Well, good morning, everyone. Welcome to day one of the Jefferies Global Healthcare Conference. My name's David Stanton. I'm part of the Jefferies Australian Healthcare Research Team. Delighted to be hosting this fireside chat with Chris and Richard from Telix. Lots to get through, gents. Perhaps we could start, Chris, question for you. Telix has been around for a decade now and commercializing its products globally. Can you talk about your competitive positioning and what you see as the requirements to be or how do you become successful in this space? Thanks, David. First of all, appreciate the opportunity, and thanks to the audience for joining. I think there's three things that are kind of unique about Telix. The first is we have a great product pipeline, but I think central to the pipeline is this theranostic concept. We've been able to monetize the precision medicine, what you would sort of commonly call diagnostics, but I think there's a lot more to it than just diagnostic medicine. We can talk more about that if you want. To commercialize the precision medicine side of the business and to build the relationship with that referral physician is so important, and radiopharmaceuticals are unique. I sort of scratch my head at companies that are developing radiopharma but don't leverage the fact that when you inject an isotope into a patient, you get a homing signal that tells you where the drug is, and you should use that information. I think that the commitment that for every target that we develop a therapeutic drug for, that we develop a companion imaging agent for, it's strange to say it out loud, but it's almost a unique position in our industry, especially these days with a lot of new entrants into this space. The second thing is, we made the decision, which was not a controversy-free decision at the time, to build our own commercial team. For us, commercial team is not just SG&A, it's a significant investment annually, but it's really about building an asset for the company that gets operating leverage as we start to roll more and more products out the door. Selling a radiopharmaceutical is not like selling a regular drug. You don't just toss a vial or a blister pack in a package insert and say, "Have at you." It's about how you inject a patient, how you manage clinical risk, how you calibrate a camera, how you infuse a patient, how you recover waste. These are all things that you have to think about when you're a radiopharma company. In fact, truthfully, when we think about radiopharmaceuticals in practical operational terms, you're not really selling a drug, you're selling a service. There's a significant service component to it. That leads to the third thing that I think is unique about Telix is that we made the decision, and I think it's the correct decision, and we look at some of our aspirational peers like Novartis, that it seems like every other week they're announcing a new manufacturing facility. We also, about five years ago, six years ago now, 2020, we launched an internal initiative around global supply chain and manufacturing verticality. We now have over 50 manufacturing locations around the globe, nuclear pharmacies, clinical material production, scale-up GMP facilities, isotope production facilities. Whilst we will not verticalize every aspect of manufacturing, there are things that we will do, and there are things that we will not do. We have infrastructure without peer as a company, those assets are becoming harder and harder to obtain. The licensing requirements of setting up radiopharmaceutical manufacturing are multi-year processes. You can't wake up on the eve of a phase III product launch and decide, "Oh, I'm going to manufacture my drug at scale." You have to sort of be ready three, four years in advance. Just to summarize, it's pipeline with a theranostics focus, the commitment to the commercial team, and being the face of the customer, not handing that over to somebody else or being very selective about who we do it with, and then really that integrated vertical integration supply chain and manufacturing. Understood. To go into that in a little bit more detail, in particular in the PSMA diagnostics space, you've got the first company to commercialize two PSMA-targeted imaging agents. How would you talk about how you're thinking about growth or opportunities within that PSMA franchise? Right. PSMA is a solved problem now. It's a mature market. We've had seven approvals in the PSMA space, right? It's a kind of diminishing return. We have about a 40% market share. We launched about six months behind Lantheus did, who did a fantastic job of creating the industry. We have consistently taken a couple of percent market share every quarter for the last 15 quarters. We believe, I think as our competition believes, that there is a great remaining growth opportunity in prostate imaging. The market's growing at 5%-7% a year as urologists get more excited and more confident around what PSMA imaging can really do. I think what we've seen, particularly in the last two years, is the urologist actually stepping up and taking real direct interest in scanning patients, instead of referring to an IDTF, where the revenue goes somewhere else or referring a patient to a tertiary referral cancer center where the patient may not come back. There's really an opportunity there to build service into the clinical offering. We see more and more PET scanners in the hands of urologists, and I think that's a trend that will continue as well as continue to grow the market. Its indication expansion. We have just a trial. There's very few things in my career that have been more exciting than the BiPASS biopsy trial. This is about bringing PET imaging into frontline cancer diagnosis. It took us over a year to negotiate with the agency the protocol for this trial, and where it gets us to is every year, over million men in America have a prostate biopsy. 