Radiotherapeutics For Neuroendocrine Tumors With Perspective Therapeutics' Thijs Spoor

On this week's episode of the Business of Biotech, Thijs Spoor, CEO at Perspective Therapeutics,  a company developing Pb 212 (lead)-based therapeutics, talks about why radiopharmaceuticals are surging again and why biodistribution is the make-or-break variable when your payload is a radioactive isotope. Thijs discusses the reasons behind Perspective's investment in a proprietary generator for therapeutic production, manufacturing and delivery strategy, workforce constraints, and building a clinical strategy around receptor positivity across tumor types. 

Access this and hundreds of episodes of the Business of Biotech videocast under the Business of Biotech tab at lifescienceleader.com.  

Subscribe to our monthly Business of Biotech newsletter.

Get in touch with guest and topic suggestions: ben.comer@lifescienceleader.com

Find Ben Comer on LinkedIn: https://www.linkedin.com/in/bencomer/

Transcript

Welcome And Guest Introduction

Ben Comer 0:04

Welcome back to the Business of Biotech. I'm your host, Ben Comer, Chief Editor at Life Science Leader, and today I'm with Thijs Spoor, CEO at Perspective Therapeutics, a clinical stage radio pharmaceutical company developing targeted therapies using LED or PB212, an alpha-emitting radioisotope. Thijs is an experienced life sciences operator whose previous roles have included chief executive leadership at multiple companies, stents on Wall Street as a biotech and medical device analyst, and as the commercial lead for GE Healthcare's oncology drug business. Listeners to the business of biotech know that radio pharmaceuticals are an area of interest for me, so I'm excited to hear about what Perspective Therapeutics is working on, what's new in the space, and how the company landed its own proprietary generator, a key element of the radio pharmaceutical supply chain, to extract PB212 for the company's therapies and diagnostics or theranostics, as well as plans for regional manufacturing. Thank you so much for being here, Thijs. Thanks, Ben,

Nuclear Pharmacy And Patient Doses

Ben Comer 1:10

for having me on. I wanted to uh start out with uh a little on your background. You went to pharmacy school at the University of Toronto. Um, is that correct? And did you intend to become a pharmacist at that time?

Thijs Spoor 1:24

Uh no, it is correct. I went to the University of Toronto expecting, I thought I needed a good first science degree. So I thought, pharmacy, why not? Let me try it out. And it turns out I loved it. And while I was in, I loved the science. And while I was in school, I thought, I don't know if I want to work retail. And I took a really cool elective in nuclear pharmacy and just really vibed with it. And I really jumped and said this is really a neat field to be in. And I was in the nuclear pharmacy field for the first uh 10 years of my career. I went to Wall Street for a bit and then got back into the nuclear pharmacy business again.

Ben Comer 1:53

Yeah, I uh I am a well, once was a registered uh pharmaceutical technician. I worked in a compounding pharmacy in high school, uh, but I never had experience in a nuclear pharmacy. And and just I can picture, you know, the pharmacy I worked in. How was a nuclear pharmacy different? Uh it's not it's not retail, I don't think, right?

Thijs Spoor 2:14

It it's not. And so the nuclear pharmacy is an interesting one. Our our lab in Toronto, where I first started, was actually we had to do about 300 prescriptions a day, and each prescription was a unit dose syringe for named patient, right? So every single patient in that Toronto area would receive doses from that facility. We would prepare it and customize for each patient. If they had a bone skin at 1030, there'd be a certain amount of drug in the in the in the syringe. If they had a lung scan at 2 p.m., they'd have a different drug with a different amount, a different activity. And so we'd prepare patient-specific doses on demand. Um, and it's a pretty interesting discipline right now. You know, there's about 18 million radioactive procedures that happen in the U.S. every year. Each of those comes pretty much in a um ready-to-go uh syringe for the patient. And so there's a huge supply chain that's that's geared around there.

Ben Comer 2:58

Yeah, and we'll get into that all different half-lives, different timetables that you have to operate on for each of those uh individual

Building Global Radiopharmacy Operations

Ben Comer 3:05

patients. Um you mentioned going over to Wall Street, coming back to nuclear medicine. Uh, you were at Amersham International and GE Healthcare. Were you working on radio pharmaceuticals back then?

Thijs Spoor 3:18

I I was. So with Amersham, I was building nuclear pharmacies around the world initially. So I built the first nuclear pharmacy in in Tel Aviv, in Sydney, and Bogota, Hong Kong, uh, did a few different facilities, which was pretty cool. And then went into uh commercial on the product side. So was uh leading the main product, tetraphosm and myob for heart scans, and there into uh strategy and strategic market oncology and really helping build out uh pet uh you know drug distribution, along with looking at a whole range of pipeline of compounds.

Ben Comer 3:49

And that so that carries through into GE healthcare as well, not just Amherstam.

