All right, we'll get things started now. Thank you all for joining for today's panel, which is titled Radiop harma Isotope Roadmap: Clinical and Logistical Considerations. My name is Justin Walsh, and for those of you who don't know me, I'm a covering healthcare analyst here at Jones Trading. With respect to the format, we're going to start by allowing the panelists to introduce themselves. I'll then ask each panelist a couple of directed questions before diving into questions for the entire panel. To kick things off, John, can you introduce yourself?
Hi, I'm John Wiggins. I'm the VP of Isotope Strategy at Lantheus. Lantheus is the leading radiopharmaceutical focus company and excited to be here today to answer some questions.
All right, you Sumit?
Hi, I'm Sumit Verma. I'm the CEO of TAG1. I've been involved in radiopharmaceuticals for almost 25 years now.
And Riccardo?
Hello everybody. Riccardo Canevari, I'm the CEO of Radiop harm Theranostics, a company that is listed in Australia and now also on NASDAQ.
Great. We'll just jump right in here with an easy question for John. Obviously, Lantheus has demonstrated the clinical and commercial viability of branded F-18 imaging agents with PYLARIFY, but the company also has gallium-68 and copper-64 agents in your pipeline. Can you just comment on the relative advantages of agents based on each of these isotopes? Assuming that the images generated by these are comparable, and you can correct me if I'm wrong on that point, how important are the differences in availability, production capacity, half-life, and chemistry?
Yeah, we obviously have a huge interest in F-18, and we think that that's a wonderful isotope for a number of reasons. One is that it has a very short positron range, and that translates into a higher resolution image. That's sort of a technical wonky aspect of this, but it has a real impact on the quality of image that's produced, and that's a big reason to favor F-18. F-18, of course, also we benefit from the decades of work in building up manufacturing and distribution, particularly around the U.S. Having this PET manufacturing facility network across the U.S. and therefore wide availability of very high volumes of F-18, and those factors together make F-18 an exceptional isotope. It does have a couple of either limitations or constraints on it.
One is that because it has a short half-life, two hours, so longer than gallium-68, but significantly shorter than copper-64, distribution is primarily local. We have to have a manufacturing center or several manufacturing centers within each metro area or region in order to supply customers in that area. If we go to a longer half-life isotope like copper-64, then we can centralize production, and that makes the management of the manufacturing network significantly simpler. It may not be noticeable to customers in the end how we do that, but we do look for operational efficiencies on our side as well. The last piece on F-18 that I'll say is the chemistry is different, the way that it attaches to the molecule from metals like copper and gallium.
When we have a molecule that's been developed to attach metals to it, fitting F-18 into that, it's not impossible, but it's a little bit more challenging. That might be a reason to favor other isotopes. In fact, where we've worked with gallium-68 and copper-64 in particular, part of the consideration there is chemistry. With a gallium agent, you can easily take the gallium out, replace it with lutetium, for example, and switch straight over to a therapeutic product. That can make development of new molecules a bit easier because you have a few more synergies between the diagnostic development and the therapeutic development. I would say that gallium is also well suited for markets where there's lower demand because you can make it efficiently in small quantities. If you only need one or two doses, that's easy to do with gallium.
You elute that much off of a generator, you make those couple of doses, ship them again within a local area, and you're good. If you need to make 40 doses or 50 doses, that's harder to do efficiently with gallium, and in many cases, even to do at all, depending on the resources there. That's a big reason to favor F-18. Finally, to go over to copper-64, we do like that advantage of centralized distribution. copper-64, like F-18, has a very short positron range, so high resolution images compared to gallium-68. It doesn't give off as many positrons or doesn't give off a positron as often when it decays. That could mean that you need to administer more activity or have a longer scan time to get the same amount of information for an image.
There are some trade-offs to look at there clinically when we think about how those isotopes work. Certainly, the clinical aspect of it is very important to us. I do think there are differences in the image quality that we get off of it, but supply chain, depending on the stage of development we're at, could be even more important. When we look at assets where we are either in late stage or we think we have an accelerated path to approval, we may want to look at isotopes that have capacity available, gallium-68, F-18.
When we have an asset like our FAPI agent that has a little bit more time before it's likely to be approved, then looking at something like copper, that's a new isotope where we still need to build the robust manufacturing infrastructure around that, we think we have that time and can then take advantages of the supply chain efficiencies that we get with copper.
Great. Thanks for that. Very, very informative. Sumit, your first question, TAG1 is looking to become a supplier of lead-212 generators. How does the current landscape look with respect to lead-212 supply, and where do you see the opportunity for TAG1?