80% of those biopsies are not added value. It's a lot of morbidity and cost for no benefit. What BiPASS does, it does not aim to eliminate tissue. Tissue is important. When you have a cancer diagnosis, you need tissue. What it does is by looking at the combination utility of MRI PI-RADS and PET, you can determine whether or not there's any value in giving a man a biopsy or whether surveillance is a better option or whether a more localized biopsy instead of doing a template and with all the joy that that entails, taking a much more localized approach. That has two enormous consequences for Telix. The first is that it more than doubles the addressable market for prostate cancer imaging. I mean, it's an enormous tailwind. The second thing it does is we believe that whoever scans first wins. As a prostate cancer patient goes through their journey, and it's a decadal journey, right? We know that they're going to get scanned time and time again, we think that there's real merit, particularly as informatics and AI and longitudinal assessment of disease and predictive factors come into PET imaging, that there will be an advantage to you're going to want to choose your product, scan that patient, and then the follow-on scans should be consistent, so that you have that intra-patient comparison. You're really doing apples to apples over a function of time. Just to summarize, that's a huge amount of tailwinds, I think, for the sector. I'm excited to see what is going to happen. We see new targets coming along as well. PSMA imaging and prostate imaging in general has got just a very bright scientific and clinical future. Very good. You're not just doing in diagnostics, you're not just doing prostate cancer as we know, you're doing brain and kidney cancer imaging as well. Could you talk to us about how you're thinking about growth opportunities there? The model we've taken in prostate cancer is a very ambitious one. I'll let Richard talk about that when we get to the therapy discussions. I'm joined here by Richard Valeix, who's CEO of our therapeutics business. The compelling thing about prostate cancer approach that we've taken is we are going to scan the patient from the time they're suspected of having prostate cancer to the time that we're assessing therapeutic impact of third-line therapy. We support global clinical trials from big pharma, where we provide imaging globally to support indication expansion as essentially a longitudinal imaging product for non-radioactive drugs in metastatic prostate cancer. We see the whole disease continuum. If you think of that wavy line of PSA levels going up and down over the course of a patient journey, we're there from the beginning till the end, right? Prostate cancer is not a single cancer. It evolves into distinct disease characteristics. We think of hormone-sensitive prostate cancer as a specific area. Obviously, there's pre-intervention, a pre-prostatectomy, then there's castration-resistant, and then there's end-of-life palliative because every prostate cancer patient eventually progresses off RLTs, and you're going to need to do something to transition that patient into palliative care. There's a role for nuclear medicine to play there as well. We see that continuum of care. We take the same approach in renal cancer, where we want to be there from an indeterminate lesion detection assessment to active surveillance, to surgical staging, to then treatment assessment response as patients go to successive lines of therapy. We want to do the same in glioblastoma. Our first entry point is pseudoprogression disease recurrence. Of course, we want to be in primary staging, right? Of course, we want to be in CNS mets from non-CNS primaries. Of course, we want to be in leptomeningeal disease. Again, it's about that disease continuum and imaging paves the way for our understanding of how these targets will play relevancy in the disease management process. Whether that's a radiopharmaceutical, whether that's a non-radioactive drug, whether that's external beam radiation, that theranostic concept is very relevant across a very broad sweep of patients. Understood. You've touched on this, but maybe we can go into a little bit more detail, Chris. Your presence in prostate cancer, can you talk about the portfolio and the different pipeline candidates like 591, 597, 592 and 090, and how they're positioned within the prostate cancer sort of treatment journey and landscape? Well, I think I'll let Richard comment, but maybe just as an opening one, as I said before, these different assets address different diseases. Yep. Castrate-resistant prostate cancer is not the same as hormone sensitive. Palliative care is not the same as frontline biochemical reoccurrence. We see distinct disease, distinct market opportunities, and don't believe that a single asset is going to span all of them, and we're really seeing that now with the latest PLUVICTO data going to earlier lines of