Hi, everyone. Thank you for joining for the presentation for Perspective Therapeutics. I'm Eva from the TD Cowen Banking team. It's my pleasure to introduce Thijs Spoor, CEO of Perspective. I'll pass it over to the company now.
Great. Thanks, Eva. Thanks to Cowen for inviting us to present. My name is Thijs Spoor. I'm the CEO of Perspective Therapeutics. I do have to caution that because we are a public company, there may be some forward-looking statements. As a result, I encourage you to look at our filings that we keep current with the Securities and Exchange Commission. I'm just going to walk around a little bit as we go through the presentation and talk through the various slides and why we're so excited about what we're doing. The radiopharmaceuticals are really the next- generation of targeted therapies. If we think about sort of what happened with chemotherapy and radiation and chemoradiation, chemotherapy turned into targeted chemo with ADCs. Radiation is turning into targeted radiation with the radiopharms.
The advantage there is that the radiopharms have this unique ability to not just know where the tumors are, but what the tumors look like. If you know what the tumor looks like on the surface, you can then actually target that directly with a targeting agent that will actually go bind to the tumor and hopefully nothing else. You can tune a little bit the molecule that you're developing. The medicine that you actually ultimately give to a patient is going to be some combination of both how you target it and what kind of payload you're bringing and what that payload looks like. The mechanism of action is very unsubtle. It smashes the cells apart. If you can bring in a radio-emitting particle, then you can actually go and actually destroy anything that that radiation touches. That is a double-edged sword.
You actually want to make sure you design these programs that you minimize kidney resorption and you minimize kidney damage overall. We've actually chosen a different isotope called lead-212. Lead-212 has a lot of unique advantages that I'll touch on a little bit later. At its core, we feel it's in the Goldilocks kind of space. It's not too short-lived. That distribution is tricky. It's not so long-lived. You have to worry about a lot of off-target toxicity or potential accumulation in the body. You have the ability to hit the tumor hard and fast and then disappear so that the immune system can actually come in and the body's natural responses to radiation can kick in. At Perspective, we have three pillars. We actually are heavily involved in our clinical programs. We have a pretty robust manufacturing infrastructure that we're building.
We are building out our own network of manufacturing sites across the U.S. We do have some partnerships in place with other potential manufacturers too. Being able to lean in on our own integrated supply chain, we think gives us a lot of efficiencies and advantages, as well as really giving us ideally the best possible patient coverage. Lastly, we've got a phenomenal discovery team. The company started as a spinout of the University of Iowa. In that case, the company founders, Mike Schultz and Frances Johnson, said, "How can we actually develop a safer medicine for kids with neuroendocrine tumors?
If we can do a safer medicine for kids, can that turn into a safer medicine for adults too? The innovations that our team has been able to identify in terms of having a proprietary chelator, locking in a differentiated isotope, but then also inventing new molecules bringing to clinic means we have a pretty phenomenal pipeline. We have three clinical- stage programs. We are expecting multiple readouts across all of our clinical- stage programs over the next 12 to 18 months. We think this is really de-risked with a diagnostics approach. The idea that you can fail quickly on assets is something that we think the scientific community really does reward. If we look at our clinical programs right now, we have our VMT-01 program in clinic. This targets MC1R. It is used in patients or initially it is being addressed in patients with melanoma.
We have two different groups of patients enrolling in therapy in the U.S. right now. There's a monotherapy cohort, and there's also a combination cohort with Opdivo. We have a neuroendocrine program, VMT-α-NET. This targets cells that surface express SSTR2. We've had some really interesting initial data in humans in the U.S. and overseas in compassionate use. We're actually now enrolling in our second cohort, and we're also contemplating opening a cohort three later on this year. Our third program in clinic is a FAPα targeting program. FAPα is really interesting in that it targets all kinds of solid tumors. We filed the IND last year, and we expect to start treating patients in the U.S. by around sometime in the middle of this year. Behind that, we have a pretty phenomenal discovery team that works around the clock to develop new peptides.
