really using that data to help inform how do we get into combination as soon as possible. We think there are challenges with MC1R, one as a target, trying to go really high monotherapy because you do get expression of MC1R in the kidneys themselves. And so given all the preclinical data, a combination seems like a great way to go. And so far, we've found a really good signal here. We don't have a major safety issue, and we get clear efficacy signals with these patients at a three millicurie dose. So that says go forward. We know what that looks like. Let's drop that dose down a bit, see if we can still get a, and we know we should get a clean safety profile. How does that efficacy profile persist? And more importantly, in combination with nivolumab, what can we do for those patients? So combination with nivolumab is, are the next cohorts that would enroll? Yes. Correct. It's openly enrolling right now, and we'll then be sort of working with our sites to allow monotherapy in one of the other cohorts as well. Three millicuries or 1.5. And so this is going after MC1R. Tell us a little bit about the target. And are you, you know, enrolling patients that are highly expressing MC1R? It's a great question. MC1R, it shows up in about 50% of melanoma patients. If we look at literature, if we look at our own enrollment histories and in other countries, it appears pretty stable at 50% of melanoma patients will express MC1R on some of their tumors. And that's where it gets so complicated because not every tumor will express it. If we're going with a combination therapy, we're looking to prime the whole immune system, go after all melanomas at once. So really, we think we just need one hot target to really get this neoantigenic activity, get the immune system primed, and allow the body to do its job. We do imaging of MC1R expression, and the imaging is variable. Some patients have a do not show any MC1R. If they don't express the target, we're not gonna enroll them in the trial. If they do express it, then they can be. Got it. And so you're driving towards an immunogenic response with the radioligand. You know, how do you think about sequencing of therapy given, you know, you would wanna, you know, first have that immunogenic response before you, you know, dose a patient with nivolumab? Yep. No. So you got that. I think you've clarified the sequence that we're exploring first, which is give that priming and then give the checkpoint inhibitor to allow the immune system to do its job best. There have been some studies in some radiopharms doing giving the checkpoint inhibitor ahead of time, but the clinicians tend to focus more on giving it after the radiopharm. I guess published literature seems to suggest that, you know, patients that fail prior BRAF seems to upregulate MC1R. Is that, you know, part of the enrollment criteria as well that patients would have to fail a BRAF? So right now, these patients are post-second line. And so that doesn't necessarily mean they had to have had a BRAF. They're post-second line means they've exhausted all reasonable options that are appropriate for that patient. And if we look at our data so far, the patients' median had five previous lines of therapy. These are very sick patients where there aren't really a lot of alternatives for them. And so the fact that three millicuries we could get a tripling of that PFS, we thought was wonderful. And, you know, I don't think we got enough credit for that, but in the changing these patients' lives is important. Changing it in a way that we think is safe is important. And then it also helps us to go to using this in combination. So the company has a third program that they're gonna move into the clinic imminently. This is a FAP radioligand, PSV-359. Tell us a little bit about that program. You know, FAP's been around a while. There's been a number of programs that have a number of companies that have evaluated FAP from a radioligand standpoint. What makes your program differentiated and increases your confidence on this target? So, as we think about FAP, I think it's a very compelling program. It clearly shows up in so many different kinds of tumors, especially in the tumor stroma. So it's either tumor expressing or stroma expressing, meaning if the tumors get advanced enough, they will start to form stroma, and we can target it. What we've seen from competitive programs that have tried to go after FAP is that they've used imaging agents and tried to turn them into therapies versus starting and actually making a therapy out of the gate. What does that mean? So from time of injection to call it two half-lives later, you wanna know, does the drug go into tumor and stay there? Does it go to other tissues, go to tumor, and then move to other compartments? And so the movement of the drug really, really matters in a radiopharm 'cause wherever the drug spends its most amount of time is where the damage will occur. So we've only designed our molecules to go to tumor quickly and stay there. And we've seen some other programs that have tried going into clinic where the first few hours didn't necessarily have tumor uptake. You had other tissues involved, or at four hours post, then the drug would move around the body. And it's an area under the curve game. And so you need the area under the curve to spend all this time on tumor for therapy. If you've got a perfect biodistribution at four-hour time point or six-hour time point, that's a great imaging drug, but that's not necessarily a good therapy drug. You've optimized, I guess, for the PSV-359, the ligand component is where you've done a lot of the optimization to target the tumor. So we use our proprietary chelator. We think there's a lot of reasons to not charge the protein and how that helps to avoid, with kidney retention. We also tune the peptide sequence to impact biodistribution. It's not just about binding affinity. It's about where does the drug go throughout the entire, entire body. And the nice thing is we have the luxury of doing these scans upfront to look at whole body, one-hour, four-hour, eight-hour, 21-hour, imaging. We've showed some of those images in our corporate deck. And what's great is that in humans, we can see that the drug goes very, very quickly to tumor and tends to stay there. And it only is really going to tumor. So if it's not going to tumor, it's being washed out through the kidneys. It doesn't retain in the kidneys. It goes to the bladder and gets voided from the patient quite rapidly. And so we have the amazing ability to look at across two half-lives where 80% of all alphas will be given, where will those alphas occur? And with that FAP program, it looks like it tends to go into FAP-based tumors. Great. And I guess, you know, we've got maybe a minute left. Tell us a little bit about why, you know, the company chose lead-212 as the radioisotope of choice. And we see companies, other companies have looked at other isotopes like lutetium-177 or actinium. What attracted you to lead-212? It's not just the isotope. It's the overall drug. How do you actually make a radiopharmaceutical as a drug that has a way to target and a way to deliver the radioactive payload? lead-212 is great. You have a perfect imaging surrogate. That's great for dosimetry and for predictive work. But the actual therapeutic potential comes from hitting a tumor hard and fast and then disappearing completely. You want a short enough half-life that you're getting all those alphas hitting tumor. You don't want there to be a long residence time in the body where it's gonna hit other tissues. And also, if you're doing any kind of combination work, you want that really heavy hard-hitting, hard-fast punch and then disappear and let the tumor microenvironment recover and do its own thing. Hard fast punch supported by all first principles of radiation biology. Great. So, some exciting data to look forward to next year. And I'd like to thank you for coming here and participating on this fireside chat. Great. Thanks so much for hosting me. Thank you. Thanks. Okay. Let's go ahead and get started. My name's Ali Bratzel, a biotech analyst here at Piper. Thanks for joining us at our healthcare conference. It's my pleasure to introduce Perspective Therapeutics. Joining us today for a fireside chat, we have CEO Thijs Spoor. So this is meant to be an informal format. If any of you in the audience have a question, just go ahead and raise your hand. We'll get to Q&A in a second, but maybe Thijs first, give us a quick overview of, you know, Perspective Therapeutics, the story, the setup into year end, and then 2025. Great. First, Ali, thanks so much for the invitation. It's great to be here with everyone. Always look forward to having the opportunity to talk about Akebia. I mean, we're at a really.