Greetings. Welcome to the Perspective Therapeutics Investor Call on VMT-α-NET 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 Cheng, VP of Investor Relations. Thank you. You may begin.
Thank you, Bill. Good evening, good afternoon. Welcome to the Perspective Therapeutics call to discuss VMT-α-NET clinical data being presented at the European Society for Medical Oncology Congress 2026, ESMO. 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 factors section of our most recent annual report on Form 10-K, quarterly report on Form 10-Q, and our other SEC filings, which are available on the investors section of our 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 call will start with prepared remarks by our Chief Executive Officer, Thijs Spoor . After the prepared remarks, we will open the call for questions with participation from our Chief Medical Officer, Markus Puhlmann, and members of the clinical development team. With that, I will turn the call over to Thijs.
Great. Thanks, Annie, and thank you everyone for tuning into this call. We are here at ESMO. We had a presentation earlier today that Dr. Thor Halfdanarson 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 is an extraordinary ability to help patients with neuroendocrine tumors, especially since the need is for deeper responses and more durable disease control. When we think about what the patients experience, they first experience a somatostatin analog, which really helps manage their symptoms. When we think about their post-somatostatin analog options, it then goes into a broad category, options including Lutathera or everolimus, sunitinib, 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 NETTER-1 data came out, which actually had a registrable benchmark. In that case, progression-free survival was the primary endpoint. Further on, if people look at the label for Lutathera, you realize that there's a 13% overall response rate in the NETTER-1 patient community. When we look at the data that's now come out from VMT-α-NET, we're extremely pleased because we've got very strong data in GEP-NET 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 lesions must express SSTR2 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 at 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 4 or 5 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 GEP-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. What's interesting about this particular tumor type is that around 90% of those tumors do express this receptor, SSTR2.
The room for next-generation therapeutic 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. As we think through the package insert approvals in the space, the 37%-47% ORRs that we're seeing now in GEP-NET patients that are all SSTR2 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're performing, we are dosing patients in dose finding. We initially dose patients at 2.5 mCi x4 doses, so 10 mCi all in. We also escalated quite rapidly to patients at 20 mCi, and we also went 20% higher, up to a cohort three of patients at 24 mCi.
Our belief around why we think we can actually move forward is underlined 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. 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 this space. We also think that alpha particles from lead-212 have the ability to give a hard, fast punch and then the ability for the body to recover. 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 with the goal to try and do this in as safe as way as possible.
Underscoring the fact that safety is critical in these patients, these are patients that are expected to live a long time. Again, that's why the approval endpoint is going to look at disease control. 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 at patients who 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 at Cohort 3, 24 mCi, and we're starting to see follow-up now on the patients across all 46 patients at the 20-mCi dose.
What's interesting to see as 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. But 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 at the overall response rate, and this is in an ITT, so all comers, everyone that's in the study. In the lower part of the table, we do focus in specifically on what the patients could look like in a registrational study.
In that case, if we just look at 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 a 47% response rate in patients at the 24 mCi. 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 we look at safety on the far right-hand side, I want to focus people to the bottom of that graph. Looking at all Grade 3 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 4 or Grade 5 adverse events. We have not seen any dysphagia whatsoever, and I'll touch upon renal safety shortly as well.
But across the board, this looks 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. 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.
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 underreporting of the overall response rate as we look through how patients come through. But when we look at the slide here, this looks 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 1 to 3, if we look 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. Then actually looking in at specifically what's happening with these patients. When we look at what's happening with Cohort 2 and Cohort 3, we're really pleased to look at the overall response rates, the PFS as well as disease control rates. This is actually the first time that we've shown the external world, physicians, investors, and patients what happens with the 24-mCi dose. What's really remarkable about this 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.
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 zero, eight, 16, and 24, and they're not dosed anymore. So we actually do want to see how durable those responses can be. We had a data cutoff 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, unconfirmed responses tend to confirm when the patients show up for the next visit.