If we can ideally tune the biodistribution to give a therapeutic, we then think we can really differentiate on the clinical data. Just to dive in a little bit in terms of what do radiopharms do and how does this actually tune the market. There has been a lot of momentum in the field from Novartis' approaches targeting SSTR2 and targeting PSMA. That is only a small part of the story. There is still probably about 93% of additional tumors out there that are not addressed by these targets, some of which we are going after and across a whole range of tumor types. Basically, if a tumor has something on its surface that differentiates it from normal tissue, that is a great target for radiopharms because then we can bind to it and nothing else and keep driving things forward.
Our initial dose-finding work allows us to then establish a proof of concept in one group of patients and hopefully be able to use that to extrapolate to other patients. Our VMT-α-NET program, we've actually tried to really think through a therapeutic window. In this case, if we can identify a clear space for how to use this in GEP-NETs, and the kind of a pure play on SSTR2 expression, that should open up a lot more potential tumor types where they also express SSTR2, even if they come from a different primary cancer. Our VMT-01 drug targeting MC1R melanoma actually allows us to do a phenomenal read-through onto combinations with checkpoint inhibitors.
This combination of priming the immune system with incredibly neoantigenic storm that you get from an alpha particle should actually allow the ability to really potentiate everything else that's currently used in dealing with these patients. We don't see radiopharms as being sort of swapping out from something else that's currently available. It's really additive. It allows you to add in more things to the different mechanisms of action to do everything we can to try and address the cancer and tumors' broad stroke head-on. Just zoom out for a sec to show what's really different with Perspective Therapeutics. Normally, people don't show you all the things that they've rejected or failed on, but I'll explain to you why we like to fail fast. If we do, what are some of those reasons?
We can do an awful lot of work in the animal model to really prove this out. Everyone's familiar with identifying a target and how you actually then think about your target moieties. What really differentiates our company, we think, is the optimization in vivo. By doing that, we can actually really then tune what happens to the drug inside a living organism to then actually change and modify it before we lock in a structure and go into further trials. By way of showing something that did not work, you can probably crack our top secret code. This was Compound 30, Compound 42, and Compound 59. Compound 30, if you look at the image here, this is sarcoma. This is the animal's kidneys, and this is the bladder. You can see the ears at the top and the tail at the bottom.
We looked at this and thought, this is pretty similar to something that actually went into clinic by another company in the space. They did not have great data. They did not show a good therapeutic window. That compound got rejected. You can kind of see why if you are getting almost an equal distribution between tumor and kidneys. We spent three or four months and iterated through several different compound types. If you look here, this is sarcoma, and this is kidney. A marked improvement. This is something that we actually could have gone forward with. The discovery team said, we can actually do a bit more work in here. Let's really lean in on the medicinal chemistry. Let's figure out, can we tune this molecule enough? Sure enough, this is sarcoma here, and this is kidneys here.
You'd be hard-pressed to find anyone that would say, I would rather put the one on the far left into a patient versus the one on the far right. When we actually put it into a patient, we can actually do it non-destructively, non-invasively. We can give the patient a dose, image, and see exactly what's lighting up in the patient. In this case, we got a pretty interesting metastatic colorectal cancer patient where you're seeing an awful lot of activity that appears to be on target and on tumor. We want to be really mindful of what the biodistribution looks like. What we do not see here, we do not see a lot of stuff we're not expecting to see. We're not seeing lungs. We're not seeing heart. We're not seeing brain. We're not seeing other structures. We're not seeing muscle.
What we are seeing, though, is anatomical structures here. By investing the time here, this is the kind of asset that we want to take forward and that truly transforms what we do, we think, compared to other programs out there that have tried looking at FAP previously. Looking at the platform across the board, we start with thinking through what's the isotope. Lead-212 is really interesting. That alpha particle should give a double-stranded DNA break that should shut down the cell's ability to replicate and actually go any further. Plus, it creates this neoantigenic storm. We can pair this with lead-203. The same chemical composition matter, we can image and treat. That is really interesting because that allows us to both screen for patients and also assess what could the dosimetry look like. We use a proprietary chelator, and I'll touch on that in a moment.
