Good morning and good evening, and thank you very much for joining us today for our Telix Pharmaceuticals Urology Showcase and Expert Forum webinar. If you could just flick through to slide three, please. My name is Kyahn Williamson. I'm SVP of Investor Relations and Corporate Communications at Telix. I want to take a few minutes today to introduce the company, our speakers, and the agenda. Joining me from Telix to present is Richard Valeix, the CEO of Telix Pharmaceuticals, anand Dr. David Cade, the Group Chief Medical Officer of Telix. I'm also very pleased to welcome some esteemed KOLs, Professor Eric Jonasch from the MD Anderson Cancer Center in Houston, Texas, Professor Rodney Hicks from MTIC in Melbourne, Australia, and Professor Neeraj Agarwal from the Huntsman Cancer Institute. Each will be speaking to you today on their respective areas of expertise across kidney and prostate cancer. I will also be pleased to welcome Pamela Hidalgo, Chief Medical Officer of Telix Pharmaceuticals, to host a facilitated Q&A session. We have a lot to get through today, but I do encourage you, if you have a question, please ask the question tab in the right of the webcast window. We will endeavour to get to as many questions as we can, but if we cannot, we will certainly answer you offline after the webinar. Please move to slide five. I want to take a few minutes for those who are not so familiar with Telix just to introduce the company. We are a global leader in theranostics focused on oncology and rare diseases. We are a truly global player with a very established footprint in urology with Illuccix, which is our first commercial product and the leading gallium-based prostate cancer imaging agent in the US. We also have a deep theranostic pipeline, and obviously today's webinar is focused on some aspects of the therapeutic assets that we are developing in the disease area of urologic oncology. Finally, we built a comprehensive manufacturing, isotope, and distribution partnership to facilitate delivery of radiopharmaceuticals to patients worldwide. Next slide, please. Today we'll be with you for a little over an hour. We want to take you through our vision for urology and a recap on the programs we are focused on. We'll then switch gears, talking to focus on our kidney cancer therapy, specifically the 250 program, which is being developed as a CA9 targeted radiotherapeutic in the area of kidney cancer, but also as a pan-cancer opportunity. I'll then welcome Professor Eric Jonasch to give his physician's perspective on the kidney cancer treatment landscape. We'll then change gears into prostate cancer therapy, highlighting our beta program, TLX591, and our alpha program, TLX592. I'll be pleased to welcome Professor Rod Hicks to talk about the mechanism of action and the antibody approach, Professor Agarwal to speak about his physician's perspective and experience in the ProstACT Global Trial, and then finally Rod giving us a viewpoint on alpha emitters and their role in the therapeutic landscape. With that, I'm going to hand over to Richard Valeix. Thank you, Kyahn. Thank you. It's my pleasure to present today the Telix therapeutic strategy, especially in urology and especially a few weeks after the ASCO GU took place in the U.S. First, why urology is an attractive market for Telix? First, I would like to highlight that radiation therapy in urology is a long-loved story. Radiation is a big rock in the treatment algorithm of urology diseases, especially in prostate. Telix's vision is to deliver radioactivity effect on a targeted manner with a systemic administration. We are focusing our attention on three main indications: prostate, kidney, and bladder cancers, which are all serious diseases with five-year survival rates between 37%- 9% for the most severe cases of bladder cancer. All these three markets are very dynamic in terms of incidence and market volume. Can we move to the next slide, please? Urologic oncology is a key area of focus for Telix. The completeness of our offering across multiple disease indications and across the patient journey is a key differentiation versus our peers in radiopharma. Our offering in prostate cancer is an excellent example of how we can harness targeted radiation across the patient journey to better find, manage, and treat disease. Find and manage with our Illuccix and Gozellix product on the precision medicine aspect. During surgery and treat again with the TLX591 compound, our therapeutic compound currently under phase III trial named ProstACT Global. Can we move to the next slide, please? As you can see here in these slides, Telix has an extremely broad urology portfolio that not only addresses major tumor types, but also brings multiple approaches within each tumor with the beta and the alpha isotopes. We are committed to pairing therapeutic with a corresponding diagnostic to enhance patient treatment. Next slide, please. Our therapeutic strategy on these slides for the year 2025 is twofold. First, in short term, our priority is to deliver three main late-stage assets for prostate, kidney, and brain cancer, which is outside of the topic for today. In urology, our lead asset, TLX591, is already in phase III. With interim readout by end of H1 2025, we focus on safety and dosimetry data first. Our second short-term goal this year is to advance the kidney cancer therapy to pivotal trial. The second part of our strategy is building our pipeline of next-generation assets. Telix has one of the deepest alpha pipelines in the industry. Now we are transforming those programs which have been stage-gated through our internal R&D and based on excellent preclinical data into clinic. In urology, our next-generation pipeline includes TLX592, an alpha candidate for prostate cancer, which has demonstrated clinical proof of concept. We have also the TLX090, a bone-seeking asset we acquired last year from QSAM. It's developed initially for treatment of pain from bone metastases. Lastly, the TLX252 targeting the CA9, an alpha therapy leveraging the pan-cancer potential of CA9. Can we move to the next slide, please? Finally, I would like to open a little bit the discussions and beyond urology. We are exploring the pan-cancer potential of our two validated targets, the CA9 and the FAP. FAP has been the latest compound that we acquired end of last year. Owing there are two different mechanisms of action on the tumor microenvironment, we can develop multiple approaches to targeting most solid tumors, as you can see on the right part of the slide. This is very promising. I would like to hand over to David Cade, our Chief Medical Officer, that can guide you through the rest of the presentation. Thank you, Richard, and good morning or good evening to everyone who's dialled in today. Thank you, Richard, for the introduction. Now I'd like to really focus in on our CA9 program, which we believe truly possesses four ideal fundamentals in radiopharma development for a truly compelling therapeutic asset. The first of these is that CA9 is a compelling target itself, given that it's expressed on over 90% of clear cell renal cancers, which is the main form of primary kidney cancer that we usually want to treat. Secondly, CA9 as a target has been very robustly validated in our own phase III