Viewpoint Molecular Targeting, Inc. (CATX) Earnings Call Transcript & Summary

Greetings. Welcome to Isoray Medical-Viewpoint Molecular Targeting Investor Webcast. [Operator Instructions] Please note this conference is being recorded. I will now turn the conference over to your presenters. Please go ahead.

Good afternoon. Thank you for joining us today. I'm Lori Woods, CEO of Isoray, and joining me today is Thijs Spoor, the CEO of Viewpoint Molecular Targeting; Michael Schultz, co-founder and Chief Scientific Officer of Viewpoint Molecular Targeting; Dr. Geoffrey Johnson from the Mayo Clinic, who will be speaking on his experiences with metastatic melanoma; and Dr. Vikas Prasad, who is working at Washington University in St. Louis and will discuss his experiences imaging and treating neuroendocrine tumors in animals and humans. First, I'd like to take a couple of minutes and give you an overview of Isoray. Isoray uses the radioisotope Cesium-131 in the form of brachytherapy seeds to treat a variety of cancers, including our primary market, prostate cancer, and other cancers including brain, head and neck and lung. We're the only company in the world who manufactures and distributes Cesium-131 brachytherapy seeds. Cesium-131 has 2 important characteristics when compared to the competing isotopes. It has high energy, which allows it to aggressively kill the tumors; and a short half-life, which means it leaves the body quickly after delivering the therapeutic dose from the inside out. Although prostate cancer has been the primary focus of the company, due to the unique characteristics of Cesium-131, we have been approached by leading cancer institutions to discuss combination therapies, which we believe will be the future value drivers for the company. I'd like to highlight 2 of our current immuno-oncology clinical trials that we're very excited about. The first is with the University of Cincinnati and Thomas Jefferson University and is the first brachytherapy PD-1 inhibitor combination study in recurrent head and neck cancer combining Cesium-131 with KEYTRUDA. The second trial with another leading cancer institution combined Cesium-131 with nivolumab to treat metastatic melanoma. These clinical trials have already led to discussions with other research institutions regarding how Cesium-131 can be used in combination therapies to treat difficult cancers. Turning to our interest in the targeted alpha therapy market. We began due diligence in this market about 18 months ago, comparing 6 potential isotopes that included lead-212. It quickly became apparent to us that lead-212 had distinct advantages over the other isotopes we reviewed. So we engaged a leading industry research firm to take a deeper dive into this market, and they confirmed our conclusions. We then profiled the companies in the space, and that led to our meeting Viewpoint. In speaking with Viewpoint, we quickly discovered we shared common beliefs of how to best deliver radiation therapy. We share the belief that radiation should spare healthy tissues and be delivered from the inside out. We also believe in a targeted, personalized approach to treating each patient's cancer. These shared beliefs along with business synergies bringing together 2 organizations that have very little overlap. Isoray has sales and marketing, finance, quality and regulatory and HR departments, while Viewpoint brings access to laboratory space, project management and strong technical and scientific teams, really creating a world-class organization in the delivery of personalized targeted inside-out therapies. I'll leave you with this last slide that provides a stunning visual on what we mean when we say inside out. This slide shows 2 patients, the patient on the left who had whole brain radiation. Please note that the areas in black and white did not receive radiation. On the right is a patient who received a Cesium-131 implant at the time of surgery. The radiation was to deliver exactly where the neurosurgeon wanted it delivered, right around the edges of the resected tumor bed, sparing most of the brain. This slide highlights our belief in treating cancers from the inside out and why we're so excited about our merger with Viewpoint, whose technology will treat patients in need on a molecular level. I will now turn the presentation over to Thijs Spoor, CEO of Viewpoint Molecular Targeting.

