Perspective Therapeutics investor call on VMT-α-NET data at ESMO Congress 2026 - PERSPECTIVE THERAPEUTICS INC

Greetings. Welcome to the Perspective Therapeutics Investor Call on VMT AlphaNet data at ESMO Congress 2026. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. Please note this conference is being recorded. I will now turn the conference over to Annie Chang, VP of investor relations. Thank you. You may begin. Thank you, Bill. Good evening. Good afternoon. Welcome to the prospective therapeutics call to discuss VMT AlphaNet clinical data being presented at the European Society of Medical Oncology Congress 2026 as though. During the call, we may make forward-looking statements that are subject to risks and uncertainties, factors that could cause actual results to differ materially from our expectations are detailed in our SEC filings, including in the risk factor section of our most recent annual report on Form 10-K, quarterly report on form 10-Q, and our other SEC filers, which are available on the investor section of the website. These forward-looking statements apply as of today, and we undertake no obligations to update these statements after the call. Today's call is being webcast and can be accessed on the events page of our website. The call will be archived and be available for a period of time after the conclusion of the call. Today's calls will start with prepared remarks by our Chief Executive Officer, Case Spohr. After the prepared remarks, we will open the call for questions with participation from our Chief Medical Officer, Marcus Pullman, and members of the Clinical Development Team. With that, I will turn the call over to Tase. Tase Jones, MD, Great. Thanks, Annie, and thank you, everyone, for tuning into this call. So we're here at ESMO. We had a presentation earlier today that Dr. Laura Heft-Onersen from Mayo Clinic presented on behalf of the investigators. We really want to talk about why we think this is so important. We think there's an extraordinary ability to help patients with neuroendocrine tumors, especially since the need is for deeper responses and more durable disease control. And when we think about what patients are experiencing, they first experience a somatostatin analog, which really helps manage their symptoms. But when we Think about their post-somatostatin analog options, it then goes into a broad category, you know, options including vitifera or aferolimus, or sinitinib or cabozantinib. And we believe that we have an ability to develop a medicine here with the potential to really be category-defining. When we think about how the category was initially created, the NETR1 data came out, which actually had a registrable benchmark. In that case, progression-free survival was the primary endpoint. And further on, if people look at the label for Lutathera, you realize that there's a 13% overall response rate in the Neter1 patient community. When we look at data that's now come up from Duke CMT AlphaNet, We're extremely pleased because we've got very strong data in GapNet patients. We look at really good tumor responses. When we actually look at how patients could perform in a registrational trial, we narrow the aperture a little bit from broader all comers that are SSTR2 positive to those where we only look at the target lesions and all target lesiones must express SSTR3 positivity. We look for durable disease responses. And in this case, we're very pleased that we've seen a 72% progression-free survival rate 18 months across all three cohorts. We've seen a very low-grade incidence of adverse events. And so without having ever seen a grade four or five adverse event, we have not seen any dose-limiting toxicities. We're really excited about having the ability to bring a very compelling medicine forward and into the clinic. When we look at the overall opportunity space for treating patients with gap nets that are SSTR2 positive, it's a clear medical need. There's approximately 250,000 people living with neuroendocrine tumors in the United States. There's approximately 12,000 patients that are newly diagnosed each year. And what's interesting about this particular tumor type is that around 90% of those tumors do express this receptor, SSTR2. So the room for next generation radiologic therapy is in the fact we can actually deliver lead 212, which brings an alpha payload to the tumors. We think that our medicines bring a very favorable risk-benefit profile. And as we think through the package insert approvals in the space, the 37% to 47% ORRs that we're seeing now in GapNet patients that are all STR2 positive, we think it lends itself very favorably to where we're trying to get to. When we look at the ongoing study that we are performing, we are dosing patients in dose finding. We initially dose patients at 2.5 millicuries times 4 doses, so 10 millicures all in. We also escalated quite rapidly to patients at 20 millicuries, and we also went 20% higher up to a cohort three of patients at 24 millicaries. And our belief around why we think we can actually move forward is underlying by the conviction of the data. We've developed a medicine that we know has a net neutral charge. We know that the kidneys like picking up charged proteins and charged protein fragments, and our proprietary chelator and targeting entity together have a net zero charge, which means we should have a broader therapeutic window than other attempts in the space. We also think that alpha particles from lead T12 have the ability to give a hard, fast punch, and then the ability for the body to recover. And so we think if we have this unrelenting focus on medicinal chemistry, on opening up the therapeutic window, we then have the ability to explore various doses and always have the goal to try and do this in the safest way as possible. So underscoring the fact that safety is critical in these patients, These are patients