Through today, and the focus is really on how Telix has built, very quickly built, an integrated radiopharmaceutical ecosystem. We have a specialist commercial organization and a deep pipeline. The breadth and depth of this company we've built is really differentiating us in this fast-growing industry. Today, we want to focus on just some of the key growth opportunities that are ahead of us. I'm very pleased to have in the room a selection of leadership team from Telix. I'll just run through those people in order. Welcoming Dr. Chris Behrenbruch, our Managing Director and Group CEO; David Cade, our Group Chief Medical Officer who's traveled here from Sydney; Richard Valeix, the CEO of our Therapeutics business; Kevin Richardson, CEO of our Precision Medicine business
I would just like to call out in a little more detail three members of the team who investors would not have met before. The first is Dr. Paul Schaffer, the Chief Technology Officer. He is in a newly created role which commenced in April, but Paul joined us from ARTMS. He is a highly respected expert in this field, and he led the development of the ARTMS QIS system. He is really here to talk to you about some new R&D capabilities. Alongside, Dr. David Cade is the Group Chief Medical Officer. We have now added Chief Medical Officers based in the U.S. for our Therapeutics and our Precision Medicine business. Dr. Pamela Habib, who is our Chief Medical Officer for our Therapeutics business, is a trained breast radiologist, trained at Harvard, practiced for over a decade.
From clinical practice, she moved into consulting with McKinsey & Co., where she advised hospitals, insurance companies, and pharmaceutical companies on their growth strategy. She joined us from Bayer, where she held roles in commercial development, medical affairs, and clinical development. I'd also like to welcome Dr. David Liu. He's our Chief Medical Officer for the Precision Medicine business. David is a Professor of Radiology and Associate Professor, School of Biomedical Engineering, University of British Columbia. He brings extensive medical practice experience as an interventional and diagnostic radiologist specializing in cancer therapy. His highlights include over 100 publications in peer-reviewed journals and involvement in the United Nations World Health Organization Blue Panel Commission for cancer imaging, as well as developing international standards for cancer imaging in China, U.S., Canada, and throughout Europe.
I'm also very pleased to introduce three esteemed physicians in the room, and we really do appreciate them taking the time out of their busy schedules to speak with you today. Our speakers will introduce them in more detail, but just to acknowledge that we have Dr. Joseph Osborne in the room, Professor Oliver Sartor, and Professor John DeGroot, who will speak about our kidney cancer imaging programs, five known prostate cancer therapy, and our TLX101 therapy programs, respectively. We do have a lot to get to today, so we will build in opportunities for Q&A at certain intervals. We do ask that you hold your questions until then. As the event is being webcast, we will prioritize questions for those in the room.
For those in the webcast who have questions, send them through, and we will respond to you separately if we do not get to those today. With those bits of housekeeping, I am going to hand over now to Chris.
I think I've got a mic. I think it'll be okay.
We're going to try my mic.
Thanks very much, Kai, for the opening comments, and welcome everybody this morning. We're really appreciative of your time. This is an opportunity not just for us to give you an update, but really for you to get some Q&A out and to interact with the company. I think that's what makes the in-person meeting so effective. Can I just have the slides on full screen just so I can, my aging sight can, I can see what I'm talking about? I think most of you know the company, although there are a few newbies in the room, and there's a growing kind of understanding of the business. I think it's starting to be understood that we are one of the leading companies in this space, and I think we have a very differentiated strategy, which is really summarized in this slide.
It's useful to think of Telix through three pillars of activity. First of all, we are a commercial stage pharma company with two approved products in the United States and a pipeline that's coming in behind that. We anchored our commercial activity in prostate cancer imaging, but we really have a bright future in many other disease areas with a particular depth of focus in urologic oncology. You're going to hear today from my colleagues in the medical and commercial side about the status of our Therapeutics program. We have, alongside our portfolio in Precision Medicine, a really deep pipeline of molecules on the therapy side, from things that are preclinical all the way up to phase three. We will be diving into most of the sort of later stage programs, the clinical stage programs during our session together today.
Then last of all, I think something that's quite differentiated and different about Telix, about five years ago, we started a program of really looking carefully at manufacturing supply chain. I think most people that are interested in radiopharma understand this is a just-in-time manufacturing environment. We have very short shelf-life products. To put that in perspective, when an Illuccix goes hot, we have two hours to get it to patients and get it into patients. It really is a logistically complicated business. You have to, to some extent, own your manufacturing and supply chain. I think we've done a really good job in the major markets that we serve of making sure that's an integral part of our operational excellence. This would be your Telix strategy on a page.
Today, you're going to hear about how we are delivering on our late stage pipeline. I think we've had a lot of growth and evolution as a company in terms of how our Therapeutics team has developed and is executing clinically. We've made a number of acquisitions and internal growth projects recently that are around that next generation of radiopharmaceutical products. These are things in the five- to seven-year timeline for Telix. In that context, we're thinking about particularly those next generation isotopes and particularly alpha emitters. Kevin Richardson, who leads our Precision Medicine business, is going to talk to you about some of the key commercial strategies behind our spectacular growth and hopefully future ongoing growth in our Precision Medicine business. There's a long way to go in prostate cancer.
Then when we think about urologic oncology as a key stakeholder in the near future, we see a lot of opportunities to build depth and breadth in that pipeline. Last of all, as I've said, to make sure that every single day that we deliver that dose to a patient with the reliability and quality that's expected of a leading company in this space. I'm not going to go through this. This is a repackaging in some respect from a sort of an operational and differentiation perspective. I think there are two things that I would like to call out in particular on this slide. I think the first one is that commitment to a theranostic strategy. There are a lot of companies out there that are more imaging focused. I just want to be clear, we're not a diagnostic imaging company.
We've made early revenue and early commercial foray as an imaging company, but that's because the pathway to market and the regulatory pathway is a lot more straightforward in some respects. In some respects, it's still a sterile radioactive injectable, but I suppose in some regards it is an easier pathway. It's enabled us to be in the unique position where we can self-finance our growth in the main. I think from a clinical perspective, what you're going to see today is this symmetry around the targets that we pursue, that for every target we go after therapeutically, we also develop an imaging agent. We believe that that delivers something important to the clinician. We think it de-risks clinical trials. We think it helps to validate targets.
I think one of the reasons why we have developed an enormous amount of clinical confidence around treating patients with PSMA therapeutics is because we know how good the imaging is and we know how good the target is. That really invites exploration into earlier lines of therapy because we understand the target so well. I think the second thing that is really unique about Telix, and you're going to see it time and time again, we don't wed ourselves to a particular technology platform. We're targeting agent agnostic and we're isotope agnostic. We'll choose whatever we think is the right targeting agent that will give the best outcome to patients. We'll choose the isotope that we think will deliver the right radiobiology for the disease area that we're trying to influence. I think that's a strength of the company.
It means that radiobiology and just a broad understanding of radiochemistry is very fundamental to the DNA of the company. In terms of our international growth, this year is a pretty special year for the company. We have been the last few years essentially a single product, single territory company. We derive most of our revenue today from the US market through Illuccix and now Gozellix sales, which actually formally launched today. We've been spending the last, since we got FDA approval a couple of months ago, we've been stocking pharmacies and getting everything organized for launch. That happens today. Coincidentally, by the way, it wasn't a crash timing exercise. It was a coincidence. Basically, we have that follow-on activity in the US. We've doubled down on product distribution capabilities through our recent acquisition of RLS.
This is about building supportive pharmacy infrastructure for the long term. I'll come back and talk about that a bit more in a second. We've just recently received our GMP certification for our European manufacturing footprint. This is a massive capability that will enable us to service patients effectively in the European market. We've also just recently taken over a partner site in Japan. We now have cyclotron capability to service the Japanese market in the short and medium term. We have a number of key strategic partnerships that we are also heavily invested in and we believe will be successful. We're running clinical trials in those countries to make sure that we have the data to get regulatory approval in some of those growth market opportunities.
In short, again, one of our differentiations as a company is that we have the aspiration to deliver these products globally. We want to make a difference to patients everywhere that we can. In terms of the U.S. market, which I know is of dominant interest in the room, we take a two-track approach. We are heavily reliant on and will always be heavily reliant on quality distribution partners in the United States. It's a fundamental tenet of the nuclear medicine industry. Bless you. It's a fundamental tenet of the nuclear medicine industry. We're really fortunate to have outstanding partners that share the same patient-centric and quality values that we do. Similarly, as we think about particularly longer half-life products and as we think about the transition to therapy, we believe that therapy, large-scale nuclear medicine therapy will not be delivered without the use of practice of pharmacy.
We have to combine traditional GMP manufacturing approaches with things that make it easy and accessible for physicians to use our products. That means that you cannot ship a vial to a customer. You should be shipping a syringe. It should be ready to use. It should be dose calibrated. As precision medicine, a component of what we do, evolves, it is going to be more and more important that that package comes ready and calibrated and specialized to that particular patient's need. That is why we have made this investment. There are all kinds of good commercial reasons for doing it, but there is a long-term strategic viewpoint as well of what the RLS network delivers to us.
Maybe just to sort of wrap it up a little bit, in terms of how to understand the company, the first few years of our commercial trajectory was really about establishing all of the components of a commercial stage pharmaceutical company, which we've now done, I think, to demonstrable success. We're now in the middle stage of our trajectory where we, or as we see it, we're diversifying our revenue streams. We're internationally expanding, which is also de-risking the business because we end up with a multitude of revenue streams away from just the U.S. market. The goal in this middle epoch of our growth trajectory is to be able to reinvest our earnings, everything that we've got back into that next inflection point, which is the therapy programs. I think you can see that in terms of our R&D mix.
We've gone from predominantly preparing to launch commercial diagnostic products to now sort of 60%+ of our R&D investment back into the therapy programs. You're going to see as a consequence, and we've reorganized the business around these lines, as you can see from our org structure, to really double down and make sure that we're prioritizing the catalysts that come from that therapy pipeline development. That's what's going to ultimately transition the company to the next stage of growth. Just to sort of give you a snapshot of that, how we see capital allocation and resource allocation side of the business is really this: what are the things that are enabling the business today to generate cash, to be able to invest? Obviously, you're going to hear about growing our PSMA market.
Zircaix has a PDUFA goal date of August, and that's going to be a very exciting follow-on product that's going to give depth. In terms of driving growth, it is really that therapeutic business, which we see as transformative for the future of the company. Okay, so that's my opening comments. I'd now like to invite Paul up to the stage. I just want to say it's really a delight to have Paul here. I think what it does is it illustrates that when we acquire a business or we acquire a technology, we think very carefully about the people that come with that. We make sure that we're not just integrating technology, but that we're really integrating the brain power that comes with it. Paul's a great asset, and you'll hear for yourself as he speaks.
All right, thank you for the kind introduction. My microphone's working just fine. Good. All right, thank you. It's a pleasure to be in front of you all today. An important fact about myself before we get into the session and for the question and answer period that's coming up, I just wanted to let you know that my hearing is not very good. If you do have a question, please speak up. Because as my colleagues will attest, if I do not hear your question, I will very readily answer a different one. It is an important fact. I am going to be speaking to you about some of the trends we see coming down the road for radiopharma.
With my background, having just taken on the new role of CTO, spending the last 15 years leading the Life Sciences Initiative at Triumph, Canada's national particle and accelerator facility, along with the spinoff activity with ARTMS, with its bringing into the family of Telix, represented an opportunity for me to focus on something exciting like what Telix is working on. I hope to tell you a little bit about that today. My background is in chemistry, physics, a PhD in chemistry. Having led the initiatives that I have over the last little while, I feel I can bring into this company some expertise and depth on things like cyclotron accelerator targetry, isotope production, radiochemistry, and ways of attaching isotopes to biologics, but also to take physics and apply it ultimately to how we deposit energy into tissue. That's ultimately what we're doing.
We have tools in development, both in hardware and software, things that involve surgical devices or artificial intelligence that are coming down the pipe that will serve us well in this particular field. I'm going to be working shoulder to shoulder with my esteemed colleague, Mike Wycroft, who's overseeing the biology, biologic aspects, so tumour microenvironment, drug combinations, and new biological target selection. This is a testament to the complexity of disciplines that are required for radiopharmaceutical development. It is atypical. We have the depth of expertise, not only with Mike and myself, but others that are in the company, subject matter experts that I have the privilege of working with, that have an extreme depth to help guide the company through all of this.
The benefits of having these people on board in-house is that they can help guide the company for the full preclinical to clinical translation aspect of what we do. The culture of just-in-time, rapidly decaying drug product bleeds right into the research aspect of what we do, all the way through into patient delivery. If it's isotope production or drug delivery, we have experts in-house to help with that, but also do important things like generate intellectual property for protecting the company's ideas moving forward. One of the trends that I wanted to mention briefly was about isotope production. You've heard about the diagnostics aspect of what we've started in. We're moving toward therapeutics. When I wake up every morning, you might be surprised to hear that I think of the world in different ways when it comes to radioactivity.
We have the diagnostic photon-emitting isotopes. The world has long relied on things like fluorine-18, highlighted in the left-hand column, that was used for imaging. The company has significant plays, Illuccix and Gozellix with Gallium-68 and Zircaix and Zirconium-89. You're going to hear more about that with my colleagues coming up. In the therapeutic realm, there's a lot of work underway with lutetium. There's a product out today based on samarium. As an example of looking down the road, there are isotopes like terbium-161. We want to make sure that if this isotope proves to be what it is, we're going to be ready to adopt it into the company's drug asset portfolio. That's because Telix wants to deliver the best isotope coupled to the best drug for the best patient outcome. That's really what we're after.
If beta emitters do not cut it, then we are going to turn to alpha emitters. With actinium-225 and astatine-211, early, closer to us on that horizon. There are other isotopes like lead-212 that we are looking at. We have some really fascinating and amazing technology coming out that is going to enable that isotope to be distributed and used more widely. Ultimately, what it comes down to is we are producing and looking at isotopes for their physicality and how they decay and what they are going to do to tissue and how we couple those to a biologic to deliver them. As the representative shows, you tether these things together molecularly, and you want to deliver it to the target tissue and minimize off-target effects. I think touching again on that, the importance of that culture of just-in-time and dealing with rapidly decaying pharmaceuticals.
This is not a pharmaceutical play. This is a radiopharmaceutical company. Telix has made some terrific investments to help that entire development pipeline. The manufacturing process, again, begins at the beginning. With acquisitions like ARTMS and with ITG in Texas and Optimal in California and so on and so forth, with the latest, with the acquisition and onboarding of RLS, it just shows the dedication that Telix has to starting early with isotope production, solving any problems, securing supply chain, ensuring there's a robust, reliable supply of those important isotopes, ensuring that the way we produce and manufacture, formulate our drugs for delivery to the patient can be done reliably in a wide logistically capable net. That is what RLS is. The investments are a testament to what the company and its commitment is for delivering that reliable patient dose supply for years to come.
Now, the portfolio currently is bookended by small molecule and antibody targeting agents. It's important to know that in the research group, we're also looking further down the road at some intermediate platforms represented on the graphic toward the right on this slide. With the acquisition of companies like Imaginab, we bring in the capabilities of the mini body shown roughly in the center of the spectrum there. With some validated targets there that may be important for us in the future in terms of other disease indication, we're also looking importantly at how these platforms can find a sweet spot when it comes to how they behave in the body, whether it's the fast and furious uptake of small molecules or the slow and precise uptake of antibodies. There could be a balance there that we could find with some of these other platforms.
That's what we're really pursuing there. Yeah, I think with the ability to also engineer those platforms to precisely take on the linkers and the chelators as well as the isotopes, we have the ability to potentially develop some very potent drugs. The R&D group is very keenly looking at this as well as other platforms through partnerships as they come through the pipe. I just close out my discussion here with a fourth trend, and that's looking at dosimetry and how it combines with emerging tools becoming available at our disposal. Really what we're trying to do is, again, understand how the delivery of radiation to tissue represents the delivery energy to the tissue. Dosimetry is really the measurement of that. We have people, subject matter experts on board that are looking at that closely.