Unconfirmed 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, excuse me, who is confirmed versus who, if anyone, remains unconfirmed. But 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? As we're seeing here, the safety's fantastic. The safety profile remains extremely favorable with no dose-limiting toxicities. We've not had any treatment discontinuations related to adverse events. We've had a very low instance of all high-grade treatment adverse events, the highest being a Grade 3. We don't have any dysphagia, and that's very important.
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. When doctors are thinking about an 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. 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, and they do not feel at all this could ever impact their care or their desire to stay on therapy.
We're quite encouraged by very good safety results. 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. Creatinine is the core biological endpoint 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 3 adverse events. 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. 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 temporary kidney injury and the resolution.
The other patient's also worth calling out. This is a neuroendocrine tumor patient, a lot of comorbidities, including hypertension, diabetes, and with a previous history of acute kidney injury. 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. 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. 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 chelator, it actually holds the alpha-emitting bismuth in place, and other chelators will leak up to 30% of the bismuth. The literature that we've generated shows that it's under 5%, less, sometimes 2% leakage. We feel the overall better, overall safer construct should lead to better clinical safety data, and that's exactly what we're seeing in the slide. We see a very, very strong safety profile as well. 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 the 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 look at being ready for a meeting with the FDA for the end-of-Phase II meeting. We will be getting some more regulatory updates later this year. We also have other programs in our pipeline. So VMT01, which is lapatinib, we expect to have some dose escalation data coming from there. We have active programs in FAP and CCK2R. So a lot of energy at 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.
With that, I'd like to finish the prepared remarks and open the 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.
Greg, good afternoon and good evening, Thijs and team. Congrats on the updates, and thanks for holding this call and for taking our questions. Thijs, 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 what you're hearing on the floor, why that is the case, and how the regulatory bodies certainly interpret that as you've alluded to the approval endpoints. Maybe you can just provide some color on the clinical perspective, the doc perspective, and how the regulatory will absorb that. Then I have a follow-up as well. Tas, thanks.
Sure, Greg. Thanks for the question. As we think about what the regulators look for, the default setting or the backstop, no matter what, the FDA would look for is disease control. What does the PFS look like as the clearest measure of disease control? We have shown in our data update today how these Kaplan-Meier 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. The ORR, which is how deep can those responses go and how quickly, triggers ORR. We showed very, very good data with Cohort 3 in terms of looking at the 24 mCi. When we actually look at the other metrics there, which is really how do we actually look at benefit/risk trade-off, the regulators are really looking at that most of all.
Is there a patient-derived benefit, and is there an acceptable risk? We think the safety profile here looks fantastic. When we look at the initial response rates, that is always good to see tumor shrinking. But really the question that is going to be on the regulators' mind is what does it mean for disease control, and what do the PFS rates look like? So it is still early. We can only report out data that actually exists for patients that have tracked through, and we feel that we are 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 is helpful. My follow-up is just on that safety side. 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. 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 are sort of thinking about the profiles and the potential registrational with respect to that comment. Thank you very much, Thijs. Appreciate the questions and the conversation.
Thanks, Greg. I am actually going to ask Dr. Markus Puhlmann, our Chief Medical Officer, to answer that.
Thank you very much, Greg, for the question. These two AKIs occurred, one from a patient from Cohort 1 and another one from Cohort 2. Thijs already suggested the patient on Cohort 1 was unlikely related to our drug. The AKI, that patient had already recovered in the meantime, that most likely was an allergic reaction to a contrast agent. The second patient was from Cohort 2. That patient, as Thijs already suggested as well, had several preexisting 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 Timashev. As a reminder, we ask that you please limit yourself to one question. Leo, you may proceed.
Yeah, thanks. Thanks for taking my question and, thanks for sharing this really exciting data. I wanted to ask on the 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, NETTER-1, NETTER-2, and 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. 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 phase III that obviously read out, or several phase IIIs. A couple of things. First of all, we differ obviously in the patient cohort between our phase I/II trial, in comparison to the NETTER-1 or 2 or several other phase III trials. We have a relatively broad inclusion criterion regarding SSTR2 expression. Not all our patients, actually, we enrolled quite a few patients with heterogeneous SSTR2 expression. These patients most likely will be excluded in a registration-type study.