Thank you, Lori. We're really excited to talk about Viewpoint Molecular Targeting today, and I know that we've had a lot of questions as to who we are. Viewpoint is a University of Iowa spin-out. We have an amazing development team in-house. We have a great team of scientists, PhDs and chemists and physicians that all together work on really developing the best possible tracer for patients with unmet medical needs. What's really exciting about the story is that we've actually developed a lot of IP in-house to really look at the isotope supply chain, to look at how to sort of chelate these isotopes and combine these metals safely to turn them into targeted drugs. And what's so exciting about our progress so far is that we actually have 2 clinical stage programs right now and actually an amazing pipeline right behind it. So we haven't stopped at their current successes. We keep innovating as we go, and we're very excited as to how it all moves forward. One of the things that any drug company really tries to think about is what are those unmet medical needs. So we're not that excited about doing me-too products or generics. That's not our business. What we're excited about is dealing with unmet medical needs. And so for example, there's something called a neuroendocrine tumor that represents an extraordinary opportunity to make a difference in patients' lives. And currently, this opportunity is valued at over $5 billion in terms of global sales for these kinds of products. I think everyone has heard about melanoma and its risks, and we actually have a very interesting drug in metastatic melanoma that we think also represents extraordinary opportunity. And what's nice for me is I look at the team of Viewpoint scientists that are working together to build this program forward as we've been recognized with actually quite a few grants from the NIH and NCI, the National Cancer Institute, and that's been around $18 million to date. So we really appreciate the scientific and financial validation of where we're going. In order to sort of talk about the development pipeline on the slide that we have here, it's really important to think about these are all different kinds of drugs, and each drug has both an imaging and a therapeutic portion. The lead program is targeting the endocrine tumors. The second program is targeting advanced melanoma. And we're going to have some world-leading physicians talk about that later on in this call. But our scientists keep innovating. And behind the scenes, we also have additional programs in place where we're looking at breast cancer, prostate cancer, pancreatic cancer and a whole range of other tumors and really trying to take personalized medicine into a very sort of clean level for patients to understand. If we can actually visualize the patient in advance of the therapeutic, we think then we can give them some of the best possible treatment options. And then last, underpinning it all, we have a core technology with a nuclide generator system. So it's a lot to understand there. But what it means is we are taking a lot of risk at the radioactive material supply chain and developing that for easy access so that patients can get drug as needed and when needed. So just thinking about what radiopharmaceuticals are. And on this slide, what we want to highlight is that this is really emerging as the new pillar in oncology. There are many, many opportunities across many tumor types for how molecularly targeted radiation can make a difference. The idea is that -- as Lori mentioned, is we're not going to hit cancer from the outside-in and run a higher risk of hitting healthy tissue. We want to target cancer from the inside-out. And we think that doing molecular targeting is another approach that can do this and actually get the patients' cancers treated inside-out, having prescreened who is the most relevant patient for that. By having these companion imaging agents, we actually think we can actually choose the right patients. So before a patient gets dosed with the therapeutic, we can see in advance that they actually have a scan that shows that we have a really good probability of success, of the therapy going exactly where it's supposed to. The therapies that we're developing can either be given as monotherapy or as combination therapies. And we have great animal data that implies that we can go in either path. We still need to do the development work with the FDA's guidance to make sure we find the right way to image a patient and treat a patient, but we see an awful lot of synergies coming off the research that we've done in our lab. And the nice thing about these technologies and therapies we're developing is that we think they're really outpatient-friendly. The fact that you've got somewhere in the range of 20 million to 30 million patients a year in the U.S. who receive nuclear medicine procedures currently, there's a well-established infrastructure that actually lets patients get access to the products. There's the supply chain that offers this to physicians in a way that is friendly to their locations. We actually think that given the overall global supply chain and the ease with which physicians have access to isotopes, we've taken a lot of the risk out. Patients get access to isotopes in whatever hospitals or regions of the country where they are based on the very well-established discipline called nuclear medicine. And a lot of patient scans and scanners and departments are well suited to actually offer our therapy to the patients that they see in front of them. I've mentioned to you previously about types of radiation and alluded to it. And I want to really kind of zoom out to first principles and really explain what's going on. On this slide, this cartoon shows the differences between alpha, beta and gamma radiation, and they're not interchangeable. So gamma rays is what everyone thinks about usually when you think about X-rays. They'll penetrate through a lot of different surfaces and they'll deliver energy gradually across their path. But we're really excited about some of these subatomic particles, alpha particles and beta particles. And as we look at these particles, that's where things get really interesting. Betas can actually penetrate about 200 cell diameters. They'll go through paper and skin and go a certain distance before they deliver their energy. But we're really excited about alpha particles. Alpha particles travel about 2 cell diameters only, and they're massive. They're about 8,000 times as massive as a beta particle, with thousands of times more energy that gets delivered into the tumor. And our whole approach is getting radiation to the tumor and targeting it from the inside-out. As we think about how to apply this, though, I want to turn the microphone over to Dr. Michael Schultz, who is one of Viewpoint's co-founders and inventors of some of the technology. Mike?