ZIRCON trial recently, which essentially demonstrated the very high sensitivity and specificity of zirconium girentuximab, which is now known as Zircaex, to both find and bind to its target, two very important but basic principles. Thirdly, as you can see on the right, in a patient from our ongoing STARSTRUCK trial, as well as other prior phase I and phase II trials, there's quite robust evidence of meaningful disease control of lutetium girentuximab. There is significant potential for this asset to be a first radio antibody drug conjugate to market for renal cell carcinoma as we pursue late-line disease. Finally, this is sort of an icing on the cake, that this target CA9 is expressed in a range of other cancers, important cancers like triple negative breast or ovarian and bladder cancer. Some of these cancers are quite difficult to treat with what we have in our armamentarium today. There is a considerable opportunity, we believe, for this target beyond kidney cancer alone. Next slide, please. This slide, I think, really nicely summarizes the current NCCN guidelines, which are US guidelines for renal cancer from early localized disease through to advanced metastatic disease. In summary, while we now have well-established early-line treatment regimens, typically comprising the immunotherapies as well as the tyrosine kinase inhibitors, the vast majority of these patients that we see and look after will progress despite these early treatments. They are left with later-line treatment options that remain limited in their effectiveness. What this means is that there are multiple opportunities in the current treatment landscape, comprising firstly, we believe, an opportunity to bring a radio antibody drug conjugate that has a new mechanism of action to patients as a monotherapy for late-stage disease. There is also an important opportunity earlier on to potentially synergize with and to improve upon immunotherapy that we currently use so frequently in these patients with earlier stage disease, as Professor Jonasch will discuss shortly. Next slide, please. Coming to a planned pivotal trial of lutetium TLX250, this represents a real opportunity to bring a much-needed new modality to patients in the late-line treatment setting. I am quite pleased to say that in recent meetings with the FDA, the agency has provided really quite positive feedback, and dare I say, in principle support for a pivotal trial design that we aim to launch in the second half of 2025, comprising two parts. If anyone follows this company closely, you will know that we have taken a similar design approach in our prostate therapy program. Familiar to the FDA, part one is ostensibly to confirm the optimal dosing regimen as well as safety, of course, before proceeding to part two to establish definitive efficacy as a first-in-class approach in patients with advanced renal cell carcinoma who have progressed despite these prior treatments that we've offered to them. What I hear you ask, would success potentially look like in such a trial setting? Typically, holding off disease or keeping disease at bay and thus improving progression-free survival usually in this disease setting does correlate to an extension in overall survival, which is what the patient and his or her clinician is after, improving overall survival in this disease population. The FDA will commonly want to see at least a few months of improvement in progression-free survival. Maybe, for argument's sake, a hazard ratio around 0.75 would be considered a win for these patients. Of course, that needs to be finalised with the FDA. With that, I'm delighted now to hand to Professor Jonasch from MD Anderson in Houston, Texas, who's going to discuss his practising physician perspective. Over to you, Professor Jonasch. Thank you so much, David, and thank you all for being here. Good evening and good morning. I'm a professor of medicine at MD Anderson Cancer Center in Houston. My practice focuses on renal cell carcinoma and rare GU malignancies. Next slide, please. It is pretty clear that in the past 10 years, treatment for renal cell carcinoma has improved considerably, although we are improving survival, but we are not curing a large percentage of patients. What we have now is individuals who have non-metastatic disease we would treat with adjuvant therapy. If they develop metastatic renal cell carcinoma, and there are about 27,000 individuals where this will happen in the US, we will treat them either with surgery if they have oligometastatic disease. We will treat them with immune therapy or immune therapy plus targeted therapy combinations, depending on their risk stratification. Once they progress on these treatments, we will then treat them generally with targeted therapies, TKIs, or with hypoxia-inducible factor II alpha inhibitors, HIF2 alpha inhibitors. As we move into the later stages of treatment here, the probability of long-term disease control diminishes, and the majority of individuals ultimately succumb to their disease. There is a clear place here for new treatments, and especially new treatments with novel mechanisms of action. Next slide. The idea that using a radio-labelled antibody against a protein that's expressed at high frequency in clear cell renal cell carcinoma makes a lot of sense. If you can deliver radiation either at a higher or an intermediate dose to those tumor cells, that might in and of itself be lethal to those tumor cells or could elicit some type of a distress signal from those tumor cells, which can then be taken advantage of with combination immune therapy. In this paper here that was published recently, we see that there is synergy in laboratory models, animal models, between the use of a radio-labeled antibody plus checkpoint blocking antibody therapy. What we have here is a figure which is a survival curve for mice that have this CA9 expressing renal cell carcinoma tumor, and they're being treated either with TLX250 or with a PD-1 blocking agent. We can see that, first of all, the control tumors in black are fairly similar to immune checkpoint inhibitor therapy alone or the radio-labeled antibody alone. In combination, we see that dotted line that the survival of these mice is considerably better. Next slide. Looking at this in a more granular fashion, just looking at growth rates, we can see on the right the animals that have been treated with control therapy, the tumour growth rates that are fairly robust. In the middle, we see that with the immune checkpoint inhibitor alone, this would be intraperitoneally administered PD-1 antibody, there's some degree of disease control. You can see then when you use the TLX250 plus the PD-1 blocking antibody plus CTLA4 antibody that the tumour control is even better. This gives one, this is encouraging that possibly this type of a treatment in humans could result in a new treatment paradigm. Next slide. To explore this, there are two clinical trials that are currently underway. There's the STARLITE-1 study that I'm leading at MD Anderson. This is going to be a multi-institutional study, actually, with TLX250 plus cabozantinib, which is a targeted therapy, plus nivolumab in individuals with treatment-naive clear cell renal cell carcinomas with biopsy-proven advanced disease. This will be