Greetings. Welcome to this VMT-α-NET update at ESMO. At this time, all participants are in listen-only mode. The question-and-answer session will follow today's formal presentation. If anyone should require operator assistance during the conference, please press star zero from your telephone keypad. Please note this conference is being recorded. At this time, I'll now turn the conference over to Annie Cheng, Vice President, Investor Relations. Thank you, Annie. You may now begin.
Thank you, Rob. Good afternoon. Good morning. Welcome to the Perspective Therapeutics call to discuss updated interim VMT-α-NET clinical data being presented at the European Society for Medical Oncology Congress 2025, 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 filing, 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 investor section of our website. These forward-looking statements apply as of today, and we undertake no obligation 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 available there for a period of time after the conclusion of this call. Today's call will start with prepared remarks by our Chief Executive Officer, Thijs Spoor, Chief Medical Officer, Dr. Marcus Puhlmann, and an investigator of the study being presented, Dr. Richard Wahl. After their prepared remarks, we will open the call for questions. With that, I will hand the call over to Thijs.
Great. Thank you, Annie, and thank you, everyone, for joining us on this Monday morning. It's been really exciting to see all the enthusiasm at ESMO and also the highly engaged interest in our program and what we're trying to do for patients. At Perspective Therapeutics, we're really focusing on developing the next generation of targeted therapies. We love the fact that our platform technology is enabling. We've been investing in our infrastructure, and these things together give us a terrific pipeline, which we think has very broad clinical potential. We've got multiple readouts through mid-2026 and beyond, and we really try and de-risk everything with how we design our medicines to really try and take this diagnostics approach.
If we can actually image patients in advance and select how we assess their responses to therapy, we think we have a better chance of developing the best possible medications for patients. We have an active pipeline in clinic right now. We have an active preclinical pipeline too. Our VMT-α-NET program, we have actually completed recruitment in that second dose cohort at 5 millicuries, and we have already recruited the DLT cohort at 6 millicuries in this program. If we look at our melanoma program, we are enrolling now at 3 millicuries in both monotherapy and in combination, and our FAP program is now enrolling at 5 millicuries, where we've actually escalated from 2.5 to 5 millicuries. We're really excited about that program too, but the focus at ESMO today was pretty exciting. We're looking at program VMT-α-NET, which has been engineered to target the somatostatin receptor.
And if it does that, we've found some pretty important takeaways from the presentations today and from the investigators' experiences. Hands down, I think the feeling at ESMO is that neuroendocrine tumors or NETs are a critical unmet medical need. And there is an approved radioligand therapy that is there. But I think the challenge to the industry is, how can we do better? Can we improve on safety? Can we improve on efficacy? Can we improve on both? What's exciting for us at Perspective Therapeutics is that the interim readout of this data is actually highly encouraging, with the ORR of 44% for the median follow-up of 41 weeks and the patients that we actually intend to move forward into a registrational trial. And that's following the NETTER-1 criteria. And we actually look at the patients that are emerging. This is emerging data as we go through.
We're going to show some of the patients and not all. We really want to make sure we've looked at a nine-month follow-up. And patients continue to achieve late objective responses as the trial progresses. And that's not unusual for this tumor type. We also have the ability to evaluate the six millicuries. And we're doing that simultaneously to really see if that establishes a broader therapeutic window. We know from preclinical data that we do have a broad therapeutic window. The question here is, well, this terrific data here that gives, we think, a very good response rate and good disease control, will there be any change in that if we increase the six millicuries instead? So the one thing we're trying to look at is how much does the patient selection criteria here inform what a registrational design could look like.
So we don't want to spend too much time going through neuroendocrine tumors since they're a clear need. And we have regularly spoken about this in the field. But when we actually look at the trial design, the goal is always to try and think through what could a registrational trial look like. And in a registrational trial, we always want to make sure we define the right population. So in this case, we want to make sure these are what we're calling Lutathera-naive patients, which is code for patients that have not received any radiopharmaceutical therapy for a neuroendocrine tumor previously. So they're naive to radiopharmaceutical therapy. And in this trial, we're looking at two different analyses, one which is all patients with at least one tumor that expresses SSTR2. And that can be assessed using an FDA-approved agent.
