Good morning, everyone, and welcome back to day 2 of Oppenheimer's 34th Annual Healthcare Conference. I'm Jeff Jones. I'm one of the senior analysts here on the biotech team, and I'm delighted to welcome Thijs Spoor, CEO of Perspective Therapeutics, to the floor to present the Perspective story. So Thijs, I will hand it over to you.
Great. Thanks, Jeff, and thanks to Oppenheimer for letting me present today. So Thijs Spoor, I'm a nuclear pharmacist by training. I trained almost 30 years ago, back when no one really knew what the field was, and that the field has really exploded now, which is so in rewarding, enabling for me as, as a nuclear pharmacist, to see such an interest in what a difference these radioactive products can make. We are publicly traded, where we trade on the New York Stock Exchange on the stock ticker CATX. And I do have to say that I may make some forward-looking statements, which I would encourage you actually to refer to our filings instead, that are. We keep current with the SEC. I want to talk to you first about a patient.
It becomes really real when we don't look at numbers, we look at people. And this is a woman that actually presented to her physician. She had a massive neuroendocrine tumor in her liver, and you can see here quite clearly. Her ACTH levels were off the chart. She was dysfunctional at home. She was in a state of emotional crisis because all of her neuroendocrine functions were out of whack. And this image was taken four weeks before the first dose of our drug, and what was pretty extraordinary to us is that after a single dose, eight weeks after that first dose of her drug, we had this kind of switch in the scan. And then, after three doses of the drug, she presented with a scan, was back to normal, was able to vacation with her family and back to work.
It truly is uplifting for us as healthcare professionals to see this kind of impact in a patient's life. So we're really excited about what happened with the first human that ever saw this drug, and I want to tell you how we got there and where we're going. So when we look at Perspective Therapeutics, we are a platform radiopharmaceutical company. Everything we do is using a second-generation alpha emitter, lead-212. We do have our own proprietary chelator that we use. We have a pretty broad pipeline that we're developing now with two programs in the clinic. We really benefit from the luxury of having what's called a theranostic pair, which is a combination of lead-203 and lead-212, and I'll explain that a bit further. What that means is we can use the same chemical to image as we use to treat.
Treat what you see, see what you treat. It's very, we think, a reasonable way for physicians to practice medicine. We do have quite a bit of near-term readouts and milestones. We're vertically integrated. We provide our own generator systems to actually provide isotope as needed, and we actually are expanding our logistics capabilities. So we're really excited about what we're doing at Perspective Therapeutics, and in terms of where the programs go. We do have a pretty amazing pipeline. As a company, we started as a spin-out from the University of Iowa, with some expertise that was done in the radiochemical space, and that evolved into what we think are best-in-class radiopharmaceuticals. We have a discovery center here that keeps rolling out new programs, and so our lead program is called VMT-α-NET.
This is an SSTR2 targeting agent that has applications in neuroendocrine tumors. There's also quite a few other tumors where this can be indicated. Our second program is melanoma, a certain subtype called MC1R. We have a companion agent for imaging that uses gamma imaging for SPECT. We also have a companion PET agent for that, the VMT02 product. Our third product in our pipeline, PSV359, targets multiple solid tumors, and we'll be describing more about that product over the year. We've got some great animal data, and we want to show the straight human data sometime in the next few months. And we also have a prostate program that we're in license in collaboration with Mayo Clinic that we'll talk about as well. But we also have a whole series of compounds behind that.
Everything we do is full composition of matter. Our earliest IP starts to expire in 2039, and so we think we've got a pretty long runway of exclusivity to really develop these programs in the best possible way. When you look near term in terms of the catalysts, we are in the midst of a phase I dose-escalation study in the neuroendocrine program. Patients are enrolling now, and I'll give you a bit more granularity about that program. We're gonna expect some sort of communication on safety and efficacy in the third quarter. We are aware of a compassionate use program that's ongoing in India right now, and we expect some of those results to be coming out later this year.