a 100-patient study. The primary endpoint is going to be percentage of individuals with a complete response. We're very excited to get this going. STARLITE-2, which is currently accruing at Memorial Sloan Kettering Cancer Center, is an open-label single-arm phase II study of TLX250 plus nivolumab. This is for individuals who have progressed on prior immune-based therapy. The study is underway, and we're awaiting results. Next slide. At this point, we're going to be moving on to a question and answer period. Thank you very much for listening. Thank you so much, Professor Jonasch, for that very informative presentation. I have a few questions for you regarding the TLX250 program. One is you mentioned the combination of TLX250 and immunotherapy. Could you explain to us what's driving your interest in this combination? Yeah. We have data showing that DNA repair is deficient in renal cell carcinoma and clear cell renal cell carcinoma. We see that by introducing agents that can exacerbate DNA repair damage, these cells will then produce a distress signal, which can then increase immune cell accrual in the tumor microenvironment and can potentially synergize with checkpoint blocking antibody therapy. Basically, what happens is you get that distress signal. The tumors will then send out chemokines and cytokines. This will result in the T cells coming in, but the tumor cells can still defend themselves by expressing PD-L1. By then blocking that with PD-1, it's game on, and you allow the tumor cells then to be killed by the immune cells that have been pulled into the immune microenvironment. That's very exciting and very interesting. Thank you for sharing that. Regarding the STARLITE studies that you just described, can you talk about what we're learning from that first trial in the late-line setting and then what you might be looking to see in the treatment naive setting? Yeah. I mean, we're waiting for results in the study in the late-line setting. What we would hope to see is that a subset of individuals who have previously progressed on checkpoint blocking antibody therapy are then going to have a response to checkpoint blocking antibody therapy, possibly through these mechanisms. It'll be very interesting for us to see that. Now, having said that, the front-line setting is very different immunologically as well. I think it's a separate question, really, with regards to whether or not use of this in synergy with immunotherapy is best used in the subsequent line setting or in the front-line setting. Okay. Thank you for that. We heard Dr. Cade mention earlier about the monotherapy that's currently being designed for our phase III trial at TLX. Where do you see the opportunity for TLX250 as a standalone treatment for metastatic CCRCC? We see that in the later-line setting that we have a relative paucity of effective agents. We do see that agents that are used in that setting have a progression-free survival in the five- to six-month range. An agent with a novel mechanism of action that can then achieve progression-free survivals higher than that and with reasonable toxicity, I think really would meet an unmet need in that disease space. Okay. Thank you for that. Another question around, do we know anything about how sensitive kidney cancer is to radiation in comparison to other tumours, such as prostate? It generally has a reputation of being "radio-resistant," but I think that's a fallacy. We do see that with reasonable doses of radiation that we can actually achieve tumour kill. Especially when you're delivering radiation with a targeted approach where you have basically the CA9 expressed on the tumour cell, and you can then deliver that radiation directly to the tumour itself, I think this is a very different situation than one we see with, for example, external beam radiation therapy. Radiation is effective in renal cell carcinoma, and I think it's just a question of using it in the best possible manner. Okay. Thank you for that. Another question that came in. Around the use of neoadjuvant, do you see a role for neoadjuvant use in large tumours? I think that's really going to depend on the degree of response we see. There, what we really need is we need something that can rapidly cytoreduce the tumor. I don't know whether that's going to be the calling card for this type of a treatment or a combination treatment. We'll have to see whether or not that's where this goes. First, we're going to need to do the work in the metastatic setting to see whether that's a place where this can be effective. Okay. Another question, and maybe Dr. Cade, if you wanted to answer this one. There's a question around there's preclinical data showing that radiotherapy works with immuno-oncology therapy. The question is, why are phase III trials testing TLX250 as a monotherapy rather than in combination with immunotherapy? Yeah. Look, it's a great question. I did attempt to cover it, but essentially, there's two options for how a therapy like TLX250, Lutetium, would be developed. The most pressing need is, as I tried to point out, and as Professor Jonasch pointed out, we've got some really good options in early-stage disease with immunotherapies and tyrosine kinase inhibitors, but they work for a period of time. Almost all patients ultimately progress, and they get to later-line therapies where the sort of durability of disease control in later-line therapies is not that impressive. The most pressing need to have an agent that's got a completely different mechanism of action is for those patients where they've exhausted all of their early treatments, and they're now on to much less effective treatments later in their disease journey. That's the obvious place where we can help more patients. A phase III trial, monotherapy compared to whatever else might be used as a comparator, the pressing need is there. As I pointed out, and I think Professor Jonasch has highlighted, there's also a second opportunity in earlier-stage disease where we aim to combine with and synergize either immune checkpoint inhibitors or tyrosine kinase inhibitors to improve upon, to synergize with and improve upon what we can achieve already with those agents. That's really sort of a stretch goal, if you will, for these patients. They're already treated and served well, but we could do better. That's typically where you take a novel mechanism of action after you've proven it out for those patients that really need it later on when they've exhausted everything that's effective. Okay. That's helpful. Thank you for that, Dr. Cade. Maybe back to Professor Jonasch. There's a question about the CA9 landscape in general. Given your familiarity with the data and your clinical practice, it seems that TLX250 has driven some renewed interest in this target. In your opinion, given that the early pipeline seems to be filling up, are we on the verge of a CA9 renaissance? If you look at other tumours, the delivery via antibody or small molecule of a payload killing that tumour cell or wounding that tumour cell, if you will, we've seen incredible success in other tumours. For example, looking at enfortamab together with pembrolizumab in bladder cancer, we don't have that yet in renal cell carcinoma, but I think there's no reason why this type of approach