Perspective Therapeutics, Inc. (CATX) Earnings Call Transcript & Summary

Great. Well, welcome, everyone, to our fireside chat with Perspective Therapeutics. We have Thijs Spoor, President and CEO of the company. Thijs, welcome.

Thank you. I appreciate you having me.

Yes. Great. So Perspective Therapeutics, of course, is in the really hot radiopharma space. And last time I checked the stock price, it was up 146% year-to-date, very impressive performance. So for the audience here, who are new to the Perspective story, maybe just give a quick overview of Perspective Therapeutics.

Sure. No. Thank you. And Perspective Therapeutics is a radiopharmaceutical company. We focus on both diagnostics and therapeutics. And this whole concept of theranostics really allows you to come to your best possible scenario if you can use the same molecule to image as you can to treat. So the whole premise is you treat what you see, see what you treat. And by doing that, you can actually do really derisked early clinical programs. So we're really excited about the fact that we can actually be in the space. We've got a lot of support from outside investors. We've had a great appreciation in the stock market year-to-date, which has been sort of really welcome. And as we work on developing our programs further, we keep innovating with new composition matter IP. We have in-house discovery. We have in-house production teams. We have in-house clinical operations teams. And across the board, we feel like we're really well positioned for growth.

That's excellent. So talk about your platform, you're using lead as the reactive isotope. So could you talk a little bit more about your decision to pursue lead and how it differs from other current standard of care?

So lead is an interesting one. I mean, if we looked at this whole gray chart of all the elements that are possible, and you see different isotopes and different epitopes and how you actually think through, lead was really interesting because it had an elemental twin. And so, lead-212 gives rise to an alpha particle, lead-203 gives a gamma ray image. And when you think about radiation, not all radiation is the same, right? You've got gammas, which are just radiation for imaging, betas, which start to have some destructive impact and alphas, which are violently destructive on a very, very tiny-focused area. So when we actually looked at what was possible, we like the idea of lead. There are 2 problems with lead though out of the gate. There wasn't a good chelator for it, and there wasn't a good generator. So we built both of those. And so, having invented both of those, we have our proprietary generator. We ship that around the world. We can ship it to Asia. We ship it to Europe. We ship it across the U.S. But the chelator is also very important because that first decay of the lead to bismuth and then bismuth back to lead, it's very important to keep all the energy on the tumor.

Got it. And those are really 2 interesting concepts, which I want to dive a little bit deeper. So talking about the generator itself, as I said, lead has a short half-life about 10 hours or so because of that, you need to manufacture it in the morning and then ship over to the infusion centers to be treated on the same day. So maybe just help us highlight some of the manufacturing infrastructures you built over the past year or so to really resolve or mitigate some of those complexities for manufacturing.

Yes. I mean, I think classically, people when they think about drugs, they're used to centralized point of manufacturing and then you have the storage life of sort of several months and then you move your product around, as you need to. In the radiopharmaceutical space, the -- if you look at Lutathera and Pluvicto from Novartis, those shelf lives are about 48 hours. So a patient being dosed today with Lutathera, Pluvicto probably had that drug made yesterday. When we look at what we're trying to do is, we have about a 24-hour shelf life. And so, we could overnight it or we could do same-day manufacture. We prefer same day. It keeps things easier. But also, we think about the overall diagnostic imaging world and the radioisotopes that people know already, you have 18 million patient doses in the U.S. that are actually made with a half-life of under 6 hours. And in those cases, the shelf life is about 8 hours. So this industry knows what to do. We know how to do just-in-time delivery. If you think about sort of what's possible with a $50,000 cancer dose, you can actually -- you have a lot of margin to go and actually move that very efficiently from one point to the other. And we're also not trying to get drug to every CVS in the U.S. or every pharmacy or even every doctor's office. We're trying to get drug to every cancer care center. And so, that distribution complexity really shrinks down quite a bit. So the ability to actually ship product to a distribution center from our manufacturing site to a cancer care center really keeps things easier. We have a site in Somerset, New Jersey that's operational. We acquired that facility from Lantheus in April this year, and now that site is operational. That's run previously under a Part 211 compliance system with the FDA. We've had multiple clean audits from the FDA prior to our acquiring that facility. We have a site in Iowa that's really appropriate for Phase I distribution. And in our 10-Q that we filed yesterday, we disclosed that we now have 3 manufacturing sites that we've purchased. We purchased a site in Chicago, a site in Houston, a site in Chino. And the requirements for the site is interesting. It's really tall ceiling and a really strong floor, right? So the hot cells that we're putting in there, they weigh about 20,000 kilos each. You may have 3 or 4 in one suite. And so, your floor has got to handle sort of several hundred thousand kilograms of lead shielding on site to make sure that you protect the operator from the product and the product from the operator.