But then if we think about a registrational pathway using the NETTER-1 criteria, we define that as being patients where all tumors express SSTR2. And so we're going to show the data with all patients enrolled. And also, we're going to show the data under what we think would be a registration-defining patient population where all tumors must express SSTR2. Whenever data sets get presented, inevitably, people want to see what's new and how things progressed. We're very excited. What we're showing here is the difference with the two data. One of those is the April 30th cutoff date, which was the cutoff for the ASCO data. And then there's the data cutoff date of September 12th, which was the cutoff date for the ESMO data. And what's exciting for us is that the difference between these two data presented at these two conferences is we're seeing more.
We're seeing more patients being treated. We're seeing a much longer median follow-up. And also, the number of cohort 2 patients with at least nine months of follow-up, which we think is appropriate to look at for these patients, has increased. We think the staging tolerability is very, very strong. We see strong antitumor activity. And really, we're encouraging that if we look at patients where all tumors express SSTR2, we think that 44% response rate in those groups looks very strong. So I do want to actually sort of turn the microphone over to one of the major investigators in the study. Dr. Richard Wahl is at Washington University. And he's the Elizabeth E. Mallinckrodt Professor of Radiology and has previously been the Chair of the Department of Radiology at Washington University School of Medicine in St. Louis. So Dr. Wahl, I'll turn it over to you.
Thanks, Thijs. So these data were presented by one of our other collaborators, Dr. Helge Dierckx. And you see the title here. This talks about the 55 patients. Next slide, please. So these are, again, as was pointed out by the September 12th data cutoff. And you see the characteristics here, a relatively even distribution between males and females, most with reasonably good ECOG performance, either 0, 76%, or 1, 24%, and an average of a little over three years from when they were diagnosed to they were treated. They all had GEP-NETs. About two-thirds were non-pancreatic, and about a third were pancreatic. A couple of patients were entered who had bronchial NET and one with a pheochromocytoma. Those can also have high SSTR2 receptor expression. So it was a broad basket of patients. The grades included 20% grade 1, about 70% grade 2, and 11% grade 3.
They had substantially been treated with somatostatin analogs, and a variety of other therapies had been included. But a broad range was included, and the median number of prior therapies was one. Next slide, please. So this may look a little complex, but the study started out with a 2.5 millicurie dose given four times in two patients. And dosimetry and tolerability were excellent. And that was increased into cohort 2, which was 5 millicuries each given at four separate occasions, two months apart. And this cohort 2 that has had over nine months, nine months or longer follow-up, are of particular relevance here. There are additional patients who have been accrued, as pointed out on the right in the darker background, who just don't have the follow-up yet. One thing I want to emphasize is that sometimes response can be gradual in these lesions.
So having nine months of follow-up, I think, is highly relevant to beginning to assess response. Not all responses are immediate. This differs from how sometimes chemotherapy would work in a rapidly proliferating tumor. In any case, we see the duration. And we're going to focus on these 55 patients who had follow-up of at least nine months. And next slide, please. So first thing, having given this to quite a large number of patients, is that treatment emergent adverse events are not common. And if they do occur, they're mild. We see two common ones: fatigue and alopecia, a little bit of nausea, not uncommon. But you notice that they're grade 1. In fact, you see most everything here is grade 1 or grade 2. Grade 3 has been infrequent. Lymphopenia is not uncommon. But I think of particular relevance is that no dose-limiting toxicities were identified.
There were no grade 4 or 5 adverse events. There were no treatment-related discontinuations, no serious renal complications, no significant myelosuppression, no dysphagia, and the serious adverse events that were seen in four separate patients were viewed as unrelated to the medication. They included fever, decreased cardiac output, a patient broke their foot, and an incidence of pancreatitis, so quite an excellent profile there. Next slide, please. With agents that are excreted through the kidneys, there can be concern about renal toxicity. These are the creatinine levels in our patients, the 55 we're referring to, and of particular relevance are those out to 96 weeks, excuse me, and we see that the creatinine has been quite stable. There was one, excuse me, seven patients, grade 1 adverse event of mild increase in creatinine, and six have reversed, and one has stabilized, so this was quite encouraging. Next slide, please.