shouldn't be effective in renal cell carcinoma. The idea that we are delivering payload with a CA9 antibody to the tumour microenvironment in a way that we're going to enhance either achieve a response with this monotherapy or enhance response with other agents, it's highly likely that we're going to see something very interesting in the future with this approach. It's great to hear. It's a very exciting time. We have a question on the treatment and the sequencing for ccRCC. Do you usually treat patients with a TKI following a TKI, or do you bring in belzutifan before you go back to a TKI? The easy thing to do at this point in time would be to use a HIF-2 alpha inhibitor in the third line. This is just because of the absence of evidence as opposed to the evidence of absence. The data that we have with the registrational study with HIF-2 alpha inhibitors was the large majority of individuals were in the third-line setting. One could think of trying a HIF-2 alpha inhibitor in the second-line setting. We just do not have as much data right now to support that approach. Okay. In your mind, I mean, is combination therapy ultimately where we think this will land, or do you have any thoughts? The answer is maybe. It's going to be a question of what's the right dance partner, what's the right dose. This is going to require, I think, a fair bit of careful work. It's going to require us to think creatively about what mechanisms we're actually taking advantage of. I really do like the idea of sting activation because that way, what you're doing is you're not really trying to use the TLX250 as something that's going to directly kill necessarily as opposed to stimulate the microenvironment in a way that's going to enhance response. I think the killing part could definitely work, but the enhancing part can also work. It just requires a slightly different sort of thinking with regards to how you dose this. Okay. Thank you. We have lots of great questions coming in. I think we probably have time for maybe one more. There is a question about when we look at the learnings from the TiNivo study and the CONTACT-03 study where we've seen TKI fail to resensitise the checkpoint, what are the considerations that we should incorporate into potentially a pivotal study where we look at the combination? Yeah. I think that's part of the reason why at this point the strategic approach here is to, A, look at this in later line as monotherapy, and also, B, look at this earlier stage as combination therapy. We currently don't fully understand why adding PD-1 blockade to cabozantinib or to tivozinib in those two studies that were mentioned by the questioner, why the PD-1 blockade didn't really add on. I think we do need to do a little bit of homework to sort of really understand why that's happening before we really embark in this. Now, it could be just through sheer empiricism because a lot of oncology arises just through empirical exercises. The study that's being performed at Memorial Sloan Kettering is going to demonstrate that whatever those mechanisms are, that they're overcome by the combination of TLX250 plus nivolumab. Time will tell, and we're going to have to see what those data show. That's excellent. Thank you again for sharing your insights. At this point, I will hand it over to Dr. Cade to talk about TLX's prostate cancer program. Okay. I think, Pamela, there are a few extra questions there. We will have time, I believe, at the end for any that were not addressed in that session. If we go to the next slide, please, let's now turn our attention to our prostate cancer program, which I'll introduce briefly before I pass to two of the, dare I say, leading minds in this field. Let's start briefly with Lutetium TLX591, which is Telix's highly differentiated radio-antibody drug conjugate approach to Lutetium PSMA therapy. I think most of this audience prefers pictures. On the right here, this is a patient who participated in the recent ProstACT Select study of Lutetium TLX591 in men with previously treated metastatic castration-resistant prostate cancer. What this case is representative of is really a typical patient from that ProstACT Select study who had a PSA tumor marker reduction of 67%, so very high reduction in tumor marker, as well as a radiographic progression-free survival of nine months. This individual is very close to the median patient outcome in this study, truly representative of the study results. The red arrows indicate sites of metastasis, which in this individual are mostly skeletal in nature. These remain stable from that baseline gallium PSMA PET scan you can see on the left out to about nine months post-treatment, at which time the disease decides to progress. Progression is documented. If we move to the next slide, this slide, I think, does a really nice job of illustrating the targeting and then the internalization and the retention or the residualization of Lutetium 591. On the left side of this series is the baseline image. This is a gallium PSMA PET scan. As we proceed from left to right, we can visualize with these sequential SPECT dosimetry scans out to about, what's that, two weeks post-treatment, the ongoing uptake of Lutetium TLX591. You can see at those red arrows really how well the agent, Lutetium 591, is residualized in the patient's prostate cancer metastases, but also importantly, the absence of any salivary gland or kidney uptake, which is critically important in terms of quality of life today with respect to the salivary glands and dry mouth and renal function in the future. As most would know, this asset's currently in phase III development in the ProstACT Global study, which Professor Agarwal is going to discuss shortly. Go to the next slide. Moving on to the targeted alpha program with TLX592 in prostate cancer. This is Telix's actinium-225 labelled engineered antibody, which in the most simple terms is very similar to the TLX591 antibody, except that it possesses pharmacokinetics that enable it to clear faster. Put simply, there are fewer alpha decay events in the blood circulation, while it also retains similar tumor targeting and retention to its parent antibody 591. If we look at the images here on the right, this is a patient from the recently reported CUPID study who in the top row has had the prostate cancer that has spread to his skeleton lit up using Illuccix, so see it, lit up with Illuccix in the lumbar spine, the lower part of the back, as well as in his right scapula or shoulder blade. Then in the bottom row, what you can see there is the same targeting of these tumors that have been identified with PET imaging, so the same targeting of these tumor deposits with TLX592, although in this case, the antibody's been labeled with copper 64, which is another imaging isotope that we can use to see where the antibody has gone. To conclude, the CUPID study was very important. It represents a successful proof of concept. We look forward to moving this into a phase I study with actinium in the second half of this year, which it's very likely that Professor Hicks will be the lead on that study. I'm delighted now to pass to Professor Hicks from the Melbourne Theranostics Innovation Centre who will discuss his perspectives on PSMA targeted therapies. Over to you, Professor