Got it. Yes, that's really interesting. And what about the chelator you just mentioned earlier, you said you have a proprietary chelator. How does it differ from other commercially available chelators like DOTA, like the TCMC?

So if we just zoom out for a second, there's a really interesting idea that we want to explain why we need a chelator. And when you have a radioactive element, it's an element, and it's going to do -- it's going to behave like what it is. If it's iodine or fluorine or lead, they all have different biochemical properties. With some of the earlier nuclear medicine drugs, we tried using a covalent bond. So incorporating the radioactive element into the molecule itself and then watching that go through. And one of the issues that came up with radioactive iodine, for example, is that iodine would deiodinate. And so, you'd have a decoupling of the radioactive element from the rest of the molecule. And when that's free and loose, it will go to other parts of the body and give off-target toxicity. The nice thing about a metal and a chelator is that the chelator keeps that metal in a cage and drags it to wherever you want to go. So the chelator is designed to not be broken from any known chemical reaction. It will get broken though with an atomic reaction. And so, we've designed our chelator, so that not only does it help with the molecule biodistribution, but it also helps with the daughter collection. So our chelator holds the bismuth daughter in place. DOTA and DOTAM don't. They leak about 30% of the bismuth daughter. The other thing is that DOTA and DOTAM, TCMC will do either minus 2 or plus 2 charge onto a protein. And we know from first principles of biochemistry that the kidneys love picking up a charge protein fragment. So if you have that situation with a charge protein fragment, you then have a problem, where the kidneys will pick up that charge protein fragment and make it a higher probability that more radiation is given to the kidneys, where you don't want it to go.

So better leakage protection, so much better systemic toxicity and also better kidney toxicity around it.

Yes. So better safety profile and actually improved labeling efficiency. And what we actually just disclosed yesterday in our 10-Q was that we'd have a composition of matter patent issued for that chelator in the U.S. And so, it helps also protect our structures with further IP.

Was it a proprietary chelator you discovered yourself? Or is it in-licensed from somewhere else?

So the company founders initially were Dr. Schultz and Dr. Johnson from the University of Iowa. We have our discovery center in Iowa, as a spinout from the University. We get great leverage from actually working -- from working on that site. When Dr. Schultz was looking at -- this is a great chart. He liked lead-203, he liked lead-212. He needed a better chelator. So he invented that in his lab and then the University of Iowa gets a royalty from it, and Dr. Schultz is still part of Perspective Therapeutics.

Got it. That's excellent. Great. And so, we can move on to talk about your lead asset, when that's kind of, let's say, the lead one is going to be the VMT-alpha-NET lead asset. So right now, it's currently being evaluated in neuroendocrine tumors. Maybe you can just give the audience a quick overview of what this asset is all about?