that are expected to live a long time. And again, that's why the approval endpoint is going to look at disease control. So when we look at all these metrics together, we're extremely excited by how this profile looks across all of our doses. If I focus on the center chart initially, if we look if patients have come in on the waterfall chart, you see that we track these patients through as long as we can. We have not had a long follow-up yet in the patients that cohort 3, 24 millicuries, and we're starting to see follow-up now in the patients across all 46 patients at the 20 military dose. What's interesting to see, if you look at the speed of the responses, we do actually see, with a slightly higher dose, some indications that the responses may be earlier and deeper, and we'll show that in a future graph as well. If we look at the overall response by cohort on the far left, there's quite a few numbers to pull apart here. We look atthe overall response rate, and this is in the ITT. So, all comers, everyone that's in the study. And the lower part of the table, we do focus in specifically on what the patients could look like in a registrational study. So in that case, if we just look at gap net patients where all tumors are SSTR2 positive, we're looking at a 37% overall response rate in those patients. And we're also then looking at, you know, sort of a 47% response rate in patients of the 24 millicuries. So a lot of patient data here. We're pleased to see that the safety signal that we've seen previously is lasting right now. If you look at safety on the far right-hand side, I want to focus people to the bottom of that graph. So looking at all grade three treatment emergent adverse events, we're looking at numbers that are not disconcerting or unnerving at all for an oncology drug. We still have zero grade four or grade five average events. We have not seen any dysphagia whatsoever. And I'll touch upon renal safety shortly as well. But across the board, this is a very compelling profile for clinicians. When we actually speak to physicians, they're really excited. Patients are coming into the study. They're usually quite sick. They have a lot of comorbidities. There's lots going on with their health. And the patients are coming in very informed. They want to be able to live longer. They want To be able To have a quality of life that's meaningful and be able TO live for as long as they can. And so while overall response rate is one metric in a slow-growing tumor that we look at, we look to see how these responses emerge over time. The other thing I really want to highlight is that previous overall response rates that we've shown looked at patients that have been on the study the longest. Andso since in some cases now in this study we've seen responses show up as late as 60 weeks, there's naturally going to be what appears to be a perpetual under-reporting of the overall response weight as we look through how patients come through. But when we look at the slide here, this is very compelling for clinicians to really think about what could be best for their patients. When we actually get into what's the approval endpoint, now it gets especially interesting. What we've shown here now is some of the initial Kaplan-Meier estimates of PFS and what that means at a landmark PFS rate. So in cohorts one to three, if we look up at the far right-hand curve three lines down, We're looking at a 72% landmark PFS at the 18-month mark. This is pretty fantastic disease control. When we actually look at all these other metrics and these curves, we know that we can give a lot of confidence in letting patients be on therapy and have that clinically important and approvable endpoint of disease control, and then actually looking in at specifically what's happening with these patients. when we look at what's happening with COVID-2 and COVID-3. We're really pleased to look at the overall response rates to the PFS as well as disease control rates. And this is actually the first time that we've shown the external world, physicians, investors, and patients, what happens with the 24-milligray dose. What's really remarkable about the spider plot is you actually see very, very rapid onset of effect. If you're looking at tumor response, we hope this should translate into longer, more durable disease control than we've even seen so far at the lower dose. And we just want to make sure we point out that the responders keep showing up over time. The patients receive four doses in the study at weeks 0, 8, 16, and 24, and they're not dosed anymore. So we actually do want to see how durable those responses can be. We had the data cut off of September 2nd for the ESMO presentation, and as of September 10th, when we actually looked at the data again, we saw that two more responses had shown up, and so those responses were unconfirmed at this stage. Though in the vast majority of patients that we studied, unconfirm responses tend to confirm when the patients show up for the next visit. So unconfIRMd is really us waiting to do the next scan on the patient, and then at a future data cut, we'll be able to clarify who has responded and who is confirmed versus if anyone remains unconfirmed. Though we look at the spider plot, we see very deep response. We're really excited about this level of activity. But the question mark is always, what about safety? And as we're seeing here, the safety is fantastic. The safety profile remains extremely favorable with no dose-lowering toxicities. We've not had any treatment discontinuations related to adverse events. We have had a very low incidence of all high-grade treatment adverse events, the highest being a grade three. We don't have any dysphagia, and that's very important. And without any clinically significant myelosuppression, all side effects that clinicians look for that may have limited other attempts to either launch