Sure. As you think about lead-212, it's one of the more newer isotopes coming into the space for targeted alpha therapy. Certainly, we have had players who've been working on it for a long time, but the popularity, especially because of what's happening in the actinium-225 space, has triggered a more demanding aspect of the supply side of things. We have very good therapeutic innovators who have done a great job looking at new products, initiatives coming into the clinical market, and then ultimately providing their own supply of lead-212. As you think about this market, it's kind of unique comparatively to most of the other isotope suppliers where most therapeutic developers are trying to do two complex things. They're working towards getting a therapeutic product to the market, and at the same time, they're trying to bring an isotope to the market.
For those who have been in the industry a long time, that's a really challenging endeavor, especially as you think about the supply side and how you have to build up that technology and the scale-up effort that's required to it. The way we see it is as there's pivoting taking place between actinium and lead and also new modalities that are providing better targets outside our typical markets from PSMA and neuroendocrine tumors, there's an influx of the need for lead-212. Today, there's not that many suppliers of lead-212 itself. In fact, in the U.S., most therapeutic developers are very focused on providing their own supply chain needs, but they can't really offer it up to the others. DOE has been traditionally a good supporter and cheerleader of bringing in new isotopes, but there's only so limited efforts that they can do as well.
Just thinking about the future, I think that's going to be even further constrained. That's kind of where TAG1 really comes in. Our view is we want to be a radioisotope supplier. This is our kind of niche that we're really good at. We're building on the backbone of what we've done in various isotope products, everything from copper-64 to molybdenum, and using that platform to bring in a portable generator. Our view is that if you can get that generator right to the point of care to radiopharmaceuticals, hospitals, and different places where the compounding effect can be done and bring new therapeutic products to the market faster, we just think that's a good place for a lead-212 generator to reside.
Got it. Now, onto you, Riccardo. Despite outlicensing some assets, Radiop harm has maintained a broad pipeline, especially considering the size of the company. What do you look for when evaluating a potential radiopharmaceutical asset and determining which to prioritize for clinical development? Are there major similarities or differences when thinking about imaging versus therapeutic opportunities as well?
Yeah, thank you, Justin. Let me start from imaging. I think that's what we started here. I believe it's a very interesting part of the business, even if we as a company are more focused on therapeutic. From an imaging point of view, I really see three main values from an imaging agent. The one is the one that we are discussing now, being the companion of the therapeutic. If you want to give Lutathera to a patient, you need to have NetSpot. If you want to give Pluvicto to a patient, you need to have PYLARIFY or another PSMA imaging agent. The companion diagnostic value is huge and will continue to grow.
The second aspect that is probably less discussed at the moment is if I do not have a companion therapeutic, can I still have value with an imaging by itself? In this specific case, for example, we do have experience with a PET agent with F-18 for brain metastasis. Now, the value is not because we have a therapeutic radiopharmaceutical, because we don't, but we have the imaging itself that can help to better qualify the type of metastasis that you have in the brain. Are they active? Are they necrotic? How much active they are? When we detect that, assume the phase two is going to be successful, physicians can use SRS, Gamma Knife, to treat patients.
The patient can have better PFS and overall survival, not because we have a therapeutic radiopharmaceutical, but because the PET agent is helping to use other modalities to support patients. This is the second one. The third one that probably is even less discussed is the so-called side effect of therapeutic isotope. They emit gamma. Is gamma bad? It depends. Sometimes gamma is very positive because you can capture gamma emission. You can do with a SPECT camera, you can assess where your product is going and where it's not going. I think that using some isotope like lutetium or terbium-161 allows you during the clinical development of a therapeutic to really understand where you are. This is unique and is a great opportunity for our sector. You cannot have that with an ADC. You cannot have that with a CAR-T.
You cannot have that with a naked molecule, but you can have with a radiopharmaceutical. You dose the patient with the objective of a therapeutic dose, but you can image the patient after and you know how much it went to the tumor, how much it went to the kidney, how much it went to the bone marrow, how much it went to the spleen. You know exactly how successfully you can run your dose-escalating trial faster because you have all this information. I think these are the three major values of imaging agent. Back to your question about selecting one molecule versus the other, that's all, it's exactly the combination. There is the medical need that I can solve with the therapeutic. Are there other modalities or not?
Our focus has always been in trying to expand the use of radiopharmaceuticals where there is no current development ongoing. There are great ongoing results with PSMA, with SSTR2, with FAPI, but there is still so much to do in other modalities. We are focusing, for example, on PD-L1. We are focusing on HER2. We are focusing on B7-H3. Three modalities where we see presence of immune checkpoint inhibitor, of ADC, but not yet as radiopharmaceutical. That is where we are trying to go.