Kaplan-Meier is usually used to score 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 2 and starting to be also very strong for Cohort 3. We feel actually very good about our PFS performance so far. We did some modeling about the PFS, which makes us feel that the PFS endpoint as a registration-type endpoint will actually help us to get this drug approved.
Thank you. Our next question is from Alec Stranahan of Bank of America. You may proceed with your question.
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 III, I guess based on this recent data cut and other readouts like ACTION-1, curious if you think you have enough information to pick a dose for phase III or whether you'd want to wait for longer follow-up from Cohort 3 or even Cohort 4 before pulling the trigger. 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-Lutathera setting. Thank you.
Thanks for the question, Alec. I think just to disaggregate studies from each other. ACTION-1 is looking post-Lutathera. We're looking in the second-line therapy, meaning your first alternative after a somatostatin analog, so as an alternative to Lutathera, for lack of a better definition. When we look at the safety benefit profile here and that risk trade-off, we think this is a very strong medicine at the 20 mCi dose, the Cohort 2. We think we have a lot of follow-up in these patients. We're showing a lot of 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 3.
We do see a path where we could actually initiate that registrational study with that 20 mCi dose, and at a predefined and pre-specified in the protocol agreement or alignment, we could then automatically escalate to the 24 mCi instead once all that data comes through. We don't feel that we are being held back at all time-wise. The 20 mCi 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? 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. Thanks, Thijs.
Thanks, Alec.
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 Alec's question. In the context of regulatory 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 II meeting to provide guidance towards that pivotal study design? One just technical clarification. Do you have the median follow-up for the Cohort 2 and 3 patients with the update you provided today? Thank you.
The first question, I am going to pass the microphone over to Dr. Belén Carrillo-Rivas. She leads our regulatory affairs.
Hello, good afternoon. Thank you very much for the question. We are super excited about the data that we have presented at ESMO today. 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.
Jeff, can you just repeat your other question about median PFS? I just want to make sure I got the question right.
Yeah, sorry. The median follow-up on cohorts 2 and 3, with what you reported today, I know you've provided that context previously, and I just wanted to make sure we had it for this update.
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. I don't have it right at my fingertips. If we can 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.
Yeah, 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 full 46 patients worth of data and given that the first 23 patients that you reported on previously, I think the ORR was around 43%, both confirmed and unconfirmed. Was there anything to note from the second 23 patients in terms of patient baselines compared to the first? Anything to note regarding follow-up between the two subgroup, I guess, cohorts within Cohort 2? Thanks.
Thanks, Biren. We always look at these things pretty carefully, trying to 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 2, 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 look 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 of Cohort 2, we still are tracking those patients through, and they haven't necessarily had enough time for all responses to show up. 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. We feel like there's a fantastic benefit-risk tradeoff. 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 Phillip Eckert. I'm 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. Cohort 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 marrow effects in the Cohort 3? Thank you.
So thank you very much for the question. We do know and noticed, of course, that Lutathera has a low grade of MDS and subsequent leukemia. We have so far seen none of these severe heme toxicities. In 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 3s, usually is caused through the initial circulation of the drug in the blood compartment. There is actually a paper that came out of Germany that investigated this, and the spleen obviously is highly vascularized and hence had the initial first-pass effect, and obviously subsequently in the first few hours, these tightly packed B and T lymphocytes are obviously hit quite hard. However, their numbers recuperate quite quickly, usually, certainly within a cycle of the therapy.
Got it. Thank you.
Thank you. Our next question is from Yuan Zhi of B. Riley Securities. You may proceed with your question.
Thank you for taking our questions. Can you remind us how grade 1- 3 neuroendocrine tumor would respond differently to radioligand therapies such as Lutathera, and whether prior therapy of octreotide would meaningfully change their response and durability of response? Are we talking about median PFS difference of more than three months here?