in the class or to be out there available for patients. So when doctors are thinking about alternative for their patients that are newly progressing, when their options could include any one of the approved agents, this profile we think looks very, very strong and very compelling. The highest incidence rate we've seen has been alopecia, which is reversible and tends to be quite mild. The patient's hair does grow back, and there has been some nausea. In a conversation I had with the clinician this morning, he reiterated that the patients may feel a little nauseous, but they're definitely coming back for the next treatments. They do not feel at all this could ever impact their care or their desire to stay on therapy. So we're quite encouraged by a very good safety result. When we look at renal safety, we continue to see a very favorable renal profile. What we're showing here is every patient that we can track through, all their creatinine levels. And creatinamine is the core biologically end point that you look at, where every other calculation derives off of. We wanted to at least highlight these two patients that showed up with grade three adverse events. And those patients, both of those were classified as acute kidney injury and not necessarily chronic injury. one patient was unlikely related and one was possibly related and the difference between those is the unlikely related patient who has resolved is a patient with a prior history of being allergic to contrast media and the clinical site feels that's the most likely contribution to the patient's you know sort of temporary kidney injury and the resolution the other patient's also worth calling out as a this is a neuroendocrine tumor patient a lot of comorbidities including hypertension and diabetes, and with a previous history of acute kidney injury. And the way to think about that is their kidney reserves are probably depleted, and this kind of patient in a registrational trial probably would not be included. So we've designed this medicine to be the safest possible we can. Actually, the company history was we were trying to develop a medicine that would be the safest in pediatric neuroblastoma. It turns out we actually think we have a safer medicine for adults too. So this relentless focus on having a net zero charge protein, a drug which then will release the alpha particle hopefully on tumor and nowhere else. We've designed it with a proprietary chelator. The chelater actually holds the alpha-mating bismuth in place. And other chelators will leak up to 30% of the bismith. The literature that we've generated shows that it's under 5%, less, sometimes 2% leakage. So we feel an overall better or safer construct should lead to better clinical safety data. And that's exactly what we're seeing in this slide. We see a very, very strong safety profile as well. And lastly, when we actually look at where the company is going, what else is coming up, there is actually expected to be a presentation, oral presentation, with the ability to have a longer period of time. The ESMO rapid oral is five or six minutes, and that's a longer period of time for us to be able to talk about data and explore a few other data cuts. We are doing an awful lot of work behind the scenes to make sure that we can show more and more follow-up as time goes by and also being ready for a meeting with the FDA for the end of Phase 2 meeting. And so we will be getting some more regulatory updates later this year. We also have other programs in our pipeline. So VMT01, which is lap and melanotide, we expect to have some dose escalation data come from there. We have active programs in FAP and CCQ2R. And so a lot of energy perspective therapeutics, we couldn't be happier that we've now dosed so many patients. We've treated over 150 patients around the world with our medicines, and great data like we're showing today tells us that we can develop safe and effective medicines within the clinical construct. So with that, I'd like to finish the prepared marks and open line up for questions. Thank you. We will now be conducting a question and answer session. Our first question is from Gregory Renza of Truist Securities. You may proceed with your question. Great. Good afternoon and good evening, Tase and team. Congrats on the updates, and thanks for holding this call and for taking our questions. Tase, you certainly described how important the depth and also the durability of the response is. I just wanted to ask if you could just go maybe a little more specific on, you know, what you're hearing on the floor, why that is the case, and how the regulatory bodies certainly interpret that. As you've, you now, alluded to the approval endpoints, maybe you can just provide some color on,you know, the clinical perspective, the doc perspective, and how the Regulatory will absorb that, and then I have a follow-up as well, Tase. Thanks. Sure, Greg. Thanks for the question. You know, as we think about what the regulars look for, the default setting or the sort of the backstop, no matter what, that the FDA would look for is disease control. And so what does the PFS look like is the clearest measure of disease control? And we've shown in our data update today how these Kappa Maya curves are evolving and what the landmark PFSs look like. the opportunity always remains for accelerated approval or breakthrough designation based on overall response rate. And so the ORR, which is how deep can those responses go and how quickly triggers ORR. And we showed very, very good data with cohort three in terms of looking at the 24 millicuries. When we actually look at the other metrics there, which has really, you know, how do we actually, you look at benefit-risk trade-off, the regulars are really looking at that most of Is there a patient-derived benefit, and is there acceptable risk? And we think the safety profile here looks fantastic. When