They are developing tools to basically take a diagnostic image, which is inherently quantifiable, I might add, and enable things like artificial intelligence and machine learning to take that quantifiable image and then apply it to how we dose and treat patients for specific conditions moving forward. Really the goal is to move from a situation today where we have image-guided dosimetry to really a computer-assisted dosimetry paradigm, where a computer is assisting a human clinician by taking arguably a larger than lifetimes' worth of data and allowing a clinician to make extremely informed decisions about how to treat a particular and individual patient. This is really where we're pushing for a personalised medicine paradigm. This final slide just represents what I would envision happening in a future state where a patient comes in presenting with disease. There is an image that's acquired.
That image is fed into an algorithm that is proprietary in nature. It is one that would help the clinician decide on which isotope and which radiopharmaceutical to apply based on the distribution pattern of the antigen you're targeting. The patient would undergo its treatment journey. There would be a validation in mid-step about how things are going. The outputs would be brought importantly into a data warehouse where there would be a learning opportunity. There would also be ways to automate this process and to feed it back into the beginning of the process and to iterate this time and time again. Human clinicians gain the assistance of artificial intelligence and machine learning to make diagnostic decisions based on more data than what a single individual could encounter as an individual clinician on their own, working on their own.
In summary, I hope I've given you a little bit of a taste of what the R&D group is looking at. Importantly, it's to note that we are looking not only at the problems of today and solving the short-term issues with the current asset pipeline, but also some product lifecycle. More importantly, looking down the road and strategically placing Telix as a leader in the field moving forward. With that, I'd like to turn it over to my esteemed colleague, Kevin Richardson, to give us some more insights on precision medicine.
Thanks, everyone, and welcome. Let me just. In the next few minutes, I'll have with you on. A couple of months of RLS and achieve 62% year-over-year growth, driven mainly by the 35% growth over prior year in the U.S., mainly driven by Illuccix sales on a quarter over prior year quarter growth.
Then the sequential growth of about 9% quarter over quarter from Q4 2024 to Q1 2025. That included about $33 million from RLS as we closed that acquisition in January. Good momentum going into Q2. How do we get there? How do we do it? Really, how do we think about growing the precision medicine business? It's really underpinned by the product offering itself. Establishing a foothold inside of the PSMA business with Illuccix. Chris just announced that Gozellix is initiating sales this month here at the end of June.
Really, as we think about what that looks like with the rest of the portfolio that we'll go in a little deeper, we really think through the lifecycle management of really just not just PSMA, which we have some really exciting things to talk about today, but as well as our other product lines too in that product. The growth strategy is pinned on the product. We really think about then what do we do with that product while we take it to other geographies. We continue to, and you've seen some of these disclosures. We continue to do the global rollout of Illuccix. If you're not flag chart savvy, we'll have the names here in a little bit. We plan to continue to roll that out through my counterpart, Rafael Ortiz, internationally.
Finally, we will continue to file on the other products that we're bringing to market, initially here in the U.S. first. We take that bundle of products, and then we expand the use of that through indication expansion. We will talk a lot more about that on the PSMA side with some exciting news, but we have those plans across all of our product franchises. If you think about just those three things, expand, expand, expand, what that really does is it shows the perfect marriage between our precision medicine business and our therapy business. Because in each of those markets, we're building key relationships with regulators, with payers, and customers. We're preparing and building that road, if you will, into those markets, as Richard talks about in a minute, how we're going to bring those into each of those markets.
We have great relationships built, great respect for each other in the relationships that we're building with the regulators and preparing the way for that. Then the question is, how do we deliver those products, that indication expansion and those new geographies? How do we deliver that to the market and achieve sales performance or success? A lot of that is about building these commercial customer-facing teams that are true specialists. We take a modular approach to that where we have market access people to help with reimbursement. We have clinical people to help with the clinical science. We have the sales and marketing people really to understand the value proposition and our message. Ultimately, we bring that to bear in each of the markets that we play.
We have a tailored commercial playbook in each market, not only internationally, but even here in the U.S., because there are many different segments of the market that we have to think through, and then we have to deliver that value proposition in a timely and frequent basis. What's happened over the last three years is that we've really developed a reputation in the marketplace for an innovator. When you really talk to customers about what Telix is and what they represent, it's about innovation, it's about service, and about reliability. We've really built this Telix brand as we prepare the market. We built it on Illuccix, and it's prepared now for our follow-on products that we're talking about. To go a little deeper in the products on the growth strategy, you've seen this slide before.
We have successfully launched our second PSMA product in the prostate market. We'll go deeper on that. We have a PDUFA date in August for our kidney product or our CA9 target, the brain product or our Pixclara product. As you know, we made an announcement on a CRL for that, and we plan to keep progressing that forward and submit sometime in 2025. A little bit deeper on the expansion or growth strategy on the global rollout, you can see from the map on the left that we definitely have underpinned it here in the U.S. We have plans across Europe, more really focused on some of the key markets like France and Germany and the U.K. Of course, there's 10 additional European member states that have got approval too.
If your eyes are good, you can read them at the bottom, and that'll explain the flag chart from before. As you move over further east, we're really focused on China and Japan, where in China, we have completed our registration study, and we're preparing an NDA there. Our phase three study for Japan is just initiating. Finally, to kind of round out the Americas, we have the first approved product for PSMA PET in Latin America, and we've commenced commercial operations there with our partner. We go to that third leg of the growth strategy. We take our products, we take our geographies, and then we add new label expansions. I'm going to go a lot deeper on PSMA PET. We've got some exciting news there.
Once we achieve approval for our Zircaix product, we'll initiate the Zermet study, and that is to take it from a diagnostic perspective into a metastatic perspective as well for recurrence in clear cell renal cell carcinoma. Finally, after we submit and achieve approval for our brain product, we will continue that label expansion as well, not only into diagnosis of brain mets, but we are also looking beyond glioma itself. What does that really look like as you kind of wrap this strategy together? It was to really establish ourselves by launching Illuccix and then launch Gozellix. If you've had time to kind of chat with us a bit, we say that hope is not a strategy. We plan very specifically for our second launch to achieve concurrently with June.
As we start thinking about what PSMA looks like, we start thinking about the other opportunities inside label expansion through KOL engagement and really through guideline expansion. No, you're not reading a typo on what we think the TAM can be. We think it can go up to over $6 billion. If we've had a quick conversation, many people have asked me about what do I see the PSMA market doing. I said it's large and getting larger. Some of that is through what I call PSMA confidence, where physicians are just using it earlier and more often. We also have some exciting programs on label expansion that we think will drive us to that $6 billion plus market. Before I go into that, I just touch really quickly on Illuccix.
We are the first company to really have two products out there. We really feel as though the two product strategies are important in this time. We have what we've given the customer's choice in terms of economics, where they can choose flexibility of scheduling. It's got a higher activity that we're able to put in, so it gives it more and we have more stability, so we can take it further. The reality of Gozellix fits into two markets. It fits into the urban market, where you can have timing and flexibility with the patient scheduling. It fits into the more rural areas, where we have what we would say is a distant PET strategy. There's approximately 3,000 PET scanners in the U.S.
Not all of them are utilized for PSMA because you just can't get the dose there because it's just too far away from the manufacture point. One of the benefits of our reliability and availability is that we have 266 points of manufacture, dispensing, and distribution. Chris showed you the map a little earlier. That puts us right next to our customer base. That gives us that high level of reliability. There are some scanners that are even beyond that point that now with Gozellix, we can reach. We believe that represents about 10% of the market and 10%-20%. Typically, it's an underserved population that just typically doesn't want to make that drive into where the PET scanners are. We believe it really enhances reach and customer service, both in urban and rural areas.
Now I'm just a few minutes diving into the patient journey, if you will. Our TAM that exists today is about $2.5 billion-$3.5 billion, and that's driven by the current label. Our current label is initial staging prior to definitive therapy and suspected recurrence, and then patient selection for radioligand therapy. The additional indications that we think will expand through confidence, AUA guidelines, SNMMI guideline expansion, and ultimately NCCN guidelines, we think can add to that as well in both managing and monitoring response to therapy, as well as managing progression to therapy. What does that look like? Where does that TAM kind of build in? I'll show you the TAM that we typically show, but I wanted to kind of show you the patient journey so you kind of understand where we see the TAM going.
Most of the TAM is in reoccurrence. If you look at indication number two, that's the biggest bulk of patients that we have out there that physicians are referring for and that we're scanning for. I think what we really want to talk about today is how do we get at the front of that? Through what we think is going to be a well-designed study, a well-executed study, we'll be able to achieve a diagnosis indication that talks about diagnosis for prostate cancer through PET imaging. Now, if we can put ourself at the front of that scan, that's also a great value proposition because we believe from a marketing perspective, we would call it a sticky position to be in. Most physicians are going to want to use the same scan throughout the patient journey.
The existing TAM is still there, and we will be able to take that patient from diagnosis all the way to monitoring through progression as they go through that time. When you put that in the way we typically show the TAM, you can see that it basically doubles the TAM and puts us right at about $6.7 billion of available opportunity out there. The indications in pink are the 250,000 scans, are really the AUA guidelines, the SNM guidelines, and really the expansion inside of what we're doing today. Before I turn it over to Dr. Liu to go in a little bit deeper on the study, we think that we know there's over 1 million men that get a biopsy every year.
Really, when you think about what it takes to be disruptive in this space and innovative, which we think is part of that Telix brand, you have to minimize patient trauma. We think you'll see that. Reduce recovery time. We think you'll see that. We think at a lower cost while improving outcomes. That is a really important thing to really change and be disruptive in this marketplace. I think what many of us will see today is that we're going to have a choice in the future. If you're a man and at some point you may have a high PSA and need a biopsy, you would either have to decide whether you want this, and David will explain, or you get an IV. Your choice. Thank you for your time. I'm going to turn it over to Dr.
David Liu, our Chief Medical Officer for precision medicine.
Thank you, Kevin, for the introduction. I really appreciate you being a participant and volunteer for our audience participation portion of prostate biopsy. Although you sat down, I guess we'll have to wait till next time. Good morning, everybody. My name is Dr. David Liu. I'm the Chief Medical Officer for Precision Medicine. I'd like to take you on a little bit of a journey and just to give you context and color as to how we got here. When I started my medical career 25 years ago, the diagnosis of prostate cancer consisted of a digital rectal examination and a needle mounted on your finger. Around 1986, 1987, ultrasound-guided biopsy was introduced. Around 1994, PSA was introduced as a screening modality. In 2011, MRI then became kind of the complementary standard. As you can see, we've gone through various epochs of diagnosis of prostate.
They all have a common denominator, and that's this. Now, I can see about 90% in the room just jumped right there. This is a biopsy gun. What we do nowadays is when we have suspicion of prostate cancer, we either see a lesion and we target that lesion, or in the vast majority of men, we actually perform what are called systematic biopsies. What systematic biopsies are, I'll give these as a sample, 1 millimeter in diameter, 20 millimeters in length, and we do that 12-14 times in your prostate. How do we do that? Either by placing the needle through your rectum, so transrectal biopsy, through your perineum, which has other terms, but it's basically the space in between your penis and your anus. You can see that our evolution really has been the final destination being a prostate biopsy.
The reason for that is because we are actually trying to fill the gap and the deficiencies that we have in conventional diagnostic imaging. What issues do we have with prostate biopsies? We have a million men going through this with anywhere from 12-14-40 biopsies in a single setting, and potentially you rinse and repeat that every year. The first issue is compliance. Of these million biopsies, up to 25% of individuals actually decline the biopsy for the various reasons of why you jumped when you heard that biopsy gun, because this is not a low-risk procedure. It is very uncomfortable. You can demonstrate it in the room. It's very anxiety-provoking. Compliance is a good portion of that.
We can actually address the anxiety, the stress, and the diagnosis in these men that would otherwise not have received adequate early diagnosis and adequate treatment. Of the million biopsies that are performed, 75% of them are duds. 75% of the diagnosis that we're looking for of prostate cancer. When we have these recommendations, they're oftentimes based on the imaging alone, and we actually have no molecular profile. As I mentioned before, the stage of disease is based on two different factors. One factor is where has the disease gone? Is it within the prostate or spread out? Also the molecular footprint or characteristics of which we use, which differentiate between clinically significant and insignificant cancer. We use a score called the Gleason score, which is essentially looking at mitotic rates within the prostate itself. We don't have that information.
In the net net of it, we have too many men receiving too many prostate biopsies, too much tissue, and we aim to change that. We have the goal and ambition of transforming the way that prostate cancer is diagnosed and thus introducing the fourth epoch of prostate cancer screening and diagnosis. This is what the current looks like. Individual men are referred for biopsy or referred for MRI based on symptoms or elevated PSA or strong family history, basically predisposed risk factors. They'll receive an MRI, which will then stratify them into a PI-RADS score. A PI-RADS 5 is basically a diagnosis of prostate cancer, high suspicion. PI-RADS 3 to 4 is this intermediate to high-risk category where you see something on the MRI, it kind of looks like cancer, but we're not quite sure. We're pretty sure.
The PI-RADS 1, 2 category is either PI-RADS 1 being absolutely normal prostate, a PI-RADS 2 demonstrating findings within the prostate, which are actually of low risk for cancer. Each of these three categories is addressed in a slightly different way. For the PI-RADS 1, 2 patients who already have risk factors for prostate cancer, they will likely not undergo biopsy, but they will actually have continued surveillance. This introduces a degree of stress and anxiety and really the risk of undetected prostate cancer. We know these people are at risk. We know that there is a good chance that they have prostate cancer. All we are doing is just watching through our imaging modalities until we see it.
In the PI-RADS 3 and 4, generally speaking, depending on the level of confidence that we have, we may potentially target a specific area within the prostate, or we may perform these systematic or saturation or template biopsies, which are these multiple random passes, or not really random. They are anatomically looking at the pathway through the prostate. We basically are just trying to sample and see if we win the lottery to find the incidental prostate cancer that we cannot see. Of course, with PI-RADS 5, with a high confidence of there being cancer, we need that tissue diagnosis to be able to differentiate, but we also need a PSMA scan in order to stage as well. Different journeys for all these individuals.
You can see the common denominator is that there's an overlay of anxiety, and really the biopsy is being driven by the fact that our imaging modalities are inadequate. We intend to change that with a new study, a clinical protocol that we've submitted. The IND has been submitted. It's going through ethics review, and we certainly look forward to the announcements of our first patients being enrolled. What we've really done is we've really tried to rethink and reinvent the way that prostate cancer is diagnosed. We confront the molecular probes that we have using PSMA-11. With this, we can then stratify these into three slightly different categories. Those that have potentially high risk in the PI-RADS 5 category, we would perform an image-guided biopsy, but a very, very precise one, and simultaneously be able to look at staging and surgical planning.
In other words, rather than getting a biopsy, a diagnosis, and then a PSMA scan to stage, we could do it all in one fell swoop. In those individuals with PI-RADS 1-4, now we're aggregating basically anybody that gets an MRI that has a positive lesion, we can actually perform a precision biopsy. Because we know that PSMA is much more sensitive in the detection of prostate cancer, we can then perform a one-and-done. In other words, rather than the 12-40 biopsies, we can do one, have the histopathology, stage simultaneously, and move on to the next step.
Most importantly, for those individuals with PI-RADS 1, 2, in other words, a normal prostate with risk factors, if they demonstrate a negative result, in other words, no uptake of PSMA, we can now go from having to do these template biopsies or giving them the anxiety to wait until the next year's cycle to no biopsy at all and perform a none-and-done. We have really been able to transform and reinvent the process in which prostate cancer is diagnosed. This really means that with this study, we will improve predictive accuracy, we will reduce the number of biopsies from up to 40 down to 1-2. For some people, for some men, we may actually eliminate the need for a biopsy altogether. As a result of this, we decrease the risk and anxiety and stress involved in an ambiguous diagnosis based on inadequate imaging modalities.
This really enables clear treatment stratification. It enables a personalized diagnostic journey and really an expedited process from diagnosis to staging to treatment. No longer is it going to be a turnstile of coming back to the hospital over and over again to be able to get the next stage of test and the next stage of test. We're really doing it and addressing all these issues in one setting. The study that we are actually implementing really is going to address this PI-RADS 1 to 4, which is basically the majority of people, and then looking at stratification of the positivity of the PSMA scan to determine whether it's going to be a one-and-done or a none-and-done scenario.