We've optimized this for lead and its daughter, bismuth. In any radiopharmaceutical story, it's not just the parent isotope, but the daughters in the body, what happens to them that we track through. We've optimized for the lead-bismuth cascade. We also optimize our peptide design to then have the entire moiety, the entire medicine, has been tuned to give us hopefully the broadest possible therapeutic window. We know with any radiopharmaceutical drug, if you give enough of it, you can induce a lot of safety signals. You also want to know, can you give just enough to then have a therapeutic benefit? Not all programs can reach a therapeutic benefit before talks. The big thing we watch for is dose-limiting toxicities across the space. It could be in any organ, but there's a few that we look at specifically.
We are trying to design for a broadest possible therapeutic window, which then hopefully either gives either safer or more effective medicine. We have to establish that with the data. In terms of just a quick recap on the space, lutetium, in our opinion, was a great iteration off of iodine-131 , the initial way to treat thyroid cancers, but iodine had limitations in other cases. Lutetium allowed you to still use a beta, but allowed you to chelate it and actually then not have to worry about daughter isotopes. It actually had some pretty compelling data in SSTR2 tumors and also in some prostate tumors of PSMA. The scientific community said, could they pack more punch? The easiest chemical surrogate for lutetium was actinium-225 .
Actinium had the power of alphas and so did not have a lot of off-target radiation from the initial alpha decay. We think that actinium has a lot of concerns about the daughter isotopes and its long life in the body. There is a much higher chance of downstream toxicity. There has been a lot of headline risk about supply chain right now that has not been addressed yet with capital. If we jump into lead-212, we actually love the alpha. It hits hard and fast. It does not hit normal tissues. There are no meaningful daughters we have to look at. It disappears from the body very, very quickly. We do not need to worry about the patient's bio-waste. We do not need to worry about the patient's radioactive urine, for example, when they go home from the hospital, as you would with some of the other isotopes.
We can actually truly stockpile the parent isotopes. We actually have our strategic reserve of the parent isotopes that we manage. We actually draw down exactly what's needed on a reasonable basis. There are two different mechanisms of action. Think about alpha particles. There is the cytoreductive mechanism of action and the immunostimulatory. One drafts off of the other. The cytoreductive is the easy one to think through. That is with the alpha smashing into the cells. What happens then is, again, a lot of antigen presentation to the APCs, the antigen-presenting cells that then allow the innate and then adaptive immune system to kick in and really sort of have their impact.
As we think about the way that the drugs can work, you can design the medicine to either, in a tumor type where the immune system doesn't play a large role, you can have the cytoreductive benefit. If the immune system is key to that, you can then actually design your drug protocol to then actually take advantage of the fact you can have systemic effects kicking in too. In terms of what differentiates us, when we think of that basic construct, we use the lead-specific chelator. This holds lead-212 or lead-203 in place. If you look carefully, it's got a net zero charge. This is a differentiation off some of the earlier assets or the earlier chelators out there that have either a negative two or a plus two charge. From first principles in biochemistry, the kidneys love picking up charged protein fragments.
If you've got a peptide with a charge on it, the kidney will hold on to that longer. If your peptide is zero charge or net zero charge, it's much easier for the kidneys to let it wash right through. If you don't have the drug lingering in the kidneys and accumulating in the kidneys, you should really then be able to lower your kidney exposed dose. We all know that kidneys will touch the drug briefly. If they touch it longer, that means you have a higher probability of off-target toxicity. Lastly, the first daughter coming off of lead-212 is bismuth-212. This chelator is designed to retain over 98% of that first bismuth daughter, whereas DOTA and TCMC will leak and then guarantee to leak the bismuth daughter where the alpha actually comes from.
Within this chelator, we can put lead-203 in or lead-212. In this case, we either have an imaging drug or a therapy drug. Same composition matter. The FDA considers all these to be microdosing. There is no pharmacologic effect from the actual drug we are giving. It is all in the picomolar levels. If it was not radioactive, we probably would not be able to measure it. It means that we can actually treat what you see, see what you treat. It lets us really go in there and drive things forward. For the sake of time, I am not going to focus on our pretargeting platform, which is really exciting in the preclinical setup. If we actually jump into supply chain manufacturing, one of the most common questions we get is, how do we actually make this product?