we look at the initial response rates, it's always good to see tumor shrinking. But really the question that is going to be on the regular's mind is, what does it mean for disease control, and what do the PFS rates look like? So it's still early. We can only report out data that actually exists for patients that have tracked through, and we feel that we're actually showing a very good response rate, which the clinicians have again come back and said, this looks fantastic, they really like the disease control they get in their patients. That's helpful in my follow-up, and thank you. My follow-ups just on that safety side, I just wanted to hear just a little more about those two patients with the grade 3s, maybe just clarify from which cohorts those patients are from. And I'm certainly intrigued by your mention that this patient that you identified may not necessarily be included, or the profile at least wouldn't be included in a registrational. So maybe just a question on how you're sort of thinking about the profiles and the potential registrational with respect to that comment. Thank you very much, Dave. Appreciate the questions and the conversation. Thanks, Greg. I'm actually going to ask Dr. Marcus Pullman, our chief medical officer, to answer that. So thank you very mucho, Greg, for the question. So these two AKIs occurred, one from a patient from cohort one. and another one from cohort two. So Tase already suggested the patient on cohort one was unlikely related to our drug. So the AKI, that patient had already recovered in the meantime. That most likely was an allergic reaction to a contrast agent. And the second patient was from cohort two. That patient, as Thais already suggested as well, had several pre-existing conditions, including an AKI that the patient had prior to joining our trial. Thank you. Operator, can we get the next question? Absolutely. Our next question is from Leo Timoshev, and as a reminder, we ask that you please limit yourself to one question. Leo, you may proceed. Yeah, thanks for taking my question, and thanks for sharing this really exciting data. I wanted to ask on PFS. I really appreciate you sharing that, and I'll keep it to one. Maybe if you could help contextualize the landmark PFS you've shown against some of the other trials that have been done in the space, NetR1, Netr2, and, you know, why those may or may not be appropriate comparisons relative to their benchmark and landmark analyses. Thanks. Thank you very much, Alec, for this question. So, this is actually a very good question. I felt a little bit during the discussion from Thomas Walter that he didn't, to be honest, do quite justice in comparing a study that is still immature with a very, you know, a phase three that obviously read out or several phase threes. So, a couple of things. First of all, we differ, obviously, in the patient cohort between, you know, our phase 1 slash 2 trial in comparison to the NETA 1 or 2 or several other phase 3 trials. A, we have a relatively broad inclusion criterion regarding SSTO2 expression. And not all our patients, actually, we enrolled quite a few patients with heterogeneous SSTo2 expression. this patient most likely will be excluded in a registration type study also Kaplan-Meyer is usually used to store actually PFS values or if you want immature PFS values you can estimate how the PFS will look like But the steps that you have with one or two events are disproportionate, and I just want to point this out. We feel and we believe that our PFS signal is very strong. It is strong throughout cohort two and is starting to be also very strong for cohort three. And we feel actually very good about our PFS performance so far. And we did some modeling about the PFS, which makes us feel that the PFC endpoint as a registration type endpoint will actually help us to get this drug approved. Our next question is from Alex Stranahan of Bank of America. You may proceed with your question. Alex Strenahan, Bank of American Banking, Hey, guys. Thanks for taking our questions. I guess as you think about dose selection as well as endpoints and eligibility criteria for the Phase 3, based on this recent data cut and other readouts like Action 1, I'm curious if you think you have enough information to pick a dose for Phase 3 or whether you'd want to wait for longer follow-up from cohort three or even cohort four before pulling the trigger? And also, I guess, on what you think the appropriate comparator would be in the pivotal, if Action 1 leads to, say, an approval in the post-Ludithera setting. Thank you. Thanks for the question, Alex. So, I think just to disaggregate studies from each other, so Action 1 is looking post-ludithera. We're looking in the sort of second-line therapy, meaning your first alternative after a somatostatin analog, so as an alternative to let it there, for lack of a better definition. When we look at the safety benefit profile here and that risk tradeoff, we think this is a very strong medicine at the 20 millikurie dose, the cohort two. We think we have a lot of follow-up in these patients. We're showing a lot efficacy here. We've got a very favorable profile, and the benefit risk is more than worth it to push really hard to move this program into registrational design. As you can tell from the graph here, looking at time on study and response, the results are still coming out of cohort three. And so we do see a path where we could actually initiate that registrational study with that 20-millicurie dose. And at a predefined and pre-specified protocol agreement or alignment, we could then automatically escalate to the 24-milli-curie instead once all that data comes through. So we don't feel that we are being held back at all time-wise. The 20 milliliter looks really, really interesting. Your other question was about comparator, and that really comes into what is the FDA looking