Hicks. As always, Professor Hicks with a tie on, right? Over to you. Thanks very much, David. You've given a lovely overview of the field, which I'm going to just expand on a little bit. If you could go to the next slide, please. If we're considering the competition, if you like, of what's the role of a radio-labelled antibody drug conjugate versus a small molecule like a radiopeptide, many of the investors would be aware that lutetium PSMA 617 or Pluvicto is now an approved product for use in metastatic prostate cancer in the castrate-resistant area. How do they differ? When we talk about theranostics, we often say we see what we treat or we can see what we treat. More importantly, in terms of toxicity, it's what we don't see that really matters. If you compare the two images of the TLX591 and the small molecule, as David has pointed out, there's fundamentally different biodistribution. It's a very important term for the investors to consider. Biodistribution is where your agent ends up. That's the first word. You can see that the biodistribution of these two agents is quite different. The small molecules have greater penetration into normal tissues and therefore are taken up in a number of different areas that don't necessarily show up on a monoclonal antibody study. The most important of which, and which are involved in the toxicity of these agents, are the salivary glands and the lacrimal glands, which make the saliva in your mouth, which is very important for taste and dental hygiene, and your eyes for tears. The second one, which is a very radiosensitive set of organs, are the kidneys, where the filtering devices, the glomeruli, are highly radiosensitive. Getting high radiation dose, maybe not in the short term, but in the longer term, can lead to impairment of renal function, whereas an antibody being much larger stays in the circulation longer, but it also is primarily degraded in the liver and excreted through the biliary system into the large bowel. Both the liver and the bowel are relatively radio-resistant organs. They are much more tolerant of having radiation exposure. The second term, which is very important on this slide, is what we call bioavailability. The longer an agent stays in the bloodstream, the more available it is for binding onto your target. If something is rapidly excreted through the kidneys, and we know from Illuccix that within minutes almost of injection, you're starting to see activity appearing in the bladder as it's excreted through the kidneys. That means that your very expensive radiopharmaceutical is not available to be taken up, even if there is very high binding in tumors. I think that both these agents are going to have a role and perhaps a different role in terms of the kinds of patients we treated, but there are significant advantages. As you can see, if you look at the recommended dose, the Pluvicto is typically four to six cycles, six weeks apart, whereas the antibody can be administered only twice because that is going to stay in the circulation and be more available to be taken up by tumor sites. Next slide, please. If we look at the efficacy of these agents in humans, we already have proof of concept from very nice work done by Scott Tagawa's group in New York, demonstrating that the median overall survival in their heavily pretreated populations was around 42 months. Anyone who knows about the natural history of metastatic castration-resistant prostate cancer knows that's a very long survival. Obviously, not good enough yet, but very, very encouraging. Further data has demonstrated that by fractionating the dose to two cycles, given a couple of weeks apart, you can get a significantly longer progression-free and overall survival with very high PSA response rates in those patients. By giving the two lower doses, it reduces the toxicity to blood. Next slide, please. One of the advantages of bioavailability and internalization of monoclonal antibodies, which is also a feature, is that there's progressive accumulation over time. This is particularly important when the target expression, PSMA expression, is relatively low. If the agent isn't in the blood, it can't access the target. For low-expressing tumours, you get much worse radiation delivery with a small molecule than with a monoclonal antibody, where being in the blood for longer, even if the targets aren't as highly expressed, you still get binding and you still get internalisation. Therefore, the radiation dose delivered to tumours is higher. We see a significant potential advantage in a subgroup of patients in whom PSMA levels are somewhat reduced. This is, unfortunately, a feature of metastatic castration-resistant prostate cancer. As they evolve, they tend to lose the features of typical prostate cells, one of which is the expression of PSMA. Having better uptake and retention within low-expressing PSMA tumors may be a specific niche application of this particular agent. Next slide, please. It is now my pleasure to hand over to Professor Agarwal, who is going to give his physician's perspective on TLX591. Thank you. Thank you, Professor Hicks. This is such a pleasure to be here. Next slide. First of all, we can see here why it is an unmet need to have effective therapies for patients with metastatic castration-resistant prostate cancer. Many of my patients ask me why they need to be aggressive when they can live forever with prostate cancer. That may be true for localized prostate cancer, which is not requiring aggressive therapy, or somebody has received surgery or radiation therapy, and they are in remission. It's true for those patients. Most of our patients who have developed this metastatic castration-resistant prostate cancer, they are not as fortunate. This is the natural history of prostate cancer in front of us. We can see here that there is a long natural history of disease in many patients until they develop metastatic castration-resistant prostate cancer. The natural history of disease can vary a lot from a few years to many, many years until they reach this time point where they're diagnosed with mCRPC, after which the median survival is less than three years. If you look at those patients who have progression of disease on an androgen receptor pathway inhibitor or inhibitors such as enzalutamide or abiraterone or other ARPIs such as darolutamide or apalutamide, the median overall survival is about 18-20 months. We are talking about one and a half years of survival in patients who have been failed by these androgen receptor pathway inhibitors. This is the study population of ProstACT Global, where we are looking at a decimal median overall survival of less than two years. This is the blue box on the right side. We can see we have thousands of patients with mCRPC in the US. If you look at the entire world, we are talking about this lethal form of disease, which is affecting tens of thousands of people, patients across the world. We really need effective therapies. What is available right now? Once patients have been failed by ARPIs such as abiraterone or enzalutamide, they receive docetaxel chemotherapy, which is associated with the median overall survival benefit of 2.8 months. After that, we have some other therapies, which are again associated with median