Waterfall plots are a not uncommon way to look at response, and this is a percentage change from baseline, and here are Cohort 2 patients with greater than nine months of follow-up. Here's 23 patients, and we see the range of responses. Most of them have had significant declines in tumor size, and next, please, and it's an interesting exploratory analysis here is to look at every patient had to have positive somatostatin receptor 2 positive scans before they could go in the trial, but the trial did not mandate that every lesion be positive on SSTR2 PET imaging, and this is a preliminary analysis where the lighter pink represent patients who were reviewed by a single reader who assessed whether there was uptake in the lesions and in all of the lesions.
And the ones that are lighter pink are those where there appeared to be lesions which did not have expression. And it's interesting that those particular patients appear to be perhaps less likely to respond. And this is kind of an interesting preliminary observation looking at the totality of somatostatin receptor expression and perhaps informing how additional studies would be defined. This study had wide entry eligibility in that only a single lesion had to be positive. Next slide, please. These are tumor plots of the patients with greater than nine months of follow-up. And here we have N equals 25. And we see here that there has been only one patient death in the study, that X sort of in the middle had progressive neuroendocrine tumor. And they had passed away, but their disease had not yet progressed.
But what we see as substantial instances is that it is quite infrequent so far for the disease to progress. At the bottom, you see three earlier progressors who only really made it through the first cycle of therapy. And we see one other progressor. So these responses and stability have been, I'd say, impressively durable so far, as shown in this swimmers' plot where we have the ability to assess longer term. Next slide, please. And here are the curves with a similar treatment looking at the patients who had SSTR2 expression in all tumors. And the other thing I would point out is that these triangular marks represent when the first responses were seen. And you see that they're scattered on the timeline. Some of the first responses occurring almost up to a year later. So these tumors can respond, that is, shrink more gradually.
So it's not just with the first dose, but these tumor responses evolve. And that's why I think following the patients longer is critically important. Here, it's still quite interesting that the patients who had a more uniform SSTR2 uptake appear to perhaps be doing better than those who have less uniform uptake. Next, please. These are changes in tumor size with time. And I think these are somewhat informative. And we see varying patterns. But the tumor diameters do not immediately shrink in responders. They can gradually evolve. And of note is you see one patient there who has their best response out at 48 weeks. But that didn't actually begin to kick in until about 30 weeks into therapy. So there are some interesting patterns of delayed response. And what we see quite impressively is that most of these curves either go down or are flat.
There is one patient who did progress who had received the 5 millicurie dose. I would also point out that the patients with the 2.5 millicurie dose have done quite well, although it's only a sample of two here. If we look at these same data next slide, please, excluding the patients who had heterogeneous uptake of SSTR2 and look at those who had more homogeneous uptake, it is impressive that there are no progressors identified. And again, these are preliminary data and a preliminary analysis. But they are encouraging and again are supportive of durability of the responses, both partial response and stable disease that we've observed to date in multi-center data. Next slide, please. So just to make it clear, the 55 patients could be assessed for toxicity.
And there were no dose-limiting toxicities, no grade 4 or 5 adverse events, no treatment-related discontinuations, no serious renal complications, no dysphagia, and no significant myelodysplasia. In the 25 patients who had over nine-month follow-up for response, 20 had not progressed. And the RECIST responses continue to evolve. But it's encouraging that the response rate may be higher in those who have uniform somatostatin receptor expression in all tumors in comparison to the entry cohort, which wasn't as restrictive. And of course, these are significantly higher than the published data with Lutathera on the label from NETTER-1. And as I said, two patients in cohort 1 at 2.5 millicuries still have stable disease and are doing well. So multi-center data presenting for the group. This is so far an active and well-tolerated therapy for patients with advanced neuroendocrine tumors.
Follow-up continues, and treatment continues with an observation at the 6 millicuries dose level. So I think I'll stop there and turn it back to Perspective.
Thank you, Rich, for your comments. We would like to thank the patients and their families that participated in this trial. It's really important for us to bring innovative therapies through. As we think about sort of what this means for us as a company and how we continue to advance this medicine, we're absolutely excited about what this data means. It tells us we need to keep going as fast as we can. That medicine really appears well-tolerated and appreciable anti-tumor activity. And we think that the initial results here are highly encouraging. The time to best response, though, is still emerging.