So we actually -- the University of Iowa has the Pediatric Neuroendocrine Center of Excellence for the United States. And we first started making the safest possible drug for kids. And what we've learned is that by making the safest possible drug for a kid, it actually ends up -- it should be safer for adults as well. So when we looked at that program, we started with the standard DOTA complex and DOTA and DOTAM, DOTA-TATE, which targets SSTR2 expressing tumors. We changed the peptide a little bit. We tuned the linker, and it's not like an ADC linker that has a very programmed release specification. It's just in 3D space changing the length of the carbon chain. And by applying our proprietary chelator, we had a huge improvement in biodistribution. And the secret sauce in radiopharmaceuticals that I think people are starting to finally learn is that the biodistribution is key. Wherever the drug goes and wherever it linkers or spends some time, is where it releases its energy. And so, you have to watch from first injection time until complete decay of the isotope, where is the metal going? Where does it stay? Where does it delivers its dose. So the VMT-alpha-NET program was designed to give the best possible tumor kidney ratio. We can actually -- we do care about kidney dose. The other thing that tends to be dose-limiting in this program and many other programs is potentially bone marrow issues and hematologic toxicities. Those we can't control as much. We try and manage that by doing fractionated dosing. But the kidney exposure, we can manage by doing a smarter design of the molecule and recognize we can only change that before we bring a compound into humans. Once it's in humans, we can't change the molecule anymore. So the alpha-NET program was designed to have best-in-class SSTR2 uptake and somatostatin receptor type 2 tumors exist in all kinds of forms, gastroenteric tumors, pancreatic tumors, some of the lungs express it, some of the breast tumors express it, pheochromocytoma, paraganglioma, neuroblastoma. So a lot of interesting tumor types start to upregulate SSTR2. You can get incredibly high receptor density. And therefore, if you can target those receptors, you can take out the tumor. So we actually had some amazing animal data. We went to the FDA and said, we'd like to get a fast-track designation in the second line setting for that. And they came back to us and said, no, you guys get fast track first line. And so, that was really great to hear is that we can actually get this amazing designation, which then allowed us to then work with the agency. They told us upfront, 2.5 millicuries, 5 millicurie doses. And then after those 5 millicurie doses, the first patients come talk to us, and it's a very polite request. And so, before we try and go higher, they said, please come see us. We have that targeted for this year as well. We are finishing off -- we're in the middle of that cohort of the 7 patients at the 5 millicurie level. And a review of the safety and efficacy of the program will be presented next week at the North American Neuroendocrine Tumor Society or NANETS meeting.

Yes. Actually, on that meeting itself, can you just help us understand some of the data expectations for the data readout next week? How many patients should we be expecting? And how should we think about the OR and what we consider clinically meaningful?

So as we look at our expectations there, we're going to have 2 patients at 2.5 millicurie dose, 7 patients at the 5 millicurie level. To put into context, some of the other programs out there use weight-based dosing. And so, we're not -- in this case, it's a fixed base. So you've seen competitive agents looking at a 67 microcurie per kilogram level. Well, once we disclose patient demographics, people can calculate how we're dosing here. The safety monitoring committee has said that we should go higher. We need to have the discussion with the FDA. And so, when we present the safety and efficacy data next week, I think people will be looking at both those metrics. With any radiopharm, if we think we're getting a certain amount of efficacy, if the safety is there, we should always push up, right? Higher doses should give better efficacy. And so, it's so important to understand what that looks like. As we look at the competitive landscape, we're seeing from RayzeBio's drug, from Novartis' drug and from Radionetics' drug that they are -- it appears like they are at ceiling for how much can be dosed. We would like to really explore the true therapeutic window of our drug, which animal data says should be much broader.

Got it. And so, then I think maybe just for the audience here, you actually presented some initial clinical data from the investigator-sponsored trial in India, where they enrolled 13 patients or so. Maybe you can just help us understand some of the initial clinical data we've seen here.

So that was a really interesting situation, where the Indian nuclear medicine market had a shortage of lutetium, actinium. There's a global shortage of lutetium and actinium. But in the non-traditional Western countries, the shortages really become more acute. And so, the physician there said, I've got a patient, who's quite sick. I'd like to evaluate in a compassionate use setting, how your product could work in this patient. She could probably really benefit from it. And the first patient was dosed had an amazing response. And when we dosed this woman, she had a very large, massive, a pancreatic tumor in her liver that was unresponsive to other treatments. And then after first dose of our drug, the functional lesion decreased. It's still -- the tumor was the same size, but after 3 doses, the tumor started to shrink. And so were the first human ever to have a tumor shrinking and the patient get her life back. She was in cortisol crisis, her symptoms improved, her tumor shrunk, she got her energy back. She went back to work. And so, she was thrilled she could take a vacation with her family. So that led Dr. Sen at the Fortis Hospital then say, great, let me open up an IRB -- to the IRB and IIT and do more patients. And she assessed a total of 13 patients. In that group, we had 2 medullary thyroid cancer patients. We had 1 breast NET patient, and then we had 10 GEP-NET patients, so gastroenteric, pancreatic. They were a mixture of first line and second line. So some of those patients had previously experienced Lutathera but had progressed and others were Lutathera naive. So a really interesting mixture of patients, and we had some amazing responses there. If we think that the package insert for Lutathera has a 13% ORR, she was showing reporting results in that sort of 60%, 70% range in a small group of patients. So when these poor patients, who are very, very sick, it was great to see clear changes to their quality of life and how they were able to sort of bring their lives back on track.