We also have an active melanoma program that's also in phase I dose escalation, and we expect in the third quarter to have some sort of communication about those results. Then, as we develop things for our pipeline, and we get validation on the targets and how it's working with the IP filed, we'll communicate out how those programs are going as well. One of the things that makes me really excited, as a CEO, is to wake up and know that I'm surrounded by an amazing team of people. Our scientific founder, Dr. Michael Schultz, and his co-founder, Dr. Frances Johnson, our Chief Medical Officer, Dr. Puhlmann, came over from Seagen. Jonathan Hunt, our CFO, and Amos Hedt, who leads our business strategy, has spent a lot of his career in clinical development as well.
So a terrific team, and we keep adding to the team and adding in experts as we go through on logistics. We don't need to talk about why radiation is good or bad for cancer. I think that's clearly well understood. The nice thing about molecularly targeted radiation, though, is that you can precisely deliver the radiation exactly to the tumor, and our tagline was: "Killing cancer from the inside out." The great thing is that rather than hitting a lot of healthy tissue, by using molecularly targeted, you're able to go in and actually only address the patient directly. You can choose those patients by using the same chemical that you're using to treat as you can to image. You have the ability to use this with monotherapeutic activity and combination activities as well, depends on the tumor.
You know, cancer can be really quirky, and so we want to fight back with any, any way we can, if it's mono or combination. The nice thing about these treatments, they're outpatient-friendly, and so you can actually use these in hospitals around the world, and this whole supply chain now is geared towards getting best possible therapy to these patients. So we look at what does Perspective Therapeutics do? And so we break down any molecule that we develop. We have full composition of matter IP on the things that we actually bring forward. We'll customize a targeting peptide. We use peptides, not antibodies, at this point. The targeting peptides we think are really beneficial because they actually localize so quickly on the tumor. Within an hour, you can actually get accumulation on the tumor.
We'll tune the linker if needed, and then combine it with our proprietary chelator. Chelator is a chemical cage that holds a radioactive metal in place, and it holds it sort of almost irreversibly in place while it exists. That can either have a lead-203 isotope. That 203 gives a SPECT image, or with the lead-212 version, which gives rise to an alpha particle at the tumor. So what's great here is that the FDA considered these to be chemically equivalent. They are. Generally, what we do is microdosing, so there's no real chemical effect that's gonna be triggered from the amount of materials we're doing. It's in the picomolar range. Instead, the effect comes actually from that release of the alpha particle on tumor.
When we talk about, you know, isotopes that can be used and how they get used, a lot of people are familiar with betas. And so betas have been around for the history of nuclear medicine with I-131. Great isotope for thyroid cancer. Kinda tricky to apply in a lot of other cases because of chemical stability issues and how the distance of beta goes. A beta particle travels about 200 cell diameters, whereas an alpha travels 2. And so if you really want to actually get on target with an isotope of some kind, the field is drifting for a lot of the tumors we're looking at from beta to alpha. Actinium-225 is available for generating alphas. We do have some concerns about the potential for off-target toxicity risk.
There are some supply concerns, and the half-life of actinium makes some logistics easier, but we think there's trade-offs that we choose not to opt into. We think Lead-212 is in that, what you call a Goldilocks place, where it's not too long a half-life, not too short a half-life. The nice thing about that half-life of Lead-212 is that it hits the tumor hard and fast and then disappears, and we think that's really important in oncology, 'cause oncology, a lot of what goes on in the patient is you actually need the body's immune system to actually go and respond, and help the body attack the cancer and get rid of the cancer.
Having an alpha that hits hard and fast and then disappears completely gives a chance for the T cells to come in, for example, and do their job. If you have a constant irradiation of a tumor microenvironment with alphas or betas or external beam, you impact the ability of the T cells to actually do their job properly. So when we build this molecule ground up, you look at the chelator, so where does that metal go? There are generic options, DOTA or TCMC.