Yeah, I think your second point on the sort of the imaging opportunity is quite interesting, particularly in the context of PYLARIFY, given that so much of the value of PYLARIFY is outside of Pluvicto in and of itself. It's the prognostic capability, which is why I think PSMA has been such a great proof of commercial viability for both imaging and therapeutic because you have this sort of great setup for that. Maybe jumping here into our second specific question for you, John. Related to therapeutic isotope selection, how do you think about the interplay between scientific rationale, current isotope availability, projected isotope availability, and clinical evidence? For context here, I understand that Lantheus's current therapeutic pipeline is dominated by lutetium-177, unsurprisingly, but the company has exposure to lead-212 via partnerships with Perspective Therapeutics. I'm sure that you're actively evaluating other therapeutic isotopes of interest.
Yeah, certainly. It's a great question that all of those factors and more come into play in selecting a therapeutic isotope. Lutetium has the advantage now that it checks all of those boxes, right? It has demonstrated success in products that are out there. We have abundant clinical data showing that it's effective. At this point, the supply chain is quite robust for lutetium. It's an easy isotope to work with and fits well as a first step in developing a new product in most cases. You're right, though, that we do look beyond that and at things, not only other beta emitters, but also alpha emitters or maybe low energy electron emitters as bringing the potential for greater clinical effect and therefore the potential to displace lutetium at some point or other beta emitters as standard of care.
I would say that we are balancing both the supply chain interest there and the clinical evidence. The clinical is ultimately most important. If there's clinical evidence there, the supply chain will develop. We know that some isotopes have maybe easier supply chains than others. Lead-212 seems to be more readily produced than actinium-225. That is no surprise with the sort of science and engineering behind that. Therefore, we are very excited about lead-212 and our partnership with Perspective there.
Where I think we have a bit more work ahead of us as an industry is in demonstrating the potential of alpha emitters because if you haven't changed the therapeutic index, if you haven't changed that kind of ratio of tumor dose to healthy organ dose, then whether that energy is delivered via an alpha emitter or a beta emitter, you're still basically getting the same dose to the tumor versus the healthy tissue, and you have the same constraints. There are some potential mechanisms by which alpha emitters could prove more effective even with the same therapeutic index.
Those have to do with things like antigen expression and immune activation or maybe the range of the particle and that if a drug is excreted through the kidney, does an alpha particle damage the kidney or is it such a short range that it does not even reach critical tissue in the kidney? Those are still a bit theoretical. We have not yet seen at least abundant clinical evidence of those. I think that is a major need for us as we go forward with our research and development effort. It is something that we are very excited about. We certainly are believers in that. We are big believers that alpha therapy and lead-212 especially will be effective. It is just not quite the slam dunk that lutetium is today based on demonstrated success.
Great. I think this is a great tie into the next question for you, Sumit, which is what has what preclinical and/or clinical evidence really has you excited about the potential of lead-212 targeted alpha therapy? Because obviously, you have, I think, high expectations that it will be favorable and see continued uptake in use.
Yeah. No, I think John's right. From a continuum perspective, lutetium, as you think about just the time spent towards development of their drug therapeutic journey, their clinical pipelines, and ultimately the supply side, we've seen a big impact recently, but it was the same challenges down in 2018. If you take a step forward and say, "Hey, what are we seeing that gets us excited?" I think at a preclinical level, we've seen significant amounts of work being done without generating itself. Right now, not a lot of information is public, but what we've seen at Dr. Carolyn Anderson's labs with the University of Missouri is super exciting. The chelator chemistry, not from your traditional DOTA and TCMC, but even more innovative chelators are showing good successes in that space. That gets us excited. We've been working with Precirix.
Precirix has had an interesting compound called CAM-H2 from a single domain antibody, taking a step away from monoclonal antibodies. We have seen that also do very good in the radiochemistry side and initial mice studies. We are somewhat bullish that as more supply comes into the market, as more clinical trials are done, we have only seven out there. It is not the same vigor as actinium, which has over 54 clinical trials out there. We think as you build out those databases, the data will speak for itself. Lastly, on the clinical side, I think some of the data is super exciting that is already published, right? I mean, if you take Dr. Delpassand's study for AlphaMedix and seeing the FDA give them also a breakthrough designation, it is primarily because of the data.
As compared to Lutathera, compared to RayzeBio 101 results, they are showing some very promising data at a very initial phase. I mean, it's too early to bet big on it, but at least as you look at the landscape and some of the success stories on what's been published today, I think it's super exciting.