When you think about any kind of radioisotope production, the easiest, cheapest, simplest, safest way to make any isotope is to literally do nothing, meaning let it decay from a parent to a daughter, from a daughter to a subsequent daughter. If you have pure thorium-228 and do nothing, it will decay into radium-224. If you have radium-224 and literally do nothing, it will decay into lead-212. You can actually, because there are different elements, they have different chemistries. You can purify them out truly based on their chemistry. They will literally transform into something with a different chemistry. If it has different chemistry, then you can isolate it using columns and resins and a lot of other sort of standard techniques. We ship the radium-224 around the world inside our generator, we call it.
It's basically a big lead shield for a small amount of radium-224. If you run saline through this column, you can actually pull off the lead-212 on a daily basis. We load the radium-224 on the column. Again, we do nothing, let it wait for a day. Some of the radium-224 will turn into lead-212, and that column gets washed. You have an ability to actually pull off pure lead chloride every day that's needed. If we ship these radium generators across to various manufacturing sites, we actually currently have a site in Iowa that's producing drug for clinical trials. We just got a site in Somerset, New Jersey, online. We acquired the site last March from Lantheus, and that came online by October, producing our drugs across the U.S. We actually are building out our own network.
We have a site in LA, a site in Houston, a site in Chicago, where we're actually working to get those sites online. There are other lead-212 programs out there. We've seen one player in the space is doing everything nationally from a site in Indianapolis by using the overnight distribution. The nice thing about all these drugs is if you look at their shelf life, the lead-212 labeled drugs have a shelf life of about 24 hours, whereas your lutetium-actinium drugs have a shelf life of about 48 hours. You really want to be mindful of the shelf life to see how far can you get the drug. We like delivering it by mostly ground if possible. We have to deliver drug not to every CVS or Walgreens. We're trying to get drug to every cancer care center.
It's a much more simple logistic path to follow, which is those sites that are actually authorized to handle the isotopes. Touching a little bit about our clinical programs, VMT-α-NET targets neuroendocrine tumors. If we have these great human images we show, it's hard to see all the other organs in the patient because the drug doesn't go there. What's so exciting about this is that all you're seeing here is either tumor, or if it's not in the tumor, it rolls off in the bladder and gets eliminated from the patient's body. The ability to see one hour post-injection that you get accumulation in tumor, nothing else, is absolutely terrific. When we actually look at what we're trying to do, we're comparing ourselves to other agents that have effectively a 13%-15% ORR benefit.
The question is, can we do better than this, or can we do safer than this? We actually looked in mice and said, what can we see? In this case, you look at our drug, tumor kidney versus a more generic construct, tumor kidney. You see that the tumor is much, much brighter here. What does that mean in animals? Over here, you see untreated neuroendocrine tumors. They grow until the animal gets sacrificed. If you look at those same animals with Lutathera, you can see why that right shift about 25 days allowed that drug to get approved and should be. The ability to kind of do that right shift and actually defer things. If you give our drug in the same mice, either a single large dose or four fractions, you see a radically different curve.
We took this data to the FDA and asked for a Fast Track designation in the post-Lutathera setting. The agency actually got us into the pre-Lutathera setting instead. We asked for almost like a second line. Instead, we got a first line. We are really excited about that. We have moved into patients. When we actually did our initial human screening, we saw sort of tumor or bladder, and 24 hours later, tumor or bladder. That is really important because it means that all of your downstream daughters, anything that happens with redistribution within the body, stays on tumor or it gets dumped from the body completely. We did pre-define with the FDA that we would have a pause point after the first seven patients were dosed at 5 millicuries.
We dosed two patients at 2.5, got through the DLT period very, very quickly, and went up to the 5 millicurie level. We have taken this data and submitted it to the FDA to give them and our investigators comfort to figure out if we should go higher, how we do more patients along the way. The Data Safety Monitoring Committee recommended we reopen cohort two and add in an additional up to 40 patients to move forward. As we look at what these patients look like, these are patients that were stable with neuroendocrine tumors, and when they started to progress again, would have been enrolled in the study. The ability to actually have disease control in patients is a major issue. What we have seen is we actually did get disease control in eight out of nine patients from the first ones we reported out.