for? The question is really, but for the existence of this experimental medicine, what would a patient's choice be? So we would really like to see the comparator being treating physician's choice. Physicians do have a lot of treatment options out there. Not all patients that are newly progressing receive the same choice, and some of that is based off of approvals, where the indications are a lot OF factors kick in there. So, ideally, we would like to see a treating physician's choice as the comparator, and we think for patients, giving them this kind of medicine with this benefit-risk trade-off again provides a really compelling value proposition. All right. Very clear. Thanks, Tate. Thanks, Alex. Thank you. Our next question is from Jeff Jones of Oppenheimer. You may proceed with your question. Hey, good evening, guys, and thanks for taking the question. Maybe just following up a bit on Alex's question, in the context of regulatory, you know, contextualization, obviously new data rolling in, continuing to look really positive. Do you have a feel for when it might be an appropriate time for a, call it a formal end of phase two meeting to provide guidance towards that pivotal study design? And then one just technical clarification, do you have the median follow-up for the cohort two and three patients with the update you provided today? So, the first question, I'm going to pass the microphone over to Dr. Carrillo-Rivas. She leads our regulatory affairs. Dr. Hello. Good afternoon. Thank you very much for the question. We are super excited about the data that we have presented at ESMO today. And as you saw, some of it is very recent. Conversations with FDA are active and ongoing, and we want to incorporate all the data in our discussion with the agency and position ourselves for success. And, Jeff, can you just repeat your other question about medium PFS? I just want to make sure I got the question right. Yeah, sorry. The medium follow-up on cohorts two and three with what you reported today, I know you provided that context previously, and I just wanted to make we had it for this update. So I don't have it handy. If we can get that behind the scenes over the duration of this call, we'll report back on that one. So I do not have it right at my fingertips. If we could find that before the end of this call, we'll make sure we announce that. Thank you. Thank you, our next question is from Biren Amin of Piper Sandler. You may proceed with your question. Hi guys, thanks for taking my questions and sharing the update. Regarding Cohort 2, it seemed that when you look at the confirmed as well as unconfirmed ORR, it came in at about 33%. Can you just talk about that, given you've got now a full 46 patients' worth of data, and given that, you know, the first 23 patients that you reported on previously, I think the ORR was around 43%, both confirmed and unconfirm. So was there anything to note from the second 23 patients in terms of patient baselines compared to the first? Anything to note regarding, you know, follow-up between the two, you know, subgroup, I guess, cohorts within cohort two? Thanks. Thanks, Barron. And we always, you know, look at these things pretty carefully to try and understand the patterns for how physicians enroll. When we look at the overall demographics of the study, we kind of back into the numbers and say maybe there's a few more pancreatic nets than GI nets in the second half of cohort two, but nothing that's away from any of the enrollment criteria. No inclusion or exclusion criteria were changed at all. We sort of take them as they come in. When we looked at this 33 number, this is our kind of worst case scenario possible now, right? Those numbers get diluted down by the fact that the second half a core or two. We still are tracking those patients through, and they haven't necessarily had enough time for all responses to show up. So we do want to look at these results pretty carefully. When we look at the overall response rates, these are still higher and quite a bit higher, double or triple what we're seeing with the standard of care and with the approved agents. And so we feel like there's a fantastic benefit-risk trade-off, right? You can get earlier, deeper responses than with other therapies, and we think we can do it safely. and all the emerging data tells us we'll have really good disease control too. Great. Thank you. Thank you, our next question is from Oliver McCammon of LifeSci Capital. You may proceed with your question. Hi, this is Philip Eckert, jumping in for Oliver today. Thanks for taking my question and congrats on the data. I guess as we put these results next to Lutathera, one of the main disadvantages of that regimen is longer-term heme tox, specifically MDS, AML risk after a longer time. Core 3 looks encouraging so far. Beyond that, could you give some color on the cytopenias beyond the 56-day treatment emergent adverse events window And I guess whether any patients have shown delayed or persistent Mara effects in the core three. Thank you. So, thank you very much for the question. We do know and notice, of course, that Lutathera has a low grade of MDS and subsequent leukemia. We have so far seen none of these severe heme toxicities. regard to cytopenias we have not seen any neutropenia of significance we see some low-grade thrombocytopenia and the leukopenia that normally is reported the grade threes usually is caused through the initial circulation of the drug in the blood compartment there's actually a paper that came out of Germany that investigated this and the spleen obviously is highly vascularized and hence at the initial first pass effect and and obviously subsequently in the first few hours these tightly packed B and T lymphocytes obviously hit quite hard and however and their numbers recuperate quite quickly usually and certainly within a cycle of the therapy got it thank