Great. Now, last one focused on you, Riccardo. I'm wondering if you could tell us a little bit about RAD-402 and how terbium-161 could be differentiated from lutetium-177. Then sort of assuming that we end up having favorable clinical data there, how much effort would it take to scale up production and supply of terbium-161?
Yeah, sure. First of all, each isotope in isolation cannot solve the problem. You need to have an isotope attached to the right molecule to go after the right target. In this specific case, of course, Pluvicto is the leading agent. It was post chemo, now got approval pre chemo, potentially can be also earlier in the treatment line. It's likely that Pluvicto will be the leading, the first line radiopharmaceutical for a number of years. Somebody might try to go head to head with a large trial. I don't know. The reality is if you take the VISION trial data and the new data, there is around 30%-40% of the patient that respond very well. At the same time, there are patients that are not responding to Pluvicto. When you give the four to six doses of Pluvicto, eventually the patient will progress.
You need a post-Pluvicto agent. For this reason, we thought about how can be that market is can be significantly commercially attractive. Of course, the answer is yes. How can you go post-Pluvicto? You can go with different approaches. We personally believe that changing target is a better option than just changing isotope. Going with a PSMA with another isotope can work, but equally can work to go with another target. We focus on KLK3 because KLK3 is expressed in 98%-99% of the patient when the disease is not metastatic and probably around 90% of the patient when they are metastatic. You need to exclude the neuroendocrine part of prostate, but all the other express KLK3. We think that is a good target to go after. The second approach is that I think is equally interesting. Pluvicto is peptide.
It is kind of a small molecule. That means that when patients receive four doses, that is the average of Pluvicto, they already consume 16 grays- 18 grays in the kidney. The limit from FDA is 23 grays. Any post-Pluvicto therapy needs to consider that they only have six to seven or eight grays before they can give more products if the 20 grays will remain. I mean, there are a lot of discussions that can change. For the time being, that is the situation. You might not be able to maximize the therapeutic impact because you can give maybe only two or three doses. We thought that for this reason, going post-Pluvicto is better if you go with a monoclonal antibody instead with a peptide because a monoclonal antibody is going to be excreted by liver, not by kidney.
You can probably manage the route of excretion without getting to the 23 grays. The third point, which is what you asked, is terbium-161. Why terbium? Again, we go to the discussion that we mentioned before. Terbium not only is a therapeutic isotope, but also has gamma emission. We like the idea that we can do SPECT after every single dose to see exactly how the clinical development is going. Terbium has a unique characteristic of not only having beta emission with a half-life similar to lutetium. It is like a week, so you can distribute easily. It also has a second emission that is Auger. Auger is interesting. Now, Auger does not work for everybody because Auger, in order to work, needs to get internalized and get closer to the nucleus. Some targets like KLK3, it is internalized or works well.
Auger is interesting because it's alpha-like. It is high energy, short distance. You have an isotope where you are combining the beta plus the Auger. There are some early papers that are interesting. Too soon to say if terbium is going to be a better lutetium or not. There are some emerging data. We said that in order to complete the differentiation in a post-Pluvicto setting, different target, different route of excretion, also different isotope might bring to a solution that can add additional value. On the supply chain, I think we go back a few years and we see that when there is early sign of therapeutic evidence, the supply chain comes. That was the example of lutetium. A lot of money went to actinium and going to lead because people start thinking that is going to happen.
That may be the same situation for terbium-161. The production is not difficult. The challenging part is the precursor. You need gadolinium-160 in order to do terbium-161. This is not widely available. That is the supply chain that you need to build on.
Got it. That's the perfect tie-in for my first question for the panels broadly, which is how has the radioisotope supply chain evolved over the last few years? Are there isotopes that are available in sufficient quantities for preclinical or clinical investigations now that were not available previously? How does this look in different geographies? Obviously, Australia is a big hub there and tons of work is done in Europe and the U.S. and Canada. I would love to just hear some of your thoughts on this topic.
I think Riccardo's example of lutetium is a perfect one of that. That's kind of the path that we expect most isotopes to follow, that early on, they can be scarce. As there is not only clinical success, but commercial success, that supply chain will become a lot, the product will become a lot more readily available. We live through several years of lutetium not being readily available. That transition period, that early success of the isotope is where it's imperative that the companies driving those products have their supply chain really nailed down and know all the way back to the enriched isotope or whatever other starting materials there are, where those things are coming from in order to be successful. A few isotopes call out there beyond the discussion that Riccardo already gave on terbium.