Thanks for the question, Yuan. There is 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, it does a very different group of patients in NETTER-1 than it would have been NETTER-2. The overall somatostatin analog baseline therapy is important. I think there is 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 not going too much into cross-trial comparisons. Markus, you want to add anything?
Yeah. Again, it is very difficult to compare really between studies. Ours here 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. So, yeah, I do not have anything else in mind, too.
Yeah, 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 is 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, 2, and 3.
Got it. Thank you for taking our questions.
Yeah.
Excellent. Our next question will be from David Dai from UBS. You may proceed with your question.
Oh, great. Thanks for taking my question. So congrats on the data here. Two from me, actually, just one on the acute kidney injury, the one that is possibly related to treatment. Could you maybe share some additional color on whether this is shown in Cohort 2 or Cohort 3, and what is the onset of this acute kidney injury, and what additional kind of monitoring, hydration eligibility or those modification measures you plan to incorporate into the phase III?
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 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. Our next question will be from David Lebowitz of BMO Capital Markets. You may proceed with your question.
Thank you very much for taking my question. When you talk about the deepening responses over time, what is the hypothesis on what makes that happen and why it is predictable that it will continue to happen?
It is a great question. It comes down to the mechanism action for a targeted radiopharmaceutical therapy and even more importantly, an alpha, but also when thinking about the disease state itself. Neuroendocrine tumors are classically known as slow-growing but also slow-dying. When the tumors actually receive enough of a burden, if they are receiving beta particles, it takes about 1,500 beta particles to kill the cancer cell. If it is an alpha, a single alpha particle can kill a cancer cell. But the mechanism action of that is a double-stranded DNA break. The classic video of, or cartoon of a long unstretched coil of DNA that cleanly sort of split in the middle is not really how it happens. DNA is tightly bound up in this massive mess inside the nucleus.
If an alpha particle smashed 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. It is not until it actually goes through its first mitotic cycle that you would actually expect to get the cell to collapse and fall apart. The cells can exist despite having the nucleus being damaged, and they do not 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. It is almost guaranteed with neuroendocrine tumors especially, to be a gap between when the cell dies and when it shrinks on a CT scan.
The only measurement that is being reported out here for that assessment is overall response based on a RECIST 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. It is 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 the responses take longer. It is encouraging to see there's a lot more energy being thrown onto how we actually look at the energy that goes into the cell. If you throw a lot more energy in, you're causing a lot more damage to those cells and a higher probability. You can actually look, for example, on the spider plot.
The spider plot is a RECIST, discrete sort of assessment that's by RECIST, that's by CT scan, and 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. 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 approvable, and we always have to zoom out and say the benefit risk should warrant it. In this case, we think the benefit risk 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. Since VMT-α-NET's 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, whether they are GEP-NETs or not, SSTR status, expression level, or tumor grade, and how can that information help you optimize the phase III design and also the enrollment criteria? Thank you.
Thank you very much, Andy. I'm taking this one. 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. I mentioned before that when we are compared with the more mature data, these phase IIIs 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.
Andy, it makes sense for first principles, and we appreciate the question. If it's a receptor-targeted therapy and the cells don't have the receptor, then they can't receive the damage. 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? It really looks like you can.
That's helpful. Thank you so much.
Thank you.
Thank you. Our next question comes from Li Watze k of Perspective Therapeutics. You may proceed with your. I think it's Li Watze k from Cantor Fitzgerald. Apologies for that. Lee, can you hear us? It appears that we have a connection issue. As a reminder, of course, you could rejoin the queue by pressing star one on your telephone pad. We'll go on to the next questioner in the meantime. Our next questioner is David Nierengarten from Wedbush Securities. You may proceed with your.
Hey, thanks for taking. Hello? Thanks for taking the question. I had one on the regulatory path on phase III planning. Just what are you looking for specifically before you engage with FDA and set up the phase III? Is it determining the correct dose? Is it something with manufacturing or just literally getting a time slot with the FDA? Thanks.