Those actually have a charge on them, either -2 or +2, and the company founder, when he looked at this, thought, "Gosh, if I actually switch to a zero charge chelator, that will actually make it more biocompatible." Meaning, if you don't have a charged protein, then the kidneys are less likely to take it up. So the kidneys will pick up a charged protein; they're less likely to pick up an uncharged, and so we have an uncharged net zero charge chelator. But we also found, though, is that actually helps with your labeling, it helps with receptor binding, it helps with internalization, it actually helps with daughter stability, and there's a lot of extra benefits conferred from having what we think is a terrific chelator for Lead-203 and Lead-212.
So we look at how we sort of take that chelator and incorporate it into a molecule. We'll tune the targeting ligand, and by tuning the the linker length as well, we can actually change the PK/PD properties. The luxury we have in radiopharmaceuticals is that we can actually see what happens with minor changes to our structure real time in an animal or a human, and see exactly what's gonna happen with the in vivo fate of every molecule we inject. The, you know, small molecule folks or the non-radioactive folks don't have that luxury. They're looking at overall impacts to the patient or animal. In our case, we can see where it goes. See what you treat, treat what you see.
In our case, by using the identical chemical, because the only thing that changes is the isotope that's in, we use this elemental twin set, we can actually match our peptide PK properties. We can identify exactly what's gonna happen. We can do almost perfectly predictive dosimetry and really identify what's gonna happen to a patient. So in the drug discovery side, in the animal model, we can look at a tumor, for example, planted in the shoulder and really get highest possible tumor activity for kidney ratio. When we get into a human patient, we can actually match our dosimetry profile as well. So we think it's a very elegant way to actually deliver very, very precision medicine at a personalized basis. So let's talk really quickly about neuroendocrine tumors.
And so these have gotten a lot of attention lately because, you know, these are something that a patient's gonna have for quite a while, but then you actually have the ability now to start imaging and start treating. And we actually did our first in-human imaging in 2021 with our agent. We started treating with, in a therapeutic basis last year, and under compassionate use. I'm not gonna spend a ton of time on here, but the neuroendocrine tumors are a really strange group. They can show up all over the body, in various different iterations. But what's common to them is that they tend to express something called SSTR2, and this is a very interesting target because we can actually target that receptor with the peptide sequences that we're developing.
When we look at how we actually do this, you know, targeting SSTR2 is not new, but how we do it, we think is differentiated. And so if you look on the right, you have a generic DOTATOC, and this is a SSTR2-validated, peptide-based, molecule, and so it's going to accumulate in various parts of the body. What should be indisputable this time is that if alphas or betas hit a cancer cell, they will damage the cancer cell. What's also undisputed is that if alphas or betas hit healthy tissue, they will damage healthy tissue. And so what we care about is really, can we tune the molecule to give the best possible tumor ratio as it relates to kidneys or any other organs? The one that's of the greatest interest that we can quantify is that tumor-kidney ratio.
So if you look on the right, anything that's going in color is going to receive a dose. And if we look on the left, there's much more, it's about an 8x improvement of our tumor-to-kidney ratio. So for any injected dose given, a lot more goes to the tumor, and therefore, a lot more of the damage of any tissue in that body is going to tumor versus healthy tissue. So what this we think is a great way to reduce to practice what we do. We can run the same series of animals in a row to head-to-head comparisons within the animal of different compounds, and as we iterate through our discovery platform, we keep tuning this until we get best possible ratios here and best possible biodistribution.
And then when we go forward and go into animals, we can then start, you know, looking at what happens if we actually try and treat. So in this case, this is an AR42J model. It's a fairly standard neuroendocrine tumor model. You're looking at animals, and you're looking at tumor growth within that animal, what happens over time. So untreated, the neuroendocrine tumors in this model grow very quickly, and they get to the point where they escape, and you actually have to sort of sacrifice the animal or it's gonna die because the tumors get so great. There's a fairly fast-growing tumor in this model. If we look at lutetium dotatate, this is similar to an approved product that's on the market. Lutetium dotatate in that model is actually really interesting because it actually shows about a 24-day right shift on the curve.