overall survival benefit ranging from four months to three months. I can talk about all those medications right now, but none of those medications have exceeded six months of overall survival benefit. There is a high unmet need for our patients who have metastatic castration-resistant prostate cancer, especially those who have been failed by these ARPIs. Next slide, please. Why this program? Why we should combine with docetaxel chemotherapy or even ARPI? The TLX591, this global phase III trial, is taking a new drug. Dr. Hicks has done, and Dr. Cade has done a fantastic job of explaining the mechanism of action. I won't delve into it, but we have a drug which is given over two doses. Our patients are pretty much done with this drug within three weeks of receiving the first dose. They are not excluded from receiving other treatments which are associated with survival benefit. We are best of both worlds in one way. Because if you look at other treatments, every single treatment which is currently approved after failure of these ARPIs, there is no room for combining two therapies. This is another unique aspect of this phase III trial, where our patients are not excluded from other standard of care therapies while they are getting this novel TLX591 antibody-based radiation, I would say antibody-based radiation therapy. I was just talking to a patient in the clinic about talking about this trial. This is how I would like to explain this. Before we move forward, I would like to show you the data on the safety of this TLX591 drug, antibody-based radiation therapy with docetaxel. This study was done in Weill Cornell Medicine by Dr. Scott Tagawa and the team. They combined TLX591 with chemotherapy with docetaxel. We can see here that chemotherapy, two doses of study drug were given while patients were getting docetaxel chemotherapy. They were able to tolerate chemotherapy pretty well with relatively low risk of febrile neutropenia. By the way, febrile neutropenia is a very common side effect of docetaxel chemotherapy. You combine with this another drug, and we did not see any substantial increase in the risk of side effects of docetaxel chemotherapy. Neutropenias are expected to happen with docetaxel chemotherapy, but we did not see any new safety signal. Based on this study, this is a single-arm study, safety-based, focused on safety, not focused on efficacy, although we did not see median overall survival, any attenuation, any decrease in median overall survival. Obviously, I can imagine patients who are very aggressive metastatic castration-resistant prostate cancer would likely offer this study and were enrolled in this study. Bottom line from this picture, we can see here the combination of docetaxel chemotherapy with TLX591 was safe and was well tolerable. This study provides the rationale from a safety perspective to combine TLX591 with docetaxel chemotherapy. We'll be studying the efficacy of this combination in this phase III trial. Next slide. This is the design of the study, the phase III trial. The first phase, or part one, as we call it, is focused on making sure there are no unexpected side effects. It is feasible to combine TLX591 with the standard of care medications we'll be using in this trial. As I mentioned earlier, our patients are not going to be excluded from other standard of care medications just because they are going on this clinical trial. Best of both worlds, receive the standard of care drugs and receive the TLX591 medicine. The first part is focused on this combining with abiraterone, enzalutamide, and docetaxel chemotherapy. We are just expanding on the safety data further. After that, we are very close to finishing this, hopefully in the next few months, this part will be finished. Patients will be randomized. New patients in the part two, which is a randomized portion of the trial, which is expected to lead to FDA approval of this agent, these patients have progressive metastatic CRPC. They will be randomized to one of the standard of care medications, including abiraterone or enzalutamide or docetaxel chemotherapy versus TLX591 and the same standard of care therapy. Radiographic progression-free survival is the primary endpoint. Radiographic progression-free survival is an FDA-approved endpoint, which is applied to pretty much all the clinical trials which are happening right now. This is considered a valid endpoint for drug approval. However, one of the key secondary endpoints is overall survival. That is included here. We will also be looking at other clinically meaningful endpoints, which are clinically meaningful to our patients, such as objective responses, responses in the PSA levels, quality of life as reported by the patients, as felt by the patients, and the skeletal events. Fractures are one of the most common complications of metastatic CRPC. How much we delay the fractures is a very clinically meaningful endpoint and will be assessing that. We expect the interim readout by sometime in the near future. This is a randomized trial, pretty large trial, which is going to be recruiting patients in different countries across the world. We hopefully will see very positive results from this trial. Next slide, please. This is basically how we will dose the study. As I discussed, unlike the currently approved lutetium-177-based therapies, our only currently approved medication is Pluvicto right now, which Dr. Hicks already discussed just now. It is given over six doses every six weeks apart. In this case, patients are going to get two doses of TLX591. If you get the first dose today, you'll get the next dose two weeks after, and you are done with the medication. I expect this to be hugely attractive to many of my patients who are traveling long distances for many, many months to receive the medication. They don't have to take care of all the radiation precautions for many, many months. We are done within 15 days. Hopefully, most of the patients will be done in 15 days. Now, Dr. Hicks has already mentioned the dosing. I'd like to repeat that. With the traditional lutetium-617-based therapies, which is currently approved, Pluvicto, and the upcoming drugs, which are very similarly designed, you see the radiation dose on the right side, 1,200 microcurie in the bottom. If you look at the upper part of the picture, the TLX591 is only going to deliver a fraction of that radiation dose. Again, this is going to be attractive to me as a doctor because, number one, I can be done with administration of a radioactive compound within 15 days, within a few weeks, rather than over many months. It is going to be so much more convenient to my patients. Next slide. With that, I will give the mic back to Professor Hicks. Thank you very much, Professor Agarwal. I'm going to now talk about alpha-emitters and how they may differ from the lutetium agent, which is a beta-emitter. Next slide, please. Ernest Rutherford, who was a very famous physicist at the early years of the last century, about a century ago, said, "In science, there's physics and stamp collecting." The difference between alpha particles and beta particles is really a physical characteristic. This schematic on the right is only sort of part of the story. If we are really showing the true size of a beta particle