Thijs Spoor 3:53

Correct, yeah. So GE Healthcare bought Amersham.

Ben Comer 3:55

Uh oh, okay, right.

Thijs Spoor 3:57

So that was a really interesting way for GE to actually go one adjacency close to the patient. They they'd historically only uh wanted to be in equipment and selling um sort of X-ray scanners, MR scanners, things like that. And this is actually one step closer to the patient because then they were actually then able to commercialize and sell contrast media for X-ray, MR, as well as the nuclear medicine drugs too, and really innovate that way.

Ben Comer 4:21

Uh you've so you you've had a chance to watch radio pharmaceuticals uh as a modality grow uh in leaps and bounds in recent years. Um, what I I guess what surprised you the most about uh the way that the field has evolved and really taken off in some ways uh here recently in the last

How Radiopharmaceuticals Evolved In Waves

Ben Comer 4:40

what four or five years? So the field's actually gone in waves.

Thijs Spoor 4:43

And so initially, the I mean, radioactive iodine was used back in the 1940s from uh Saul Hertz. And then the real realization was that diagnostics could be interesting. Bone scans helped drive a major wave of adoption in the 70s, 80s. And the 90s and early 2000s, then cardiac really kicked in. And so you went from 2 million procedures a year to nine million procedures a year in cardiology and the ability to do a rest stress test in a patient, non-invasively, and get all this diagnostic information at a time when the hardware technology got to the point where you could do what's called cardiac gating, meaning you could image a beating heart by timing the acquisition of the scan with the rhythm that the patient's heart is beating. So you can actually uh get an image of a moving object because you know how that's gonna be moving. So really cool technology that advanced to really amp up the resolution. And then the field was saying what are the next waves of growth? And so the feeling in the uh 20 teens was going to be this kind of jump into neurology, especially with Alzheimer's and Parkinson's diagnostics. And those medicines are really interesting. What's difficult about any diagnostic procedure is what is the disease modifying therapy? So what you can do a cool scan, you can answer an academic question, but you always have to ask yourself what the so what? Right. So if there's a physician uh that's skeptical of diagnostic tests and and just really wants to manage their patient better, they don't want to do a test and not have the results of the test impact anything about patient management. Why do it? Yeah. And so the field, yeah. So the Alzheimer's question was really cool diagnostics. Could you actually image beta amyloid? Could you image uh Tau proteins? I think the Alzheimer's community is still um undecided as to which of those is the most important. It's a major kind of heated battle. Yeah, absolutely. The academic circles. But irrespective of what that is, to the degree that you can image the um Alzheimer's plaque burden or the Tau burden, if there are no disease modifying therapies, no changes to patient management, why do the test? And there's obviously cases where the families want to know, and we can have them prepare more if they know for sure it's Alzheimer's versus pseudodementia or something else. But without a major disease modifying therapy, then it it was difficult for that field to really kind of gain a lot of adoption. Um, and then it was really interesting what happened, not by accident, but by just the field being so innovative, where a lot of academic sites started treating patients with newer isotopes like lutetium. And so you had a lot of really interesting academic work in Europe using uh lutetium dota to treat patients during the tumors. And AAA was smart enough to figure out this could actually be a drug, got the drug approved, and the Bartis made the doctrine, and a site did the same thing with Lutesian PSMA, uh, which yielded plebicto. And all of a sudden, then the field thought, okay, where can we make a difference? We can image a tumor, but we can also treat a tumor. And that's where it got really exciting for the first time you could actually go away from treating thyroid cancer with iodine. There was initial runs with Bexar and Zablin in the early 2000s that suffered from adoption issues in terms of really trying to get a new therapy through, and the field stalled out on the therapy side for a while. And then you all all of a sudden had lutather and plebicto. And that's created this wave of people saying, hang on, we can scale. These are great businesses to be in. They are disease-modifying therapies, they're better than standard care. Yeah, back in the day, say late 20 teens, when Lutathera was approved. The only thing you could actually treat these patients with was um was osmatostatin, which was a way to manage symptoms. But I think technically it had an overall response rate of 3%, right? Meaning it helped symptoms, but didn't really treat the tumors. So Lutathera was able to go and show in the package insert an overall response rate of 14%, and more importantly, disease control. And so these advances uh really made a lot of sense. And then with PSMA and prostate, wow, all of a sudden you have a new therapy where you could actually image a patient to see if they have the receptor. And if they have it, they can then treat them with the therapy.

Ben Comer 8:31

Right. And now, of course, we have a whole range of new isotopes that are being tested and developed uh in clinical trials. I want to come back to that in just a minute. Is um is GE healthcare still uh working in nuclear medicine? Are they doing diagnostics or are they developing therapies?