Thanks, Thijs. I really appreciate the conversation. And if the forms of radiation were one of the fundamentals of the technology that we're developing for therapy for cancer, then the selection of the isotopes is another very important fundamental. And on this slide, we talk about sort of the 2-step approach that really represents the foundation for the theranostic approaches to cancer therapy. So in step 1, we do an imaging scan where we use an isotope that emits a gamma ray that we can use for developing a detailed understanding of the biodistribution of the drug and the tumor accumulation and clearance from other organs. And then we can use that information quantitatively in step 2 to develop a treatment plan that could be used for delivery of the, in this case, lead-212 for delivery of alpha particles to the tumor microenvironment while monitoring the distribution of the dose clearance out of the body. And in our case, we chose lead-212 and lead-203 as elementally identical isotopes that we can be confident that the lead-203 diagnostic scan will give us quantitative and accurate information about what the biodistribution of the lead-212 will be in the cancer therapeutic stage. So there are several isotopes that could be selected for this type of therapy. And I mentioned that we're looking at these elementally identical lead isotopes. And what you might not know is that there is a long history of the use of isotopes for cancer therapy, beginning with iodine-131 for treatment of thyroid cancer followed by that with a beta emitter called lutetium-177 that turned out to be easier to produce and easier to ship. And it was -- it's a good isotope that has provided benefit for cancer patients. But over the recent years, it's really emerged that alpha particle emitters are -- have the potential to truly be transformative for cancer patients. And that leads to some more decisions. And there's really 2 isotopes that have emerged as the frontrunners here. One, actinium-225, you see there with a 10-day half-life versus our selection and what my research led me to choose as lead-212 with about a 0.5 day half-life. And there's a real reason for choosing lead-212 over actinium-225. The molecules that we designed to target cancer cells, we've designed them so that they rapidly accumulate in the tumor microenvironment and the residual dose is rapidly cleared from the rest of the body. And so biologically, it just didn't make sense to me to have a radioactive isotope with a 10-day half-life that was bound to a molecule that cleared to the body so quickly. So I felt like the idea here is to deliver the highest effective dose that you can to the tumor and the lowest dose to all of the other organs and tissues in the body, and lead-212 was the choice. And I guess the second part of actinium-225 that really led me in this direction of lead isotopes for alpha particle therapy for cancer was this idea of daughter radionuclides. And so here on the left-hand side, you see that actinium-225 decays through a series of other isotopes. So when actinium -- and there's a key fundamental property here of alpha particle decay that leads to the decoupling of the daughter radionuclides from the chelator that's supposed to deliver the therapeutic dose. And those daughters in the case of actinium-225 also have decays of radiation. And those decays then would be deposited in other parts of the body that aren't targeted to the tumor microenvironment. And so this really led me to think that lead-212 had a much higher probability of targeting the alpha particle dose to the tumor microenvironment with minimum dose to other organs and tissues. So if radioactive decay is one of the fundamentals, of course, then the third fundamental that we're going to talk about here is this idea of the development of the targeting ligand. So a great amount of my research in my laboratory has been around development of the targeting ligand. So on the right-hand side of the screen here, you see the cancer cell with the cell surface protein that's found in high concentrations in cancer cells, but not on normal cells. And then we have a targeting ligand that we link to a proprietary chelator that binds tightly to the lead-203 and the lead-212 to deliver that radiation dose and to help us to ensure that, that radiation dose is being delivered to the tumor microenvironment where we're killing the tumor from the inside-out, as Thijs and Lori mentioned, rather than from the outside-in. And my laboratory, as Thijs also mentioned, has 2 of these targeting ligands that we've developed that are going in the clinical trials. And we have 2 world-leading experts in the development and clinical translation of this type of therapeutic agent that are with us today. Geoff Johnson from the Mayo Clinic in Rochester, Minnesota, will speak on metastatic melanoma. And Vikas Prasad, who is now with Washington University in St. Louis, will speak on neuroendocrine tumors. And so now I'm going to turn it over to Dr. Johnson to talk to us about the work that we're doing to target melanoma cells.