you thank you my next question is from one Z of be Riley securities you may proceed with your question thank you for taking our questions can you remind us how how PRED-1 to 3 neuroendocrine tumor would respond differently to radioligand therapies such as Lutathera, and whether prior therapy of Octiride would meaningfully change their response and durability of response? Are we talking about median TFS difference of more than three months this year? So thanks for the question, Yuan. There's a couple of things in play, which is trying to understand this data within the constraints of a well-controlled study. If we look at the Lutathera package insert, does a very different group of patients in Freneter 1 than it would have been Freneder 2. The overall somatostatin analog baseline therapy is important. I think there's some data that came out actually in the session today implying that there could be differences between patients that if they stay on somatostatin with and without, for example, Lutathera. But we want to be really careful of not going too much into cross-trial comparisons. Marcus, you want to add anything? Yeah, again, it's very difficult to compare really between studies. Our SEER is an early study with a very broad patient population. And it is difficult in the moment to deduct really from these early patients how responses are obtained. And so, yeah, I don't have anything else in mind, too. I think once we get enough patient responses in G1, G2, and G3, we may be able to have enough sample to pull those out. That's an interesting question. But I think at this point, the answers are still quite small. But if I may add, we do see responses throughout all these histological groups, G1. G2 and G1 and G2. Got it. Thank you for taking our questions. Our next question will be from Andy – David Dye from UBS. You may proceed with your question. David Dyes, UBS Health Services, Oh, great. Thanks for taking my question. So, let's congrats on the data here. Two for me, actually, just one on the acute renal injury, the one that's possibly related to treatment. Could you maybe share some additional color on whether this is shown in cohort two or cohort three? And what's the onset of this acute reno injury? And what additional monitoring, hydration, eligibility, or those modification measures you plan to incorporate into the phase three? Thank you very much, David, for this question. So this one patient that is pointing up at week 40 is in cohort 3. That patient had previously progressed and had obviously a progression event that seemed to have obstructed one of the ureters of the kidney. As such, the patient is obviously has an event that was caused by disease progression rather than by the drug itself, and that patient obtained only about three doses. Thank you. Thank you. Our next question will be from David Leibowitz of BMO Capital Markets. You may proceed with your question. David Leibaowitz, BMO, Capital Market, Thank you very much for taking my question. When you talk about the deepening responses over time, what's the hypothesis on what makes that happen and why it's predictable that it will continue to happen? David Leiberowitz, It's a great question. comes down to the mechanism of action for a targeted radiopharmaceutical therapy, and even more importantly, an alpha, but also when thinking about the disease suit itself. So neuroendocrine tumors are classically known as slow growing, but Also slow dying. And when the tumors actually receive enough of a burden, if they're receiving beta particles, it takes about 1500 beta particles to kill the cancer cell. It's an alpha single alpha particle can kill a cancer cell, but the mechanism of action of that is a double-stranded DNA break. In the classic video or cartoon of a long, unstretched coil of DNA that's cleanly first split in the middle isn't really how it happens. DNA is tightly bound up in this massive mess inside the nucleus. If an alpha particle smashes through there, then the whole thing gets blown up, which means the cell loses its ability to repair itself, and it loses a lot of its function. But it still exists and can be alive. And so it's not until it actually goes through its first mitotic cycle that you'd actually expect to get the cell to collapse and fall apart. So the cells can exist despite having the nucleus being damaged, and they don't change their volume on a CT scan until the cell actually goes through an actual death cycle and then gets turned over and replaced by something else. So it's almost guaranteed with neuroendocrine tumors especially to be a gap between when the cell dies and when it shrinks on a CT scan. And the only measurement that is being reported out here for that assessment is overall response based on a resist assessment, which is a CT scan, which looks at the volume of the lesion or tumor, and if it's shrunk above or below 30% or not. So it's generally well known and understood that in these really slow-growing tumors, They're slow to grow, but they're also slow to die, and so their responses take longer. It is encouraging to see there's a lot more energy being thrown onto the, you know, how we actually look at the energy that goes into the cell. If you throw a lot mehr energy in, you're causing a lot meer damage to those cells in a higher probability. And you can actually look, for example, in the spider plot. The spider plot is a resist discrete sort of assessment. That's by resist, that's by CT scan. and so you want to see the tumor shrink and then you also want to see no matter where they are, it's going to stay at a certain level and not grow. So the approval endpoint and the clinical endpoint is not growing. Shrinking is pure bonus. At the end of the day, disease control really is what we're going for in a provable and we also have to zoom out and say the benefit-risk should warrant it. In this case, we think the benefit