I think that astatine-211 is an interesting one where the raw material is natural bismuth that's readily available, but it takes a special cyclotron in order to make astatine-211 astatine-211. We are seeing companies now come out with these specialized cyclotrons specific to astatine-211. We've had the first couple of those installed recently. Astatine is becoming a little bit more available for at least early research stage, probably not yet all the way to a robust clinical program. We are seeing the beginning of that growth curve there. I'll certainly let Sumit talk to lead-212. Actinium-225, to me, is an example of a difficult isotope. We have seen huge amounts of investment in actinium-225 because production is so challenging. Despite all of that investment, at this point, we still see shortages that cause delays in clinical trials and challenges with getting enough supply.
I think maybe that gives you a little bit of the spectrum of isotopes that can come up that curve more quickly versus those that are going to take a little bit longer. The last category I would touch on is the PET isotopes, which are very short-lived typically. Like astatine-211 on the therapeutic side, they are going to require somewhat localized, maybe very localized depending on the specific isotope production route. There, it is not so much access to reactors, but it is access .to PET cyclotrons. PET cyclotrons, thanks to the success of products like PYLARIFY and probably Alzheimer's agents that are growing pretty rapidly now, are going to become more and more heavily utilized.
Looking at the number of those cyclotrons that are available, the capacity that those cyclotrons hold is a key piece for us as we think through what our supply chain for future products is going to look like. Again, the enriched isotope supply of knowing how we're going to get, in the case of copper-64, where are we going to get nickel-64? Is that all coming out of Russia or do we have Western sources of that? Usually those raw material costs are not a significant portion of COGS in the end. To the extent that tariffs come into play there, do we have U.S. sources of those or whatever national market we might be in in order to mitigate those kinds of risks?
Yeah, I think John's right. The way I think about it is that just like the lutetium story, you're going to see huge investment wherever it goes. You will see the supply become more robust over time just because of the need of these isotopes. In the grand scheme of things, I think there are three limiting factors. One is how is the isotope produced? The production route is rather key to this overall effort. The second being the source of the starting material. I think John's alluded to a few, and especially with actinium, that becomes super challenging. Thirdly, it's just now going to be this supply chain constraint. When you think about these alpha cyclotrons, there are only four companies that make cyclotrons, let alone how many companies actually perfect the alpha cyclotron. Same thing with hot cells.
All these are going to become natural constraints that are going to impact overall processes. Lastly, as you think about it, today, there's not a really big push towards cost of goods, but that's going to play out very in real time when we have multiple therapeutic products in the market with different isotope starting points. To me, that's going to be a bit of a game changer. If you go back towards looking at the overall supply chain, if your starting material, things like thorium-229 or radium-226, how do you accessible, let alone the price point to them? That just changes the cost module for products like actinium-225. gallium is like one person owns it today. How do you break that supply chain when you put all the pieces together?
As you think about some of the benefits that we see with some of the isotopes like lead-212, thorium-228 is not constrained today. It's very easy to follow through from a supply chain and see, hey, as the modality grows and the supply grows, it could follow the lutetium story and get to the place where alpha is a favorite towards being more lead-212 based than actinium-225. I think that's a good silver lining on thinking about the raw material aspect and the production routes. While we've done a lot of investment in cyclotrons and reactors, there's still a bit of a lag in capacity. That's been rather challenging. We've seen it in the traditional imaging plate out where molybdenum was rather constrained for quite some time.
You have the same reactors trying to produce some of these isotopes, which put even further constraint to these actual infrastructure because they're so old. Having early on investments, and some companies are doing that, right? Some countries are doing that too. I do think that's going to play out in real time. The last point that John made about the PET cyclotrons, I do think that is a worthwhile effort to look at because if you can at least get the imaging point out of the equation and move towards more PET imaging agents, I think that opens up these bases towards targeted alpha therapies and therapeutic products much faster than anticipated.
Yeah, I'm curious if you, because Japan has made heavy investments in astatine-211, I think largely because of geographic considerations and not wanting to have to import therapeutics. I'm just curious, just thoughts on if it seems like, I guess the thinking would likely be that if the clinical data is compelling enough there, then we'll get more investments in other markets. Just curious if there's other maybe either related to astatine-211 or other sort of little geographic considerations that might have an impact. I mean, Australia in particular, I'm sure you have to deal with geographical considerations quite a bit.