And we do expect to have more patients expect to reach the end of the treatment period by early 2026 and mid-2026 as well. We do have some key learnings that we're focusing on, is that if we look at all those patients where all tumors express SSTR2, and that's consistent with NETTER-1, then in that case, seven responders out of 16 or 44% had a median follow-up at 41 weeks. We think the five millicuries shows really compelling clinical profile. And the safety should not be ignored on this data. These are patients that have a disease where they're expected to live a very, very long time. And we certainly don't want to be in a position where we induce a chronic condition into a patient that otherwise can live a very, very long, healthy, normal life.
In terms of explaining Perspective Therapeutics to the investors in the company, we do have additional data points coming out, especially with the VMT-α-NET program. We think as we've guided early 2026, we'll be able to see anti-tumor activity data from nearly all these cohorts of patients. And then by mid-2026, we should be able to see the anti-tumor activity from those patients longer, as well as including some of the patients, the first eight that we've actually dosed in cohort 3 at the six millicurie dose. So we want to thank everyone for dialing in and listening to this first portion. We'll now open up the line for questions and answers.
Thank you. We'll now be conducting a question-and-answer session. If you'd like to ask a question at this time, please press star one from your telephone keypad. And a confirmation tone will indicate your line is in the question queue. You may press star two if you'd like to withdraw your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, for our first question. Our first question is from the line of Leonid Timashev with RBC Capital Markets. Please receive your questions.
Yeah. Thanks for taking my question. I had maybe one for the KOL and then maybe one for a brief follow-up. I guess when you think about the uniformity of SSTR2 expression in your patients and in the real world, I guess how common is it for patients to have expression in all tumors? How do you think about what therapy you'll ultimately use in those patients?
I guess, as you think about using a radiotherapy, would you use it in patients who only have expression in all their tumors and you'd select a different drug for the more mixed expression? But I guess I'm trying to understand, in the real world, should we be thinking about that 44% response rate? Should we be thinking more about the 35% response rate? And then maybe a quick follow-up after. Thanks.
Well, I think you're asking me is Dr. Wahl. I think it's early, and I think maybe we don't fully know. I mean, in principle, higher uptake in all lesions would be desirable. It is interesting that one patient who had 60-some% response in a preliminary analysis appeared not to have uptake in every lesion, or at least not uniform uptake, so I think it's kind of an open issue.And, you know, b ut I think it also depends on what the other options available are to the patient. My colleagues at Perspective may have additional thoughts.
This is Markus Puhlmann speaking. So thank you very much, Rich, and Dr. Wahl. If we look at, of course, we just have two levels here. This obviously are data from a phase one study. In a phase one study, the important aspect is to determine, first and foremost, the safety of the drug. And usually, efficacy evaluations then are pushed to later phase evaluations. In more definitive trials, of course, then one would change the eligibility criteria more to determine the actual efficacy of a drug. And if we look at the therapeutic landscape in this indication, then it is clear that the NETTER-1 criteria were chosen in a way that favors, of course, a positive outcome.
Hence, in these more definitive trials, you see that there is much more emphasis on higher expression in target as well as in non-target lesions. And the NETTER-1, I just want to point out, had about a 30% reported failure rate or ineligibility rate based actually on this particular criterion alone. So I think it is important to understand and put these data into perspective.
Yeah. Understood. Maybe I can have one quick follow-up. Just maybe response rate isn't necessarily the best way to think about more indolent, longer-progressing disease. Have you looked at sort of landmark PFS analyses or how that may compare and any thoughts there?
So we have currently, with our current database lock, of course, a still relatively immature data set where we haven't really looked yet at landmark analysis. We have preliminary analysis, of course, that show if you look at the data set and you apply the NETTER-1 criterion, then it is quite obvious you have, out of the 16 patients, 14 that are currently ongoing. One patient was a rapid progressor and failed quite quickly in a non-target area, whereas another subject passed away. It is currently unclear whether this is due to progressive disease or any other comorbidities.
Thanks, Leo. Maybe we can take the next question since there are a bunch of other people on the call still.
Oh, yes. Thank you. The next question is from the line of Jeff Jones with Oppenheimer. Please go ahead with your question.
Good morning, guys. Congrats on the data. And thanks for taking the question. I guess drilling down onto the SSTR2 positivity issue, can you clarify how you're actually defining SSTR2 positivity beyond sort of one tumor or multiple tumors? And maybe compare or contrast that with what has been done with NETTER-1 or ITM's COMPETE trial and certainly the AlphaMedix study. Then I have one follow-up.