therapy that the risk-benefit profile just isn't there. Maybe Richard, perhaps you could give a bit more color on the different assets and why we have them. Yeah, exactly. As you mentioned, we have different assets depending on the patient population that we want to address. Recently we have disclosed a new-generation peptide asset named the 597 in our portfolio that we, Louise Emmett, by the way, disclosed these results months ago at the IPCS Congress, where she was treating patients, and the dosimetry data were exceptional. That's something that we are extremely proud of, but I can come back on that in a minute perhaps. Okay. Yeah. Perhaps we could dive into that in a little bit more detail. What was the encouraging data for you in that TLX597 trial? As I was just mentioning, Louise Emmett disclosed recently this data at our congress in Lugano. We identified this compound as what I call a therapeutic window, which is amazing. It is mainly because of the very low salivary tumor uptake and also very low kidney uptake, which confer to the molecule the capabilities to have what we call a load dose, which is 8.5 GBq as a dose that we can administer to the patients versus the 7.4 GBq, which is the empiric way of treatment with the third generation of PSMA compound. Here we can provide three doses in two weeks, which is amazing because until now it was completely impossible to administer this amount of radioactivity with a PSMA compound. To make a long story short, this compound will be a game changer, especially for patients, as you mentioned, where the quality of life is important. We would position this compound as a first indication, probably in the hormone sensitive setting. Yes. Where, by the way, we just obtained the clearance from one center in Australia to run a phase II trial in this hormone-sensitive setting with this compound. In parallel, we have also the TLX591, which is under the phase III trial, ProstACT GLOBAL, that we position in the mCRPC setting, first and second line. I would say that it's a good portfolio complementary of assets. If I can add to that, I think one thing that's good to remember when you're dealing with very bulky late-stage disease, a macromolecule and a beta emitter where you have a large protein sink is a very credible way of pretty assertively treating a patient. When you get into a low disease burden, where tissue penetration matters much more, imparting really much more localized energy matters much more. That's where the alpha emitters, I think, are going to really come into their own. We are, of course, lutetium is a great workhorse. Lutetium has broad potential across the continuum of disease. What we're really hopeful for, and that's reflected in our R&D pipeline on the alpha side, is really that eventually we'll see alpha emitters get used in that low burden of disease. I genuinely believe beta emitters will never, in my opinion, based on the data I've seen, give curative intent in early metastatic patients. I don't think that's likely. I do believe that there's a possibility if we can keep renal excretion out of it, alphas don't belong in your kidneys ever. If we can keep salivary glands, exocrine glands in general out of it, I think alphas can provide that curative intent in early metastatic setting. Particularly when we combine it with good imaging and probably external beam radiation. We forget kind of at our peril that standard of care in that early metastatic setting includes external beam radiation, and how wonderful to be able to do combined dosimetry where you're combining endoradiotherapy with external beam radiation. That's going to give you a super durable response. I think prostate cancer landscape is really transforming. To Richard's very good point, quality of life is we've shifted the needle a lot on prostate cancer. Now we need to focus not just on therapeutic outcomes, but quality of life as well. I think that what we saw at ASCO this year was really a very big focus on, okay, we're getting durable responses, we're improving survival, but now what shape are we leaving our patients in when we've finished treating them? That's a pretty interesting question to solve. You've announced recently a collaboration with Regeneron on co-developing and co-commercializing some next-gen candidates. Can you give us some highlights from the announcement and what you're hoping to achieve over the longer term with this one? Well, Richard, that was your baby. You did a great job at closing that deal, so would you want to? Thank you. We approached Regeneron, and after a good discussion, we decided that we can develop what we call a CoCo, which is a co-development, co-commercialization contract. You know that Regeneron is really extremely well known in oncology for having a platform for developing antibody-drug conjugate. They wanted to develop and try to test some compounds with radiopharmaceutical activity. Now it's what we call the radioactive ADC, I can call it like that. We have a contract with four compounds, the first four compounds that we have to develop jointly with them, and then with the option to have four additional compounds. I would say that we are surfing on the wave of the ADC, which is, as everybody knows in the room, probably a AUD 100 billion market by the end of 2030. It's normal from a life cycle management perspective and also exploratory perspective to test radioactivity with ADC. We are paving the way