Thanks, Mike. I'm going to talk to you about the promise of alpha particle radiotherapy for melanoma. And melanoma is widely known that once it goes metastatic, it is basically a death sentence. We have a multiple different therapies, including immunotherapies that we can try to slow down the disease and aid in patient comfort. But we have very few things we can do that could potentially lead to cure. Alpha particle therapy is a promising new option, and Viewpoint is leading the way. And you have some disclosures I want to highlight that I do have a know-how agreement with Viewpoint. This is the core team from the Mayo Clinic that brought the study forward, funded by the NIH, where we used imaging versions of the therapy to show the promise of the potential therapy to kill the cancer. So what is the basic concept here? On the left, you have a cancer cell in green, and you can see that it has multiple proteins on its surface. Those proteins are targets, are chosen because they are expressed on the surface of just the cancer cells and very few if any other cells in the body. So that when you inject a medicine that's designed to stick to that target, it only sticks to the cancer cells and what doesn't stick washes out of the body quickly. And so the medicine or radiopharmaceutical is designed to be injected into the vein and circulate through the body, stick to the cancer and kill it. And you can see in here that there are 4 components to the design of these medications. In green, the circle you see is the ligand. That's designed to bind to the target, and Viewpoint has created its own specific ligand. Then there's a linker, which holds the molecule together and carries with the ligand a chelator or a cage that you can see in the circle on the right. That is designed to hold a radioactive atom. And we can put 2 different kinds of radioactive atoms in there. We can put a radioactive atom that gives off photons or radiation that can be seen by a scanner such as a PET scanner or a SPECT scanner that lets us see where in the body the medicine went. Once we've identified that a patient is a good candidate, we can inject a different version of the drug that's therapeutic. And in that case, it would contain a lead-212 atom, which gives off alpha emissions and kills the cancer. Here is an example to show you why I and many of us in the field of nuclear medicine and in oncology are excited about alpha emitters in particular compared to the current standard-of-care beta emitters. So this is not the same technology that Viewpoint is developing. This was the Image of the Year from a group in Germany based on what the Society of Nuclear Medicine voted on at the time, because it shows the promise of alpha emitters where beta emitters fail. So on the left, under A, you can see a 3-dimensional image. You could rotate this around in 3D if we were looking at a PET scan. You can see all of these black areas, which are areas where the PET radiotracer or radiopharmaceutical went in the body. And those are sites, in this case, of prostate cancer. So what was injected is a gallium PSMA-11 radiotracer. Unfortunately, this patient continued to progress. And then they received 2 doses of lutetium PSMA. This is now known as Pluvicto. It was FDA approved in March. And in many patients, you can see a response. But in many other patients like this one, the cancer continues to progress because the cancer, for some reason, is resistant to the beta emissions coming off of the drug designed to kill the cancer. This patient then switched to an alpha emitter. So instead of lutetium, which is a beta emitter, they loaded the medication with actinium, which is an alpha emitter. Then you can clearly see that after that, infection in image C, the cancer is almost gone. After one more cycle of therapy, the cancer is gone. And so this, together with other data, has led to a lot of excitement that alpha therapies are the future. There are a number of issues with actinium, and lead-212 is a different alpha emitter that Viewpoint has decided to move forward with, which has some distinct advantages. So beta versus alpha, let's go into it in a little more detail for those who don't understand. On the left, you can see that's the listing for beta emissions, which is -- beta is another term for an electron. It is a very tiny subatomic particle coming off the nuclide. It doesn't have much power. You need many electrons to hit the cancer cell to kill it. And it also has a range of 2 to 12 millimeters, meaning it's going to kill cells around the cell the medicine is bound to, not the actual cell it's bound to. It only causes what are called single DNA strand breaks. So why does that matter? A single DNA strand break in the core of the cancer cell won't kill the cancer cell by itself. You have to have multiple of them to die. And the cancer cell can turn on defenses to protect itself, like we saw on the patient we just looked at. In theory, if the cancer cell repairs itself, but repairs itself incorrectly in its DNA, it can mutate further and become more malignant or you could even have new malignancies that start in the bone marrow, which is a problem with our current beta emitters. An alpha emitter by comparison is a much larger subatomic particle that's emitted from the medicine. It's actually a helium atom's core. It is orders of