Yeah, I mean, again, for lutetium, it's not a problem with seven days. In Australia, you have the local institution of ANSTO that is producing for entire Australia. If you have, and when we have some maintenance of the reactor, we can ship it from everywhere. I think going back to the isotope, I think that finally in 2025, we will have some actinium data. Because until now, look, we have phase one and half phase two. We don't even have a full phase two. That's probably what is also keeping maybe investment from isotopes like astatine a little bit on a pause. If you have great data on actinium, long half-life, central distribution, expected efficacy, I think there are no questions on that. All the questions are about safety.
Giving that dose of an alpha, if you have a peptide, you give it to the kidney. If you have a monoclonal antibody, you likely give it to the bone marrow. It's good or not good. Until we know this, it's difficult to have any other assumption. Because the interest of astatine is all based on the fact that a single emission is better than what actinium does. Do we really know if these daughters are bad daughters or good daughters? Logically, it doesn't seem to be nice to have the daughter circulate, but we don't really know. I think that based on evidence-based medicine, we know that lutetium is the safe bet. Actinium is the next big isotope where we all need to see this data. When we see this data, if the data are positive, probably why you really need astatine? I don't know.
Maybe you need for scientific interest, but does the market really need it? If actinium creates some area of concern, then we'll definitely people would like to experience other alpha even more. More investment on lead, more investment on astatine for sure. There is all the element of the further unknown that are the pure Auger emitter. Are these isotopes that in the family of iodine? I remember it is the iodine- 123 or iodine-121 or iodine-125. One of the two is a pure emitter. There is bromine- 77 people are looking at. I mean, those are pure Auger. Is there a space for those in some specific disease? Maybe when you look at areas that are more radio-sensitive, like, I don't know, brain cancer or other area where you know that is highly internalized. So it's interesting.
I think that probably in 2025, we will know more about actinium. This will be very helpful for the community to really go full speed in one direction versus another.
The only one point I would add to what Riccardo said is just the geographical positioning of some countries and their populations, which could tip the scale in favor of astatine. If you think about Japan and the density populations, it actually does make it a really good target to have high populations centered towards hospital care that can provide them these therapeutic products. I think Japan was early on to bet on that for that reason. Because if you think of the overall supply chain and the constraints that are resolved in many countries like Australia and Europe and America, those are not there in China and India and such. If they were looking to make a long-term bet, it does sound like having smaller alpha cyclotrons located in big cities and bringing the populations that therapeutic care could be advantageous.
The piece around astatine, which from just a therapeutic side, which makes it a bit exciting, is a chelated chemistry as well. They do not need that. Depending on how you look at some of the targets, that could be an interesting play as well. I am not ready to bet on astatine too, I think, to Riccardo's point. Let's see what the clinical data comes out from astatine this year. If you are looking long-term geography, there may be some advantages for astatine over others.
Yeah. Got it. Maybe, and I think we've sort of been talking on this subject in some respects, but I'm curious to your thoughts on how you see the supply evolving over the next one, five, or 10 years and where you see the bottlenecks emerging. I mean, we've mentioned some of this, but it's reactor uptime is going to matter, the cyclotron distribution, accelerator beam capacity, the feedstock to actually make the isotope. Of course, this will all be informed by the emerging clinical data. Where do you guys see some of the bigger pain points and how things are going to play out?
I think on the reactor side, I'm really excited about the increasing use of power reactors for irradiation of medical isotopes. Because when you look at the research reactor infrastructure that's been used for decades, those reactors tend to be up somewhere around 40% of the time. They are not designed to run day in, day out. Therefore, you have to piece together this huge network of reactors around the world to have steady supply. That's worked so far, but it's not ideal. As we see more and more companies moving to use of power reactors for irradiation, where those reactors are designed to be up 95%+ of the time, now you're getting to much more stability of supply and much greater capacity, even with only a handful of reactors. That's a really exciting piece of the irradiation infrastructure.
I think on the raw material side, we have seen more and more Western companies getting into the isotope enrichment basis business specifically for medical isotopes. By and large, those have been using electromagnetic separation systems, which are suited to certain types of isotopes. They may be more limited in their ability to produce other isotopes like nickel- 64, which just means that the capacity is a bit more constrained, but likely will need centrifuge-based enrichment systems for some of these isotopes. That is a longer range investment than the electromagnetic separation systems. I think looking at the availability or dedication maybe of those centrifuge cascades to enriched isotope production is an area that I'm interested to see develop over the next couple of years.
Finally, on the irradiation piece, I think we've mentioned a few times that the PET cyclotron piece is really interesting to see the increased investment in that, the number of companies within the U.S. that are putting in new PET cyclotron capacity, and also the wider variety of isotopes that are being produced on those now. We're seeing not only F-18, but also copper and gallium being produced on those. It's really exciting to see that increased availability of PET isotope production as well.