When I look at the patient's journey and the accumulation of my 25-year medical career, what I realized was that what we've actually been doing is we've been repeating. I had alluded to before, addressing the inadequacies of conventional imaging as a result by performing these biopsies. In this cycle, in this turnstile, in this rinse and repeat cycle, for those individuals that have biopsies that don't demonstrate a prostate cancer, they undergo the same thing the next year. They get another PSA, they get another MRI, and they get another series of biopsies. Not only is this cumulative with respect to the initial diagnosis, but as Kevin had mentioned, there's also the stickiness factor where with this single diagnosis and staging modality, we've now not only decreased the requirement for repeat biopsies, but we can now stage, monitor, and potentially treat with our therapeutic pipeline.
We've gone from a finger to various imaging modalities. Above, you can see what the ultrasound looks like with Doppler applied. I would challenge many of you who are in the non-medical nature to identify where the prostate is on that image. In fact, to make it even more difficult, here's the MRI below, which is actually a little bit of a molecular probe looking at protons and proton density and behavior behind the prostate. A little bit harder to see. At the bottom, which is where we are now with PSMA imaging, not only can we find the prostate, but I think it's pretty obvious where the cancer is. That's the type of fidelity that we have and the confidence that we have in diagnosis based on implementing these types of molecular probes to really, really look into the biology and behavior of disease.
Simultaneously, as I mentioned, with a PSMA scan, we can also look at the whole body to look at immediate staging. Therefore, there's no ambiguity with respect to the presence or absence of more advanced disease. The determination of whether local curative intent or potential systemic therapies, such as in our Alpha therapeutic programs, may be most appropriate. 2026 and beyond, with the successful implementation, execution, and readout of our clinical study, will really change the paradigm of how prostate cancer is diagnosed. For those that are at risk, either due to elevated PSA, clinical risk factors, or clinical examination that's suspicious for prostate cancer, the combination of an MRI plus a PSMA would really eliminate the need for biopsy in approximately 40% of those individuals, also instilling confidence in those individuals that they're not in this stressful purgatory of whether they have cancer or not.
For the 60% of individuals, of men that do require biopsy, no longer do we need to do these saturation systematic or template biopsies where multiple biopsies are performed, but we can be very precise, and we can really, with no pun intended, but with surgical precision, be able to localize, diagnose, and prognosticate for these individuals. I think I hope that in these last few minutes, I've been able to present to you kind of the narrative with respect to how this complicated topic of trying to compensate for inadequacies of imaging is really solved through the introduction of this PSMA protocol and study. Furthering our relationship with the urologic and uro-oncologic community is critical. I think it's a perfect segue to introduce our CA9, our carbonic anhydrase 9 asset, otherwise known as Zircaix.
What this is, as many of you know, is zirconium-89, which is the isotope attached or linked to girentuximab, which is an antibody that targets carbonic anhydrase 9, which is associated with upregulation of angiogenesis, which is part of the cycle of cancer. It's present in 95% of clear cell renal cell carcinomas. You're aware of the Zircon study, our phase three clinical trial that reported out sensitivity and specificities of 86% and 87%, really a blockbuster diagnostic tool. What this really does is it mitigates the risk of biopsy in the kidney. The kidney is a highly vascular structure. 10%-15% of these lesions are very, very difficult to biopsy, and about 5% of them bleed to the point where an intervention is required. The bleeding itself is not only a factor with respect to immediate management, but also tumor seeding.
You can see, as an interventional radiologist, as somebody who has had the lived experience of dealing with these complications in the patients that I'm trying to help, it's not a good feeling, and it's not necessarily an exciting part of my practice for renal biopsies. It's with a lot of hesitancy. Really, the Zircon trial, the phase three clinical trial is truly practice changing. In the setting of clear cell renal cell carcinoma, we really do have that unmet need. Once again, the narrative of this is that the biopsy compensates for our inadequacy of imaging. With these types of targets, whether we're talking PSMA or CA9, we're really actually doing these molecular probes to be able to perform almost a virtual biopsy. We can get the diagnosis without doing the intervention.
This decreases the unnecessary surgeries, decreases the potential complications of bleeding, as well as tumor seeding. It really changes the way that we look at the diagnosis of renal cell carcinoma. In those individuals with Zircaix PET positive lesions, we reduce the time to diagnosis. We do not actually cause an intervention that could cause further consequences and complications. In those individuals with Zircaix PET negative scans, we have now changed those individuals' status from ambiguous, not sure, to a lower probability of aggressive disease. As a result of that, really putting this front and center in terms of the assessment of renal masses is going to become, I am very confident in saying, is going to become and should become the standard of care before biopsy.
I think with that background, because I know we have a very learned audience with respect to Zircaix, I'd like to hand the mic back to Kevin to address some of the opportunities that we have with this asset.
Thanks, Dave. Thanks, everyone, and thanks, Dave. Just to finish out the precision medicine piece, kind of back on the commercial piece and what we're really trying to do with the patient population. We're really committed, as you can see, to the renal cell carcinoma patient. It really aligns with the way that we treat all of our patients, and it aligns with our commercial strategy. Because of what Dave just went through, we believe it does enable first. We're going to enable this biopsy replacement even inside the kidney with an indication of really diagnosis and characterization.
Like I'd mentioned before in the growth strategy, we want to grow that both through just increased market adoption. We showed you the TAM for that a little bit earlier. Through guideline inclusion, really we've got a lot of work that we've done there, and then label expansion studies through Zircaix. We believe this is a transformative target. We believe that the CA9 target expresses in cancer across, and we think that we've got really good data that we're generating concurrently through some ongoing studies that we have right now. We believe that in the CA9 program, we will enable it, we'll grow it, and then we will transform it. That's the way we see the TAM as we think through just the diagnosis and characterization of clear cell renal cell carcinoma.
Then we believe that there's the potential new indications of metastatic disease that we talked about with Zircaix. We believe that TAM is $750 million plus that we have the opportunity now. One of the exciting things commercially is we're the first one to market with this. It is practice changing, we believe, through David's comment, and we're excited to get this to market. How does that really kind of work inside of what we would call the Telix portfolio or the Telix bag? Many of these patients start in your PCP. After some sort of test or screening, they move over into an imaging either through urology or a radiologist with nuclear medicine.
Then when they continue down that pathway, they get into treatment or management through a urologist, a med onc, a rad onc, or an interventional radiologist is involved in that as well. What's nice to see is that lines up perfectly with what we're doing inside the prostate business and that we've already been building relationships and building confidence and building that critical mass inside of that urological call point across all of those diseases, both those diseases and the specialty of really urology is kind of the main point in there that is referring those patients. With that, I'd really like to dive now a little bit deeper. We had a big deep dive into prostate and into our biopsy program. I'd like to turn it over to Dr.
Joe Osborne, who is the Chief of Molecular Imaging and Therapeutics, and he's a Professor of Radiology at Weill Cornell Medicine. Thank you, Dr. Osborne. Are we going to try the mic or? Blue?
Yeah. Blue.
Good?
I'll be back up if you need it.
All right. Awesome. Today I'm going to talk about Zircaix. Before I start, I want to thank Telix leadership and also give a bit of a personal perspective of PSMA because that is really what has happened across my career. When I started in 2008 as a molecular imager, before I was chief, I was just a junior attending. When we came to the GU management team group, we were basically the ones who were supposed to bring the snacks and look at some of the images that no one could interpret, like the ultrasounds.
They kind of had us there, but we did not really have a role. At this point, very recently with PSMA, our urologists and medical oncologists, and they are like, "Maybe we can have, can we have like a specific hour, like an additional meeting so we could go through all the PSMA scans? Because the hour is not enough. And maybe then we could also talk about some new trials and some things with the Zircaix on another meeting." I am like, "No, like three hours. We cannot do it. That is like too much." I know with everything with my chairman, "No is not the right answer," because we just are going to need a bigger boat.
Everything that's been described is the expansion of the really exciting things that have happened in my career that included PSMA, but also what I'm going to talk about today, which is Zircaix, which is the future, which hopefully, and certainly the other people of the GU management team group hopes will expand as quickly as PSMA has really changed our practice. We do things completely differently from the way that we did 10 years ago. For Zircaix, that is also important, not just for my career as a clinician, but I'm a clinician scientist. These are things that we were talking about for years. We were talking about antibodies and their specificity. We're talking about Zirconium-89 and the ability to label these antibodies so we would get not just the specificity, but also we would be able to look at the finding specifically.
We were talking about it for years, but we did not know whether there was going to be a group that had the flexibility and really the growth that Telix has had to really take this product, take it, have the big trials, and actually find that it was useful and have the flexibility to change, right? We knew there were many different ways this could go. We did not know what it was going to be, but we knew something had to change. The reason we knew things had to change, this was also part of my training. During the time, and this was in the early 2000s when I was a radiology resident, we were getting better and better at CTs and MRIs. Back in the 1970s, there really were not many renal cells being diagnosed because we just did not have the machines.
When I was training the machines, you know, foresight CT, 16, 64, and then by the end of my residency, we're like, "Okay, we're seeing all these renal masses, but what are they?" Right? Really that's the conversation that we have to have with patients. They don't want to hear necessarily about the sensitivity or the specificity. They want to know once something is identified, what is it? You've told me I have something. What is it going to be? That's where we came in as molecular imagers. They first asked us, "What can we do about it? Can we use a regular FDG PET?" Turns out that's not good at all. We had to say at the time, "There's really exciting stuff on the horizon. It's going to happen.
It's really going to happen where we're going to be able to have the kind of specificity that's going to change these conversations with these patients where you could say, "Okay, this is, we've seen it, and this is what we're going to do." The unmet need for the diagnosis is about these conversations. It's about the conversation of finding these small renal masses and saying, "Okay, well, before things progress, we want to deal with this definitively. We want to deal with it. Do we have to biopsy it? Do we have to do something specific?" Even worse, the number that's on the bottom of this slide. If you have 30% of nephrectomies come out with benign lesions, is this a conversation that you want to have? We did a nephrectomy. All these things happened. By the way, it turned out, yeah, it was benign.
It was actually fine. We did not have to do all these things. What people want to know, and this is what has happened through the trial and the specificity and the numbers, and decreasing these non-diagnostic biopsies, decreasing the need for the nephrectomies, you are able to get to the point where you can see that image, you could see that hotspot and have a very good sense with specificities that really start in 86% and 87%. When you look at this, even smaller renal masses, even higher, and being able to tell people, "Okay, this is what we see, and this is in the 90%," which is really as good as we get in terms of sensitivity in medicine.
It's the kind of number where you can have a conversation and say, "Well, anything's possible." Yeah, it could be something that's within the 2%, but that's not what medicine is. Medicine is getting you to the above 90% confidence number where you could say, "This is what we think non-invasively, so we don't have to proceed further with the next step, which could be a biopsy or a nephrectomy." This is just going into the numbers with the renal masses because this is something also in my training, which was unclear. You find something really small. Is it small and benign? We used to give a differential. There were things that we knew what they were. Okay, this is an AML. This is a small cyst. Then there's this like 80% that could be all these different things.
It could be like an oncocytoma or you do not have to do anything. Actually, it could be a clear cell renal carcinoma that you might want to actually jump on right away, but we were not really sure at the time. We were just giving them impressions that you never want to give as a radiologist, which is number one, no appendicitis, no this. Renal lesion of uncertain significance and behavior, follow up in a year. You would get a call, and they were like, "Really? What does that mean? It means I am not really sure." That is where the molecular imagers came in because we had to give a little bit more certainty. Of course, where does that come from?
It comes actually from Telix and actually running the trial because you have to know if you're getting to those numbers and getting to that level of certainty, that is a very hard trial to run, right? Because getting to that level of sensitivity and specificity and making decisions based on it means you need to have the just right antibody or just right vector. You need to have the just right nuclei. So with Zircaix, which has a life of 3.3 days, that's going to be around the time of the circulation of antibody. Perfect. Antibody, very specific, and you're looking for a surface molecule that is going to be a differentiator, something that is on a cancer cell, but not on benign. And that's the body. The body does that. You just hope to find something that's a surface molecule that's going to do that.
That is actually what was the driver here in getting to these numbers where you have an under 4 cm lesion with a sensitivity of 85%, specificity of 90%, and less than 2 cm at 97%. With that, you could say with these uncertain renal lesions, you could get to the level where my GU oncology group is happy, right? When they ask us what we see, and then we see what is in this case, which is something we see all of the time, where they say, "Okay, so you smart guy, like we've done the PSMA scan, that's really helpful." You know what? A lot of these gentlemen who are in their seventies, they have a second cancer. Is that a second cancer or is that a cyst? What's going on there?
Because you do not want to solve one problem and then have another one just fester, and then the person actually has a consequence of the second cancer. In this particular case, when PSMA could not provide the answer, the girentuximab did, right? You could say, "Okay, it is a small renal lesion. We could deal with both the prostate cancer and we can deal with the renal cell and then put the patient back into the area of some certainty where you can do follow-up without doing something more invasive." There are these lesions. These particular lesions and these images right here have our colleagues, the interventional radiologists, the urologists. They are like, "We could read this. Do we really need you?" I mean, we could find something like this across the room, especially when it is like an anatomic shaded surface display.
They're like, "We're actually better with the anatomy because we actually cut people open. We do people biopsies." We say, "Zirconium-89." They're like, "What's that?" We're like, "Job security." You definitely want to have this kind of image to convince. Patients actually love this, right? When you can bring them into your office and say, "We did a scan and we saw this." They love it when there's something more definitive than a scan that even the ultrasounds that even the imagers didn't want to look at. This even the patients will love. I'll leave you on this because this is also equally important.
If you see something on a scan and it's the size of a baseball, when you're having a conversation with a patient and you're like, "Yeah, there's this baseball-sized thing on your kidney," it doesn't go well if you can't say, "Is it good or is it bad?" I mean, baseball always feels like bad, right? If you can then do the scan and show that it's this lucent lesion without uptake with a specificity in the 90s, you're like, "Okay, well, I'm not 100% sure what it is to biopsy, but what I can tell you is it's not going to be a clear cell renal carcinoma. That's going to metastasize, and then you're going to have five months of chemo and suffering and everything else." We can do a number of different things. The conversation completely changes.
I think this is one of the things that people actually like the most, like knowing that there may be something, but it's not something that has to be dealt with aggressively. Thank you.
I will have a presentation on 591, and then we will take a break for coffee and morning tea for those who need some caffeine. I'd just like to call up to the seats Dr. Joe Osborne, thank you so much. David, Kevin, and Chris. We've got a couple of microphones. If you have a question, please raise your hand and we'll get a microphone to you to ask those questions.
Hi, Brandon Carney, B. Riley Securities. Thanks for taking our question. Just on the biopsy use case here, just wondering how useful MRI has been in guiding those biopsies and if that itself has been able to reduce the number of sample sites. Also, what the potential for PSMA negative disease is and how that plays into the potential of those scans in the early case here.
It's okay. I'm trying to grasp this. Just to kind of level set our discussion, we're talking about PSMA and MR in reference to prostate cancer, but renal stones has been kind of some complications along those sides. With the introduction of MRI, we are able to.
We're able to.
Thank you.
It's more of an anatomical probe. Although ultimately there are some aspects to cellular density that we can examine, the PI-RADS stratification is really just a risk stratification scoring system. For those individuals that have PI-RADS 1, 2, which are the ones with risk factors, they generally have somewhere between 20%-30% occult disease. In other words, they have prostate cancer somewhere. We just don't know where. We can't see it. The overall diagnostic performance of MRI, if we go across the board for those individuals that are at risk, is about an accuracy of around 65%-70%. We miss about 35% of cancers.
Now, as far as the targetability, if you do have an individual that demonstrates these PI-RADS 3, 4, and 5 categories, which really give you an anatomical target to biopsy, they do actually, it may potentially decrease the need for these saturation or template biopsies depending on the PI-RADS score. A PI-RADS 5, for instance, has a very high probability, 80%+ of it being prostate cancer on the MRI. Therefore, you may be able to just do a single biopsy in that setting. However, and this is kind of a further discussion that we're having in regards to the lifecycle management of PSMA, sometimes biopsies are performed in order to provide information on the neurovascular bundles and proximity of cancer to the neurovascular bundles. This is what's referred to as nerve-sparing surgery.