magnitude bigger. It is much more powerful. And it travels a much shorter distance, therefore it is much, much more precise. It literally kills the cell it's bound to or a couple of cells nearby, and that's it. It causes double DNA strand breaks, which the cancer cell can have no defense for. It literally kills the cell that it radiates. And it can even therefore kill tiny tumors and potentially could lead to a cure in some patients. So Viewpoint developed the technology of a specific ligand that targets the melanocortin receptor sub-type 1. Okay, what is that? It is the target on the melanoma cancer cells that we are trying to use to bind our drug and kill the cancer cells. It's a particularly good target because it is highly expressed or abundantly on the surface of cancer cells, and it is almost nowhere else in the body. Having said that, not every melanoma expresses this receptor target. Therefore, we need to use imaging to select a patient and say this patient is a good candidate versus that patient is not. Another thing that Viewpoint did, which is critical to this development, is they developed their own chelator. On the left in green and blue, you can see some standard chelators for holding on to lead, and it can be either lead-203 for imaging or lead-212 for therapy. Their particular chelator holds on to the lead much more tightly in the body. Therefore, the drug doesn't fall apart after you inject it, which is critical, because you want the radiation to go to the tumor and nowhere else, if at all possible. So the 2 different medicines or radiopharmaceuticals that we studied already in our practice funded by the NIH were both for imaging. We're getting ready for the therapy in the next phase. The top one you can see is with gallium-68. This is used for PET imaging. We use this for patient selection. It's very precise at being able to see a very small amount of the pharmaceutical stuck to cancer to identify a candidate. The bottom one is with lead-203. This is identical in structure to the lead-212 version, which is used for therapy. It's not necessarily as good for imaging, because it has to be imaged with a SPECT scanner, which is a lower-quality technology. But it allows us to have the exact same biodistribution in the body as the lead-212 imaging -- or lead-212 therapy. So we can accurately predict how much of the therapy we're going to need to have a good effect in a given patient. Here's a preclinical animal. It's hard to see because almost all of the medicine that was injected into this mouse went into a tumor melanoma, tumor that you can see circled as T. And what else didn't go to the tumor is being washed out of the body. You can see it in the kidneys, it's going out in the urine. So very precise to the tumor and very few other tissues. This is a description of the study that we had funded by the NIH where we're imaging. I can tell you that our internal safety review committee, which is independent from the study, concluded there were no side effects from either imaging agent in any of the human patients we tested. We enrolled 7 patients, 1 withdrew because of personal reasons in their cancer. So we had 6 that we imaged, and half of them were positive, which is similar to what we were expecting based on what we know about expression of the tumors. So the positive patients on imaging are the ones you select for therapy. I'm going to show you a few of them. Patient 5, 65-year-old woman who had melanoma in the eye that 20 years later came back and metastasized to the liver, was on immunotherapy. You can see on this MRI image on the right, the white rounded areas in her liver, which is a classic appearance for melanoma. We also did an FDG PET/CT. FDG is sugar. It's a radioactive sugar. And when the cancer cells consume it, it lights up. It lets us know that the tumors are alive. Now here down below, you can see with the gallium VMT02, the first research test product here, that the tumor is expressing the melanocortin receptor and the imaging agent is binding to the cancer, meaning that this patient is a candidate for the therapy. Patient 6, 39-year-old man diagnosed in 2007 with a BRAF mutant melanoma on the skin on the back and metastatic to lymph nodes. The patient then later had a number of metastases of cancer in the right pleura. On the right here, you can see a PET scan from the vertex of a head all the way to the toes. This is the FDG PET scan. This is the glucose PET scan. The brain lights up, that's normal on this type of scan, because the brain consumes a lot of energy. You can see a number of black spots to the right of midline in the patient's chest. Those are cancer metastases in around the lung in what we call the pleura. The patient was on chemotherapy between that scan and the subsequent images on the right, which are the VMT02 medicine that we're using to select the patients. So some of those tumors may have died. But you can clearly see that many of them do light up. And I've got 3 images here at 1 hour, 2 hours and 3 hours. And you can see the dark spots in the pleura continue to hold on to an increase in the amount of radioactive drug that they have bound while it's washing out of everything else from the kidneys and the bladder and leaving the body. This is what you want to see with a therapeutic or when you're selecting a patient for a