Thanks, Jeff. Sorry, this is Dr. Wahl. I was just going to say, just to be clear, the NETTER-1 included Octreoscan and single photon imaging. And current practice involves PET imaging with PET imaging agents. So the PET technique is a more sensitive technique. So the SPECT technique is biased to finding lesions which are hotter and bigger, more intense than PET. And maybe I'll just turn it back to, but just to be clear that the entry criteria, the imaging technology evolved in that period of time.
Steve, go ahead.
Sure. Thanks. Jeff, as Marcus mentioned, we had a relatively forgiving way of bringing patients into our study so that we could achieve the objectives of a phase one trial, which is primarily to determine safety and also to really understand how the drug works, not only in patients where we expect a much higher chance of response, but also to see how the drug works in patients who maybe have less SSTR2 expression. So NETTER-1 initially was designed with the requirement that all technically evaluable lesions express SSTR2 by functional imaging. And as Dr. Wahl said, that in the NETTER-1 era was from octreotide scanning, which is a different scanning mechanism than what we've used. But anyway, bottom line is this. For NETTER-1, at the beginning, it was modified slightly during the study.
But from the beginning, it was any tumor that you can see on cross-sectional imaging had to have SSTR2 expression on functional imaging. So it's a higher bar for expression. And the point is to try to select for patients who are more likely to derive a benefit from the therapy. That's all well and good for a phase three study. And again, it's a different objective that we had in our study. But we wanted to look to the future for this drug and see what we are likely to see when we get to registration and also provide a little bit better consistent comparison between our results and what's been seen with other studies. So I hope that answers your question.
Appreciate that, Steve.
And then quick follow-up, just any update on your thinking about response kinetics and what drives these early versus late responses? Any thoughts on relative dose intensity now that you've increased the population and have a little more visibility on sort of what equivalent weight-based dose these patients are getting? So maybe I'll just go ahead, Marcus. It's fine. Sorry. Rich, please go ahead.
Oh, I was just going to say I'll comment as to the response. In a tumor that's not proliferating very rapidly, the most radiosensitive cells are typically the proliferating cells. So sometimes with cells that don't proliferate rapidly, the tumor shrinkage for a variety of mechanisms is slower because a lot of times the cells with radiation in particular don't really die until they try to divide. So I think in slow-dividing tumors, they may be reproductively dead, but they may be metabolically still active. So it's not totally surprising that the tumors may shrink later.
It is impressive how much later they shrink and fairly dramatically in some cases. But I don't think it's completely surprising given the slower proliferative rate of some of the tumors included in this study. Yeah. And Marcus?
Thank you very much, Dr. Wahl. I just want to, Jeff, I just want to point out we actually have, since the data cut from ASCO, the patient that responded actually quite a bit earlier than what we've seen before. So there's obviously a little bit of a selection bias as well where before we had some patients that responded a little bit later. This time, we added quite a few patients that also responded early. And just to close with the last thing, Jeff, we haven't seen any major patterns or any patterns that have emerged about weight-based dosing. And so that's why we stopped sort of emphasizing that. Great.
Really appreciate it, guys. I'll jump back in queue. Thank you. Thanks.
Thank you. Due to the availability of the panelists we have joining us today, we ask that you please limit yourself to one question. Our next question comes from the line of Alex Stranahan with Bank of America. Please proceed with your question.
Hey, guys. Thanks for taking our questions and congrats on the update. Maybe just one on how you're currently thinking about future studies for VMT-α-NET and ways to maybe accelerate past the registration given Sanofi is planning their phase three for AlphaMedix. Obviously, this depends on what we see in cohort three. But I guess what are sort of the gating factors that you're looking for from the current study to get confident on pushing this towards the pivotal? Thank you.
So Alex, it's a great question. Thank you. I mean, as we looked at the data presented a year ago at NANETS, one of the things that the data showed, clinicians, was that this is an incredibly interesting option for patients, and so the physician and patient engagement to come into our program and into our studies has been absolutely fantastic. Our clinical operations team is in full gear looking at adding more sites on board. We keep opening up more sites with the expectation of getting into registration study mode. We know that our supply chain is amping up its capacity as well, so we know that the clinical need is there. We think patients who are more stable with somatostatin and then start to progress seek options when they need an option.