relative to an alpha particle, which is two protons and two neutrons, the nucleus of a helium atom, you wouldn't see the beta particle. It's really, really tiny. The way that I explain the difference to patients and my students is that if you give someone a bag of rocks and they start throwing those rocks in all directions, it depends on how many people throwing rocks are close together who gets damaged. How much damage is done is related to both the velocity and the size of that rock. If you have a cluster of lots of cells together, beta particles are very effective through what's called crossfire effect, where each tumor cell that concentrates the radiopharmaceutical irradiates its neighbors rather than itself. Whereas an alpha particle is so big, it's like a boulder. You can only throw a boulder so far. If you're very close, it inflicts a lot of damage. Most of the damage done to the DNA by beta particles is what we call single-strand DNA breaks. As it goes through the DNA through the nucleus, it will break one of the copies of the two copies in the DNA helix. The cells are very efficient at repairing single-strand DNA breaks. Being much more massive, alpha particles break both strands of the DNA much more often. They're much more difficult to repair, particularly in slowly dividing cells where that repair is not robust. When we have very actively dividing cells, there's duplication of the DNA, and you get more efficient healing. For slowly growing tumors like prostate cancer and some cancers like renal cancer, where the proliferation rate, the number of cells dividing, alphas have a very significant advantage. The downside of alphas is obviously that they can also damage non-cycling cells elsewhere in the body. We want very excellent targeting. We want to limit the off-target radiation. Ideally, if there is off-target radiation, put it into less radiosensitive cells. Next slide, please. If we look at that particular question of improving targeting, the TLX, we know, stays in the bloodstream for a long time, but it does accumulate very well and stay in tumors. TLX has done quite a lot of very innovative work to modify the structure of the antibodies so that they're cleared more rapidly from the circulation. In antibodies, there are two major parts: the binding part of the molecule and a so-called FC, which is involved in some of the immunological functions of monoclonal antibodies. By modifying that FC area, which is not critical to the binding to the target, it can change the handling, the biodistribution that I mentioned. That can lead to a shortening of the time that this agent stays in the blood by about tenfold without changing the uptake in the tumor. Thirteen hours or twenty hours is more than long enough to be bound to PSMA in tumor, but you're clearing the blood much more rapidly, reduces the radiation dose to bone marrow in particular. Next slide, please. Also, using different amounts, different masses of the antibody can also dial in how quickly it clears from the blood. Using a higher mass of the antibody, as you can see with the top series, cohort three, four, and the combination of both has a longer circulation time. Being able to dial in the bioavailability of the agent so you get good binding. If we compare the images on the right of gallium-68 PSMA-11 or Illuccix, these images are acquired 45 minutes to an hour after administration. You see very high uptake in the kidneys by that stage, high uptake in the tumor, but we're getting very similar uptake using a copper-64 monoclonal antibody modified in this way, given at that mass of 20 milligrams. These images are acquired at 20 hours or so after administration, showing both high uptake and retention in tumors. Next slide, please. By delivering radiation more specifically to the tumor and less to normal tissues, we have actually the opportunity to move radionuclide therapy earlier in the pathway. The earlier you treat someone with an agent that involves radiation, the longer you have to manifest the effects of the radiation on normal tissues, particularly the kidneys, as I mentioned. We tend to reserve the small molecules for later in the course of treatment. Using an alpha antibody that's going to give very little radiation to salivary glands and to kidneys gives us an opportunity to potentially move it earlier into the treatment pathway. Next slide, please. There is also quite a deal of evidence that these agents can have very high efficacy even in resistant tumors. Here we can see some elegant studies done by one of my long-term colleagues at the University of Melbourne, Paul Donnelly, demonstrating that the actinium-labeled specific antibody gives very deep tumor control and prolongation of tumor growth in a renal cell cancer model. Next slide, please. Moving on from prostate cancer, the second asset, which I think is really attractive because CA9 is not highly expressed in a lot of other tissues, and therefore it has already that intrinsic advantage of being able to be delivered across a range of different cancers with relatively low toxicity. Particularly the alpha particles, because they're much less dependent on oxygen levels in the tumor, we think that alpha-emitters may help to overcome the radioresistance that may otherwise exist in CA9-expressing tumors. This has been demonstrated in clinical proof of concept in other cancers other than renal cell carcinoma. We're looking to a basket trial to look across a wide range of tumors that we know on immunohistochemistry express this particular target. Next slide, please. As you can see here, while we get extremely high uptake, if you look at the ratio of uptake in the tumor compared to normal kidneys, for example, how intensely we see the renal cell carcinoma, but other tumors like colorectal cancer and mesothelioma, and particularly mesothelioma, where we know that there's a very high expression of CA9, it's an area of unmet need. The ability to demonstrate high uptake, retention, and particularly to combine it with an alpha emitter to overcome the intrinsic radioresistance of those tumors we think is a very attractive option. There is an ongoing trial using this also in triple-negative breast cancer, another cancer of significant unmet need. With that, I think it's time for me to hand over to Pamela for the next Q&A session. Thank you, Pamela. Yes. Thank you so much, Professor Agarwal and Professor Hicks. Both of your presentations were very insightful. Now we'd like to move on to the questions we have for you regarding Telix's prostate cancer program, but then also our alpha therapies as well. Professor Agarwal, maybe I'll start with you. You touched on the treatment a little bit earlier about prostate cancer, but maybe you could go into a little bit more detail on the prostate cancer treatment landscape and how you see it evolving. Maybe you can walk us through what's considered best standard of care now and how physicians are using taxane therapy or ARPIs. Yeah. Obviously, these therapies, we are happy to have these therapies, but the effectiveness of any therapy after failure of an ARPI remains suboptimal in my view and based on the data. If you look at the median overall survival benefit, as I mentioned, all the drugs which are outlined in that picture, each