Thijs Spoor 8:48

Uh so GE Healthcare right now is not that I'm aware of in the therapy space, but they do have diagnostics and so they actually make a lot of the infrastructure behind how the drugs get made. They have an automated chemistry system that can be used. They do have some work on just imagery on the scanner technology. Um, and they do have some drugs as well

GE Healthcare Perspective And Leadership

Thijs Spoor 9:05

that they're trying to bring to market on the diagnostic imaging. Uh, but I think at this point I haven't seen any major bets on the therapeutic side yet.

Ben Comer 9:12

Uh last thing on GE Healthcare. I I think that you were there while Jeff Emmelt was there. Uh any any Jeff Emolt stories uh from your time at GE Healthcare?

Thijs Spoor 9:22

Uh many. I mean, it's so Jeff Emmelt was a was a really interesting leader. He was able to actually uh I was amazed in in various strategy sessions of with each different vertical coming in to meet with him, where he could dive in at the customer segment level across power, healthcare, uh, plastics, and really had a good handle on on named customers within each vertical. And I thought he actually had a terrific grasp on this business.

Ben Comer 9:46

Really? Okay.

Thijs Spoor 9:47

So he he was just focused on the details and knew the details, it sounds like yeah, and and really knew the details, knew the customers, knew the people there. You know, and someone would say, Well, we've got this thing we're putting a trade publication, and he could cite the readership of that publication was in there. So uh really interesting guy.

Ben Comer 10:03

Uh, I want to ask you about your uh time as a leader at a series of companies. Um, but but just quickly before that, I wanted to ask you, you know, you mentioned your time at Wall Street, uh, you covered devices at Credit Suisse, I think, biotechnology at JP Morgan, you were a strategy consultant at Oliver Wyman. Um maybe first, what what pulled you in that direction? Uh, and then what did you learn from that work uh before, you know, coming back to industry?

Thijs Spoor 10:31

So, I mean, digging in my personal life, my wife uh kind of worked for investment bank for most of her career and said, you know what, you're no smarter or dumber than the people I meet in Wall Street, but they make good money. Uh, have you thought about it? So I I went and and uh went to equity research and found it fascinating, the ability to actually go in and look at so many different companies and think about

Wall Street Lessons And Operator Mindset

Thijs Spoor 10:50

them from a big picture, not on the sort of you know, hands-on uh sort of field. So very interesting to look, keeping pace with the innovations. Remember being at one radiation therapy conference, I was asking a radiation oncologist about the latest iteration on one of the companies' equipment. And she said, How do you know so much about the radiation therapy business? I said, Well, it's my job. And she goes, Well, it's kind of my job too as a radiation oncologist. Um, but what you find is that people on the street go very deep in the details and really do understand things very carefully within the verticals they cover. The limitation there is that you're either commenting from the outside or you can be on the field. And so I'd rather be on the on the field creating companies. Did some great strategy work at Oliver Eyman as well. And again, it's really interesting to think about things, but I want to live with the decisions. I want to make sure I can see them become reality, right? And so rather than being paid for my advice, I want to get in the implementation business. And what I'm really excited about with prospective therapeutics, for example, when I joined the predecessor viewpoint, we were 23 employees, and now we're over 180 that have all been able to lean in on the vision that the founders had to really develop innovative uh Bassin class radio pharmaceuticals. And there's so many different things that entail getting the right drug to the patient. Um, and it's been great to draw upon all my learnings.

Ben Comer 12:06

Um, you were a leader at a series of companies uh before coming to viewpoint molecular targeting, which became perspective therapeutics. Um, can you tell me maybe we we don't need to go through all of the companies that you worked at, but I wonder if you could highlight an achievement or a challenge uh during that time. And also uh as a follow-on to that, what circumstances brought you to the CEO role at Viewpoint Molecular Targeting?

Thijs Spoor 12:31

So a lot of things come in play uh when you look at the early biotech

Drug Development Risk And Animal Testing

Thijs Spoor 12:35

space. And it's always uh interesting to disaggregate the person from the technology from the successes. You know, most good ideas, if you have a good animal uh data, you have a reasonable thesis behind it, you want to figure out does it make sense to try the next couple steps? You're never gonna be able to handicap will this go from an idea to full approval. But you can kind of figure out the next couple steps and try and de-risk those to figure out do you have a better than even chance of actually having success for the next iterations and learning? Oftentimes when companies don't work out, it's because something was fundamentally wrong with the product, right? Meaning that the idea is great, but the asset, the technology just didn't perform in a way that warranted further investment given the current investment climate. So I had one program, for example, I was working on it, which is a fantastic drug for cystic fibrosis patients that would have dropped their enzyme burden from 40 pills a day down to five pills a day. And that was really transformational and had a lot of things I'd looked up earlier in my life dealing with cystic fibrosis kids. But in parallel with that, when vertex pharmaceuticals comes along and not have these fundamental disease-modifying therapies that are so core to the physiology that that that whole need goes away, right? And so you may have great science, but if the competitive landscape moves around you where that technology is obsoleted or the need is obsolest, then um you know things won't work out. Other times of drug just may not make it, it may not have a good enough therapeutic window. Uh it may not have the right profile because mice aren't humans, right? And the data doesn't scale. And so you always have to be careful of that too. The the analogy I give my kids when I'm talking about drug development is that you know, if chocolate was the best drug in the world, you'd stop at the dog studies, right? And so just because something is is toxic for one species doesn't mean it is for another. And you try and extract as much learning as you can from one way to do it and really think through what how you go to the next step. But nothing beats the ability to actually evaluate the medicine in a human, which means you have the obligation to do it very carefully and very cautiously uh to actually make sure that the medicines you bring for are both safe and effective. And there's always a race to jump in and say, make, you know, show the efficacy right away, but you have to show safety first and really sort of proving that point out. If you can document and defend that, then you actually dial in the efficacy setting too. So learnings are that not every medicine or every not every science or technology can be scaled up and is relevant in humans. And also there's there's huge issues of timing and really identifying things that are not just relevant for current market need, or what's the what will the market need be at the time of approval? So to make sure that you do have that relevance.