And so the alternatives are a standard of care with a defined ORR and the chance to sort of get a much higher overall response rate with a better safety profile is very, very compelling for those patients. So we think that's being driven a lot by clinical interest, clinical demand, and our ability to add on new sites and open up new sites to allow more patients to be able to come in.
Okay. Thank you. Our next question is from the line of Li Watsek with Cantor Fitzgerald. Please receive your questions.
Hey, guys. Thanks for taking our questions and congrats on the data. Maybe just on dysphagia, that looks very differentiated from AlphaMedix. For example, why do you think you guys are not seeing this side effect? And maybe Dr. Wahl can just comment on how clinically relevant this is.
Maybe I'll just comment that having seen dysphagia and the safety profile has really been quite excellent. I mean, obviously, if patients do have dysphagia, it can be, depending on how severe it is, it can be disabling. So I guess it's hard for me to comment beyond not having seen this as an issue. Maybe I'll turn it back to maybe Dr. Schultz or others who could comment on or who else is on about the reasons for not seeing dysphagia.
T hanks for the question. This is Steve Keith, medical oncologist with the company. We do see the toxicity profile for VMT-α-NET as being a really important differentiator for our product in the field. We see a really manageable side effect profile that includes, importantly, no dysphagia. We also are seeing no serious renal complications. These are things that really matter to clinicians.
These patients live for a long time, and what we heard about another product this morning at ESMO was that the adverse event profile includes dysphagia, which was experienced by 48% of the patients in the population. Some of those cases were high-grade, and many of those patients required interventions that were not necessarily trivial things and also didn't always result in patients achieving a good long-term effect, so we don't see that in our product. We don't know exactly why that's the case, but some of the things that we would note that may be areas for further exploration are that the products are different in three key respects. Number one, the targeting moieties are different. Number two, the chelators are different, and number three, the linkers are different. Our product in all three aspects are unique.
And we think that, for instance, with respect to the targeting moiety, that we probably have a differential affinity for receptors in the SSTR family. Of course, SSTR2 is the target, but there are many receptors in the SSTR family. And these are expressed in neurologic or neuroendocrine-type tissues. The muscular control of the lower esophageal sphincter is controlled by a very complex network of nerves that includes the myenteric plexus. It includes the vagal nerve. It includes splenic neurologic innervation. It includes the phrenic nerve. And we think that because what we're hearing from the other product is that they're requiring Botox, that they probably have constitutive constriction, which means that they're probably also having some kind of neurologic toxicity that's long-term. So again, we don't know exactly what it is, but there is a very clear difference. We see absolutely none. It seems like it's a very real problem with that product. We think it's an important differentiator.
Thank you. Our next question is from the line of Yuan Zhi with B. Riley Securities. Please go ahead with your question.
Thank you for taking our questions. Can you clarify the disease control rate from your five-patient cohort? And for all RECIST evaluations, is it local assessment or central review? Thank you.
Thank you very much for the question, Yuan Zhi. So at the moment, all the reads are performed by the sites. We have very experienced sites, often with specific radiological units that are specialized on RECIST readings. We have not conducted a BICR yet, but we are collecting and holding all the scans. So we could do this in the past. At this moment in time, since the study is ongoing and is not mature, it doesn't make too much sense.
Thank you for the question. I might add to that. At the Washington University site, as Marcus referred to, I think we're the second-highest accruing site. But at our site, we have a specialized tumor response assessment unit. And the assessments of tumor response are made by observers, experienced radiologists who are blinded to the therapy that the patient has received. So our site response assessments are blinded. And I do, and Marcus talked about the other sites.
Our next question is from the line of Philip Ecker with LifeSci Capital. Please proceed with your question.
Yes. Good morning or good afternoon, Berlin time. Yeah, this is Philip jumping for Oliver. Thanks for taking the question.
Just on the safety data, really, and an indication where quality of life for the patient is so important. We just really saw this great data here. But still, could you give some light on the grade three, I see diarrhea and also hypertension patients and perhaps any causal explanation on why those show up?
So thank you very much, first of all, for the question. So clearly, diarrhea, one has to understand how it's actually quantified. It's the number of stools per day. Usually, more than six would qualify for a grade three diarrhea. This particular AE is usually limited and could constitute or is very often associated with the actual drug administration, but usually is self-limited and can be treated with over-the-counter drug quite effectively. Regarding hypertension, it's sometimes difficult to discern hypertension caused by the underlying disease.