What nerve-sparing surgery does is it preserves a man's ability to achieve and sustain erection. It has major implications to the health and welfare of men in the future. As far as the implementation of PSMA, time and time again, it's been demonstrated that PSMA across the board has much greater sensitivity in the detection of prostate cancer. There is a defined population in the single digits, about 5%, that are PSMA negative in terms of their expression. That's one of the reasons why we're looking at this as a strategy as an adjunct to MRI. In other words, we're not saying that PSMA is better than MRI. This is like peas and carrots. They're better together than they are individually.
I'm not sure if Dr. Osborne, if you might have some comments.
Yeah, I think that there is a time when people, the MR community, the molecular imaging tech community would believe that their modality was going to solve everything. I think the jury, it doesn't, right? As you said, there's better together. There are ways and there are aspects of the diagnosis where you're at the end, you're really trying to get to clinically significant disease. What is this going to do? There's aspects of anatomy that get you to that because there are, especially with surgery and with procedures, there are adverse events that you want to avoid. There's also the likelihood of it being aggressive, which you might see with PSMA and some other modalities. When you put them together, especially if it's something that's non-invasive in its diagnostic phase, it's incredibly helpful.
These days, the MR community and the PET community are kind of getting along a little bit better because I think there's no way to have one without the other.
Even integrated machines.
With integrated machines. We have three Petimars, which we bought at Cornell in anticipation of this. Although an interesting aspect of it is sometimes, even though they're better together, sometimes as a single machine, not quite as good. Although my chairman bought that, so I hope this video goes nowhere. Yes, it has actually driven device development because it's believed that that's going to be the way forward.
Thank you.
Dave Dodd from UBS.
Oh, okay. Great. Yeah, Dave Dodd from UBS. Just a couple of questions on the commercial aspect of Illuccix and Gozellix. We know that Illuccix, their transition pass-through will expire end of June. How should we think about the potential impact on the top line for Illuccix? For Gozellix commercial strategy, any kind of thoughts around cannibalization of the existing Illuccix market?
Maybe I'll open up and then hand it over to Kevin. I mean, our guidance for the year is based on how we feel we will transition through that pass-through period. We have the benefit of being in the mid-commercial cycle for a year. So we've been able to manage that process proactively with our customers. We're going to know in a couple of weeks' time where we stand on pass-through. That helps with respect to things like temporary coding in the interim. Also, it's a really dynamic environment right now. We feel that we've got a lot of momentum going into the Gozellix launch. Our customers understand not just the advantage of Illuccix, but also the real benefits that Gozellix brings as a follow-on product. I don't know if you want to chime in.
Yeah, I say many times that this wasn't a surprise like it seemed to have been. We've been planning for this for three years and have worked Gozellix to the point where it's launching basically this month. To Chris' point, we've planned for this proactively through the next three months. We've got the teams out executing that playbook in those particular accounts. Just as a reminder, not every patient is a CMS patient, and not every patient of that age is under normal or regular, we call traditional Medicare. They might be under Medicare Advantage. We are managing that on a hospital-by-hospital basis or IDN-by-IDN basis in our contractual language. Not a surprise. We're planning for it. The guidance is based on that. We feel comfortable with that.
Hi, thanks. Rich Newitter from Truist Securities. Thank you for hosting this day. I have two. Just maybe on the piggybacking off that commercial question on Gozellix and Illuccix. You made a use case for Gozellix is going to allow you to extend your reach to harder-to-get-to areas, huge underpenetrated market. I understand that. Just from a pricing standpoint, in institutions, not the ones that are hard to reach where it sounds like Gozellix is the solution, but where you actually have customers that might be thinking about using one or the other in different portions of their patient population, Medicare versus not. How does price differentiation work there, if at all? Can you just talk about what's involved in terms of getting both products on formulary and to make sure that it's a smooth process and then follow up?
Yeah, I mean, it's erroneous to think of the two products as being equal. Sorry. Sorry about all the audio problems we're having today. It's erroneous to think about the two products as equal. They're not. They have really different characteristics. They allow very different scheduling flexibility. The way in which we deliver product to the site in terms of the dose volume that's available at a particular point of time is completely different. We think it's fair to garner value for that. It's really a good way of if there's a concern about what's the basis for pricing differential, it's really about pricing service and its manifest in the product itself. They'll exist side by side, just as PSMA agents exist side by side today. From a billing and an ordering perspective, there isn't a lot of magic to it.
It'll just come down to preference based on the patient category and probably above all else, preference around scheduling and patient management. I don't know if you want to add anything or.
Yeah, the only thing to add is that these are most often urban centers. They're sophisticated ordering and delivery systems and well set up to be able to manage two products that are for a similar patient, but definitely for a different reason based on the hospital and what they require.
Yeah, maybe one more question.
Thanks, Anthony Petrone from Mizuho. Thanks for hosting us and appreciate all of the detail on the pipeline and existing product portfolio. Maybe just a quick one on Gozellix, just the update on the transition pass-through status, code timings. That would be one. Then going to biopsies, when you think about NCCN guidelines, I mean, what type of clinical programs are going to be needed to sort of secure guidelines to maybe have PSMA PET replace some level of biopsies? You also mentioned there's 3,000 PET scanners in the United States. Just wondering, what do you think the PET scan capital capacity is going to be needed over the next few years when you think about expanding not only the oncology side of the equation, but we're seeing cardiology in other areas? Thanks.
Yeah, there's a bit to unpack there. Maybe I'll start on if you want to handle the timing on the reimbursement. Now, I just think that so this is the biopsy study that we're talking about is a phase three trial. It'll be an extensive protocol. We'll obviously be socializing the details of that as the IND gets approved. We have had it was a heavily consulted protocol from a regulator engagement perspective. So we're filing the IND with confidence that it's a protocol that will be accepted. I think everybody in the room understands that biopsy is a challenging topic, right? Moving up into that front line of use of imaging is clinically contentious. We've got to make sure that the protocol is well thought out. I'm convinced you've seen the chubby brain in the room.
I'm convinced we've got the right people that are behind that. That's, I think, the answer to that question. From a machine capacity perspective, there's a huge amount of pressure to expand the service provision of PET depending on the territory. You're looking at between three and eight weeks of backlog on PET scanners at the moment. It's a pretty vibrant time for the GEs and Siemenses of the world. Urology practices are buying heavily into the concept of PET as a must-need instrument, just the same way to some extent as cardiology did in the past. We're going to see more and more PET service provision become something embedded in a urology or very much adjunct to a urology practice.
I think three to five years from now, 25%-30% of patient volume will really come through directly from, I hesitate to, from a compliance perspective, to use the term self-referral. But that's effectively what it's going to be. Urologists have seen that this is big. They're the owner of the patient. The industry has to pivot to accommodate that. That's how we think about clinical management very acutely in the next couple of years.
Just from my perspective, it was just last night I had a call with our manager. I'm like, "Okay, we're going to be scanning all weekend." I'm like, "That's the new thing. We're going to set it up. We're going to scan it. We're going to use these two agents. We're going to have it done." The imagers are also on the NCCN. One of the things that we did or one of the things we were pushing for, which worked, was to because they wanted to have conventional imaging done prior to PSMA PET because you needed to have a scaffold for that. We were like, "Get rid of that," right?
Because you can't scan on a Saturday if someone is like, "Okay, but you have to do a bone scan first or you have to do something else first." It is actually we're also pushing on the other end to make it really more simple to get to the end because it helps us as well. It helps the patient care as well because when they are diagnosed, they want to be scanned. They want the scan to be read immediately. We have to get to that point because there's no other answer than, "Yes, we're going to do it.
That'll cause a redistribution a little bit of scans out further and further out of the urban areas and more rural, which is a part of the Gozellix strategy to alleviate that and redistribute. From a Gozellix perspective, we have filed for transitional pass-through, and we plan to hear from them in this quarter as well. Getting ready for that October 1 approval date for that. That's the expectation. That's what we've done, so. Yep. Thank you very much for your questions.
Thank you.
Thank you. I'm going to pull up your show now. Presentation on 591, and then we'll have some more Q&A and take a break. Thank you. Lots more opportunity for questions. Thanks.
Yeah, I don't know. Hi, everyone. I don't know if the microphone is working, this one.
Currently, yes. Oh, no, I have one in case of. Thank you, everyone. It's my pleasure to be with you today to present the therapeutic Telix portfolio. Without waiting, let's deep dive on what I have to present to you today. On these slides, you can see that our ambition at Telix is to build a really deep and breadth portfolio for therapy. You can see that we are focusing our attention on mainly three pillars or disease areas, I'm used to say. The first one, as you can see, is urology with the focus on prostate and kidney. It resonates with what you heard from my colleagues a few minutes ago. The second one will be for brain and rare cancer, but mainly for glioblastoma. The second one will be the pan tumor.
The third one, sorry, will be the pan tumor. We have two targets that we have well identified, the TLX400 and the TLX252, but I will come back on that in a minute. If you agree, let's focus on the upper part of the slides with the late-stage assets. You recognize the well-known lutetium TLX591, which is currently in a phase three trial named Prostac Global, where we try to treat the mCRPC patients. We have also the lutetium TLX250 compound that is dedicated for the treatment of clear cell renal cell carcinoma. The third one is the iodine TLX101 with the potential to be the first radiotherapy for the treatment of refractory glioblastoma. You can see that for all these diseases, we have treatments at different stages of development.
The bottom part of the slides represents the next generation platform where we have all our alpha programs. You can see the variety of alpha programs with the actinium or astatine that we tried to develop for the lifecycle management of these treatments in these precise disease areas. This slide illustrates the clinical and commercial interests of the diagnostic strategies that we develop within Telix. You understood that we have our precision medicine compounds. For each of the diseases I previously mentioned, you can see our precision medicine compounds are associated with at least two therapeutic compounds that we want to develop. That is really the strategy that we have. You can understand that the diagnostic and the precision medicine compounds will provide near-term revenue to fuel, if I can say it like that, the development of our therapeutic compounds.
More than ever, you can see that the total addressable market of this disease area from a therapeutic standpoint is very significant. It is paving the way for the future of Telix in terms of potential revenues. The next two slides are there to illustrate the amazing and very complete portfolio that we have. If I do my math properly, you will see here the late-stage assets. On the next slide, it is the early programs. We have more than 10 compounds under development. I'm in this business of radiopharma since 15 years now. I can tell you that we are probably the unique company, the radiopharmaceutical company with 10 compounds under development currently. We have here the early programs that are the next generation with the alpha I was just mentioning, which are entering in clinics for all of them.
I even do not add to this pipeline with the recent acquisition of Imaginab, where we have two additional lead compounds in preclinical, namely the DLN3 and the Integrin alpha V beta 6, which are already well known from the medical community because they are ADCs under development currently. Now we envisage to put some radioactive isotopes on these targets, and we will develop them in the future. The road is long in front of us, but fascinating portfolio within Telix. Here, what are the catalysts for the year 2025? We already disclosed the IPACS LINT data for the 101. Professor DeGroot will come back on that in a minute with some more granularity details. We have also filed the ethics submission for the pivotal trial for the 101 trial in Australia.
We expect by mid-year, end of summer, the results of the part one, Prostac Global phase three trial with the safety and dosimetry data. By end of the year, we also plan to launch the 250 pivotal study trial for the 250. In the middle of the slides, you see that we have also some next generation compound. The Telix 90, I did not mention that, but it's the perfect companion product for the urology franchise because here we are targeting the bone pain for the patients which are really on the salvage therapy. We are initiating the IND this summer for a phase one study. The 252 and 592, which are the alpha programs in the lifecycle management of our urology portfolio, will be the first alpha therapy that we do plan to initiate by this year.
All are the catalysts that we have this year. Let me hand over to my colleague, David, our Chief Medical Officer, that will go deeper on the urology portfolio and more precisely on the 591 to start with. Thank you.
Thank you, Richard. I think that's, I mean, there's a clear level of passion that I think you exhibit for your portfolio in the theranostics business. Let's now turn our attention a bit more specifically to our prostate cancer program, which I'm going to introduce quite briefly before I pass on to one of the truly leading contributors to this field. I think over the last decade, he also coincidentally serves as our co-principal investigator on our phase three Prostac Global study. That's none other than Professor Oliver Sartor. Before I hand over to Professor Sartor, I would really like to make, I think, a very important observation.
The identification of the PSMA target itself, as well as the development of agents against this target, really have, as you've seen, I think in some of the earlier content, utterly transformed the way that we manage and look after patients with prostate cancer over the last five or so years. While the currently approved peptide-based approach is important, and Professor Sartor had a pivotal role in bringing that to patients in the United States and now in other parts of the world, Telix's lutetium TLX591 asset is indeed a highly differentiated approach. That aims to differentiate itself and overcome some of the limitations that we know exist with small molecule and peptide-based approaches. I think it's worth covering these in a little bit of detail. These differentiations really can be classified across four key domains.
The first of those is that the mechanism of action characterized by an antibody really sees it internalize into the prostate cancer cell, where its prolonged retention at the target and its functional selectivity for that target is markedly different from a peptide or small molecule. It is very prolonged and sustained at the target site. Secondly, from earlier trials, phase one and two trials, there's been some quite prolonged survivals demonstrated. This asset has clearly earned its right to be examined in more detail in the phase three setting. Thirdly, the patient-friendly simple dosing regimen comprises two fractions over two weeks, which really facilitates the use of this agent in combination rather than instead of the available standard of care agents.
An antibody by virtue of its immunospecificity has very limited off-target effects on the salivary glands and the tear glands, which do not sound major, but they do have a major impost on the quality of life of patients, particularly as we see these agents become used in an earlier disease setting. As well as that, this asset has a very predictable toxicity profile as well. I think most in the audience are highly familiar with our Prostac Global phase three trial. This is our phase three of lutetium TLX591, which is currently enrolling patients. It is actually very close to completing dosing of patients in part one. Part one, as you can see, is more on the left side of the schema, is the safety and dosimetry lead-in in 30 patients.
As you can see, part one's evaluating the safety of TLX591 together in combination with the androgen receptor pathway inhibitors, abiraterone or enzalutamide, or the quite widely used chemotherapy agent, docetaxel, as well as evaluating the tumor and normal tissue dosimetry. Docetaxel eventually, ultimately, is offered to a patient, typically in the United States, but very widely used, particularly in other parts of the world, Germany, Europe, Japan, and other parts where we are conducting this study. What does success look like for this trial in part one? Ultimately, success for those 30 patients would be really a safety profile that confirms the feasibility of administering 591 together with this broad range of standard of care agents that really is consistent with the extensive data that we've got that's been well established in terms of its safety profile from prior studies.
The same outcome really for dosimetry, which would enable us to advance the asset, the randomized treatment expansion, which is really the main game of this study once we've finished part one. This study currently has very significant investigator interest. I think the momentum's rapidly building in this trial. It's important to note while we have to pause when we are enrolling patients in the United States at the end of part one and take the data back to the FDA, we have the permission to seamlessly proceed into part two in other sites where we are running this trial outside of the United States. That's a brief introduction. I have now truly the great pleasure in handing over to Professor Oliver Sartor. I'd like to invite you up here, Dr. Sartor.
Thank you. Thank you. Pleasure to be here. Chris, in particular, I'd like to thank you for your support over the years and what you're doing. Chris is a pretty remarkable entrepreneur. He started with not much, and now he's got something. So well done, Chris. By the way, I have a new title. I'm no longer at Mayo Clinic. I just made up my new title. By the way, I'm Director of the Transformational Prostate Cancer Research at LMC Hospitals. I like the transformational part. That's what we hope to do down in New Orleans, be heading down there next week. I think most of you are aware of the differences between small molecules and the antibodies. Many of you know that I've been very involved with the small molecules. They're good. There's an opportunity to change practice. There's already been FDA approvals.