If you look at these two curves side by side, you can see why the FDA approved Lutathera, because you actually have a shift, and so you do actually have an impact in... You should expect an impact in PFS, progression-free survival. What you're not seeing here, though, is that you have any kind of, sort of tumor lytic activity, and so you're finding that there's a deferral of the tumor being able to grow. We actually then did this in that same model. We actually ran a whole series of different isotopes and, and, and molecules together, and the best results that we got from this was our compound, and given either as a single dose on the left or as four fractions on the right.
So if we compare in this model, the results here, you can see. You know, you don't need to be a statistician to see these are different. You're getting almost complete control in 10 out of 10 animals in the bottom right curve. One of the questions we get is, why 4 doses rather than 1 large dose? The one thing in radiopharmaceutical development that's really hard to try and predict is bone marrow toxicity. And so the way to mitigate that is you fraction out the doses to do less, so that if there is any damage, you do have a chance to kind of have things come back. You can't predict bone marrow toxicity well off an imaging study. Just about every other side effect, you can get a pretty good read for what should happen.
But we took this data to the FDA, and we asked for fast track designation, second-line therapy, so after patients have had Lutathera. And the FDA came back with the best letter I've ever seen. They said they're gonna give us fast track designation, first-line therapy, all SSTR2-expressing tumors. So we're absolutely thrilled. There are some competitors in the market that are actually going pretty actively in second line, so after Lutathera fails, but they only have approval to go in patients that are prior Lutathera responders. So a very, very small segment of the market in the neuroendocrine space. We have been given permission to go forward and study this very early in the patient's disease cycle, and based on this data, we're actually thrilled to kind of move on very, very quickly.
So one of the things we try and do is we try and sort of image an animal, treat an animal, then we go and image in a human, and then after that, treat in a human. So imaging in a human, what we found is that we actually get. There's an awful lot of information on this image. I've seen many compounds fail in early discovery development because on the radioactive side, they, if they don't go where they're supposed to, you can actually learn pretty quickly and kill the program if you need to. What's amazing about this image on the left is what you don't see. You don't see brain, you don't see lung, you don't see anything in the thyroid, you don't see anything in the kidneys, you don't see liver.
All you see really are is metastatic disease or bladder. Then 21 hours later, so in our case, two half-lives later, 80% of the dose has been delivered. The only drug that's not staying in tumor is again being dumped out through the bladder. So we actually like this sort of dosimetry. Hit the tumor hard and fast and then completely disappear. We can image the lead-203 directly on the left. We can also image the lead-212. There actually are now abilities to do post-injection dosimetry, which we think is really, really interesting for best practice of medicine, to actually look at literally what did the patient get versus perfectly predicting what they can get. When we look at these intensity projections after one dose, we see an overall macro resolution of what's happening from a dosimetry perspective basis.
You know, you can see various tumors will all decrease. It's amazing, imaging techniques that let you see real-time what's happening in a patient. So I showed this patient's journey before, you know, a dose before, excuse me, the imaging scan before the first dose, an image after the first dose, and after 3 doses. It's really very rewarding to see these patients come back and, and, and get back to their quality of life and, and have it restored. Dr. Ishita Sen approached us about doing a compassionate use program at her center in India. Results from that program were presented September 28th at the European Association of Nuclear Medicine conference, and she and her collaborators showed some very interesting results in effectively a basket of patients.
Some of these patients on the far left had prior radiopharmaceutical therapy, some did not. There's a mixture of GEP-NETs, so these gastrointestinal or pancreatic neuroendocrine tumors, and there are two medullary thyroid cancer patients. Dr. Sen's collaborators have told us they intend to present the full data set in June at the SNMMI conference in Toronto. And presumably, some of the abstracts for that will come out about a month before. So we expect to see her present her final results from 10 patients with GEP-NETs and two medullary thyroid cancer patients. Right now, we're looking at their kind of response rates, and we're very, very encouraged by what we're seeing. The average dose that was given in her assessment was about 2.9 millicuries.