Those are confirmed response, just to confirm?

So there's a mixture of confirmed and unconfirmed responses there. And if you look in the -- in her publication, she mentions, which ones are confirmed and unconfirmed. In a single-arm trial, in order to have a confirmed response, in order to truly call a response, you have to confirm it, which means 2 subsequent CT scans have to show consistent readings. And so, she had some unconfirmed, but the majority of responses were confirmed.

Got it. That's really interesting, actually. And can you elaborate on the safety side of things because that's one of your differentiations?

So with any radiopharm, we know that there's always going to be a dose that will then cause a lot of systemic toxicity. So if we go high enough, we'll get a safety signal. And so, in this case, we were really trying to figure out what we could learn from it. Initially, she reported only -- she reported 2 grade 3 adverse events with anemia. And these were patients that had come into the study already anemic. They were not considered severe. Anemia is really easy to treat. It's a simple iron injection, you can resolve that as an adverse event. No other major adverse events were seen. The patients in her trial had some alopecia, so some hair loss, but it's transient. It grew back. And that's considered an on-target effect because SSTR2 receptors are expressed in hair follicles. We had seen from some competitor programs this concept of dysphagia, which is difficulty swallowing. And initially, she said she hadn't seen any of that. And when we asked her to check with her patients, she really interrogated them and said, and she almost had to force them to admit to it because they said, ma'am, we're really -- we're so thankful you've cured of cancer. We didn't want to complain about a little bit of sticking in our throat. But we want everything documented. So that's out there, too. So mild dysphagia. But we didn't see anything that would cause us concern, as it relates to thrombocytopenia, lymphopenia, any of these potential adverse events that could show up. No change in kidney function. And so, we look really, really carefully to find any possible signals. We want to learn. She was dosing at a 67 microcuri per kilogram rate as well. And so, she adjusted her dose based on her patients. She had some very small patients, and her patients are 40 or 50 kilos. So these are adults at 50 kilos. And not a lot of American adults are 50 kilos. They tend to be almost twice that. So we'll see ranges, as it relates to per weight dosing. We also had compassionate use data presented from Iowa, which followed fixed kidney dosing, and that case is a different approach as well. So looking at either weight-based dosing, looking at kidney exposure dosing, looking at tumor weighted dosing or just fixed dose dosing, we're learning quite a bit about the drug, and we'll learn a lot more next week about what happens in a fixed dose environment.

Can you just maybe elaborate on that fixed kidney dosing data and maybe help some of the audience understand what we saw there?

So in that case, it's really interesting by actually injecting patients first with the lead-203, the imaging version of the drug, we could do full body dosimetry and dosimetry is an often-confused term. Dosimetry is specific to any one patient. It's not translatable across a group of patients. So in each patient, using the lead-203 biologically equivalent elemental twin labeled version of the drug, we could calculate over a 24-hour window exactly what the total kidney dose would look like and what the total tumor dose would be if the patient was injected with the drug. And in that case, the investigators at the University of Iowa, they looked at patients post Lutathera, SSTR2 expressing tumors. And if they solved for a fixed dose of the kidneys of 3.5 grays, they had different doses they gave to patients. They gave 5.5, 6.5 and 13.5 millicuries total of these patients over 2 doses. And that really high dose ended up with an amazing response. So only 2 doses at 6.6 millicuries gave a really good response after 3 months of really shrinkage of the tumor. In that case, they calculated that all those doses in those patients had a very consistent kidney exposure. So a lot of different things you can solve for. Do you solve for weight? Do you solve for tumor? Do you solve for kidney function? Do you solve for blood volume, all very appropriate scientific ways of doing it. And in drug development, you really want to try and do what's the most feasible.

So actually, on the dosing front, right now, you're going up to 2.5 millicurie and 5 millicurie and then you're dosing higher to cohort 3, undisclosed right now in terms of the dosing. Is it possible for you also to move into a fixed kidney dosing regimen if you were to change up some of the protocols? If so, what was the process like if you were to do that?