Yeah, I'll pick up from John saying, hey, that's the advantage of lead-212. You really avoid going through a cyclotron or reacting completely. To the points John's made, if we can get to that enrichment and secure the supply long-term side of things, I think that is a big game changer. Going back to the 15-10 year outlay, I think for now, centralized manufacturing is going to play a key role. That's just where we are today. As you go forward and think about precision medicine and where we want to go with therapeutic development, there is a need to start thinking of how do we get it to point of care? How do we get the experts to provide precision medicine from a rare disease perspective of oncology? That to me is the next phase of our product development.
We're very used to a bit of a copy and paste of, hey, 75 kilo patient, this kind of dose, and that's what becomes your clinical trial and dose escalation. I don't think that's going to be the future state of what we're looking for. It's going to be based on kilos, understanding our genetic data, how we think about the patient experience itself, and all the things Riccardo has already touched on. That's where if we can get to a point where we move away from a centralized manufacturing and do what we did in diagnostic and bring the generator right to the point of use where you can compound products and make them to the point what's needed for that personalized medicine, to me, that's what the 10-year outlook could look like with compounds like lead-212.
Got it. We tend to focus on the risk of not having enough isotope. I'm curious if any thoughts on if there could be a risk that there's an overinvestment in a given isotope and then that could reflect negatively on the space. Maybe just if we think about, let's say that there are safety concerns with actinium-225, and then investors have put in so much money to build that capacity and they feel burned by that. Do you think that's a legitimate concern or not? We're really still focused on we need to get enough isotope.
Honestly, I never thought about that, but it's a fair question. Some investment, some capital investment in infrastructure are long-term. If something doesn't go as you expect, of course, it's becoming difficult. At the same time, many of the companies' ability to readjust from one isotope to the other, not from everything. I think personally, I'm more concerned of the increasing cost of good. Without going to any political discussion, but only purely from a cost point of view, today, if you, let's say you like a target and you want to do a monoclonal antibody, it costs you $4 million, if not $5 million to do in China. It costs $7 million if you do in Europe. This is assuming zero tariffs. Now, if the tariffs are 100%, then the $5 million become $10 million.
It would be very difficult for any biotech or institution to create a monoclonal antibody. Peptides are cheaper, but still are not zero. The potential increase of cost of good might be a problem for biotech companies that count every single dollar. The same is for CDMOs. You can use today CDMOs from Canada, from U.S., from Europe if you have isotopes that are a week of half-life. Now, in all our budget, we have assumed that this is zero increase cost. Today it's like that. If we get the products from Canada to U.S. to hospital, we don't pay any tariff on that one. Is it going to stay like that or change? If it goes up 30%, 40%, of course, it's a problem. We see now that the cost of treating any single patient in a clinical trial is going up.
Because hospital and center realize that there is more competition. They can choose between one trial and the other. Australia is an example. Australia is becoming more expensive because everybody is going to Australia. The phase one clinic got a limited number. Before you were doing something with $120,000 per patient, now it is getting to $180,000 per patient. Maybe it will keep going up. I think this is another element of the cost that personally I am thinking about more than the overcapacity. That is a fair question, but we need to consider this as well.
Yeah, that's interesting. I'm curious. I hadn't thought as much about the targeting vector costs, which is considerable. Is there, I guess, concern or potential impact for either the cost of the feedstock or the isotope itself? I mean, the therapeutics themselves tend to have premium pricing, but of course, you still have to get it through development and get there. When we're talking about some reasonably large scales at some point, it could be pricey. I'm just curious how, and obviously, we're all sort of waiting to hear what exactly will be impacted and in what ways. Wondering sort of the balance of the risks on the cost side for that.
I mean, we can always say that we are still in a better shape than cell and gene or CAR-T. You always need to realize how much we want to complain. It still costs much less, but it costs more than other targeted molecules, in particular if they are small molecules, small size. When you go to protein production, that's a big increase because we see a lot of biologics, not in radiopharmaceutical, but in general, ADC or targeted therapy. You always need to do with capacity. If you go to a producer, they can say, we are fully booked, come back in six months. Nobody wants to lose or to miss six months. You need to look at cost, but also availability.
That's why many companies go outside the U.S., go to Europe, go to China, go to other areas to produce proteins because you need both the capacity and the cost and the cost element.
I might be a bit more bullish on that. I do believe that there's not adequate capacity today. If you go and take the lessons learned from the launch of Lutathera and Pluvicto, it would have been nice if we had all that lutetium-177 capacity. Today, it being such a big blockbuster, to me, it's all about the patients that desire. Reasons why cell and gene and CAR-T and some of the monoclonal antibodies are not working is because we're not getting that kind of response that we're looking for, unlike radio-imaging therapy. Today, we are very focused on PSMA and GEP-NETs. Those are just the two indications that are out in the market.