Yeah. Thanks, David, for the question. I will take part of it and pass it over to our regulatory affairs colleague. There is a lot of interaction going along with the FDA. It is a pretty active process. We have a Fast Track designation. We are eligible for the CDRP, which is like a Fast Track on the CMC. We have committed to be ready organizationally by the end of this year on our side. And there are many things that get ready in order to move forward with a clearance to go ahead with a phase III study. Dr. Carrillo-Rivas , do you want to add?
Yes. No, thank you for the question, and I just want to add that, yeah, it has been very busy this year with regards to engaging with the FDA. And right now, as we discussed before, we have very recent data. As the conversations with the FDA are active and, as we 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.
Great. Thanks. Based on what you know so far, what percentage of the patients that you've treated in Cohorts 1 through 3 are patients that would be appropriate for the phase III in terms of the patient profile?
It's a great question, Kemp. 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's really 60%-75% of patients as we look at the screening rates. You can do some back-end 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 criteria. I appreciate the question because that's exactly why we broke out the ORR on that slide in two different buckets, one which is through intent to treat all patients in, and there's the second through the slightly tighter aperture of all patients having homogeneous SSTR2 expression.
Real world, we're seeing in that kind of range, and we expect that to continue.
Okay. 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-GEP-NETs. We had one patient with a paraganglioma pheochromocytoma. We had two bronchial NETs. In a likely approval pathway for GEP-NETs, so gastroenteric, those patients would not be included. Also, those patients with GEP-NETs that did not have all lesions positive could be excluded if we had a tighter criteria. If we look at the prior approved therapy in the space, they had very tight all lesions had to express. That's why to make things easier for you to interpret, we've shown those numbers. As we look at that number, 37% in that Cohort 2 OR and 47% in that Cohort 3, we think those are very meaningful numbers for those that only want to look at the OR 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. Our next question is from Jeet Mukherjee from BTIG. You may proceed with your question.
It's Blake on 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? Then separately, a quick follow-up is just how Cohort 4 is enrolling and when you expect any initial data from that cohort. Thank you.
Sure. At this point, Cohort 4, we don't have any data that we've shared. The cohort is enrolling. That Cohort 4 is actually a slightly different flavor of 20 mCi, and so it's a way for us to move forward. We see the 20 mCi all in at Cohort 2, a very compelling dose with very good benefit-risk trade-offs and the one that we'll be driving forward to bring to initiating a phase III study. Jeet, I apologize. What was the first half of your question?
Just on response kinetics, time to response, and how it differs from other SSTR2-directed therapies.
Yeah. 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 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 RECIST 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 better, and that will be usually an indicator of disease control. Then further, when you actually get a reduction, that's when you actually have the ability to actually look at a decrease in RECIST.
There isn't good data on any other program to see what the initial time to first response looks like that we can find.
Thank you. Our final question will be from Li Watzek 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 Li. 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 and/OR signal you would expect from a pool of physician choice drugs.
Sure. I will let Dr. Puhlmann take that question.
So thank you very much for this question. As we know, there is a variety of drugs approved in this space. Clearly, there is PRRT. There are now several drugs in this space, starting from Lutathera. There is now a biosimilar also, and we expect at some point probably ътретята to come to the market as well. At the same time, there are small molecule inhibitors. The VEGF TKIs come to mind, sunitinib and cabozantinib, as well as everolimus as an mTOR inhibitor. And of course, chemotherapy is also being used, in particular for patient with more aggressive tumor types such as NEC. So, we could envision that the physician's choice could have a variety of those drugs I just mentioned as a choice. How this actually look like in the end, we are still discussing with the regulators.
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 quotas or caps, but you want to guide towards those ranges. So again, this is if we get treating physicians choice as the active comparator, which we would 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. 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 mCi 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 registrational 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 mCi profile, those initial responses with onset of response look compelling, and the disease control rate looks very compelling as well.
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. 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 move forward and track things through. We've done our best to describe a lot that's here. As a reminder, there will be additional presentation at the NANETS conference, North American Neuroendocrine Tumor Society, that's coming up in several weeks. We appreciate everyone for the interest in Perspective 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.