Ben Comer 15:11

Yeah. Uh on animal studies, uh, the FDA seems to be, you know, pushing away from animal studies at this point. And I'm curious about your view, Tays, on, you know, do you think AI in silico testing has reached a point now where we could potentially completely eliminate animal testing, or are we not not there yet? What do you think about that?

Thijs Spoor 15:34

I I guess without being too cute about it, would you want to be the first patient to try something where you're told, listen, we're not bothering testing this to anything else? No, I would not. If you are the first living organism to ever take this medication, we have no idea what's good. But don't worry, the computer says you'll be fine. Right. That's that's a big stretch. Um, that being said, I'm all for getting more fish and getting more learning. So I think the FDA has done a really good job to really lower the burden that's needed for how we actually do this research, what we test on, how we test. And that's very important for as a society. But we should never forget the obligation to make sure that we're developing safe and effective medicines for humans. And we have to really make sure we feel comfortable with that.

Ben Comer 16:16

Um what about the circumstances that brought you to viewpoint molecular

Biodistribution As The Core Design Rule

Ben Comer 16:20

targeting now perspective therapeutics? How how did you end up uh as the CEO there?

Thijs Spoor 16:26

So I uh my the previous role I'd been in was doing some really interesting work getting ready for a US listing, and we changed directions and went to uh uh end were looking actually towards an Asia listing instead. Um and so I decided it didn't make sense for me to try and move to Asia to help with that during COVID. Um and so uh I was looking for a job that could keep me in the US. And I looked at a lot of different ideas, and some of the ideas I looked at didn't seem to make a lot of sense for me. I I couldn't get behind the science. Um, and it's something where I have to know the science is viable to take it, be able to take it forward and have my own conviction. You know, I don't want to just um you know sort of promise an idea to an investor without having my own conviction behind it, and and I will directly invest in the companies that I lead. So I wanted to make sure I had conviction around the science. Um, when I looked at some of the opportunities in front of me without um naming the opportunities that I did not go forward with, I also wanted to make sure that there is a real there is an ability to create in the landscape. And I thought the radio pharmaceutical space was so important, but what really locked me in was my diligence. So if you remember, we did we talked about for earlier in my career, I was in the cardiac space, and cardiology was the cash driver for the business. We actually looked at a novel way of actually imaging cardiac patients, and looking at that, we actually wanted to assess um, is there a drug that could give a better cardiac scan? And so we looked at digitalis or digoxin like fox glove. So something used, you know, over for you know for for decades or millennia even uh for treating patients with heart dysfunction. And the the idea of using digitalis made a lot of sense. We made it radioactive and it went to the heart, but it also went to the liver. And so heart and liver right next to each other. And if that's the case, then um you can't really tell what's what. And what we realized is that yes, 3% or so went to the heart, but 80% went to liver. And there's such a massive disconnect. And so any medicine that you're gonna take, that you're gonna swallow, you usually don't know where it goes. If you're taking acetaminophen or ibuprofen, you you can tell that you're feeling better wherever you have pain, but you don't really know or feel everywhere else that's going in the body. And where the radiopharmaceutical sort of unforgiving and unrelenting uh is that they're gonna go everywhere where they're gonna go and you can image it and see it. And that's it's not a double-edged sword, it's only a benefit timeline because you can tell before you treat a patient where will the drug be going. We can actually make the drug radioactive just enough to give an image without any major radiation harm to the patient's body. We can inject the drug and see, is it going to tumor? Or we can see, is it going to liver, is it going to heart, is it going to brain, is it going to kidneys? Does it never clear the bloodstream? Like we can learn a lot about the biodistribution. And the biodistribution is critical. I mean, it's important in every field, especially in radio pharmaceuticals, because wherever that drug spends some time, it's going to burn. Okay, think about the radio farms like bits of hot metal. And if a piece of piece of hot metal kind of you catch something that's that's hot in your hands, you can throw it away quickly and you're not really gonna get burned. But if you grab a piece of hot metal and you hold on to really tight, you're gonna burn your skin the longer you hold it. And it's the same thing with any tissue in your body. The longer you hold on to that radio radioactive compound, the more damage will happen. So we want to design these medicines so that they're gonna go and stick into the tumor and burn the tumor. We don't want them sticking into the kidney or sticking in the liver and burning those organs instead. So it's really, really important to understand that therapeutic window as it relates to the biodistribution, which is informed by uh the imaging drug. And so it's a great application of the technology. And when I looked at Viewpoint, I asked the founders who had a really great uh path to getting the company started, they thought we want to design a safer drug for pediatric neuroendocrine tumors, meaning kids with this really funky disease. And by doing a safer medicine for those kids, they actually realized it was safer for adults too. I said, love the idea, but show me a human image. And they said, if you show me a human image with good biodistribution, I know how to read that. Uh, and I'll uh I'm in or I'm out. And the first human image they showed me was fantastic, right? The patient's tumor is lit up and you did not have the drug staying uh anywhere where it wasn't supposed to over 24 hours. And that's really important that you match how long the drug stays in various tissues with the half-life of the isotope that you're using to treat. If it's a 10-day half-life, like some people are trying, you need to make sure where is the drug going to be for 30 days inside the body. And that's a really tough way to kind of guarantee that the medicine only stays where you want it to be. In the case of the lead T12, it's a 10-hour half-life. So we need to kind of figure out 20 to 30 hours, where is that drug going? And that's enough time in biology to really get a good sense for uptaking the tumor and tumor retention. So we want to make sure that the tumor retention time is longer than the half-life. If it's not, then you're going to get the drug temporarily to going into tumor and then washing out. And that that that ruins your therapeutic window.