trade-off with this kind of a safe medicine is fantastic. Thank you very much for taking my question. Thank you. Thank you. Our next question is from Andy Hsieh from William Blair. You may proceed with your question. Great. Thanks for taking our question. So, since the EMT-alpha nets progressive disease rate is so low, and that drives PFS events, can you tell us a little bit about the six PD patients in terms of disease? So whether they are gap nets or not, SSTR status, expression level, or tumor grade, and how can that information, you know, help you optimize the phase three design and also the enrollment criteria? Thank you. So thank you very much, Andy. I'm taking this on. This is a question, obviously, that is keeping us busy quite a bit. We are intensively interrogating our data set. We have done quite a bit of imaging analysis. And I mentioned before that, you know, when we are compared with more mature data, that these phase 3s are usually done with patients that have very homogeneous SSTR2 expression. What we're seeing in these early patients is that quite a few of these patients have a lot of lesions that are not pet-avid, meaning they have a heterogeneous expression. But again, we continue to evaluate. And Andy, it makes sense for first principles, and we appreciate the question, right? If it's a receptor-targeted therapy and the cells don't have the receptor, then they can't receive the damage. So the nice thing about targeted radiopharmaceuticals is we can actually use non-invasive imaging to discriminate in advance which patients are all positive versus not. There are some patients, though, that were heterogeneous that actually had some nice responses. But when you think about how to enrich for a Phase III registrational trial, it's really important to look at metrics like these to figure out, can you actually rule out some early progressors? and it really looks like you can that's helpful thank you so much thank you thank you our next question comes from Lee Watzek of prospective therapeutics you may proceed with your question I think is Lee Watsik from cancer Fitzgerald Apologies for that. Lee, can you hear us? It appears that we have a connection issue. As a reminder, of course, you can rejoin the queue by pressing star 1 on your telephone pad. We'll go on to the next questioner in the meantime. Our next question is David Nierengarten from Wedbush Securities. You may proceed with your question. Hey, thanks for taking the question. I had one on the regulatory path on phase three planning. Just what are you looking for specifically before you engage with FDA and set up the phase three? Is it determining the correct dose? Is something with manufacturing or just literally getting a time slot with the FDA? Thanks. No, thanks, David, for the question. So I'll take part of it and pass it over to our Vigorous Affairs colleague. There's a lot of interaction going on with the FDA. It's a pretty active process. We have a FAST-TRACK designation. We are eligible for the CDRP, which is like a FASTCRACK on the CMC. We've committed to be ready organizationally by the end of this year on our side. And there's many things that get ready in order to move forward with a clearance to go ahead with a Phase III study. Dr. Kalia, do you want to add? Yes. No, thank you for the question. I may just want to that, yeah, it has been very busy this year with regards to engaging with the FDA. And right now, we just, as we discussed before, I mean, we have very recent data as the conversations with the FTA are active and, as you said, ongoing. We do really want to incorporate in our current discussions all the data that we have generated and we would want to position ourselves for success. So I hope I addressed your question. Okay. Thanks. Thank you. Our next question is from Kemp Dolliver of Brookline Capital Markets. You may proceed with your question, Kemp. Great. Thanks. so far, what percentage of the patients that you've treated in cohorts one through three are patients that would be appropriate for the phase three in terms of the patient profile? It's a great question, Kemp. Well, what we've shown actually in the table for best overall response by cohort, and I think it's slide six in our investor deck, we think it is really 60 to 75 percent are patients as we look at the screening rates. But you can do some back in math and see that of the 46 patients in cohort 2, 38 of those 46 would have hit that criteria for all lesions being SSTR2 positive, and 17 out of 20 patients in Cohort 3 so far would have hit that criterion. And I appreciate the question because that's exactly why we broke out the OR on that slide in two different buckets, one which is through intent to treat all patients in, and the second through the slightly tighter aperture of all patients having homogeneous SSTR2 expression. So real world, we're seeing in that kind of range, and we expect that to continue. Okay, so some of the other exclusions that were mentioned earlier, I think, around how much they've been treated would have only a marginal effect. Well, a lot of things play in here. So, we've actually had some patients with non-GAPNets. We had one patient with a paraganglioma, a phenochromocytoma. We had two bronchial NETs. And so, in the likely approval pathway for GAPNETs, so gastroenterotic, those patients would not be included. Also, those patience with GAP NETS that did not have all lesions positive could be excluded if we had a tighter criteria. And if we look at the prior approved therapy in the space, they had very, very tight, all lesions had to express, and so that's why to make things easier for you to interpret, we've shown those numbers, and as we look at that number, 37% in that cohort 2 ORR and 47% in the cohort 3. I think those are very, meaningful numbers for those that only want to look at the ORR number. At the end of the day, we do