So that's very possible to do. One of our concerns there is actually developing a commercially feasible product. So not every hospital has a robust medical physics program that would allow them to do that work. And so, it's a lot of work to do. If that's your only therapeutic window, then that's where we'd go. But right now, the therapeutic window of our drug looks broad enough that we don't need to go down that path. It's really interesting work, and we love seeing it there. We could actually spend 30 years trying different combinations, dosing frequencies and never really get to drug approval. That's not good business. And so, we want to try and find out what is a reasonably approvable product profile.

Got it. And then -- maybe for the audience here, just help us understand the sort of market potential of alpha -- VMT-alpha-NET program in NETs.

So we have some interesting surrogates with Novartis' sales with their Lutathera compound. And so, I believe that they are tracking over $700 million in sales for that program. And that's really been focusing on GEP-NETs. There is a lot of interest from physicians to go into other tumor types. And so, what we're really trying to do is looking at these patients with GEP-NET. These are patients that have had the disease for many years. Initially, the patients are treated for symptoms only. So somatostatin is given just to control the secretory function of these organs -- of these tumors. Keeping that under control, but when the patients progress, they've been treated. So we'd like to treat patients earlier. We'd like to treat all the patients that start to progress. But then we can also go into these other adjacent markets, where SSTR2 positivity is well known. And a lot of HER2-negative breast cancer patients can express SSTR2. So lung cancer patients can express SSTR2, as the disease progresses and then some of these smaller indications, too. So we think it's got a pretty -- I think one other player in the space called it a pipeline and a product, right? There are many different indications to go after. And we'd want to systematically work out and establish safe and effective doses in as many tumor types as reasonable.

And the one thing that I think we talked about this privately too, actually, just thinking about the combination strategies for VMT-alpha-NET. Right now, you're going after monotherapy, but any thoughts around potential combo strategies to give rise to a deeper and more durable response overall?

So we always want to push science and see where it can take us. We've done some work in-house looking at combination settings between VMT-alpha-NET and various regimens. There are some really interesting signals there. At this point, there's such strong activity in the mono space that we want to focus on that initially and then work with our collaborators to figure out what makes sense in combination. And in a lot of oncology, usually the first approval pathway is combination because that's the easiest way to not take anything away from a patient and allow them access to additive medications, which we're doing in our VMT01 program. But VMT-alpha-NET, it appears as if a monotherapy on its own is accepted by physicians and patients, is well evidenced scientifically and can be a cleaner path to approval.

Got it. That's really helpful. Great. I think we can move on to the second program, which is the VMT01 program you just mentioned before, which is a program for melanoma. Maybe just give a quick overview of what the program is and the enrollment status right now for the trials.

Yes. So the VMT01 program targets patients with melanoma, but not all patients. We're targeting metastatic melanoma patients, where they express MC1R. So the melanocortin type 1 receptor shows up in about 50% of metastatic melanoma patients and not in all tumors. What we've seen from work with a collaborator in China looking at uveal melanoma only is about a 50% positivity rate. The Mayo Clinic did an imaging study with our drug, and they showed a 50% positivity rate. And with our current screening so far in our program, we've had about a 50% positivity rate. And so, if any one tumor appears to be brighter than liver or background, we consider that to be positive and then that's a patient that could be eligible for the trial. These patients that we've been treating so far have been very, very sick. So they're post second line. So on average, they've seen 3 checkpoint inhibitors and a total of 5 other ways to treat the tumor. The expected progression-free survival in those patients coming into the study is about 2 to 4 months. And then we're absolutely amazed, where with a 3 millicurie dose, we extend those patients out to 9, 11, 13 months without any progression. The disease was absolutely frozen in time. So we had disease control. But we also want to go into a combination therapy as well.

Yes. Talk about the combination benefit here. Maybe just share with us some of the preclinical data you've found using the combination with PD-1s that could potentially have a synergistic benefit for the melanoma patients.