therapy. If we do a cross-sectional image, where you have a CT in black and white showing the anatomy of the patient, and in red now and white, you can see the radioactive medication we injected. Again, on the left, this is in the pleura, you see one lesion with the arrows pointing of a live tumor consuming glucose. On the right, you can see it's taking up a significant amount of the VMT02 imaging radionuclide. That tells us that this patient again has fairly high expression of the melanocortin receptor on their tumors and is a good candidate for therapy. Patient 7 is a 67-year-old man diagnosed in 2021 with a different mutation NRAS-mutant melanoma. And this patient had widely metastatic disease. The patient was on a number of therapies. And unfortunately, after the imaging was completed, the patient did pass away due to their cancer, unrelated to the imaging medications. On the left, you can see an FDG PET scan. Again, the brain is normal, but almost all of those black spots are active live tumors. On the right, you can see that the lymph node underneath the right shoulder and a number of the liver metastases are clearly visible. And as we scroll through the images in more detail, some of those smaller lesions also show up. Having said that, likely all of them express the melanocortin receptor. And the reason we can't see them has more to do with the resolution of the scan than it has to do with whether they express the tumor target. On the left, now you see a cross-sectional image through the chest with the [ aeroplane ] at a large FDG-avid or glucose-consuming tumor. On the right, you can see that the patient, again, has uptake of our research radiopharmaceutical, the VMT02, saying that they're eligible for therapy. And I'm going to show you also here that the patient -- this is the lead-203 VMT01 SPECT CT. This shows you that even though it's a less -- SPECT is a lower-quality scan type. The molecule that is structurally identical to the therapy also clearly shows up in the tumors. And that allows us to calculate how much medicine we should be giving to these patients. And with that, I want to say thank you for your time and say, next, I'm going to pass it off to Dr. Prasad, who is going to talk about alpha therapy and imaging in neuroendocrine tumors.

Thanks, Geoff. That was a nice overview on the melanoma. I am going to speak on the Pb-203, Pb-212, VMT-a-NET and the management of the somatostatin receptor-positive neuroendocrine tumors. Just briefly about me, I'm not going to take a lot of time. I'm an professor of radiology and Director of Clinical Theranostics in the division of nuclear medicine at the Mallinckrodt Institute of Radiology. I just arrived a [ few years ] back in U.S. So what I'm going to briefly walk you through is the journey of a neuroendocrine tumor patient as well as the outcome and the symptoms, which these patients have to deal with. And I'll also explain why we think there is an urgent need for a very effective therapeutic option. So neuroendocrine tumor is a highly heterogeneous kind of tumor, has its origin from the abnormal neuroendocrine cells in the gastrointestinal, pancreas and lung region. They are the places where they can actually originate, but these are the major ones, gastroenteropancreatic neuroendocrine tumors as we call it. They have different grades, slowly proliferating, the G1; mild to moderately proliferating, the G2; and aggressively proliferating, the G3. And if you only look at the life expectancy of the patients with G1 and G2 neuroendocrine tumors is somewhere around [ 30% to 70% ] if they've already -- if the tumor has already metastasized. And it's also important to remember and to stress upon that already approximately 175,000 people are living with this diagnosis and 12,000 patients are adding every year. And the symptoms, apart from the -- caused by the metastasis, the symptoms of these neuroendocrine tumor patients are also due to the functionality of neuroendocrine tumors. What do we understand by the functionality? It means that these tumors actually produce a lot of different kinds of hormones, and that makes patient's life only a problem. For example, patients having diarrhea or flush. Sometimes some of the patients go for 10 to 20 times a day. The other hormonal symptoms, which make their life not that easy, although the life expectancy, I will say, it's good enough in metastasized stage, but the quality of life suffers significantly, and that has an effect on the economic and psychological wellbeing of that patient as well. And despite significant advancement, specifically, for example, with the Lutathera approval and there are new treatment options, despite the significant number of drugs which are already available, the patients are still suffering. And we really need to develop and make these patients different and new kind of treatment available. And alpha particle therapy is actually one of the most promising treatment options for the somatostatin receptor-positive neuroendocrine tumor patients. Before I explain how it actually works and which data we have, I would like to stress that probably the reason why we are still seeing a lot of escape from those already effective treatment options available is that we are using those treatment options in the last stage or second or third or fourth line of treatment. And