I think there is going to be more to come. There are some shortcomings as well. Here we are going to be talking about some of the opportunities that I think are present with the antibody. TLX591 is by far the furthest along. There are other antibodies out there, but they are considerably behind. I might point out the one from Bayer. By the way, it was a failed attempt with the Thorium-227. They are trying again, but they are behind where Chris is for sure. One of the real advantages of the antibody is the two doses, which are pretty simple, just two weeks apart. It turns out that they are going to be retained, circulate for a while, really, really good tumor uptake. We are going to look at some of the tumor uptake.
One of the cool things about lutetium is you use SPECT scanning to be able to see exactly where the isotope is. You can see the localization. No salivary, no kidney. You're going to be able to see it in the tumor. You'll see hepatic uptake. Initially, when I looked at it, by the way, on the hepatic uptake, I said, "Oh, goodness. That could be dangerous." It is not. It turns out that very few in the way of liver function tests are going to be problematic. When we move to thinking about the clearance, and I'll just talk a little bit about this now and come back to it later, the limitation on the small molecule has been built around these two organs, salivary and kidney. The salivary toxicity on the small molecules is probably rate limiting.
When you go to actinium, you'll see that to a much greater extent. Not a huge problem with lutetium, but the limitation on the dose on lutetium with the small molecule is related to the renal dosimetry. The FDA has drawn dosimetry guidelines. Again, I'll come back to this. Typically around 23 gray. If you look at, say, the SPLASH trial, which you may or may not know, it was 6.8 gigabecquerels q6 weeks. That was really too low. It's about the renal dosimetry. If you look at the 7.4 gigabecs on the small molecule q6, that is built into the renal limits. It's not due to the DLTs that are observed. If you look at the DLTs that were done in terms of the dose escalations, the small molecule, it's not about the DLTs at all. It's about the renal dosimetry limits.
The antibody is going to avoid that problem. That is going to have another potential DLT. Nevertheless, the renal dosimetry problem is solved with the antibody. When we look at on the left side, we are going to see basically the PSMA 617 RLT, six infusions over 30 weeks, a little bit longer to administer. You do have some dry mouth. That is present probably in the majority of patients in the PSMA 4 setting, which is the taxa naive setting, castrate resistant. You begin to see that is over 50%. It can be a problem in some patients. It is a persistent problem in a few. It is a relatively common complaint. This is an advantage of the antibody, which simply does not have it. The renal toxicity issue, it is not so much renal toxicity. It is the renal dosimetry limits that are the problem.
I think there is an opportunity to improve efficacy, tolerability, and dosing regimen. That's where the TLX591 comes in. You have a two-dose regimen that's 14 days apart. You have the hepatic clearance, which really solves the renal dosimetry problems. You also avoid the salivary uptake. That's kind of where the opportunity lies with this molecule. Now, on the left-hand side, I think we're all pretty familiar with the landscape and the evolving landscape in prostate cancer. By the way, if you were at ASCO, one of the best things about ASCO for me was not presented at ASCO, but it was the PSMA-617 reporting on the metastatic castrate-sensitive space and the RPFS positive, OS trend positive, more analysis will be needed on that trial. It's likely to lead to an FDA approval upfront.
If you look at the TLX591, the Prostac Global, which was presented a little bit earlier, is the phase three that has the lead-in. Currently, they're in the lead-in phase. I try to get some up-to-date information. There were three components to the lead-in, as discussed with the FDA. Number one was the abiraterone combo. Number two was the enzalutamide combo. The third was the sequential use of docetaxel. The abiraterone is already fully accrued. The enzalutamide is very, very close to being accrued. There are a few more. I think there's six more to go on the docetaxel. I'm just giving it a sequence. One of the things I like about this trial is that you integrate the standard of care in combination, unlike the PSMA4 trial, which was a monotherapy with the PSMA617.
To emphasize the prostate select, and that is the data that has been accumulated predominantly coming out of the Cornell Group and more, there is an interest in these outcomes. You'll see that the survival outcomes have been outstanding. Of course, that needs to be verified in the phase three trial. This is the survival outcomes that are outstanding. Again, this was with the two doses of the antibody. There were some sort of eye-popping overall survivals, 42.3 months supported for castrate-resistant disease. That's rather phenomenal. These are patients who had pretty high burden. There does seem to be this survival benefit that attracts people's attention, certainly attracted my attention. This was presented by Scott Tagawa. Scott Tagawa, by the way, at Cornell is a close collaborator, close friend. We've worked together for many years. His data is very reliable. I trust Scott completely.
This is the distribution. I think it's a little bit interesting. On the left-hand side, you'll see a PET scan, typical PSMA-11 gallium-68 PET. You'll see the salivary uptake. You'll see the renal uptake. Of course, you'll see the tumor. On the right-hand side in the box, you'll begin to see SPECT scanning. This is taking advantage of the lutetium, which has the ability to be imaged with SPECT. You'll see 4 hours, 24 hours, and then 4, 7, and 13 days. When you see the injection, you'll see the vasculature because of the antibody that's going to circulate in the vasculature. You don't see the salivaries because it doesn't hit the salivaries. It's very interesting. There's seemingly a barrier for the monoclonal that you don't see with the small molecule. That barrier obviates the salivary toxicity.
Then you begin to look at the kidneys. You do not see the kidneys either. You see the liver. You see the spleen. When you carry it through over 24, 4, 7, and 13 days, you begin to see the remarkable retention within the tumor. That also caught my attention when I was first looking at these scans. That retention within the tumor is really, really, really good. You, again, do not see the salivaries. You do not see the kidneys. You do not see anything in the bladder. You do see the liver. First of all, the liver, like I said, I had kind of alarm bells go off. It turns out there is really no liver toxicity. We look at the dosimetry limits. It is nowhere near the dosimetry limits within the liver. This is the 617 over five days. Interesting, you will see some gut excretion.
That is something that was not necessarily anticipated. If you look carefully at the AEs, you will see some GI side effects for the smaller molecule. Occasionally, these can be problematic. It is typically some diarrhea or maybe some abdominal discomfort and kind of cramping. We do see that in the clinic. You see the salivary retention, which is, of course, very, very well known. The kidneys do wash out. You are approaching the dosimetry limits. That has been well shown and well studied. This is the safety data from the Prostac SELECT study. The issues really revolve around the hematologic toxicity. You can see the anemia that is present. In terms of grade 3, grade 4, did not see it in this study. Lymphopenia, which, by the way, is not really clinically relevant.
I mean, we've seen the lymphopenia with a variety of both cytotoxic chemotherapies as well as radiologic therapies. I'll simply say that if you're looking for consequences of lymphopenia for opportunistic infections, you just don't see it. People have labeled it, by the way, as grade 4, implying that it's really dangerous. To the patient, it's not. I've treated many, many, many patients and have never seen any of the pneumocystis or other opportunistic organisms that might accompany lymphopenia. Neutropenia, you can see, is grade 4 only in a very small percentage of patients. Neutropenic fever is not a problem. It doesn't particularly last that long when it does occur. It's a small incidence of grade 4. Yes, you can have some grade 2s and 3s. Clinical consequences from that for the patient are pretty minimal, if not at all.
Thrombocytopenia, you do see some thrombocytopenia in the grade 4. You're probably running about 6% or so. You do get some grade 2s and 3s. It is relatively predictable. I'll show that here in a second. You can get some fatigue. You can have a little bit of nausea. You can have some loss of appetite, probably just due to the circulation and the radioactivity. Not completely clear. Fatigue does accompany this in some patients. The dosing regimen kind of covered it before. It's really just two weeks between treatment. You give infusion one, give infusion two. The infusion goes in over about 5-15 minutes. Pretty short infusion. This has real advantages compared to some of the RLTs, which are going to be using higher doses of the activity here.
The actual amount of radiation administered is much lower than with the typical RLT peptides like 617. You can have a very rapid discharge. You can also turn over your chairs a lot quicker and not occupy the chairs as often. That is advantageous for patients, advantageous for the treating physician. There is an assessment typically around day 11 where you are looking at the potential for hematologic AEs, get a blood draw, have the patient come back in. Overall, the burden for the patient in terms of the overall treatment is pretty simplified. That is a good thing. This is the predictable and relatively consistent findings from the hematocs. If we are looking at the platelet counts, you can see that the depth of the platelet decline is going to predict to a significant degree about the duration of the decline.
If you're sitting grades 0-2, you're back over 150,000 pretty quickly in the majority of patients. That has no consequence. You certainly don't get any bleeding when you're talking about 100,000 platelets. It's just not consequential. If you end up with a grade 4, you see that there can be a little bit of a delay getting back to kind of 100,000. I'm unaware of any bleeding that's actually occurred. There have been some platelet transfusions given. I think that's going to be a rare event. I think for those patients who are used to chemotherapy and physicians who are used to chemotherapy, this is going to be pretty well tolerated and not anticipating much in the way of problems. It's going to be easy for both the patient and the physician. At least that's certainly the hope.
This is what I was mentioning about the cumulative actual amount of radioactivity administered. If you're using the PSMA 617, you're talking 200 millicuries times 6. You're talking basically about 1,200 millicuries. For the antibody, it's 76 millicuries just two. That leads to easier discharge, easier management of the patient who has to worry about sleeping in the same bed with their spouse, being exposed to grandchildren and stuff. The lower dose of radioactivity is going to be a little bit easier on the patient from that perspective, minimal safety requirements. It's actually a pretty dramatic difference between 152 millicuries as opposed to 1,200 millicuries. I think that that could have some advantages as we go forward. These are the dosimetry thresholds that have been calculated.
I'm just going to take you through this quickly. On the right-hand side for the liver thresholds, about 32 gray, salivary about 25, and for the kidney about 23, and bone marrow about 2. These are typically accepted limits, by the way. I think we do have to have dotted lines here because they're debatable and they're limits. Nevertheless, this is what has been guiding some of the dosing, a fair amount of the dosing throughout the globe. This sort of dosimetry limit is what basically killed the SWASH trial, just kind of putting that out there. That has not been very well discussed because it was presented at ESMO, what, two years ago, and it's never been presented since. The antibody is going to be shown here in the histograms. You're going to be looking on the right-hand side in the tall part of the histogram.
That's liver, but nowhere near the threshold. Next to spleen, nowhere near a threshold. Didn't show the spleen threshold, but it's up there. Kidney threshold with a 23 gray, not even close. Lungs, we didn't put it up there, but not even close. Red marrow is 2 gray limit, and you're running about half. Everything else is way below. The bottom line is from the dosimetry estimate perspective, the antibody looks pretty good. If you look at the small molecule, the salivary is getting right up around the threshold. Particularly, by the way, we're not talking about actinium today. If you're talking about actinium with a small molecule like 617, that's where there's going to be trouble.
If you look at the kidneys, and this has been, again, the limitation for some of the dosing that has gone for the PSMA 617, you're approaching the kidney limits when you're giving the 200 millicuries times 6. That's what's prevented people from going higher with the small molecules. The salivaries and the kidneys are the two kind of areas of concern. You do end up with more colon radioactivity than expected. Again, AEs there are not so bad. It's okay. Questions and answers. I think we're going to have the panel. Is that how it's going to work? I'm looking for direction.
Yeah. Pamela, Chris, Richard, and David can join to have a few minutes of questions.
Okay. I don't have four of us. Three of us.
Three, four. Okay.
Test, test.
Hi. My name is Robert Burns from H.C. Wainwright. When we think about the competitive landscape here, obviously, most people will point to the Convergent Therapeutics compound, which incorporates actinium-225 and the exact same targeting moiety. So I'm curious where you see the differentiation there, especially when we take into account that the meta-analysis has shown that actinium-225 has produced more efficacious results than lutetium-177 in MCRPC.
I can comment on that. Convergent is probably going to be targeting the post-lutetium space.
They're working hard to be able to move forward. It turns out that it's creating a little bit of a problem if you haven't started your phase 3 at this point. I think one of the things about the TLX molecule is they've started the phase 3. These phases are getting sort of taken up. It's going to probably end up with some head-to-head trials if you're going to be able to move it up any further. The delay, there's always an advantage to the first mover. I think there's an ability for TLX to slip in on the current phase 3. In the future, those trial designs and control groups are going to change. I don't know if anybody else would like to comment.
Yeah. Perhaps I can complete the answer because they are working with the 591 actinium. That's a good thing. You probably saw in our portfolio that we are also anticipating that with the 592. We have customized the development of this antibody to confer very typical specificities in terms of pharmacokinetic, which will fit perfectly with the alpha therapies, which is the actinium that we will attach to this compound. They are paving the way. They have to demonstrate the efficacy. I'm really confident that we have also a game changer with the 592 actinium. Both lutetium and actinium will coexist in the treatment algorithm, I think, in the future.
All right. We have one here.
Thanks for taking our questions. Andy Shea at William Blair. Two questions, really, about the cumulative dose administered versus cumulative dose absorbed. You kind of quantify the two metrics almost 10 times higher, right, for the small molecule. I'm just curious, obviously, with data coming with the dosimetry, you might get that with an antibody. How correlative is that with the absorbed dose and also the cumulative dose given? How does that, the implications on the clinical front?
You know, love your question. I don't know the answer. Maybe I'll see if somebody else can answer it. You end up with a really remarkable retention time. Please remember that the absorbed dose is the area under the curve. The curve is going to be a little bit different here. The key value to me is a therapeutic ratio. You see the retention. You see the SPECT scans. You do have remarkable retention here. I'm not sure about the exact absorbed dose. I don't know if anybody can answer that.
Yeah. Andy, great question. Nice to see you again. Obviously, as I presented on Prostac Global, part one does have dosimetry, not just what Professor Sartor showed, which was the radiation absorbed dose delivered to the non-target vital tissues, but also, obviously, the tumor compartment itself. That will be part of the data that we'll have very shortly. That's a very interesting piece of the data. I think it's a very important one, together with the safety profile, of course, with the three different combinations. That will be presented.
The second question has to do with the RCC program 250. Very exciting, second program going into the phase 3 or pivotal studies. I'm curious about the potential for an accelerated approval there. There's one example before, the lenvatinib, everolimus phase 2 approval there.
I'm just curious about how you're thinking about the kind of potential speeding up the development path there. Thank you.
Yes.
It's true. We already obtained an accelerated review process, but it was a long time ago. Now the FDA is a little bit more skeptical on accelerating review process on that. Let's see. We have to pave the way with the 250 in renal cell carcinoma. DRKX is explaining the expression of the CA9 in CCRCC. I think we all agree that it's a game changer. For the therapy, we have to run the phase 3 trial and in due time going to the FDA. It's what I can say.
All right. We've got a question here.
Yeah. Brendan Carney from Bureau of Lead Security just wanted to ask on the 23 gray limit to the kidney. I think you mentioned that that's a controversial limit. I'm wondering what you think the possibility of extending beyond that in any near-term scenario.
Yeah. There's been a very active discussion. I don't know if you're aware. There was an FDA SNMMI meeting last May. And you're nodding. Were you there? No. Weren't there. But a lot of it focused on this. Let's talk about 23 gray. Where did it come from? What's the current status and what might change? Number one, it came from the use of EBRT. The risk is 5% of renal failure at five years, which is remarkably low and irrelevant for many of the patients with advanced cancer because they don't live for five years. Just vision trial where we have good data, 15 months. Even in the PSMA 4, which is taxing naive, 24 months. The 23 gray limit begins to crumble when you're treating advanced cancer patients. That's one of the strongest arguments against it. The FDA has a couple of divisions.
One division is the one that everybody is familiar with every day, oncology. Rick Pazdur on down, okay? They're pretty reasonable people. There is another division called DIRM, D-I-R-M, Division for Investigational Radiation Medicine. They're filled with people who believe that they can calculate efficacy and calculate toxicity. They have been imposing some limitations on the entire field that, quite frankly, I don't think are reasonable. There is a debate going on in part. This is interesting. This is a personal interpretation. Not sure I want to be quoted on this. Do not quote me. The oncology division and the DIRM division are not always seeing things eye to eye. Because all the isotopes are passing through DIRM, there is a sign-off there. The limitation is beginning to get some potential relaxation, but it is still a bit of a problem.