If we look at the dark blue bars, which are the higher dose level, we now have two unconfirmed responses and one confirmed response in this group of patients. If we look at the spider plots, you see that the early onset showed some evidence that maybe there's activity there. You see if you wait long enough, a lot of these lines start bending down. What we think happens inside the cells, especially with a really slow-growing tumor cell, is that if the alpha particle damages the ability of the cell to heal itself and repair itself, it learns this the hard way by dying the first time it tries to replicate. Once it goes through mitosis, that's actually when the fact that the alpha has smashed apart its DNA has an impact and the cell will die.
We're really encouraged by this data. The initial cut of the data, just looking at an earlier time point, only showed one responder. If we keep watching and seeing what goes on, we'll see that we actually are getting some late responses. This is consistent with other approaches in the field. We've seen very, very clear safety signals, nothing that was sort of major concern. The two patients to mention is one patient that had a grade 3 was diarrhea. That was a one-day event in only one patient. An elderly patient who was diabetic got dehydrated and was admitted to the emergency room with syncope but was treated there and sent home. She was dose-reduced after that, but it was not considered to be sort of attributable to the drug.
We actually have looked at kidney parameters, and for the sake of time, I'll move through. We actually didn't see any DLTs, nothing grade four or five. We hadn't seen any impact on renal function. What we have seen is that we had one confirmed ORR, two unconfirmed responses, and eight out of nine patients remain on treatment, sort of even sort of tracking through this timeline. A picture always is really helpful if we look at the structures inside the patients. Initially, we didn't see anything tracking through. After cycle three, cycle four, we then started to actually get reduction in at week 36. We see a pretty meaningful reduction in the tumor itself. We are not clear if this is a lymph node that was cancerous and has shrunken down or if this is a cancer itself.
We will be watching these patients very, very closely and continue to monitor. Our melanoma program, VMT-01, that targets MC1R. What's really exciting about the scans we can do in these patients is we can see brain activity. The ability to see brain mets is pretty amazing in these patients. Brain mets is an area that's usually off-limits for a lot of programs in melanoma. The fact that small proteins can sneak across and get into that tumor and bring a diagnostic isotope means it should be able to bring across a therapeutic isotope as well. We are pretty excited about where this program can go. What we have seen on the preclinical side is that it's a U-shaped response curve. In this case, the dark blue was actually the lowest dose we tested in combination with therapy with checkpoint inhibitor.
That actually gave the best response, was the lowest dose that we tested. There are U-shaped curves that show up. You know that the immune system is really actively engaged in this tumor. If you actually shut down the immune system by going too high, you then let the disease go unchecked. In this case, dose optimization is really, really important, especially when we look at what happens in animals' combination. This dark line here, and it's kind of a cold tumor in a hot mouse. It's an immunocompetent mouse model. The dark line is untreated. The light blue is Ipi-Nivo. This dashed line is a monotherapy with alpha. The pink line is a combination of alpha plus a checkpoint inhibitor. Such a radical transformation in terms of what this means.
In fact, 75% of these animals could never regrow a tumor if re-challenged with new tumor cells. Really phenomenal transformation in the space where we think things can go. There is a different expression level between what you see on an FDG scan versus an MC1R scan. 50% of patients that have metastatic melanoma will show an MC1R positive tumor. We just need one tumor to really move the patients through. We are dosing patients. We tried three patients at 3 millicuries and then another seven at 5 millicuries. Based off of the data we've seen, we are going to drop down to 1.5, both mono and combination with Opdivo. We have a partnership with Bristol Myers Squibb to use this in a combination setting. To explain that rationale, we look at these two cohorts. The pink cohort got 3 millicuries.
Given these patients had a PFS of about two to four months on best pulse standard care, these are post-second-line plus patients, average of five prior therapies, and the expected PFS is three months. At 5 millicuries, those patients hit that natural progression of the disease. No meaningful change on their disease progression. At that lower 3 millicurie dose, all three patients did very well throughout treatment duration. In the post-follow-up phase, in fact, we actually even got a late responder. This tells us that this drug clearly has activity. For the clinicians, they said in patients that are rapidly progressing with metastatic melanoma, the disease was frozen in time. There was no progression of those tumors at that lower level.