want to make sure we have disease control, and that's looking fantastic as well. Thank you. Thank you, Dr. Kuhn. Thank you. Our next question is from Jeet Mukherjee from the U.S. Bank BTIG. You may proceed with your question. It's Blake. I'm for Jeet, and thanks for taking our question. Can you elaborate on the kinetics and time to response with VMT and how it differs from other SSTR2-directed radioligand therapies? And then separately, a quick follow-up is just how cohort four is enrolling and when you expect any initial data from that cohort. Thank you, Sure. So, at this point, you know, Cohort 4, we don't have any data that we've shared. The cohort is enrolling. That Cohort four is actually a slightly different flavor of 20 millicuries. And so, it's a way for us to move forward. We see the 20 millicoaries all in at Cohort 2, a very, very compelling dose with very good benefit-risk tradeoffs, and the one that we'll be driving forward to bring to initiating a phase three study. And so, Gita, I apologize. What was the first half of your question? Just on response kinetics, time to response, and how it differs from other SSGR2-directed therapies. We haven't seen anyone produce spider plots or show these kinetics to date, and so it's very unclear. There is no data. Generally, you tend to have sort of only very, very long follow-ups that were reported out at a macro level. So we don't know how to track that through. When we speak to clinicians, anecdotally, they like the responses. When patients feel better, that often precludes a reduction on the spider plot or in resist criteria as well. So a lot of factors kick in, but the physicians know that they are convinced the drug is active because the patients feel bitter, and that will be usually an indicator of disease control. And then further, when you actually get a reduction, that's when you actually have the ability to actually look at a decrease in resist. So there isn't good data on any other program to see what the initial time or first response looks like that we can find. Thank you. Our final question will be from Lee Lotsek of Cantor Fitzgerald. You may proceed with your question. Hey, I hope you can hear me this time. Yes. Great. It's Dan on for Lee. Our question was focused on the potential therapeutics that you would include in your physician choice control arm and if you have a good sense for what kind of PFS or signal you would expect from a pool of physician choice drugs. Sure. I'll let Dr. Pullman take that question. So thank you very much for this question. As we know, there's a variety of drugs approved in this space. Clearly there's PRT. There are now several drugs in this base starting from Lutathera. There's now a biosimilar also, and we expect at some point probably to come to the market as well. At the same time, there are small molecule inhibitors. The wedge of TTIs come to mind, sunitinib and carbazantinib, as well as iverolimus as an M2 inhibitor. And, of course, chemotherapy is also being used in particular for patients with more aggressive tumor types such as PNAT. So, we could envision that the physician's choice could have a variety of those drugs I just mentioned as a choice. How does it actually look like in the end? We are still discussing with the regulators. And just to clarify that if that comparator ends up being treating physician's-choice, it has to be in a pattern representative sample that tracks the U.S. population practice patterns at the time you start the study. So if we initiate the study early next year, whatever the current U. S. treatment patterns that are representative of how patients get assessed in the U S. is how the patient should be enrolled in the study at not quite sort of, you know, quotas or caps, but you want to guide towards those ranges. And so again, this is if we get treating physicians choice as the active comparator, which we'd like to see. Great. Thank you so much, and congrats on the update. Thank You. This now concludes our question and answer session. I would like to turn the floor back over to management for any closing comments. Thank-you. And we've received quite a few questions that have come in electronically during the course of the call, and we've tried to address those as we go through. As we think about what this program means for us right now is we feel we have a very, very effective medicine at the 20 millicurie dose. It's got a very compelling benefit-risk profile. We think we've got enough safety follow-up that we think we can make a strong case to move forward into a registrational design. The registritional design we'd like to see against treating physician's choice. We are excited by the other results we're seeing right now, which is in patients if we go 20% higher to the 24 millicure profile. Those initial responses with onset of of response look compelling, and the disease control rate looks very compelling as well. So no matter which dose ultimately moves forward, 20 or 24, we think so far the efficacy and disease control rates look compelling. We'll relentlessly focus on safety and track that all the way through to make sure that we maintain that benefit-risk ratio. And as we look at how this data has been received by investigators, they're very excited. We have a regular outreach of clinicians and patients who want to be included in any cohort when it shows up, and as we kind of move forward and track things through. So, we've done our best to describe a lot that's here. As a reminder, there will be an additional presentation at the NANNATS Conference, North American Neurotic and Tumor Society, that's coming up in several weeks. And we appreciate everyone for their interest in prospective therapeutics. Thank you, and have a great weekend. Ladies and gentlemen, thank you for your participation. This concludes today's teleconference. Please disconnect your lines and have a wonderful day.