with, I would say, our two first antibody compounds, the 591 that we just talked a minute ago, but also with the girentuximab compound that we named the 250 therapeutic compound. It was a natural path for us to work with Regeneron on this setting. We've always been targeting agent agnostic, but I think most people in the room appreciate it takes a lot of R&D resources and clinical resources to develop biologics. Actually, there aren't very many radiopharma companies developing biologics. The reason for it is historical. Radioligand therapy was traditionally run in mostly European and Australian nuclear medicine departments, where they didn't have the financial capacity to develop biologics. If you look at radiopharma today, it's actually a book-ended industry. You have small molecules on one side, and then you have mostly intact IgGs on the other end, and there's very little in the middle. That's an enormous real estate space to study. When you think about the things that are really exciting in next-generation isotopes like lead-212, actinium, astatine, and you think about some of the half-lives, and you think about some of the radiobiology of these things, that middle real estate is kind of where you want to look. I'm excited about some of the things that are coming down the pathway, small protein formats, novel scaffolds, things that have mid-ish blood half-lives, like 12- 36-hour half-life. Things that are hepatically excreted rather than renally excreted, because those will be better for your alphas. There's a really long way to go. I feel like we've just scratched the surface. To Richard's point, it's very early days on the Regeneron deal, and there's not too much to talk about other than what we've put out in the public, but for the fact that it also signals that biologics have got some time in the sun coming up ahead, I think. If we move on to brain cancer, you've got that phase III trial for glioblastoma, the IPAX BrIGHT trial, that you're doing a combination with lomustine. Can you talk too about how this trial is designed and what's the status? Perhaps that's one for Richard. Richard? Yeah, with pleasure. IPAX BrIGHT is our pivotal trial for the TLX101 compound in the treatment of metastatic, recurrent glioblastoma. The clinical trial is, in fact, in two parts. We have a dose optimization with lomustine is the part one, followed by the part B where we will use the recommended dose and treat the patients. The clinical trial has already started to recruit in some European and Australia countries. We intend to obviously start the clinical trial in the U.S. a little bit during the year 2026. That's exactly what we intend to do with this treatment. I have to confess that it's part of our portfolio, my preferred asset, because we know how debilitating is this disease. There's no additional treatment that has been disclosed during the last 20 years. On top of that, in Europe, perhaps you don't know, but some physicians in some countries can do homemade or home-brewed compounds that they can inject the patients. We have already some publications and also compassionate use programs that we push at Telix to help some patients, and the results are just striking. That's something we need to transform in a pivotal trial to obtain a marketing authorization and propose for all the patients across the planet. Richard, you've also got another clinical trial in glioblastoma, the IPAX-2 trial. That's for newly diagnosed glioblastoma patients. Can you comment on that and how that's going? Yes, you're right. IPAX-2, we just disclosed the beginning of the year some preliminary results on IPAX-2. It's on early-stage patients. Why? Because in glioblastoma, one of the first intent of treatment is also the EBRT radiation therapy. We decided to associate EBRT plus temozolomide with the TLX101 compound, and we received the first result there. We will have some additional results coming during the year with the long-term follow-up. That's amazing. It's a phase I study. We will pursue the development there. As you know, when you discuss with the authorities, we need to start the development first in last line, and then we climb the lines to the additional indications. That's the rationale for the IPAX-2 study. More to come on this area. Richard, you're on a roll, so we may as well stick with the therapeutic side and moving to renal cell carcinoma. Can you provide an overview of the TLX250 program in clear cell renal cell carcinoma, please? The TLX250 program is what we call also the antibody, the girentuximab compound, which is targeting the CA9 receptor, very well known in oncology, and our lead indication is in clear cell renal cell carcinoma. We have a clinical trial named ZIRCON, which is a phase II/III, which has already started in. some European countries and Australia. We just obtained, beginning of May, the IND clearance to start the clinical trial in the U.S. also. It's, as I was mentioning, a phase II/III where we have a dose optimization and validation before starting part two, which will be the confirmatory phase for the efficacy, where we are looking for PFS and OS in order to get the registration for this compound. Once again, I would say it's an amazing portfolio because, as you mentioned, we have a prostate, a phase III trial, a ccRCC, a phase III trial, a glioblastoma, a phase III trial, so that's a lot. Coming in behind the prostate portfolio, it's obviously the most