So we've done a lot of work in mice with melanoma. We've tried different mouse models in both immunocompromised mice, as well as immunocompetent mice. And what we saw was that we actually have the ability to take a cold tumor and make it hot. So cold tumor and a hot mouse actually gave a really interesting result, where if we just tried sort of ipi/nivo, like a checkpoint inhibitor, the mice had a slight improvement. If we just gave a drug alone, there was a slight improvement that's better than checkpoint inhibitor. But given the 2 together, all of a sudden, the curve jumped out, where we saw the majority of the mice were still alive at 100 days post the rest of their lives. And what was even more exciting was that 75% of those mice could never regrow a melanoma tumor. We tried rechallenges with new tumor cells, and they could never regrow. The body end up actually having this amazing ability to learn how to fight melanoma directly.

It's really interesting. And now you're going after a lower dose compared to the monotherapy dose. And maybe just some rationale behind that, why going after a lower dose?

So look we -- as part of this work, we always want to do dose ranging. And so, you want to sort of -- you have Project Optimus, you want to see how high you go, you want to see how low you go to get maximum tolerated dose, minimum effective dose. And in our animal work, when we actually started doing that, we learned that when we started lowering the dose, we actually started to get improvements. And we think what's happening is that the immune system in any animal, mouse or human with melanoma is so fragile and compromised that the less challenged immune system we give, the better the animal can be. We also know we need a little bit of activity on the tumor in such a neoantigenic situation. These alpha particles smashing into the tumor cells, presenting all new antigens to the immune system, that's really, really important. So our animal data imply that lowering the dose gave a better effect in combination. We presented that data at the Melanoma Conference in Hawaii last year. And we're following the data. And right now, the human experience is tracking the mouse experience.

Got it. And what about some of the safety things we saw in the initial clinical data that you presented in Hawaii, where we saw some accumulation of radiation dosimetry in kidney. I mean, just help us understand, could it read through to VMT-alpha-NET?

So it's a great question. And so, the melanoma data was using a drug targeting MC1R in patients with melanoma, whereas our VMT-alpha-NET targets SSTR2, totally different drug in patients with neuroendocrine tumors. So there's a huge difference in the number of copies of those receptors in each of those disease states. But you also have MC1R expression in the kidneys and melanoma patients. So going in, we know there's going to be quite a bit of uptake in the kidneys in patients with melanoma with an MC1R drug. And when we looked at it, we calculated the dose -- potential dose exposure that didn't show up anywhere biochemically. So it's a calculated number that's theoretical that started to hit some limits that people are used to dealing with external beam therapy. We have not seen anything show up clinically in these patients implying any kind of issues with their kidneys. But under the abundance of caution, because that 5 millicurie dose didn't have the beneficial impact on progression-free survival, whereas 3 millicuries really did, it makes sense to stick with the active drug that's safer at a lower dose. So we did not have dose-limiting toxicities at 5 millicurie, but we started to get a theoretical kidney exposure that made us think that we should start to walk the other way. And since the efficacy data showed the same thing, it made great lean in on that 3 millicurie and then 1.5 millicurie.

Got it. And so, maybe just help us understand some of the catalysts for this program. When should we expect another update from the combo study?

So the study is now enrolling patients, and that's a combination setting in patients, who are with metastatic melanoma, if they screen positive with MC1R and also post second line, meaning they've had kind of everything else they're supposed to have seen. They'll come into the trial, they'll receive our drug. They'll also receive OPDIVO, Bristol-Myers Squibb drug, and then we'll be looking at those responses. So we need to enroll the patients before we can communicate the results. And so, we expect to update the Street next year on how that's going.

Got it. That's helpful. And what about the whole space for melanoma? It's getting really crowded. We see many different therapies going after second line plus cell therapies, including. What do you think will be considered a clinically meaningful bar that you want to hit to actually show that VMT01 could be a feasible therapy in this line of therapies?

Well, we're really excited that all 3 of the patients at the 3 millicurie dose had complete disease control. And so, the only thing better than complete disease control is actually if that leads to shrinkage of the tumor and then overall survival benefit. That's going to take a lot more time to accumulate and show that. With any of these therapies, you have to think through what's feasible, what patients are eligible, how you determine if they are eligible. We like the fact that we can actually image the patients in advance and get a very clear answer, yes, no. Do they screen positive for this or not?

So I think some of the latest competitor data for melanoma is showing around somewhere between 2 months to 3 months of PFS. Is that the kind of bar we should be looking at here?