In fact, then we got that deferred response that implies there was it's so far out that does imply then that the immune system played a role. This is really, really compelling to see, especially given the safety profile. We saw a very, very clear, clean safety profile across the board and nothing that was really considered extraordinary to the drug and really mostly indicative of the disease state. With such a low level of toxicity seen, we think it's really important to keep going. We're actually actively enrolling patients now in the 1.5 millicurie dose monotherapy and combination with Opdivo. The third clinical program I want to talk about, just have a few minutes left here, is in our PSV359. This targets FAP alpha. What's great about the nuclear medicine companies and the radiopharmaceutical companies, we can show images.
We can show you exactly where a drug goes in the body. When you look at the scan, you're seeing drug in the bladder, and you're seeing drug across all these other tumor sites. You're not seeing lung uptake. You're not seeing bone uptake. You're not seeing kidney retention. You're not seeing cardiac. You're seeing just a really clear pattern that shows the drug can work. If we actually look at this target itself, FAP alpha is a really interesting target. It can either show up on the stroma or on the tumor or both. When tumors get large enough, they can form their own stroma to help support their growth, their kind of infrastructure. The nuclear medicine community has shown many, many tumor types that all have high expressing amounts of FAP alpha.
From breast, ovarian, colorectal, lung, head, neck, cancer on the primary, all these tumor types can actually start showing FAP alpha. We can prove on the scan ahead of time that the patient has that receptor. Therefore, if you could target it, you can actually then deliver a lethal dose of alpha to the tumor environment. We've shown you how we develop our drugs, which is really picking best possible candidate. These have almost identical binding affinities for FAP alpha, but radically different binding distributions. This compound on the far right makes sense to really move into patients. A lot of times, people ask in radio farms, the animal data doesn't always translate. How can you prove this? You can prove that with human images. If you look at the side by side here, you've got an FDG scan.
Every glucose-hungry cell in the body, you see all the brain uptake. We see various sites where this patient with colorectal cancer was clearly metastatic. If you compare that with that same patient's scan with our FAP alpha agent, we can see that this patient clearly would have a strong uptake on tumor that we've not seen in other places. We've shown some other patients as well. We've shown a lung adenocarcinoma patient. We've shown a neuroendocrine patient. This is an osteosarcoma patient. What's really important in any radiopharmaceutical is look at the early scan, so one hour post. This is the chemical twin, identical twin to the therapy we're delivering. If you look at that one hour after injection, you're either seeing activity in the osteosarcoma or it's being dumped out in the bladder.
If you follow it through over two half-lives, you see phenomenal retention in the tumor, and you see the drug clearing through kidneys and being dumped in the bladder. The ability to actually see these human images means that if we like what we see, we push on. If we do not like what we see, we fail fast. That is just as important in a capital constrained environment to actually be able to go and develop medicines that are truly innovative and can actually drive a more appropriate adoption if you can target exactly what you want to see in a patient. Lastly, with this FAP alpha, it looks really strong. We have actually done some human imaging work. We did file an IND last year. We do expect some of the first- in- human therapeutic studies to start mid-2025. We are very excited about that.
Using our distributed network of manufacturing sites, we can get this drug across the whole country right now. We are looking forward to seeing how these patients can do after they have enrolled in the study. Lastly, we have an amazing team of talented people around us. I do not have enough time to mention everyone, but we have tried to really ramp up in experts wherever we can and really drive things forward. What we do is generate a phenomenal amount of intellectual property. Everything we do has got composition matter, IP around it. We have a lot of IP around the constructs, the formulations as well. We start with the chelator that has a proprietary backbone. What we are trying to do is develop proprietary medicines that have a lot of longevity to their life. Lastly, we have a very strong financial position.
Our cash runway should last us until late 2026. As of December 31, we reported that our cash balance was $227 million, which allows us to fund our current programs in place of our clinical programs for VMT-α-NET, VMT-01 melanoma, our FAPα program, as well as to build out our manufacturing infrastructure. I'm at time. I'd like to thank you for your attention and thank Cowen for allowing us to present here. Thank you.