mature, but the Pixclara asset, which has got a PDUFA date of 11th of September, and then Zircaix, which is the renal cancer imaging product, which is just about to get our BLA resubmitted after our setback last year on the manufacturing side. These two imaging agents, they image the targets we treat. Girentuximab is actually the same targeting agent as our therapy program. In fact, with the manufacturing changes we've had to make, really the future CMC pathway for the therapeutic is really cross-referencing the diagnostic BLA package. It gives us a lot of confidence. We've imaged, with Zircaix, I don't know how many patients we've imaged. Hundreds and hundreds of patients. We've had an expanded access program open for a long time. I think we've had a couple hundred patients in the U.S. alone under that expanded access program. That gives us really a lot of confidence in our understanding of the target, what the dosimetry looks like, what the patient profile and disease presentation looks like. I think it's, again, I mentioned in the beginning that we don't call it diagnostic imaging because we don't think that the diagnostic piece is actually all that important. The precision medicine piece is really important. The imaging allows us to run smarter clinical trials. It allows us to do better patient selection. It allows us to measure treatment response assessment. Even in the case of the TLX250 program, it actually de-risks our regulatory pathway. Because that's an example of a kind of a true theranostic pair. I think that the imaging provides just really profound benefit to the therapy programs. We always think internally, "How do we integrate?" What's the imaging going to tell us? What's the edge that we can get out of a therapy program from what we know imaging that target? Understood. You've already mentioned that you're agnostic to the targeting agent. A question maybe for both of you. You're agnostic to the targeting agent and the isotope. Can you talk to us about how you think about the development of the next generation candidates that you guys are going to go after? So really that's like- In two minutes that's not a fireside chat. In two minutes. That's like a bonfire chat- Yeah. conversation with a couple of bottles of whiskey, I think, or tequila or something. I think, look, at the end of the day, I've always said it, and it's not a popular sentiment, but I hate platforms. I think that you say, "I've got a particular targeting moiety that I like, and all of my biology is going to be based around the limitations of that moiety," or, "I have a particular isotope that I like, and all of my biology is based around that particular radiobiology." Just not the way we manage cancer. When we think about it, in fact, one of the reasons why we've started to do some internal innovation around protein engineering is to think about, okay, what's the biodistribution of the disease we're trying to tackle? What are the clearance organ considerations that we are trying to map into the target product profile? If we want something that's hepatically excreted or renally excreted, we make decisions like that. Sometimes it really matters. It's cost, right? I keep hearing that, oh, terbium will be the next thing to cannibalize lutetium, but are you going to really set up a global supply chain for terbium for 10% more clinical consequence, right? The answer is probably not. Right? Economics plays a big role. Distribution plays a big role. What's your half-life of your product? When we dispense a dose of Illuccix, we dispense it from 266 nuclear pharmacies in the United States with a two-hour shelf life. That's got a whole supply chain associated with it. We made decisions in the chemistry and in the physics of that product that map onto that supply chain infrastructure. That's why we do take that agnostic approach. As far as studying, Richard's team is studying very closely the future of all of the alpha emitters. Well, not all of them, but there are many more than what we are looking at. Certainly the three front runners of astatine, actinium, and lead-212. We have a really good handle on that, and we have our own lead generator. We make the Tc-99m. We are partnerships around actinium that are very advanced in the R&D phase. We want to understand these isotopes very well so that we can factor them into our economic, clinical, and development decision-making. Very good. Well, maybe we will get that drink later and talk about it some more. We're getting to wind up. We've got just one minute to go. Look, Richard, perhaps over to you for the last question. Any sort of underappreciated assets that you think the market's sort of not looking at that they perhaps should be? In our portfolio, perhaps, is the FAP. I would say we acquired last year a portfolio of FAP compound. One for diagnostic and two for therapy. We are currently developing that also. FAP, as you know, is targeting the tumor microenvironment and I'm a big fan of this mechanism of action because it's for all resistant cancer where the microenvironment is there and does not authorize the classical therapy to treat the patients. There's a lot to explore in this dimension, with alphas or beta probably more, because we need to target a bit broader than just the tumor cells. Yes, that's the FAP I would position in our portfolio as something which is not currently valued and that we are developing. Yeah, that's a great point. Very good.