Ben Comer 21:18

One of the things that

The Pb-212 Generator And Vertical Integration

Ben Comer 21:20

uh stuck out to me as I was preparing for this conversation, uh, Thijs is the fact that Perspective Therapeutics has its own proprietary generator that you use to manufacture uh lead-based alpha-emitting therapies. Um, can you just explain maybe to the audience why that's important to the business overall? Sure.

Thijs Spoor 21:40

So back when uh Dr. Schultz and Dr. Johnson formed the company that's been out at the University of Iowa, you know, they had this great idea that the drug could actually work better for kids. Well, they had two issues. There wasn't a good key later for the drug and there wasn't a good generator for the drug. And so 10 years ago, the US Department of Energy did provide a Light C12 generator, but it wasn't always available. It's usually one day a month. Month. And that's very difficult to do research with and how to time your animal research and your patient research and your patients showing up. So we invested into actually scaling up the technology and making it more available to ourselves. Since then, we've actually had a whole raft of patents issued around how to actually use the generator system and not just, you know, what do we do with the generator, which is good for one or two patient doses a day, but how do we scale up to do hundreds or thousands of patient doses a day, which we've also invested in that scale up to. So the generator is an enabling technology. We didn't want to jump into that space, but we realized that no one had the know-how necessary to make the isotopes in a safe, consistent fashion. So we did it because we had to. And now, you know, to the degrees that we can vertically integrate, we have been. We actually are investing a lot into our manufacturing capacity. We don't want to be beholden to people. You know, one of the good business disciplines that General Electric has is that if you're a GE, you never want to have a sole source supplier. You want to multiply multi-source, you want to have a preferred band of relationship. But it's really, really tricky to be in a situation where you're single source dependent and you need to understand those relationships, not for necessarily for any economic reasons, but from a just a risk, uh, risk assessment. You want to make sure that your business is sustainable.

Ben Comer 23:16

Yeah, absolutely. And I I've heard from other uh radio pharmaceutical leaders uh about this exact issue. And I think maybe in the case of Actinium, there was one where, you know, there were only a couple of generators, and it was kind of a you know, a a little bit tricky to line up the time frames and make sure you're getting your your your full supply chain in place. And and I just out of curiosity, and you you mentioned you didn't want to go into this necessarily into this business of having your own generator, but why is that? Is it just because it's uh you know it's a big cost base or it's so complicated and and it's regulatory burdens, or or what, you know, what is it? Why aren't radio pharmaceutical companies, you know, having their own generators, their own cyclotrons? Uh there's probably a you know an easy answer to this question that I that I don't get, but explain it to me.