So sadly, for patients, that is the current standard of care. The best case that I've seen so far is maybe 4 months. And so, the fact that all 3 patients at 3 millicuries were out at a year and still counting, meaning they still have not had progression after a year, in my mind, is a huge win, and it's one I don't think we get enough credit for.

Absolutely, especially in combination with KEYTRUDA, for example, I would imagine this to be additive, right, not just getting monthly, but also having the benefit of PD-1 to potentially improve immunotherapy there. Great. And then I think I just want to spend some time -- we only have about 4 minutes left. Spend some time on the third program, PSV359. Maybe just give a quick overview for the audience here, what the program is all about?

So PSV359 targets either the tumor or the stroma, and we're targeting FAP alpha. And so FAP alpha shows up on certain tumors that are epithelial derived, but it also is highly expressed in the scaffolding that tumors develop, as they grow. So if a tumor is untreated or doesn't get resolved with other mechanisms of action, it's going to grow and grow. When it grows, it gets fiercely independent. It forms its own blood supply. It forms its own scaffold infrastructure, and that scaffold infrastructure is what we target. So a lot of people remember seeing the ship hit the bridge in Maryland and the whole bridge came down, a few months ago in the news. We're looking to do something like that to tumors. And so, by targeting just the whole infrastructure of the tumor, there's a lot of sort of cell biology happening within that overall complex structure. And if we can destroy that, then we can actually really make a meaningful impact sort of on those tumors and therefore, on the patients. Whenever we develop a molecule, we look at the biodistribution very carefully. In our corporate presentation, you'll see various iterations of how we have developed that drug to really just target the FAP alpha and not to have it lingering in other tissues. We've seen some other FAP programs from other people not have great success yet, and we think that's related to biodistribution, having looked at some of the animal data there. So it's a very strong program. One of the things that we also like to do is show human images. And so, in our corporate deck, we show various human scans of patients having received our drug with the lead-203, the diagnostic variant of it. And those should be very informative for what could happen on the therapeutic level. So in cases, where, for example, we had the osteosarcoma patient, we had a neuroendocrine tumor patient, we had a lung adenocarcinoma patient, all of those patients showed very, very interesting scans, where we saw a lot of tumor uptake, and we didn't see much off-target.

Got it. And then this program right now is being -- is currently ready for IND filing. Is the IND filing is on track?

So we've guided towards having that IND filed this year. And so, we would hope to then start enrolling patients in that program next year.

Got it. And what about some biomarker strategies? Maybe it's a little too early to say, but any initial thoughts around what are some of the biomarker strategies you're thinking about to identify solid tumors that could potentially work?

So the nice thing is that our own drug can be used as an imaging agent, so we can track things through. But there are also other FAP imaging agents in development. And so, with our neuroendocrine program, for example, there are approved drugs to look at SSTR2 expression. And right now, there are companies trying to develop imaging drugs that show FAP expression. And so, with several drugs being moved towards commercialization with FAP, that's interesting, as a screening path. We know that when the tumors get advanced enough, they will start to build stroma. We don't think something like FTG is necessarily a good surrogate. It shows metabolic activity, but not structural sort of presence. So either our drug on its own, it's elemental twin could be used or some of the commercially available agents that are being developed now.

Got it. Great. And then for the next 12 months to 18 months, could you just highlight some of the key milestones and key catalysts that you're looking to achieve?

So a lot of things are going to be happening over the next 12 months to 15 months. We've got -- we'll see continued maturation of the data in the first monotherapy cohorts from melanoma and seeing how far those patients do. We've got data coming out next week at the North American Neuroendocrine Tumor Society meeting that's showing with our neuroendocrine program, how those patients doing. That data will still mature over the next sort of 15 months, 18 months. We'll see how long responses exist for. We'll have an initiation of our FAP study in humans. We have patients already initiated enrolling in our combination with melanoma. We have a very prolific discovery team, and they do an awful lot of work with new compounds. So we will be showing some human images, as we think they're appropriate with drugs that work. And we are going to keep building out our infrastructure with our manufacturing site. So we're staying very, very busy.

That's excellent. Well, I think we're out of time. Thank you, Thijs, for this time, and thank you, everybody, for attending.

Great. Thanks so much.