But we see hypertension grade three only in a small percentage of patients. And usually, medical oncologists are quite astute in treating this particular side effect. And maybe I can ask Dr. Wahl to comment here as well.
Yeah. I mean, I must say that we haven't seen symptomatic hypertension or I have not seen hypertension in my site. So I have not had to treat any patient for hypertension. And I don't have line of sight to the other exact cases that were identified. The other thing about assessing diarrhea, just to be clear, is patient reported how often do they have a bowel movement in a day. And so there is some, probably, variability in patient assessment of diarrhea.
I mean, clinically, I would say that in patients who've responded, the typical clinical scenario has been their diarrhea has improved substantially clinically, and their quality of life has improved as their functional neuroendocrine tumors have come under better control. That's helpful. Thank you.
Our next question is from the line of Justin Walsh with JonesTrading. Please receive your question.
Hi. Thanks for taking the question. As it looks like, Pb-212-based radiopharmaceuticals are showing strong enough effects to support potential approval in NET patients. I'm wondering if you can comment on how the treatment experience is similar or different to that of Lutathera for these patients. Maybe we can ask Dr. Wahl for his opinion and experience here.
Well, they're actually quite similar in terms of how patients are treated. The 10.6-hour half-life of Pb-212 is long enough that it's workable.
We typically get it shipped in and treat our patients in the morning. There's an amino acid infusion that starts before the patient is treated and then continues after the infusion, but it's actually very similar in terms of the patient experience. We don't typically see any kind of immediate adverse events, so I would say the patient experience is really quite comparable, and sites that can do Lutathera should be able to do the Pb-212. You typically will do them in the morning because of the half-life or maybe early afternoon, but you have the amino acid infusion, which is part of the reason the patients are around for several hours, but obviously, sites need to have the right license to receive Pb-212. It's different than lutetium, but the radiation safety is actually easier with Pb-212, in my estimation, because of the shorter half-life.
If for whatever reason you have any contamination, the Pb-212 decays away quite quickly with the lutetium. Half-life is substantially longer and is a little bit more of a challenge radiation waste-wise and in terms of cleanups. But they're really, in my opinion, quite similar in terms of how they're performed. Thank you.
The next question is from the line of David Nierengarten with Wedbush Securities. Please proceed with your question.
Hi. Thanks for taking the question and one for the KOL. I noticed on the AlphaMedix product that some of the side effects or treatment emergent effects were well after the Pb-212 should have been gone from the system. And I was just wondering, how do you think about that from a practice point of view? These adverse events pop up much, again, well after treatment's concluded. How does that figure into your treatment choice when you think about that potential for those adverse events? Thanks.
I think maybe you're addressing that to me. I mean, with this particular product, which is where I have the experience, we follow our patients routinely. We get labs several times after the last treatment or after each treatment cycle. The safety profile has been really quite good, and there hasn't been any, other than routine visits, there hasn't been any major unexpected issues, honestly, in the safety profile. I don't have, and I wasn't in attendance at the presentation about the other product. So I don't think I can comment about that. Maybe others from Perspective can comment, but this routine follow-up of these patients, just like we follow up a Lutathera patient, seems to work very well. And obviously, we stay in regular contact with our patients after the treatment. Maybe somebody from Perspective could comment.
We did discuss some of these latent toxicities that were reported during the AlphaMedix trial. In particular, dysphagia was reported initially in a smaller percentage of patients, but apparently appeared in a much larger extent during or at least in the follow-up period. It's not clear why there's a delay. Clearly, investigators who participated in the trial weren't completely certain why that was. But what is clear is that AEs such as dysphagia did occur during the therapy period as well. It's not that suddenly nothing happened and suddenly AEs did occur. There were instances where AEs such as dysphagia or deterioration in the renal function occurred during the treatment period. Okay. Thank you.
Thank you. The next question is from the line of Christopher Lui with Lucid Capital Markets. Please proceed with your question.
Hey, guys. Congrats on the data. And thanks for the question. Maybe one for Dr. Wahl. In terms of the profile we see here for VMT-α-NET, how would you think about it in terms of the landscape with Lutathera and potentially AlphaMedix?