Thijs Spoor 24:06

So it's a it's major capital intensity. So if you have a certain amount of money um and you have the choice between running a clinical trial, starting a new program, or investing in infrastructure, you you want to figure out what's going to get the best return on your on your on your dollar. But let's take a slightly absurd situation and a big pharma company, for example, they need saline, right? That's just kind of like what you know, water with a little bit of salt in it. They would much rather buy saline off the shelf than invest into a saline manufacturing facility, right? Because it's it's just something, it's a component, it's an ingredient that gets used, but it's not the active ingredient. And so if you think through where do you want to deploy your capital, it's into getting the most value from your proprietary ingredients. If you can't buy saline off the shelf and you have to make it, you do it, right? In the case with the isotope game, if I could know I could buy an isotope every day without worrying about it, I'd do it. But we it's a tricky supply chain. There is a huge gap, though, between the different isotopes and what's needed. So the capital equipment required for actinium or litesium or terbium involve or acetine involves major cyclotron or reactor or accelerator technology. So massive, massive capex equipment dedicated to isotope production. An elegant way of just creating the LED T12 is if you have thorium T28, you don't need any of that. You're using resin-based chromatography, meaning you can have a little cartridge resin like this. You can run saline through it and pull off your drug every day as you need it. That's a much simpler way to go than actually running a major nuclear facility for isotope production. So we're we're trying to use, we're trying to develop drugs to um to treat patients with cancer. We're not trying to be in the isotope creation business, but we vertically integrated where it made sense.

Ben Comer 25:47

Got it. Okay. And can you uh tell me a little

Regional Manufacturing Beats Single Hub Risk

Ben Comer 25:50

bit more about um Perspective's regional manufacturing plans and maybe what that looks like?

Thijs Spoor 25:57

So there was a measure that certain players were talking about a couple years ago where they said, well, you should do everything for one central uh hub. And if you build a site in Indianapolis, for example, where the Five X dangerous goods hub is, you can then get product across the US overnight. Um that doesn't job with modern supply chain theory, which says that you for all uh any distribution network, you need a distribution network, right? And so a network with multiple nodes, it's always more reliable, guaranteed more reliable to have multiple points of backup than to have a single point of failure with a single uh distribution hub. Navartis has announced five sites in the US that they're building in and sort of the five uh corners of the country, you know, sort of east coast, west coast, Midwest. Um, and we're we've been publicly doing that for four years as well. Yeah. So the reality is that if you are in the isotope business, you're always better off with the network. Uh you look at all the PET scans that happen in the US that's got a two-hour half-life isotope. There are 105, 104, 105 GMP facilities that make uh fluorine 18 every day and make the drug and distribute it. Um, someone like Lantheus, their commercial prostate imaging drug, for example, use Zoro50 GMP contracted sites to actually produce the product and distribute at a local regional level. You're always going to be more efficient than trying to do it all from a central location. The reality is that no matter where you are in the country, there's weather, there's various dynamics. And if you can just have a same-day delivery by road, that's always more reliable than relying on overnight air constantly for everything that's in your supply chain or same-day air. So we want to build multiple sites. We actually have a site in New Jersey that has been commercially ready before. We're building a flagship site in Chicago. Uh, that site is um will be state of the actually the leading radio pharmaceutical facility in the world. We've engineered it to handle any isotope uh that that is currently contemplated and in radio pharmaceuticals. Oh, we're dedicating it for LED T12 because that's where our pipeline has been, but it can handle any isotope at all. We're also building additional sites across the US uh to make sure we can then bring product to the patient. With our current sites, we'd we're delivering to 30 states right now, um, and we're adding more and more sites. So you need to get the drug to the patient, but the it logistics aren't quite as difficult as you think they might be. We're not trying to get the drug to every local retail pharmacy. We're not trying to get the drug to every general practitioner or family doc. We're trying to get the drug to cancer centers, right? So we're dealing with cancer patients. So anyone, any site that's imaging patients with cancer with a PET scanner, yeah, that's where we think about it, where we're trying to get the drug to. The drug can only be given in a site where they have qualified personnel for radiation safety, how to actually give um radioactive medicine safely and appropriately. So we're not trying to solve for every patient, uh, no matter where they live. We're trying to solve it for every cancer, every cancer care center.

Ben Comer 28:47

Do you think that uh lead is an uh an

Alpha Versus Beta And Daughter Isotopes

Ben Comer 28:50

alpha emitting isotope, but but do you think that alpha emitting isotopes uh as a class of isotope, I guess, will become the market leader in radiotherapeutics, or will there you know continue to be a long-term role for beta, gamma emitting isotopes as well? What do you think about that?