The calculators at DIRM are imposing limitations that extend beyond the clinical DLTs. Now, let's talk about how that could be reasonable. I'm sorry. I'm giving a long answer because it's really complicated. It's a great question and a very important question. The DLTs are typically observed over 42 days, 49 days, 56 days, pretty brief period of time. The problem what people are fearing is that there could be deleterious effects long term with the radionuclides four, five, six years down the line, particularly if you're looking at actinium. Let's imagine you're going to be treating neuroendocrine patients, SSTR2s, actiniums. Guess what? This could be a real problem. That risk is a bit unknown. The longer the patient lives, the more likely it is to be problematic. That's where the 23 gray could be more of an issue.
By the way, nobody knows how to really equate particles like betas and alphas as compared to EBRT. The EBRT extrapolations are probably not so great. That's a long answer. Hopefully, I got to the heart of your question.
We're going to take one last question here.
Hey, thanks, David Nierengarten, Woodbush Securities. To kind of follow that and another question on 591, you mentioned the PSMA ad study. We've seen taxanes come and go in earlier lines and later lines. Is there a level of toxicity, a level of efficacy thought that would really change practice to incorporate PSMA 617 into frontline use, or do you think it's more likely still going to be relegated a little bit later just because of the toxicity profile and cumulative radiation exposure potential in the longer-lived patients or patients with longer likely lifespans?
Yeah. You have a couple of interesting points rolled into there. If you move the 617 earlier, and I think it's likely to go earlier, there'll be many questions about the tolerability of the chemotherapy down the line. I can say that I've looked at this to the very best of my abilities. I can say so far, there doesn't appear to be much in the way of chemotherapy distinctions, like in the randomized trial. PSMA 4, we do have the follow-up. We can look at it. It appears to be equal between the two arms. We can't really pick it out, but it may be a little shortened in duration. One of the things I do like about the Prostac Global trial is you're building in the dose of Taxol to both arms.
By the way, one of the things that the FDA has moved away from is using hormones only, as PSMA 4 did in the control arm. When you put the dose of Taxol into the control arm, you introduce a conflicting and potentially mitigating factor because typically the RPFS and the OS in the dose of Taxol treated patients are going to be better than the ARPI, right? Okay. Here you bring the ARPI into the isotopic arm, and you bring the dose of Taxol into the isotopic arm. Now, is the dose going to be able to be delivered in the same way, same effectiveness, same duration? I think they're questions. For the hormones, there's not a question. I do believe that there is potential synergy between the hormonal, even in the second line setting of RP, plus the isotope as compared to the isotope alone.
You get a little extra boost, in my opinion. You probably saw the NZP trial if you follow the space. Yeah. There was an unequivocal benefit of the combination of the enzalutamide and the PSMA 617. I think you'll be able to take advantage of some of that synergy here, which was missing in the PSMA 4 trial. By the way, why was it missing in the PSMA 4 trial? The original design was very similar to the vision trial brought forward with the standard of care, being able to include ARPI. FDA nixed it. They said no. It was monotherapy as a result of the FDA feedback. Here, the FDA feedback has allowed it. I think it'll be advantageous to the trial design.
Thank you. So we're just going to take.
I have one more thing.
Oh, sorry.
Really, really good questions. These are thoughtful questions.
Appreciate it. We're just going to take a very quick break, five minutes. If I can have you back in here at 10:45 for just a chance to grab a coffee, and we'll continue on with the presentation.
[Fore ign l a nguage]
Take our seats, please. Dr. Liu. I hope that biopsy needle's safely stashed somewhere. Yeah? Good. All right. I think we're into the second half here, Kai. I have the real pleasure of moving into the—there was actually a very good question about the Alpha program. It was just here, I think. And the comparison with Convergent, there are Alpha programs. I think the TLX Alpha program is a very exciting program that I'm really looking forward to talking to her about briefly. This is our TLX592 asset in prostate cancer, which is an actinium-225 labeled engineered antibody. It is a different antibody from the father antibody, TLX591, which in its most simple terms, it's very similar to TLX591, that antibody, except that it possesses pharmacokinetics and a biodistribution pattern that clears from the circulation faster.
What that really means is that there's fewer alpha decay events that occur in the blood circulation, while the modified antibody that's been re-engineered retains a very similar tumor targeting and retention profile to the father antibody, TLX591. If we look at the two main differences between 592 and 591, I think it's important to sort of have an appreciation for these. The first of the differences is that the 592 antibody has been FC engineered. That means that it rapidly clears faster from the circulation. Because of the choice of payload for this drug candidate, what we want is to remove the excess radiation out of the circulation reasonably quickly, while also balancing and ensuring that there's enough circulation time for it to target, localize, and internalize the payload into the prostate cancer cells. That's the first difference.
The second difference, of course, is an obvious one, and that is that the payload itself is different. This asset delivers actinium-225 instead of lutetium-177. Actinium is an alpha emitter that has a very potent but high-energy localized deposition of radiation. It really only—its path length is really only a few cells deep, unlike a beta emission, which goes millimeters and possibly in a higher energy beta like yttrium. It might go over a centimeter in distance. This asset delivers actinium instead of lutetium. This may lend itself to being more suitable for treating early-stage prostate cancer in men with a lower disease burden or disease volume. In general, beta emitters, we believe, like lutetium or yttrium-90 or iodine-131, are ideal for effectively irradiating larger bulkier tumors, whereas alphas lend themselves to be more suitable for localized small-volume disease. TLX591, it is still hepatically cleared.
Professor Sartor showed the profile for lutetium-591, but 592 is still hepatically cleared. This is very important because alpha emitters should be really kept away from the kidneys and not filtered or extracted from the circulation via urinary excretion by the kidneys into the bladder and then out of the body that way. The liver, as we saw in those bar histograms, is a much more radiation-resistant organ. I recently, earlier this year, January, had the pleasure of the honor of actually reporting the results from our earlier Cupid study. This is a phase one study presented to the CISCO GU, which evaluated the biodistribution and the dose to the organs of the copper-64 labeled imaging version. This is the imaging version of this asset at escalating mass doses that range from 2 milligrams up to 20 milligrams. This study enrolled 11 patients.
It was a phase one trial with advanced prostate cancer comprising four groups. The patients in groups one to three had low-volume disease, which we defined as five or fewer lesions, really oligometastatic disease. Group four had higher tumor burden, which we defined as having 10 or more metastatic lesions. What this study was able to demonstrate was that in terms of pharmacokinetics of 592, the agent clears from the blood much more rapidly than 591. To put some numbers to it, the blood clearance half-life of around 20 hours accompanied this asset compared to about 34 hours for 591. It otherwise had a very similar biodistribution pattern. 592's biological half-life in the blood showed a clear mass-dose relationship.
The more antibody mass that was present, the more it was pushed out of the liver, which is the clearance organ, and its residence time in the circulation was higher. If we look at the images in the panel on the right, this is one of the representative patients from the Cupid study. This is the patient who, on the left-hand panel of those images, obviously has prostate cancer that has spread to his skeleton. This is lit up using Illuccix, a Gallium-68 PSMA PET, in his lumbar L3 lumbar vertebral body. That's in the lower part of the back. On the right-hand panel, you can see the same targeting of this tumor deposit with TLX592, albeit in this case, the antibody's been labeled with copper-64, so you can visualize where the antibody has gone. You can't do that to the same extent with actinium.
To conclude, really, the Cupid study, what do you take from this study? The Cupid study ultimately constitutes a successful proof of concept of this asset. We really look forward to moving into a phase one first-in-human study with the actinium version of TLX592 in the second half of this year. With that quick fly-through, I'd like to invite Pamela up to move into the 90 asset. Over to you.
Thank you, David. That's all right. Thank you. I'm Pamela Habib, Chief Medical Officer for Therapeutics. I'll be talking about TLX90 and TLX250 today. I'll start with TLX90. This is our Samarium-153 labeled DOTMP agent. This is being developed to treat the pain palliation in patients that have osteoblastic metastatic disease. This fits in nicely with our urologic platform because frequently, the patients that have osteoblastic metastatic disease have prostate cancer. Another common patient population that presents with osteoblastic metastatic disease is the breast cancer patient population. We acquired this molecule from another company. It's a proven isotope platform. We've now attached a novel chelator to the isotope. This is expected to lower the bone marrow dose and to have increased tolerability for the patients. As I mentioned, we're developing it for pain palliation.
There is a potential for also treatment of the osteoblastic metastases in the future development pathway and also for multiple doses. Currently, we're developing this as a single-dose agent, but there is a potential in the future for multiple dose regimens as well. We have early studies with this agent where we have seen improved quality of life in patients with diffuse metastatic disease. I'll talk about that data a little bit later on. Currently, we're in the process of designing a phase one bridging study. As I mentioned, we acquired this asset from before designing a phase one bridging study, which we feel will accelerate our path to a registrational trial in the future. We're planning to commence this phase one bridging study later this year. On the right-hand side of the slide, you can see an image.
These are the types of images as radiologists that we love to see. This is a patient with metastatic prostate cancer. He received samarium therapy for his pain. As you can see, his entire left side, which is on the right side of the image, but it's the patient's left pelvis and his left femur, are lighting up more than the other side. This gives us confidence that the samarium that was injected into the blood has made its way to the lesions in the pelvis that we were trying to treat. There is a significant unmet need in these patients that have diffuse metastatic disease. Any clinician that has spoken with a patient who has mets all over his body will tell you these patients are in tremendous pain. They wake up with pain. They walk around with pain.
They're sitting in a chair, and they just feel pain everywhere. There are treatment options, but there's definitely room for improvement. There are opioids, but as we all know, there is a potential for dependency with opioids. There is steroid therapy. There are bisphosphonates, but they all come with their own side effects, and they don't offer complete relief. There's definitely room for improvement. EBRT, or external beam radiation therapy, is also an option, but that's difficult logistically. In patients with metastatic disease all over the body, it's a little bit less suited for that. It's more suited for limited numbers of lesions. 80%-90% of patients with metastatic prostate cancer will eventually have a bone lesion. Similarly, with breast cancer, 65%-75% of metastatic patients will eventually have a bone lesion.
In terms of the immediate market opportunity, there are about 30,000 patients that have late-line prostate cancer or stage four breast cancer that are expected to progress. I mentioned that we have some data from previous studies. In our earlier phase one studies, we saw that all patients experienced greater than 20% reduction in their pain scores within six weeks. They also anecdotally talked about just an overall improvement in the ability to move around and to walk around because they're feeling reduced pain. There is also an opportunity to decrease the dependency on opioid or other analgesic use. In terms of the safety profile, we did not see any dose-limiting toxicities in any of the patients. The hematologic toxicities that we saw were mild and transient. We did not see any clinically significant impact on liver function or kidney function.
Of the two adverse events that we saw, they were both deemed to be isolated events. One was thrombocytopenia in a patient that had metastatic disease throughout the entire skeleton. The second patient who developed changes in his EKG had pre-existing cardiac abnormalities. That brings me to the phase one bridging study that I mentioned previously, our SOLIS trial. This is being designed as a two-part study where part A will be the dose escalation phase, and we will have three different activity levels that we will recruit in a parallel fashion. Part B will be the dose expansion where we will select two of the doses from part A and then expand on those with the primary endpoint of determining the optimal biologic dose depending on the safety profile as well as the reduction in pain score.
The 16-week time frame we feel will allow an opportunity for a relatively shorter clinical trial compared to the longer trials that look at overall survival or PFS in terms of efficacy because we're expecting to see the reduction in pain develop within 16 weeks after receiving the injection. Now I'll move on to TLX250. TLX250 is lutetium-labeled girentuximab, which is a CA9 targeting agent, as you heard mentioned previously as well. This is a validated target. We already know that it's expressed in greater than 90% of clear cell renal cell carcinoma. You heard the Zircaix trial mentioned this morning. It's also been shown to be expressed in a number of different solid tumors in addition to clear cell renal cell carcinoma.
We have phase one and phase two studies that have already demonstrated durable disease control with this agent as a monotherapy with a manageable safety profile. I'll talk about that a little bit on the next slide. There is, in general, a high unmet need in this advanced patient population in the third and fourth line. On the right-hand side, you can see images again. This is a patient with metastatic advanced renal cell carcinoma. The top row shows the initial images that they had. They received a zirconium-labeled girentuximab scan. You can see intense activity in the sacrum where there was a metastatic lesion.
After three cycles of therapy with lutetium-girentuximab, you can see on the bottom row that the amount of activity in that sacral lesion has significantly decreased, again, giving us confidence that the injected therapy has made its way to the bone lesion. The earlier studies that I mentioned, there is a phase one and a phase two trial that were performed with this agent as a monotherapy. The phase one study was a dose escalation study that determined the maximum tolerated dose after evaluating this in 23 patients who had advanced clear cell renal cell carcinoma. The phase two study expanded on this and dosed an additional 14 patients at the maximum tolerated dose. In all patients, we saw a favorable safety profile. We saw the potential to stabilize metastatic disease in this advanced patient population with monotherapy.
In this patient population, which has rapidly progressive disease, even disease stabilization is a positive outcome. The disease control rate we saw in the phase I trial was 74%. We saw a median PFS of 8.1 months in this patient population who had a different pretreatment profile, but the results are still very encouraging. On the right-hand side, this is a patient who has diffuse metastatic disease from clear cell renal cell carcinoma. They received lutetium-girentuximab. On the SPECT CT that was performed after the therapy, you can see numerous metastatic lesions throughout the body in the brain and the chest and the abdomen, all lighting up, all giving us confidence that the therapy made it to these lesions. This slide shows the overall complexity of the treatment pathway for these patients.
We wanted to really look at this in detail and determine where we want to focus our efforts in our development of this compound. When a patient first presents, if they have localized disease, they may only get surgery at that time, and they may not need any type of medication. However, if they have intermediate or poor risk, or they recur, that's when they start to receive different types of medications. In the first line, that may be an immunotherapy, such as an immune checkpoint inhibitor. This may also be a tyrosine kinase inhibitor, or it may be a combination of the two, or perhaps two different immune checkpoint inhibitors. Once they get into second line and beyond, the treatment options become very limited.
Although there are some newer agents, there's belsudafen, there's everolimus, and different physicians try different combinations of therapies, we really haven't seen significant overall survival improvement in the second line and beyond. That's really why we are focusing our development in two different areas. First, I'll talk about on the next slide in detail of our trials. Because there's such an interest in combination therapy in first and second line, we are focusing on a number of trials looking at various combinations of TLX250 and other classes of drugs. We're also looking at the third line beyond because these patients really have no other option. They're very sick. There are no treatments that are consistently showing a positive benefit. We are focusing our pivotal trial in this monotherapy for advanced third and fourth line patients with clear cell renal cell carcinoma.
This is an overview of the trials that we currently have exploring TLX250. I mentioned the combination therapies. We have StarLite One, which is currently enrolling patients. This is looking at treatment-naive patients who present with advanced disease. The patients are receiving TLX250 in combination with an immune checkpoint inhibitor, nivolumab, and a tyrosine kinase inhibitor, cabozantinib. StarLite Two is also enrolling patients. This is looking at a more advanced patient population. These patients have already received one immune checkpoint inhibitor, and now they're presenting with disease progression. We've already determined the maximum tolerated dose in this trial, and it is currently enrolling an expansion cohort at this maximum tolerated dose. StarStruck is another combination trial that we have that is enrolling patients. This is looking at not only clear cell renal cell carcinoma, but any solid tumor that expresses CA9.
This is treating with TLX250 in combination with peposertib, which is a DNA damage repair inhibitor. Finally, the pivotal study, which I mentioned previously. We are focusing on advanced late-stage third and fourth line beyond patients. This study is going to be a monotherapy, and it is currently being designed, and we are planning to commence it later on this year. That rounds out our urology portfolio. I will now hand it back to David Cade. Thank you.
Thanks, Pamela.
Nice to be back up here. I think this is my third time. This is the type of asset that, as an industry physician, is critically important. This is where, as an industry physician, on behalf of my colleagues, I feel that we have the potential to make major inroads into a malignancy that's somewhat catastrophic in its diagnosis. Dr. DeGroot is going to go into the history of this disease and, more importantly, the history of the development of assets for this disease. There's not a lot of history to tell, I think, as we'll see a bit later on. When you've got an asset like this that's showing promise, it really is a very sort of exciting period of time in what we do. I'm going to start and, again, introduce our neurooncology program before handing over to Dr.