I think radioligand therapy has the potential to be moved upfront the first line as soon as the patients are diagnosed with a function of the active neuroendocrine tumor, somatostatin-positive metastasis over the body. And these patients should be treated in the first line. It's my personal opinion. And which kind of radioligand should we use for the first line of treatment? Not all. Well, these patients also live for a significant period of time. So we want to have a treatment option which does not lead to an increase in toxicity, and thus, decreases the quality of life for patients because that's very important for the neuroendocrine tumor patients. So we need to have an ideal radioligand, which can be defined as having a very high therapeutic index. What do we mean by therapeutic index? That means that the dose delivered by these radioligand to the tumor should be significantly higher as compared to the dose -- radiation dose being deposited in the normal organs. And this is the therapeutic index, the ratio between tumor to the non-tumor tissues relation dose deposited there. And then when we deposit and when we inject the radioligands in a patient's body, sometimes some of the radionuclides may actually get free at the location of their admission. And that actually can theoretically and, in some cases, it has been shown that can actually lead to an unnecessary additional exposure to the normal tissue. So you actually need to have a very good chelator, which keeps the radioligands tight and bound within itself. Then, because this therapeutic index is very important, there should be a way to assess the amount of radiation dose delivered to the tumor and the amount of radiation dose delivered to the normal organs. And this can be divided into micro macro dosimetry. Let's not make it very complex. Dosimetry means that the doses delivered in and around the tumor and also in the normal organs. So there should be a way to calculate it. And an ideal radioligand should be a radioligand, which gives us a very good quality of image for allowing us, our medical physicists to do this calculation. And of course, any kind of treatment has to be very effective, because these tumor cells are quite smart. So you really need to kill those tumors. It should have very high killing property for these tumor cells, right? So these are the ideal radioligands, which are -- properties of an ideal radioligand, which should then allow us to move up in the first line. But before I go on to the imaging study done in a patient, I will just briefly highlight an extremely interesting and extremely important preclinical data, which actually compared the already approved Lutathera treatment in the mice containing the somatostatin receptor-positive neuroendocrine tumors. And these results were then compared to the Pb-212 VMT-a-NET, which is [ immunotherapy ]. And the results here on the left-hand side on the upper one you are seeing is the vehicle. What do I mean by vehicle? It's like those mice did not receive any treatment. So of course, if you don't treat, these tumors grow. Again, it shows that we really need to treat those patients, that's true. And then on the right side upper panel -- graph, what you're seeing is that these mice are treated with 3 cycles of 500 microcurie -- actually, it was planned to treat with 4x 500 microcurie. But as you have seen, those 3 red arrows from [ 0 until ] 20 days, within the 28 to 29 days, the tumor progressed so rapidly that the animals had to be killed. So those animals could not receive the fourth treatment cycle. And then on the left side lower panel and on the right side lower panel, you are seeing what happens if you treat these mice bearing somatostatin receptor-positive neurocrine tumor with 1 cycle of the Pb-212 VMT-a-NET, that's on the left-hand side; or 4 cycles of Pb-212 VMT-a-NET on the right-hand side. You see those graphs, these dots which you are seeing, if you follow the curve, you are seeing that immediately, only after the first, I'm going to stress it again, only after the first treatment cycle, the tumor size has disappeared, it has gone significantly very quickly down. And even more important is, on the left-hand side, that even when the treatment was stopped and no further treatment cycles were given, there was no escape, the tumor did not come up. And on the right upper panel in the Lutathera arm, you are seeing that there was a rapid escape after 28 days. And the dosing materials, of course, performed and assessment was done and the -- I can tell you that the results are extremely positive in favor of the Pb-212 VMT-a-NET. And that again stresses upon using such kind of treatment in the first-line treatment. We performed or injected in a patient with a functionally active neuroendocrine tumor with very significant amount of metastases on the -- in the liver. These metastases in the liver were producing a significant amount of hormones, and these are certain hormones. And they actually led to a damage of one of the walls on the right-hand side of the heart, which led to kind of a heart dysfunction, and the patient who was only 45, 47 years old, actually had very poor quality of life. And in this stage, the patient was not responding to any other treatment option. The patient came to us when I was at Ulm. And I injected in this patient the Pb-203 