Thijs Spoor 29:08

So I think there's always gonna be a role for gamma. Gammas are used for imaging, right? So I think there's always for imaging drugs and for for spec and pet. Uh, I think there'll always be a role for those. When it comes into a targeted radio pharmaceutical, um, the focus is really going to be on the targeting mechanism. And so if you're gonna target a certain cell type, how do you actually get those cells? What vector do you use? Do you use a peptide? Do you use antibody? Um antibodies are really challenging. It takes a long time for them to circulate in the bloodstream before they finally localize, which means depending on what payload you pick, it will really impact your safety profile. So if you're using an ADC, for example, you're using a non-radioactive payload, unless it's detached, the payload doesn't do anything. So you can afford to have a week, week and a half of circulating antibody before you actually get your ADC to target. If your payload is radioactive, that's when the game changes, because as it's sitting in your bloodstream, it's going to be firing off betas or alphas, whatever it emits, and those receptive daughters are going to have their own biochemistry. And then you're exposing the whole human circulatory system to these payloads. So you ideally, in our view, want a very fast localizing uh payload vector, right? So in our case, we use peptides. We've designed our peptides to clear the bloodstream within about 30, 40 minutes. And if they do that, then you either bring the payload straight to the tumor cell or you're hoping it gets flushed out of the body. That's an important flush out of the body concept because if it doesn't get flushed out quickly, that means then the payload or the isotope will accumulate in non-tumor targets. And that's where where problems happen. Because that means if it's accumulating anywhere but tumor, you're getting off-target damage. And that's what's so important for understanding a therapeutic window. You know that if you give enough radiation to a healthy cell, you you can damage it, but you don't want to do that. You want to give the radiation to the cancer cells. And that's why the biodistribution is so important. You know, your question about what's ultimately going to survive. Lutesium as a beta um hits limits for its efficacy. It's if the betas, you know, need a certain threshold to actually cause damage and destruction. You need 1500 betas roughly to kill a cancer cell. You need a single alpha particle to kill a cancer cell. But that single alpha particle killing a cancer cell, that single alpha particle can also cause a lot of damage to a healthy cell as well. So it's a double-edged sword, right? With great power comes great responsibilities, the quote. You need to really make sure that the alphas, if you're using them, are only going to tumor because if they're going somewhere else, then you're going to cause a lot of extra damage. The current theory is that um that with the targeted radiofarms, that's you really want to make sure you're getting the drug there. You need to be aware of the payload and what's being given. You also need to be acutely aware of any other um daughter that shows up. And the daughter game is a little like a toxic metabolite, right? So if you've got an active drug and a toxic metabolite, you need to understand where both those are happening. With the radio farm game, you've got your first decay, the lead C12 actually emits a beta. That's a low energy beta, and that the lead C12 turns into bismuth T12, that's where the alpha plug comes from. And so you really want to make sure that that active one, that bismuth, is also where you want it to be. We've engineered our chelator, for example, to hold both the bismuth and lead together, wherever one goes, the other goes. That's not the case with the accelerator set will leak. Um with actinium 25, you have daughter decay. And those daughters each have their own biochemistry and differ in resonance times. So you need to make sure you can control every single daughter where it's gone. So the net impact of the patient is that you're heading more counts onto tumor and less counts onto healthy tissue.

Ben Comer 32:39

Great. Um, I wanted to ask you a question about workforce. I I had a conversation, uh, it's been two years ago now, probably with the former CEO of Fusion Pharma, John Valiant. Um, Fusion was acquired by AstraZeneca for 2.4 billion, one of the two big radio pharmaceutical deals that that happened in 2024. Um,

Workforce Gaps And Training For Radiopharma

Ben Comer 33:00

but I remember that he was saying that the, you know, it's fantastic, the growth of radio pharmaceuticals as a field, wonderful, uh, a lot of potential patients. Uh, but also it was becoming difficult uh to find people with the right science backgrounds and the required uh nuclear safety qualifications. Is that are you running into that at all, Tays? Or do you is there a uh a budding workforce, you know, ready to come into the field of of uh nuclear medicine and radio pharmaceuticals? What's your experience with that?

Thijs Spoor 33:33

We've had us that we've we have talent. There's a lot of talent available as it relates to cell therapies, sterile products, how people manage um, you know, sort of on the supply chain side in drug development. There's a lot of people done college experience. There are some specialists that are in the radio farm field that are available, but it's a growing pool. I think if you're trying to do supply chain talent in Indianapolis, it's a very competitive market. A lot of people are located there. We're not. Um, and so it's really kind of a matter of where you're going to be and uh who you have. We're having to teach the field a little bit. We're having to really get good people. We've actually had fairly low employee turnover. We're a great place that people want to join, people stay. Um, but it there is a learning curve on the supply chain side. And it

Clinical Programs In NETs And Melanoma

Thijs Spoor 34:15

really is uh a know-help that not a lot of people have.

Ben Comer 34:19

Uh I want to ask you just a couple of final questions here, uh, Thijs, uh, about Perspectives clinical programs. The first one, your lead program, I believe, VMT A N E T net, uh in neuroendocrine tumors. Um is that tar is there a specific uh organ that you're targeting with that program? And correct me if I'm wrong, I I think neoendocrine uh or neuroendocrine tumors are are maybe most often found in gastrointestinal tract, pancreas, uh, and lung. But is there one is it potential is that drug potentially applicable in all of those uh um organ systems, or or is it are you looking at one in particular with your LEED program?