John DeGroot, who will delve into the program in more detail. Dr. DeGroot has come across to New York from the University of California, San Francisco. This is our TLX101 asset, which is an Iodine-131 labeled small molecule. That's a very important point. I think Chris talked earlier about being agnostic to isotopes and to the delivery vector. That's important because it's a small molecule and therefore able to cross the blood-brain barrier and therefore then become able to target the L-type amino acid transporter, which we know as LAT1. This is a very well-validated target. It's highly expressed in malignancies of the central nervous system, including glioblastoma.
While I'll go into the clinical studies that have been undertaken with this asset in a moment, it's important to note that its safety profile and its tolerability when administered in combination with conventional external beam radiation therapy has been demonstrated, as has encouraging preliminary efficacy results, including quite extended survival durations in prior studies. Given the absence of effective options for glioblastoma, we are very pleased that this agent has been granted an orphan drug designation both in the United States and in Europe for the treatment of gliomas. Our initial focus with TLX101 is going to be in glioblastoma, which is the most common and aggressive form of primary brain cancer, with approaching almost 15,000 new diagnoses made in the United States each year.
If we look at, I'll try to simplify it for you, but if we look at the flow diagram on the right of those patients diagnosed with glioblastoma, if we say there are 100 patients diagnosed, about 90 of those 100 will be well enough and will be willing to undergo initial first-line treatment, which comprises maximal surgical resection followed by adjuvant chemoradiotherapy. That is very, very well accepted and very conventional. What then typically happens to those 90 initial patients that then get treated is that, on average, after an elapsed period of seven or eight months, 90% of those patients will experience disease recurrence. At this point, really, there is no settled-upon established second-line treatment that we would offer universally. If we look at the NCCN guidelines, it tells you the whole story.
A clinical trial is a recommended option for treating these patients with recurrent disease. We see that while the five-year survival of patients with glioblastoma remains stubbornly stuck at just under 5%, so five-year survival under 5%, a key challenge for potential new therapies that we might want to bring to these patients is that crossing the blood-brain barrier is a challenge. It limits the sort of the pool of potential systemic options that we might want to deploy in these patients. This slide, I think, really nicely summarizes the development pathway for TLX101, both prior and future planned. While I won't go into too much detail, as Dr. DeGroot will discuss the clinical trial results in more detail in his session, there are two key points I think that are important to take away from this slide.
Firstly, the data from prior studies, IPACS1 and IPACS LINZ, in the recurrent disease setting demonstrated an acceptable safety profile as well as really quite encouraging overall survival durations, both from the time of initial or first diagnosis as well as from the time from initiation of treatment. These range in the range of 12-13 months and 23-32 months, respectively. The second thing to take away from this is that we have a pivotal registration-enabling study for this asset, which we call IPACS Bright. That study is expected to open for patient enrollment in the second half of this year. Dr. DeGroot is going to go into the study design in a bit more detail shortly. Finally, turning to our targeted alpha approach in neurooncology, there are two very important takeaways from this slide.
I think the first of those is that TLX102 uses an identical targeting vector as TLX101, but it's labeled with astatine-211, which is a short half-life alpha emitter. I described earlier the key properties of alpha emitters: high energy, very short path length, which may help overcome some of the radiation resistance that we commonly see in cancers of the central nervous system. We believe the combination of TLX101 with its longer beta path length, iodine-131 radionuclide, may be well-suited for patients with larger tumors, while TLX102 may be well-suited to patients with smaller and more diffuse disease where that short path length and high energy deposition of astatine-211 is more ideal.
Secondly, the key takeaway here is that a recent case report from our collaborators at the University Medical Center Utrecht, which is in the Netherlands, published, I think, a very important piece of research. It was a single-patient case study, but they are continuing to examine this approach. This patient received TLX101 via intra-arterial administration, so not systemic IV administration, which is the way radiopharmaceuticals are typically given, but via the middle cerebral artery in this instance administered via a temporary catheter. This represented proof of concept that this administration method is safe and it's feasible and can potentially deliver a much higher radiation dose to the tumor. We do intend to further those studies and evaluate this administration approach in a first-in-human study in glioblastoma.
With that brief introduction, I have great pleasure in welcoming to the podium here Dr. John DeGroot. Over to you.
Thank you. Thank you, TLX, for inviting me to talk. Thank you for everybody in the room for taking a few minutes to actually think about glioblastoma. I think David set it up very nicely, sort of describing our current state of affairs, which is not great. Despite really intensive research, a lot of great discoveries in the genomics, a lot of advancements in technologies, hundreds and hundreds of clinical trials, we've basically had two drugs that have been approved for this disease in the last 25 years. One of those drugs, bevacizumab, did not actually lead to an improvement in overall survival. We really are in a sort of a very desperate sort of place and very, very excited about the potential for other forms of radiotherapy. You saw the flow diagram.
This is sort of in additional words, really, this is the evidence-based management of adult glioblastoma, so maximal safe surgical resection, external beam radiation with concurrent and adjuvant temozolomide, that one drug that has been shown to improve overall survival. At recurrence, really, there is no standard of care. Bevacizumab is approved for that use, and we do use it, but it's not great and doesn't provide a survival benefit. Tumor treating fields, these are alternating electrical currents. This company called Novocure has done some studies and showing sort of a very modest benefit in recurrent and newly diagnosed disease. Uptake and use in the community actually is really quite low. As you heard, this is a very rare disease, maybe 15,000 patients diagnosed every year, but it really does hit sort of patients at the prime of their life.
If you look at the number of sort of productive years of life loss, it is really, really quite devastating to patients and their families. The five-year survival rates, as you heard, were less than 5%, and the three-year survival rates hover around 10%-12%. What is LAT1? LAT1 is a large amino acid transporter that is expressed in the brain. You heard about this from David. One of the biggest challenges, I think, in developing effective therapies for any primary brain tumor is getting the drug across the blood-brain barrier. This transporter is expressed on both sides of the blood vessels. It allows the drug to get across the luminal surface and then across the abluminal surface, actually into the brain and the tumor. We know it gets across the blood-brain barrier quite well.
We know this target is also highly expressed on the cell surface of gliomas and other primary brain tumors. Its overexpression is associated with worse prognosis and more aggressive disease. As you heard, TLX101 is really a potential first-in-class systemic radiotherapy. It can be given by IV administration. It does bind to the LAT1 receptor on the tumor cell, gets internalized, and then the payload, the I-131, induces cytotoxic radiation cell death. We know it's potentially synergistic with external beam radiation, both from preclinical and clinical studies that I'll describe in a second. As I mentioned, one of the big benefits is it does get across the blood-brain barrier, and it can be given outpatient through IV administration and is shown to be quite safe. This is a case report, essentially a patient who received TLX101 on a compassionate use basis.
I think this really describes sort of the potential that we would see with this agent. This patient was treated by Dr. Bratt at the University Medical Center in Utrecht in the Netherlands. This is a 59-year-old gentleman who had newly diagnosed glioblastoma and went through standard of care treatment and then had recurrence there, which you can see sort of at the beginning of last year. The patient received the TLX101 and received four doses. I think it was 5 GBQ every 28 days. You can see on the panel on the far left after two doses showing a significant reduction in contrast enhancement. As you go further over on the right in the third panel and the fourth panel, you do not have to be a radiologist to be able to see really quite significant reduction in the contrast enhancement.
That's associated with the FET/PET showing reduction in metabolic activity as well. Both imaging and metabolic imaging confirmation of response, which is really quite exciting and quite impressive. IPACS1 is sort of the legacy study. This was a trial combining TLX101 with external beam radiation. There were three cohorts in this phase one study in patients with first recurrence of glioblastoma. There was a single dose prior to external beam radiation. There was a second arm looking at fractionated TLX101 in parallel with external beam radiation. The third arm was fractionated TLX101 with sequential external beam radiation. All of the different dosing regimens were well tolerated. The radiation doses were confirmed with no radiation-associated toxicities and really some very early impressive results showing that 44% of patients had stable disease at three months.
If you looked at the metabolic activity using FET/PET, 60% of patients actually had stable disease based on the peak uptake. If you looked at sort of the mean lesion uptakes, it was even higher than that at 78%. Survival outcomes were also impressive: PFS of 4.3 months, but a median overall survival of 23 months from the time of diagnosis, which is very impressive compared to sort of what we would typically see at 14-16 months. IPACS LINZ, this is an investigator-initiated study for patients with first or second recurrence of glioblastoma. There were a total of eight patients treated. These results were just presented a couple of months ago. Some of these patients had very poor prognosis, obviously recurrent disease, but also were MGMT unmethylated, which we know is associated with worse outcome.
These patients received TLX101 with external beam radiation and with adaptive dosing regimens up to 6 GBQ, which was well tolerated and no adverse events were noted. The top-line results really are very impressive if you look at the survival outcomes, median overall survival of 32 months from initial diagnosis, again, compared to what we might expect to see of 14-16 months. Median overall survival from the time of treatment on protocol was 12.4 months. Typically what we would see is overall survival somewhere between six to nine months in that group of patients. This has given us confidence to develop a registration-enabling trial. This is a pivotal global registration trial in recurrent glioblastoma. This would be for adults with first recurrence of glioblastoma.
There'll be sort of two parts to it: a dosimetry safety part where patients would be treated with TLX101 with Lumustine. This has a built-in de-escalation void design if needed. Once the safe dose is identified, there'll be a safety cohort expansion. Whoops. After data review, knowing that the dose is safe and tolerable and there is evidence of efficacy, that would open up into a randomized registration trial for patients who receive either TLX101 with Lumustine or Lumustine monotherapy, which is sort of standard of care for patients with recurrent glioblastoma. This study is currently under ethics review in Australia. It is to be open in Australia and the EU, with plans to open up in the U.S. for part two.
I didn't go into the imaging very much, but I would just say that this is a really amazing opportunity to use the diagnostic FET/PET for patients' eligibility on this trial. One of the challenges that we face in this disease is looking at an MRI scan, seeing contrast enhancement, and actually trying to figure out what that means. All contrast enhancement is not tumor. The FET/PET really gives us a lot more confidence that what we're seeing is recurrent disease. Those patients, I think, would give us a lot more confidence to enroll in the trial. We also will be using FET/PET to look at responses and hopefully sort of validating the new PET/RANO criteria that were just developed in the last year. I think that's my last slide. With that, pass it off.
Thank you, Dr. DeGroot. I think that I would share with you that it's one of my favorite compounds because it's once in a lifetime that you can work on a disease like that where there's no treatment, and you can really bring hope. These amazing prior results, I would say pre-validated results with the 30-month OS, where all the patients usually are disappearing in 15 months, it's amazing. I feel the pain with you because we provided you more than 100 slides, plenty of information. I promise I will have only five slides before the end of the session. I asked for switch off the air conditioning because perhaps I'm European, but I was freezing. I don't know if it's the case for you.
Let's come back on what we call internally the pan-tumor approach with the two targets, namely the CA9 and the FAP. That's the near future for Telix also in terms of therapy. We have the CA9. We have extensively talked about CA9 for renal cell carcinoma, but CA9 is much more than that. It's a marker for the tumor hypoxia. The second compound that I would like to discuss with you today is the FAP compound, the FAP target that is a marker of the fibroblast and more precisely of the tumor microenvironment. These two markers are expressed in a large variety of solid oncologic tumors, as you can see on the screen. What does it mean concretely? What about first the CA9 target?
It's well known, and I speak under the control of the physicians, that the CA9 expression results in what we call a poor overall survival prognostic with shorter disease-free survival and a great risk of recurrence and metastasis. How it is translated for the physicians? It means that unfortunately, when they have patients with a high expression of CA9, they will face chemo resistance, resistance to the recent immunotherapy drugs, and even time to time radioresistance. That's why we have identified this target as a potential great opportunity for radiopharma treatments because we can bring the activity and the destruction effect of the alpha isotopes like the actinium directly to the tumor cells, which are expressing this resistance. That's the reason why we have the ambition, and we will start a phase one clinical trial with the new compound 252 attached with an actinium isotope.
We ambition to do a pan-tumor clinical trial phase one because, as I was mentioning, there's a lot of solid tumor expressing, and we have selected five tumors, and you will see the first one, CCRCC, but mesothelioma, bladder, triple negative breast cancer, and ovarian. All these diseases are critical, and I know the physicians treating oncology patients, which are resistant to the classical treatment, will appreciate. The idea is to plan and to commence the clinical trial beginning of 2026. We will use our Zircaix compound for patient selection and eligibility for the treatment. We will have a cohort dose escalation with two cohorts. For the first time in the radiopharma world, we are going to customize what my colleague was presenting in terms of dose adaptation and personalized treatment for the patients according to the dosimetry and the data coming from the imaging compound.
That's very important for the future. I know many physicians and many nuclear physicians are expecting this novelty in the treatment of the radiopharma. My second target is the FAP. The FAP is not a new kid on the block, I would say, because if you look on the right part of the slides, the Society of Nuclear Medicine has elected the gallium FAPI image that you can see as image of the year, almost six years ago. The diagnostic part has been already confirmed. As you can see, you have a large expression in many solid tumors because, once again, we are here addressing the stroma, the microenvironment of the tumors. I would say that if I would have to characterize or give some properties of this target, three points. It's broadly expressed in the tumor microenvironment.
It's even cherry on the cake time to time expressed on the tumor cells directly. Specifically, sarcoma, ovarian, and pancreatic are expressing the FAP receptors. It's not expressed in most normal adult tissue. You will agree with me that that confers key priorities for radiopharma treatment. That's exactly the reason why we have integrated in our portfolio recently these FAP compounds. Why I say compounds with an S? It's because we internalized with a recent acquisition from the University of Essen in Germany. It's not because I'm European, but a lot of good things are coming from Europe in terms of radiopharma business. We acquired these two compounds, the gallium FAPI, so it's FAP inhibitor, and lutetium FAPI. These are clinically validated targets.
I'm used to say that it's fantastic in radiopharma because we can de-risk acquisitions like that because we have already patients which have been dosed in terms of diagnostic. We have more than 550 patients which have been diagnosed with the gallium FAPI. We have more than 150 patients which have been treated with this compound in Germany and in India. There are several publications to support that. Our ambition now is really to bring that to clinic. We will initiate beginning of 2026 two clinical trials, a pan-cancer basket study, phase one, and also a lead indication based on the data that we have collected from these different sites where the patients have been treated. It reminds me the story for those of you which are following radiopharma since a while, the Lutathera story and the Pluvicto story was exactly the same.
We are collecting data from the expanded access program or clinical trial patchwork and going to the FDA to negotiate a phase three trial that will authorize the registration of the trials. That is exactly the ambition that we have behind these two new compounds. Let me now give the words to my CEO and founder, Chris, to finalize the presentation.
Thanks very much, Richard. I think aside from the fact that we bombarded you with slides today, I think the really good thing is that you did not have to listen to me all morning. That is a refreshing trade-off. Maybe just to wrap up, I think the goal for today was really just to give you a sense of the breadth of what is going on inside the company. Clearly, from an analyst perspective, I think when we get together, we sort of tend to deep dive into one or two specific things, but we never get a chance to have the broad overview. This is the opportunity that we take to force that discussion around the breadth of what is going on inside the company. Clearly, we do have priority areas.
The priority areas are the commercial programs, the phase three trial, really getting some of the renal cancer data out in the next few months. These are things that are the priorities for the company. Also, you can see there's a number of clinical activities that are going to come into prominence in the second half of this year. I think if you're a skeptic in the room, you say, "Wow, there's a lot that's coming in the second half," but there actually is a lot. We have been having regulator consultations. We've been getting packages together. There'll be a lot to talk about in the coming months. Just to wrap up, I think I've really given a slide, but just to reiterate, our commercial team is growing and executing really well.
Notwithstanding the odd speed bump here and there, we see this really great progress towards a multi-product, multi-jurisdiction revenue stream. We continue to grow our revenues well. Of course, from your perspective, that means that we have the firepower to invest in this great pipeline. You can see the bench strength that we have. Last year, on the back end of our decision to walk away from a US IPO, we really sat down as a management team and thought about how do we restructure the company to be more clearly delineated between commercial precision medicine activity and therapeutics.