We're now actually doing a phase I/II study in the U.S. in first line, so patients that are radiopharmaceutical therapy naive. We completed out our first dose cohort 1 at 2.5 millicuries. We're now recruiting in the second dose cohort at 5 millicuries. We don't think we're gonna have to go up to our fourth dose cohort. And we also expect results from this to come out in the third quarter of this year. Yeah, since we will have some read on safety and efficacy that we'll want to communicate to the FDA, we'll also be communicating that to physicians and patients, and so we'll want to make sure the investment community is updated too. But we feel pretty confident about how this trial is going. We're getting great cooperation from the clinical trials.
We are, we actually do have quite a few patients that are recruiting and trying to get into this trial, so that feels like we're on the right path there. I do want to talk about our second program, which is our melanoma program. This is using a different peptide. So if we change the peptide and change the linker, we actually target a totally different, you know, sort of disease state. In this case, we're targeting something called MC1R, which is the melanocortin receptor type one. On the far left, you see a few different images from a trial we did at Mayo Clinic in Rochester, where we actually did a comparison between FDG on the top left, and then two different variants of MC1R expression imaging on the middle and the bottom.
Those results were presented last year, and based on that IND, we actually moved forward and opened up our IND on the therapeutic side, and we're able to actually initiate this trial. I don't want to go too much into melanoma, you know, in terms of explaining the disease state. I think everyone knows what that is. But what we're focusing on is a subgroup, which is the MC1R positive, because that's where we know if the patient expresses on the surface of their cell this marker, then we know we can target it. And one of the things that really kind of blows us away as we look at kind of images is we look at this image, and side by side, same patient, a melanoma patient, clearly metastatic disease.
This poor person, if you look at their FDG scan, they've got tumors riddled throughout their body. And on the far left, what you're seeing is every cell in the body that's glucose hungry. So the brain is quite dark, which is typical for an FDG scan because the brain uses so much glucose. The other parts of the body that are active in glucose uptake and consumption are cancer cells. And so it's been really important to a great tool to use, you know, sort of staging throughout the body. But you want to go one step further. And so if you look on the right, these are all the cells that surface express VMT02 MC1R, excuse me, and then therefore, we can image it with our VMT02 drug.
What's amazing here is that we can actually see some of these metastases in the brain. By doing that, if we can image it in the brain, we hope we can then treat in the brain. Because, again, that small peptide that sneaks across the blood-brain barrier or any leaks in the blood-brain barrier that show a tumor, can also bring the therapeutic isotope and not just the diagnostic one. The kidneys are quite bright here. This is early in the sequence. A later scan of this patient would show that the activity would have dumped out of the bladder. The nice thing is that we actually do think we can add this into existing therapies. There's a lot of demand, we think, in the realm of combination therapies in oncology.
If we look at some of the early animal data in melanoma, if you look at an immunodeficient melanoma model and you see the untreated, you see the kill curve here. The light blue line here is using continuous Zelboraf, which also tends to upregulate MC1R. But then, if you look at the combination with Zelboraf plus a single dose of our drug, you get an extraordinary shift to the right on that curve. If we look at an immunocompetent mouse model that's also checkpoint inhibitor resistant, you see that it's designed to be checkpoint inhibitor resistant. You see that there's not a lot of difference between the control and the dual checkpoint inhibitors.
The dashed line is a monotherapy of our drug, and the solid line is dual checkpoint inhibitors, plus our therapy in this checkpoint inhibitor-resistant model, and we're getting this extraordinary 43% complete response rate. The NCI has given us additional grant to actually push this forward, and we're really excited about what this opens up. As we're looking at dosing our patients right now, we started dosing in our first cohort. This is in sort of post second line in melanoma patients. We enrolled our first cohort fairly quickly. We're now enrolling in the second cohort, and we expect to get results from these two cohorts for safety and efficacy in the third quarter, out to the FDA, out to patients and physicians, and then out to the investment community as well.
So we're really excited to have two different programs that all should be kind of reporting out some view on safety and efficacy as we go forward. We also announced a prostate cancer program. This is in partnership with Mayo Clinic, Rochester, something that they developed in-house that we have a collaboration agreement with. Slightly different structure. It's got two different chelators, and those two different chelators, you can make either copper 64, excuse me, either copper or lead radioactive. So you can have either or, the lead or the copper radioactive, which opens up an additional field in PET imaging as well. And the design of the molecule also, we think, will allow for lower salivary uptake. We've also announced our pre-targeting platform that's come out now.