Thijs Spoor 35:03

So we actually um we don't sit look at organs, we look at receptor positivity, and we don't really don't care where it is except if it's not a tumor, meaning, okay, so for SSTR2 or the neuroendicant tumor per profile, there are it's not just neuroendocrine tumors that actually express that receptor. You can have it showing up in breast, lung as major, major tumors, but also some really uh discrete niche ones like theochromacytoma or paraganglioma or meningioma. And with a targeted radiofarm, we want to be able to actually bring uh that medicine to all those different tumor types as best as we can. So it's very important to think about where does it, where is a receptor showing, where does it not show? We actually looked at one receptor type, rural, which is a really exciting one in oncology. But there was so much that was uh was seen on the healthy tissues that we decided we didn't want to go there um and didn't want to spend a lot of uh time on um on actually investing into a system if we thought the off-target damage would be too high. There's so many targets we can go after where if it shows up in the tumor nowhere else, great, then we can make that a great target. So we go after targets that show up in high concentrations on tumors only. And so that helps really filter down what's important because whatever we touch, we're gonna burn.

Ben Comer 36:16

Does it complicate the regulatory submission later on? Like what do you are you gonna have to choose a specific tumor type or indication, or or can you kind of remain, you know, receptor focused where wherever that receptor may occur?

Thijs Spoor 36:29

Well, I mean, approvals are really tied through an explicit indication that matches your clinical trial testing. So think about one of the biggest oncology drugs ever, Key Truda, right? You know, MERC spent a lot of energy because they had to go tumor by tumor, showing the data, imply that in different tumor types that the drug could be safe and effective. So you can't say, well, it's a good cancer drug without describing what the cancer is, what it looks like, how that ties to your mechanism of action. You may believe it works everywhere, but you still have to prove it with the agency. And so you wanted balance between things with fast paths to approval, things with large addressable markets. The one thing you don't want to do is a very expensive trial in a tiny, tiny market. Um, and that that that tends to be quite tricky.

Ben Comer 37:12

Yeah, the other thing I'd want to mention quickly, I know uh VMT01 uh is being tested in melanoma, and at least I think one arm is uh in combination uh with uh Naval, uh BMS's uh Opdevo, um, which is an interesting uh pairing of a radiopharmaceutical and a and a PD1. Um you know, you mentioned Katruda. How did that uh come about? And is that can you give me a sense of where that stands in the clinic? Is it is it going into humans or what phase is that in?

Thijs Spoor 37:42

So with the BMC1 program, we target a receptor called MC1R that shows up in about half of melanoma patients if they're metastatic. So in metastatic melanoma patients, we can do a scan and see if they're a receptor positive or not, which means we can determine if the drug could ever work. And that's a great thing about the diagnostic pairing is that you can actually know in advance if a patient should never get a response. So you just you don't treat those patients. The idea of combining with the checkpoint inhibitor means you're actually helping the immune system do its job. And what an alpha particle especially, so you don't see the external beam, you don't see as much of the beta, but an alpha particle causes such a what they call a neoantigenic storm, meaning the alphas are smashing into the tumor cells, throwing up all this debris. And that debris is something that signals for the immune system to lock onto. So the immune system can actually then say, great, now I know what to do. Uh the immune system can get a lot more activated if it knows what it's targeting. Um and so the combination looks very, very exciting. We're actually we've been enrolling patients into that program in both a monotherapy and a combination approach uh in patients with a metastatic melanoma.

Ben Comer 38:46

Uh, last question for you, Thijs. What are your top priorities for the remainder of this year? Maybe there's uh a specific uh uh data reveal coming up or

Year Priorities And Closing Remarks

Ben Comer 38:55

or um uh the start of a new trial. I don't know. Like what are you what are you most focused on right now? What would you say about your top priorities?

Thijs Spoor 39:03

Well, we have the three pillars of our company discovery, uh, clinical, and production. Each one of them has things that that are going to be uh big milestones for them for this year. And the discovery program, we'd hope to have first in human images with at least one new compound. On the clinical side, we have three programs in clinical development uh for melanoma, for neuron consumers, and something called FAP targeting. So we expect to have safety and efficacy data from each of those three programs this year. And on the production supply chain side, we'd hope to finish construction of our Chicago site and be well in the way with another site uh sort of building as well. So uh we're making investments across the board and things that either add to our scalability, add to our infrastructure, uh, add to our pipeline, or advance product with the regulator.

Ben Comer 39:46

Great. Well, thanks again for coming on the show, Thijs. I really appreciate it. Well, Ben, thanks for having me. We've been speaking with Thijs Spoor, CEO at Perspective Therapeutics. I'm Ben Comer, and you've just listened to the Business of Biotech. Find us and subscribe anywhere you listen to podcasts, and be sure to check out our weekly video cast of these conversations every Monday under the Business of Biotech tab at life scienceleader.com. We'll see you next week, and thanks as always for listening.