What this has really led to is kind of doubling down strategically on our therapeutic strategy, really focusing that investment to make sure that we start to really show the patient outcomes that have been bubbling away in the background for the last year or two, but now are really starting to get some momentum. Last of all, there's not much point in talking about delivering these therapeutic assets to the market if we do not have the supply chain and distribution capability behind it. Again, that's not something you can do and wake up on the eve of a commercial product launch and go, "Gee, it'd be really nice to have a supply chain for radiopharmaceutical." You've actually got to plan that well in advance. Just as an illustration point, we just got the GMP license for our Cinef facility two weeks ago.
That took four and a half years to go from designing what the facility would look like to having the ability to ship a hot dose out of that facility. There is lead time. There is planning. There is risk management involved in getting a radiopharmaceutical product out to the end. There are just not enough companies thinking about that when they have assets in sort of mid-stage development. I think, again, that is a very differentiated part of the company. Anyway, I'll stop there. Thank you again so much for being here. Obviously, we're available. We're going to do a Q&A to wrap up just in case you've got any lingering questions. Again, thank you for your time commitment to be here today. It's really appreciated. Fire away.
Yeah.
Come on, guys.
Basically, it's a question actually to Dr. Liu and the computer behind. Just obviously, heroic effort, really kind of moving PSMA tech to the diagnostic setting. I'm curious about the uptake. It can be positive results for those looking forward to the future, but do you need outcomes or significant uptake in order to actually understand from biopsy, conventional imaging to kind of a head-dominated schema or workup?
Sure. I think perhaps to address the issue of the adoption curve, there's a combination of winning the hearts and minds of the physicians as well as the operationalization of it. There were some discussions that we were having about the potential health economic outcomes, discussions about how this could potentially lay out. If it's okay with you, I'd actually like to ask Kevin a comment on that because really the evidence will speak for itself and the adoption from the academic and physician community will naturally follow suit. We're very confident in the clinical trial protocol that it will be transformative as a screening and complementary to, sorry, got distracted from it, that this will act as a revised kind of version of screening.
I think the access and the commercialization operationalization is something that the commercial teams have actually thought out. Kevin, would you mind commenting on that?
Yeah. As long as the data passes the hurdle, then it's payers, guidelines, and patients, right? You saw the graphic illustration we tried to use of a choice that we're going to have in the future, we believe. Guidelines, payers, and patients will drive that through that advocacy and results. That's the plan that we put together.
If I could chime in on that, I do not think for this indication, given the size and the impact on the healthcare system, that just relying on kind of guideline evolution is going to actually cut it. I think payers are going to want to see the pharmacoeconomic benefit. That is why it is worth our while investing in the study. It is not just about showing our continued leadership in PSMA imaging. There are clearly other products that are coming in behind. The space is going to become more competitive. It is really whoever continues to push the formal label objectives of the asset and demonstrates the pharmacoeconomic benefit. Those are the actors that are going to deliver the best outcomes for patients and continue to own the space. I think it is really important that we do that.
Can I ask one question about that? Given that you're at the forefront of kind of diagnostic imaging in this early stage of patients, does that leave the burden to yourselves in order to prove up more data that may be required in future?
Definitely. We also have the benefit of the label, and we also have the benefit of the dialogue with the payer. There is no pain, no gain. I think that we've been very, because of the momentum of PSMA, we've been very lucky to see guideline—I wouldn't call it expansion, but it's really flexing what are the eligible patient definitions in each area of care. I think a good example of where guidelines will really continue to evolve is in treatment monitoring and treatment progression, because that's a place where many, many clinical trials are being run. I mean, we don't put up, unlike some of our competitors, we don't put up a slide of logos of companies that we're providing PSMA imaging to, although we are the only company that really does it globally. You can imagine we're quite busy.
We provide doses every day to clinical trials. That collective clinical experience will move guidelines, I think, for treatment monitoring, treatment response, and outside of radiopharma because this is being used in many other prostate cancer drugs as well. I think in that frontline early patient management piece, you can't leave that up to chance. You're going to have to demonstrate it clinically. As I said, I think it's really worth it for patients, and it's really worth it for the company to do that.
Hi. Nicole Germino at Truist Securities. Two questions, one for Richard and one for Dr. Sartor. Richard, can you talk about the limitations of FAP as a target and your rationale for how you feel confident in your molecule getting to the tumor? How do you get through the stroma given what we've seen from the recent failures? How do you know you're getting good tumor retention? For Dr. Sartor, from ASCO, we saw some early and potentially promising data from ADCs, bispecifics, EZH2 inhibitors, and prostate cancer. One advantage of those is that they're relatively off the shelf. How are you evaluating the competitive landscape in prostate cancer, especially the competitive landscape in the frontline setting in MCRPC?
Competitive landscape is really interesting. The surprise, I think, was the KLK2 data from J&J, which was outstanding. They're going to be launching multiple phase threes, and it looks like a good agent. The key thing is on most of the bispecifics, like the steep one, you end up with this CRS risk that is very, very real. Plus, they have the musculoskeletal risk down the line. It doesn't appear that KLK2 has that risk, and they're discharging after two hours. That's really pretty cool. That's a good product. We're going to need to see a little more data. What we saw was a phase one. There's a big phase one, 174 patients. I'm watching that very, very carefully. I'll be on the steering committee for one of those phase threes. Keeping a close eye.
Yeah. And maybe just to add from a company perspective, I mean, now, just because we have a moiety that targets the same target, I think if you go and talk to J&J is actually a great example. They take a pan-modality approach. They take a target that they really like. In fact, that target's a great example. They say, "We're going to do a cell therapy. We're going to do an ADC. We're going to do a radiopharmaceutical." You'll find that the mechanism of action is so different across those things. What we really expect to see is to see synergistic effects. Radiation is a substrate to so many other treatment modalities. I think, and I've said it in public many times before, I think 10 years from now, we'll look back and we'll say, "Radiobiology is something that works with immunotherapies.
It works with DNA PK, DNA damage repair, very naturally, of course. I think that to get maximum patient durability, you're going to still take a multimodal approach. By the way, that's the way oncology is moving. The reason why it's taken a long time for people to get comfortable with the risk-benefit profile of 591, for example, is the whole message behind that is it's about how do you bring radiopharmaceuticals into the orbit of a medical oncologist because now it's an interdisciplinary treatment team that's delivering outcomes. The target is not the important thing. It's the different modalities that you have at your disposal to maximize treatment durability.
Chris, thanks for raising that. I was going to mention one more thing there. The question I have on the KLK2 bispecific is durability. I don't want to get into T-cell exhaustion because I'm not an immunology type, but there appears to be some type of diminution with time. I think to Chris's point, the opportunity for the combination therapies is going to rise. It'd be speculative at this point to say what you might combine with. It happened with the radioiodine therapies, but you're raising some really good points. We need to look at durability as the real issue here.
Richard, do you want to quickly comment on FAP and stromal irradiation?
Yeah. I completely agree. You're completely right. FAP is not a new target. I demonstrated that. When we were running the due diligence with the SN University, we were paying high attention because the first-generation FAP are completely different from the new generation that we just acquired. The difference is coming from the structure even by itself of the FAP. It's named internally a TRIS linker, meaning that you have two points where the FAPI is going to be attached on the FAP receptors and confers some great difference in terms of pharmacokinetic of the compound. When I'm talking about a de-risk acquisition, it's because we look and we pay high attention to the patients which have been already treated with this compound versus the previous first generation.
We can see what I call the wow effect when you have the before-after treatment, like for the glioblastoma compound. We have that. To add on that, we have even now in Germany two sites which are currently running expanded access programs because they have tested that with patients, and they want to treat their patients with the FAP therapeutic compound. It is currently ongoing. We will collect more and more data from there.
You know, the funny thing about FAP is it's actually a case study in the challenge of radiopharmaceutical development. And it's something that I feel like we're, again, we pioneered the thinking around, but it's taken a long time for everybody to catch up. It's as simple as this. A really good imaging agent is not typically a good therapeutic because the goal of an imaging agent is to target and clear very fast. It doesn't mean that you can't get therapeutic index. You can. It doesn't mean that you can't get a good safety profile from that because clearly, if you're targeting and clearing fast, your off-target effects are going to be diminished, right?
It is a fallacy to think that just because you have a beautiful imaging agent, that's what we saw with all of the first four or five FAP molecules that were in patients, had a super fast off-rate. The PET images looked amazing because you had a great target to background ratio, but we saw zero therapeutic efficacy in those patients. Not even just not very good, but nothing. Now with the FAP portfolio, we're in the interesting situation where we have a very fast off-rate, low retention time molecule, which gives the most beautiful images. Then you have something that has an engineered retention time.
What you're starting to see is a lot of the small molecule strategies are adding half-life extenders, using avidity approaches, adding albumin binding domains, doing all of these things to slightly prolong half-life so that you have better tumor retention. To some extent, we started our life at the other end of that spectrum. Now we have great experience with multiple antibodies in patients. We see great potential. The whole field is now kind of at both bookends, is kind of moving into the middle where there's things that have really different pharmacology and where the pharmacology is truthfully better matched to the half-life of the isotopes. In some respects, the first generation commercial PSMA and even SSRI agents are kind of violating that principle of pharmacokinetic half-life versus isotope half-life.
Now as we get into things like lead-212, actinium, alphas, maybe terbium-161 is going to be one as well, we can start to think much more cleverly about how do you align the pharmacology of a targeting agent with the radiation profile of the isotope. That in a nutshell is why this field is in its nascency. The needle's not going to move by having on the imaging side another small molecule prostate agent or another choose your favorite isotope. That's not what's going to move the needle. It's going to be something that's biologically fundamentally different. On the therapy side of things, we're going to see that explosion of opportunities in that, I call it engineered molecule space, that's going to be a better fit for the next generation isotopes.
That is why this field is so early in its potential.
All right. Can we get this one to us?
Thanks, Anthony from Mizzou. One commercially on Illuccix in Europe, just a little bit on is the market size the same? It's fundamentally different just in terms of hospital economics. How do you think Illuccix in Europe is going to play out? Follow up on glioblastoma. You mentioned that iodine-131 has efficacy in thyroid. Should we be thinking about the overall survival statistics in thyroid with iodine-131 as the bar for glio?
I'll answer the second one just real quick. Then Kevin, you should do Europe. There would be no way to clinically extrapolate. Thyroids are a very radiation-sensitive disease. When you treat a patient with thyroid cancer, you're injecting a curie of I-131 into the thyroid. That, of course, means that patient management is challenging. It's an inpatient procedure. In most places in the world, you're in a lead-lined room. It's a prolonged observation period. By the way, it's also super efficacious. The really nice thing about the GBM product, even though we use iodine-131, is that about four hours post-injection, you have no peripheral dosimetry anymore. You have about 3%-5% of the injected dose residualized in the tumor. There's very little of the iodine-131 floating around.
That means that even though it is iodine-131 and even though there are some higher radiation handling requirements, there is no actual real requirement to have a patient sitting. There is no real reason to do it on an inpatient basis. Now we have to show that, and we have to show the dosimetry management. Yeah, they are completely different products. By the way, iodine-131 is a great radionuclide. It is a workhorse radionuclide. It is just that, I guess, with all of the newfangled and exciting isotopes that we have right now, the attention has somewhat drifted. That is nuclear medicine. We have the attention span of a gnat. When there is a new isotope come along, it is like, "Ooh, we are going to work on that now." We forget that we actually have great tools in our arsenal. On the Europe?
Yeah. I think I just answered that simply that typically the rest of the world outside the U.S. market eventually gets to 40%-50% of the overall mix of the companies, if you will. That really changes in terms of units and scans versus ASPs. You've got great ASPs that we're chasing after in Japan. In Latin America and other emerging markets that we're in, the ASP is much less. Revenues kind of follow suit into that. That's the plan.
Maybe just to preempt a question on that, obviously, we're now in a reimbursement landscape where rest of world benchmarking may matter a lot more. That's one thing that's really important to understand. In the U.S. market, there is no market for providing a packaged drug substance or a kit. The market is delivering hot doses to patients. The majority of the value that you're delivering is in a ready-to-use product. That's a business model that we don't replicate anywhere else in the world. That's a really U.S.-centric phenomenon. In Europe, everything is done in a hospital environment. You're essentially compounding under hospital pharmacy practice. Whilst there is a difference in ASP, there's also a difference in cost of delivering your service. Still, the profit margins are quite decent in Europe, even though the ASP is lower.
The business strategy still stands. We want in those markets to make inroads for therapy, build those relationships.
One last question.
Hey, guys. Robert Burns from H.C. Wainwright. Sorry, I've got two questions. I forget to sneak one additional one in. The first one goes to you, Pamela. I was really intrigued by 090 considering the unmet need there. And while I recognize it's a small molecule, so it's going to be clear relatively fast from the blood, when you link it to another PSMA targeting agent for the treatment of, let's say, MCRPC, I'm wondering about how you're thinking about potential radiation stacking effects within the bone marrow. That's going to be the first question. The second question is, with regard to the LAT1, LAT2 programs, obviously, we saw phase two data last year that was published in the JCO for a LAT1 inhibitor in relapse refractory biliary tract cancer. That seemed to produce promising PFS effects.
When we think about the LAT1 expression profile across tumor types, it seems like you could potentially go after several other different cancers other than GBM. I know that 102, you said undisclosed. Is this strictly going to be a CNS type of program development scheme, or are you also thinking about other solid tumors here?
I can start with the 90 question. That's a great question. I think it's something that we're still learning in the radiopharmaceutical space when it comes to what we do with concurrent radiation therapy and then subsequent therapy. That's why when we design our trials, we'll have careful dosimetry calculations. We've been in discussions with the FDA. Initially, patients usually can't have had radiation therapy within a certain amount of time before they enter into trial. As we learn more and as we learn how the current EBRT limits apply to radiopharmaceuticals, I think that'll be a question that we'll be able to apply.
Do you want to comment on GBM?
It's more broad.
Other chemicals.
The other chemicals program outside of CNS, given the expression profile and that phase two data set that we saw last year.
Yeah. That was for a non-radiopharmaceutical inhibitor. Our product is a synthetic amino acid, and not every LAT1 inhibiting molecule. This is also an inhibitor in the sense that it does not cleanly traverse the transporter. That is actually part of its cytostatic effect and radiosensitization effect, that it gets trapped in the transporter because it is synthetic or it is non-natural. It has been published. We do not see a ton of uptake in the periphery for this particular targeting agent. Part of it is a compartmental effect. It crosses a BBB, and it gets trapped in that compartment. We do not necessarily—and it is not for lack of experimentation. We have not seen a lot of utility in tumors of the periphery. It seems to be well-suited to CNS. That whole class of synthetic amino acids, that is a consistent characteristic.
I just want to add one little comment on Pamela's question as well. The samarium-153, samarium has a totally different radiation profile than lutetium. It has a different energy and different path length. The cumulative radiation dose on top of lutetium is very small. You're also typically dealing with patients that, from a hematologic capacity, are really tapped out at that point in time. I'm almost self-conscious talking about it because the man that ran the original approval studies for samarium-153 is sitting in the corner of the room over there. For full disclosure, I would say that Oliver is a bit of a skeptic of this particular approach. I don't want you to think that we have acquired opinions in this room. I think that the reality of it is that all patients progress on lutetium radioligand therapy. All of them do.
The manifest symptom is bone pain. There is a need. Unfortunately, in nuclear medicine, we've lost the capability to do that. We no longer have cost-effective agents for providing that capability. We also have this perfect storm of living in a post-Sackler-Purdue era where opioid compliance costs are very high. There is an unusual opportunity there to revitalize a practice of nuclear medicine that's been long established but lost, with a better quality product, a better safety profile, a better radiation dose, and a much lower imparted dose to the patient—not injected dose, but imparted dose through a more efficient chelator. Certainly, the results that we've seen to date in patients have been really promising. You're talking about four months of pain-free existence with a single shot. That's compelling if we can demonstrate that in larger patient populations.
Thank you. That brings us to time. We really appreciate your attention and attendance today. Thank you to our KOLs again. We know you've got such a busy schedule. We really appreciate you being here. Thank you to our team for being here, answering the questions. I know that some people have to rush off, but there is some food if you want to grab something to eat on your way out. Once again, thanks very much.