Once you start flooding it, so to speak, with all the clinical trials coming out from breast cancer and other modalities, I do think you're going to see some signs of hope that, hey, we do need to be ahead of the curve and try to get this capacity out there. Just from a reimbursement perspective, it's still a better option than CAR-T and cell and gene. It shouldn't be built in and they shall come, but it should be a bit of a phased approach of building it as you see clinical data favoritism coming out from each of these isotopes.
Just one thing for me on the, I guess, the cost question. I think that the enriched starting materials that we work with in producing isotopes are usually not a significant component of the ultimate cost of the drug product. So I'm not terribly concerned about those. I think where I see a bigger risk of cost increases from tariffs is maybe in the irradiation area where we're having to use research reactors, a lot of which are overseas. But there's a question there of whether you're buying a good or a service.
If the thing that you're doing is taking an ampoule of this enriched isotope, shipping it off to someone to irradiate, and then getting that back and processing it yourself all within the U.S., and there's a robust infrastructure in the U.S. to do that, then I think that tariffs are at least a bit less of a concern. I think overall, it's a very manageable thing for the industry, not to say that there's zero risk there, but I think that it's something that's, I don't know, it's not existential by any stretch.
Got it. We only have a couple of minutes left, but I'm just curious if you could speak a little bit to whether or not you think that we're going to start seeing some fault lines emerging in terms of the capacity of the healthcare system because we have a very large amount of imaging already done, but there's increased interest in the neuroscience space. If some of these large pan-cancer targets prove effective, as we hope, then we're going to start seeing a lot of a large demand. Just curious how you're sort of seeing things shaping up if you think that the building of theranostics centers or if hospitals will have enough space for these patients, just how you think about that.
Yeah, maybe I could start there because we're very much on the forefront of that with the volume of PYLARIFY and we love to see the success of that product. It does start to push the boundaries of what's available in terms of PET imaging. I would note for PET imaging, though, that we're starting from a base of 2 million doses, 2 million scans a year of FDG. When we add on hundreds of thousands of doses, which is fantastic, of PSMA PET, it's still a relatively modest growth of the overall PET imaging business. Nonetheless, we do see areas where specific sites where there are constraints on camera capacity and folks are starting to add weekend hours, evening hours to do more scanning. There is a need for growth in the healthcare sector.
I think there are also a lot of areas where the pharmaceutical companies can help with that. We look at things like with PYLARIFY, talking to the earlier advantages of F-18, can we shorten the scan time because it's a better isotope and then enable higher throughput of patients with our product versus others? Do we have the, as we look to neuro, we use the cardiology market that Lantheus, as a predecessor, created for Cardiolite 25 years ago where nuclear cardiologists came into being. Cardiologists would have SPECT scanners to do Cardiolite scans in their office. Can neurologists do the same thing with Alzheimer's and having the head-only, brain-only PET scanners, which are on the market now in their offices to do neurology scans?
I think that's a great evolving the neurology market where the cardiology market went is a great analog for us as we think about how to increase that capacity on the provider side and ensure that we can handle the volume of scans that we're expecting.
Maybe a different perspective on this is how we need also the evolution of the healthcare system from a physician point of view. If we stay in oncology, that is the area where most of the trials are, still we see some discussion in some center where the tumor board decides who is the right patient for the trial, allocate the trial, and you have the nuclear medicine physician or the radiation oncologist that is doing the dose. All the question opens, is my patient, is your patient? If a side effect that is non-radiation related happens, who is managing? Cannot be the nuclear medicine physician. It's not their experience, but cannot be only.
I think we need a shift now that more therapies are becoming available on the approach on how to use radiopharmaceutical therapy and an alignment in the patient journey on how is the best way to allocate patient trial and managing the patient after they have their number of doses. Because at the end of the day, this is not a chronic treatment. If you are lucky, you give four to six doses, and then the patient will need something else again. I think the system is not 100% functioning in this new approach that before was only neuroendocrine tumors, so it was simple to manage. With prostates, it's becoming now more difficult. With new indication, potentially is going to be a big topic.
All right, great. We are just about out of time. I'd like to thank you all again for participating and the audience for tuning in. If all of you would like to stick around, the next presentation will be with Soumit Roy in a fireside chat with Nuvation Bio titled Reshaping an Established Market. That should just get underway in a few minutes. Thank you all again for your time.