VMT-a-NET, which is the diagnostic component of the Pb-212. Why as a diagnostic? Because it gives gamma rays, which can then be captured. On the middle panel, this black and white image which you're seeing, on the right-hand side also, 1-hour and 21-hour images, the whole body images acquired because the gamma imaging of this Pb-203. And those arrows, which you are looking at on the upper side, they are actually the tumor. And you can see immediately within 1 hour, on the lower side, there's a fast renal clearance and majority of the activity was already out into the urinary bladder. And in the kidneys, there was hardly any significant amount of uptick. And on the 21 hours, you can see that there was an even faster clearance from the kidneys. And most remarkably, and this is, again, very important, it's not only that the radioligands cleared them. So they should stick on to the tumor, and that is their purpose to treat. How can you treat? Only when you can have a good response, when you achieve a significant amount of radiation dose. How can you achieve a significant of radiation dose in the tumor? By having a radioligand, which sticks on to the tumor cells and bombards it internally for a significant period of time. And on the left side, what you are seeing, we have got 4 images, axial -- from the PET/CT on the left-hand side and from the SPECT/CT on the right-hand side. The SPECT/CT is the one which was scintigraphy, Pb-203 VMT-a-NET images. And those white arrows where all you are seeing, those are the tumors, which were present which could be seen on PET as well as on the SPECT/CT. Mind you, PET has a much higher resolution than the scintigraphy images, but still because of a very good target/nontarget ratio because of the excellent clearance on the normal organs, we could actually see that the tumor showed a very good uptick immediately within 1 hour and persisted for 21 hours. And if you treat using this VMT-a-NET peptide, combining with Pb-212, you're going to achieve a very high radiation dose from the alpha therapy. And this alpha therapy will lead to significant decrease in the tumor size. And if we are lucky, in some of the patients, we can achieve complete remission as well. And in some of the patients, they can really make a very big difference. And I'm pretty sure this kind of treatment is going to move upfront in the first line of treatment of the gastroenteropancreatic neuroendocrine tumor. With that, I would like to thank you for your attention.

Great. Thank you, Vikas. And so with that, we'll turn it over to Q&A.

[Operator Instructions]

Great. Thank you. Looks like we have a lot of questions here. So the first question is actually for Dr. Johnson. In the melanoma patients, not every tumor was positive on the experimental scans. Does this mean that only the positive tumors will respond to treatment?

Thank you for the question. Hopefully, you can hear me okay. So when you look at those scans, one of the things I mentioned was the FDG scan, when a glucose scan was done prior to the VMT02 scan, so the one in the pleura where I mentioned that the patient was on chemotherapy, those tumors had decreased in size. So some of those tumors that were VMT-negative, if you will, where we didn't see the melanocortin receptor radiopharmaceutical that Viewpoint has designed in the tumor was probably because the tumors were dead. So this is an early proof-of-principle concept here, and we were able to show that there's proof-of-principle that it's finding tumors. But we will need more data to go out and say whether or not all tumors in a given patient take up the target. But you're correct, if there was a patient who had mixed disease, who actually had live tumors that were VMT-negative, where we expected to see it, they were big enough, we should be able to see them with the resolution of the scanner, the patient would probably be a poor candidate for the therapy.

Great. Thank you. Next question -- actually, there's a few questions I'm going to combine together and ask each of you. The first is, are these radio therapies approved in the U.S.? And then -- that will be for Dr. Johnson. And for Dr. Prasad, can you tell us what the landscape is in the European Union in terms of adoption of this type of therapy? Is there infrastructure and is reimbursement in place, I guess, in both geographies? Geoff, do you want to take the first one?

Yes, sure. So in the U.S., there are about 6 different radiopharmaceutical therapies that are currently in use. Two of them you heard mentioned, lutetium dotatate or Lutathera; lutetium PSMA, which I mentioned, which is Pluvicto and I showed you a slide of. There are some other older ones like [ radium ] and Zevalin for hematologic disease. And then the really old one, the iodine for thyroid cancer, which is just simply a free atom. When you look at the path coming -- those are all reimbursable, used in our practice commonly. In our practice, we give about 35 to 40 doses a week of these various medications in cancer patients. When you look forward and you see all of the investment coming with a number of different companies, there is a clear wave, a growing wave of investment in this space because of the recent successes of the lutetium drugs and the kind of data you just saw from Prasad showing just how effective these alpha therapies can be.