Well, I'd say it's good that patients with neuroendocrine tumors are going to have options. As I said, I have not used the AlphaMedix product. But clearly, registration-phased trials will tell us more about how these agents really compare. My initial assessment is that compared to what I've seen in our Lutathera patients, I think we see a higher frequency of anatomic tumor response. And they're quite durable with this VMT-α-NET as compared to what we're seeing with lutetium Lutathera.
Clearly, the safety profile will be important because, as was pointed out, many of these patients live, if they're fortunate, for quite a long period of time. So the longer-term safety is important. I think it's good that there will be options. But as the data emerge, we'll know more. But if I have a choice between a possibly lower response rate and a higher response rate with comparable favorable toxicity profiles, I'd probably go with the agent that had a higher response rate and seemingly highly durable responses. But the data have to emerge in larger comparable populations. Other comments?
I think it was very well said. Thank you. Yeah.
Our next question comes from the line of Kemp Dolliver with Brookline Capital Markets. Please proceed with your question.
Great. Thank you for taking the question. This is for Dr. Wahl. Just thinking broadly about your experience treating patients and the time to response, what patterns do you see generally? And the reason I ask this specifically is there are two patients that are on the cusp of response. And I'm thinking about the possibility that at some point, they may become responders. So if you could give some color on that.
Okay. Well, I think just to be clear, I've done a lot of work on tumor response over the years. And tumor response is a continuum. And I think looking at the waterfall plots, it's probably more important than an arbitrary 30%. It's not somewhat arbitrary 30% decline in tumor volume. So I mean, I think looking at that waterfall, if you got 29%, there's measurement error. I mean, will they possibly continue to respond? Yes.
But I think you kind of have to look at the whole of the response curve and also the whole of the lack of progression curve, what happens after they respond or they stabilize. So I think it's a little bit dangerous to just talk about response on its own and say that 30% is somehow magical. I mean, 28% is good. 49% is good as opposed to 50. So I tend not to think about response perhaps as originally about partial response or not. The other thing about these tumors is, as these evolve, how they respond still needs to be determined. Do they necrose in the middle? If they have dead tumor in the middle, the tumor size on CT hasn't completely. There's a size and a residual abnormality that may never go away, but it could all be dead.
Criteria for using somatostatin response, PET scanning response for evolving, which may be more informative. So I would view this, the RECIST response is well accepted, but it's an imperfect metric. And I think you kind of have to look at the totality and the nature of the responses. And again, with slower-growing tumors, and some of these are, the responses being delayed is not in any way shocking.
Great. Thank you.
Yeah. You're welcome.
Thank you. Our last question is from the line of Jeet Mukherjee with BTIG. Please proceed with your question.
Great. Thanks for taking the question. While acknowledging the difference in follow-up between the two studies, how does your current response rate compare using the AlphaMedix enrollment criteria? And how does that differ from the NETTER-1 criteria? Thank you.
T hank you very much, Jeet. Yeah. So the AlphaMedix criteria are a little bit less stringent than the NETTER-1 criteria. And if we apply these criteria, actually, we would regain one of the responders for an objective response rate of 47%. So does this answer your question?
Yeah. And just how that differs from NETTER-1?
So NETTER-1, as I said, we have a 44% response rate. Again, this is an exploratory analysis of an ongoing phase one. With the Radiometics, it goes up to 47%. But of course, Dr. Wahl just mentioned that we fully agree. The benefit that patients gain from the therapy of the drug cannot necessarily be just measured and evaluated by the RECIST criteria. We fully agree, a patient with a 29.6% tumor reduction probably has a very similar benefit than somebody with a 32% reduction.
So I think there are many other criteria that play here, such as quality of life and the lack of, certainly, the safety of a therapy is equally important.
Thank you. This concludes our question-and-answer session. I'll now hand the floor back to management for any closing remarks. Great.
We'd like to thank everyone for taking the time to learn more about our program. I think you can see why we're clearly very excited, encouraged, and enabled by the results that we're seeing. We think this is a potentially meaningful, relevant tool for clinicians to use when thinking about their patients with neuroendocrine tumors. These patients are expected to have long lives but for their existing tumor condition. And anything we can do to help them, we're absolutely committed to developing to the best of our ability. So with that, I'd like to thank everyone for their time and enjoy the rest of your week.
Thank you. Ladies and gentlemen, thank you for your participation. This does conclude today's teleconference. You may disconnect your lines and have a wonderful day.