In this case, you would administer a cold antibody to a patient, and without any sort of major therapeutic impact. And after several days, then you're going to actually have that sort of, you know, accumulation of the antibody on the tumor, and totally cleared out of the blood. And when that's happened, you then administer a radio-labeled ligand, which will bind specifically to the monoclonal antibody that's covering the cells. And so we think this opens up a whole new range of tumors for us as well. Lastly, I want to touch on manufacturing, and it's probably more of a deeper dive. But Lead-212 precursors are actually readily available. The isotope source occurs naturally. Most of what we do is just purification. We don't need to actually scale up massive pieces of equipment to synthesize isotopes that don't exist normally.
If we look at the thorium-228, it's a naturally occurring element. It's plentiful. We've identified multiple supplies of it. It can get warehoused or stored. It's got a 2-year half-life. You can chemically pull out radium-224 from that thorium-228, and that's something you can distribute local regionally, and that allows for the daily production of lead-212, which is done at the local manufacturer level. And then in the body, that gives rise to this bismuth-212 that also kicks out an alpha particle. So we actually can purify these things fairly quickly using resins. Something well known to most scientists is but you're actually going to put your isotope into a column. If you just leave it there, it will turn into a different isotope, and the one that's then it's turned into, you can purify off by running the solvent through. So a very elegant system.
We actually ship this radium-224 in a generator-type form factor. This can be shipped around the world. We've shipped it to Asia, Europe, across North America, and this is something that we actually do on a regular basis. Once a week, our sites or our CDMO partners receive this, and then actually kind of produce the drug real time. When we look at actually what the supply chain dictates, we actually don't need to get our drug to every single person in the U.S. We need to get our drug to every cancer center in the U.S. The big difference there is that we can house that thorium centrally. We can distribute the radium-224 to a contract manufacturer, and then the contract manufacturer will then produce that daily lead-212 and distribute it.
And as we look through what this means for patients, there's 110 GMP PET facilities. There's 340 radio pharmacies that can just drop up patient-specific doses. The technology infrastructure exists. There's a lot of experience and know-how in terms of delivering just-in-time unit doses to patients, a mixture of therapeutics and diagnostics. And we're investing in the infrastructure to make sure that we have the appropriate level of manufacturing rigor to distribute products out there. And we're looking at building out a map of distributor partners that can really help us deliver the product as needed, to wherever the patients are. So great intellectual property portfolio. Everything we do has got incredibly strong composition matter IP, and we keep rolling things out.
For the sake of time, I'm going to pause here, and see, Jeff, if there's any questions.
Yeah. Just maybe on the, on the distributed manufacturing, just to, you know, highlight, what is the, you know, sort of footprint you think you need in terms of number of sites to support, I guess, near-term, your clinical trial plans? And then how many sites would you be talking about for, you know, commercial?
Great, and that's a great question, and it's going to depend a lot on the commercial demand. As we look at right now, we've got two sites that can produce product or that we're scaling up to produce product. And right now we're delivering, for example, our site in Iowa, we deliver to Wisconsin, Minnesota, St. Louis, Chicago, Iowa. We cover a pretty broad swath of the Midwest. We've got a site in Somerset, New Jersey, that will cover a lot of the East Coast. And ultimately, for a registrational trial, we'll probably want 6-8 sites across the U.S. that can cover the U.S. with a combination of air and ground. That's reasonable.
Steady-state commercial, I look at the FDG map, and so at a high volume demand, there's 110 commercial facilities that produce GMP product, but it's in four competing commercial networks. So you're probably going to need, you know, 12-15 commercial sites at commercial scale.
All right. No, that's really helpful. And we are unfortunately up on time. So Thijs, thank you very much. Have a great set of meetings throughout the day, and look forward to catching up again soon.
Sounds great.
All right.
Thanks for having me.