one of them is associated with a median overall survival of a few months, pretty much. You look at cabazitaxel, docetaxel by itself, 2.8 months, 2.3 months. Even you look at the most recent therapies, for example, just radium for the sake of discussion, three-month overall survival. Sipuleucel-T, three months approximately. Lutetium-177, Pluvicto, again, a bit longer, maybe four months, five months. Really, the median overall survival, despite having so many drugs being available, we are talking about a few months of survival benefit. That is reflecting on the choice our patients are making in the real world. When they see the relatively low survival benefits and the side effect profile and having to deal with long therapy courses, they are choosing not to have too many therapies. If you look at the real-world data from Flatiron, which actually is not SIA database, it's not an indirect collection of the patient records. It is direct extraction of patients' records from the electronic medical record. We are talking about large medical oncology practices, NCI-designated comprehensive cancer centers. Despite so many drugs being available, how many patients are getting more than one line of systemic therapy in metastatic CRPC setting is one. Like up to 50% patients don't choose to go with many therapies. Either they are not able to choose, or they do not want to choose, or they are losing their performance status very quickly, that they are not eligible for many therapies. This is the backdrop. This is where we are coming from when we are talking about this trial. Any drug which is not very difficult for our patients to get, in this case, for example, you come to a cancer center two times, get TLX591, and you are done. You can go back to your local doctors, local oncologist in a small town, or even like many patients are spending an hour or two, even in commuting, in New York City, in Chicago, big cities, even though cancer center may be 15 miles away. Any treatment which is effective, effectiveness needs to be established here with this trial. That's what we are going to do. Assuming everything goes well, we are talking about a drug for which our patients will have to come to a large practice for two times. After that, they can go back to their local oncologist. I think this, I see this as a huge attraction. I decided to just talk about my view on what is happening in the real world, how many therapies are available, overall survival benefit associated with those medications, and what is the potential we have here with this new drug. Yeah. No, thank you for that. That was very helpful. Maybe we'll move to Professor Hicks for a question on alpha treatments. Can you talk about what or where you see the opportunity for alpha treatments in the real world? Yeah. As I pointed out, I think that there's a significant opportunity where there's a very high target-to-background ratio so that where the tumor accumulates very intensely. Particularly if they've already demonstrated resistance to a beta-emitting radionuclide, there's a substantial advantage to using alphas in that setting. We know from neuroendocrine tumors that patients who are resistant to lutetium peptide receptor radionuclide therapy, that using an actinium-based agent can give substantial responses in those patients. I think the slide that David showed very early on in the prostate, sorry, in his presentation about the J591 program, if we look at the patterns of failure after radionuclide therapy, it's not so much progression in the areas that we've treated. It's actually new areas developing. Conceptually, I think a lot of that is related to micrometastatic disease, disease that's below the level of detectability on a PET scan, that we're inefficiently irradiating. The boy throwing the stone is throwing it away from the target. We're not getting the benefit of crossfire effect. Whereas with an alpha particle, we anticipate that we'll much more effectively treat those very small metastatic deposits from which patients subsequently fail. Having a monoclonal antibody that's circulating in the blood, its penetrance into small tumors is actually going to be better than into the large tumors. The ability to get into these small deposits and deliver very highly targeted radiation to reduce the recurrence of disease, the pattern of failure in small deposits, as you've seen, may give not only as good an effect or even a better effect upfront, it may give longer progression-free and overall survival by also simultaneously treating those micrometastases. Okay. Thank you for that. Professor Agarwal, maybe going back to ProstACT Global, how is the availability of an approved radioligand therapy impacting patient recruitment for ProstACT Global? And is the dosing schedule that you talked about earlier, is that having an impact on patient recruitment when you compare it to other PSMA-targeting radioligand therapy trials? Yeah. Absolutely. Great question. Whenever we develop any therapy, there are always going to be some treatments which are going to be available. For example, when Vision trial was being conducted, cabazitaxel, although trial was in late stage, a more pertinent example is PSMA-4 trial. When PSMA-4 trial with Pluvicto was being conducted, was enrolling patients, we had cabazitaxel approved, we had docetaxel approved, we had radium approved. There are always going to be medications which are approved at a given point of time when we are developing a drug, especially earlier in the disease, not in the patients who have terminal, who have no other options available. That is a phase I trial. We are not talking about phase I. We are talking about a registration phase III trial. There are always going to be options. Ultimately, patients will be making decisions regarding whether they like to go on this clinical trial or they would like to get a standard of care treatment. Five of them are approved right now. This is mostly swayed by two or three factors. Number one, a patient knows that by getting a drug, they are not being excluded from other drugs. They can always, when they have disease progression, choose one of the other drugs or can choose one of the hundreds of trials which are ongoing. We have trials with alpha therapies. We have trials with other novel immunotherapies available, AR blockers, AR degraders. Patients are not excluded from any standard of care therapy or a trial therapy. The decision here is pretty straightforward, in my view. They get two doses, and they're not excluded from any standard of care agent available. That is what makes it so attractive. If I had said, if this trial had only, say, just for the sake of discussion, if I only had TLX591 in one arm and placebo on the other arm, it would be more difficult. Because the patients who are getting placebo, they have the option of getting other location therapy. In this case, patients are going to get docetaxel chemotherapy or other ARPIs if they choose to do that. I think one of the biggest attraction is the shorter course. Patients know they are done with radioactive therapy in two weeks or three weeks. They are not being excluded from other standard of care therapies. I do not see much problems here. Okay. Thank you for highlighting that. Back to Professor Hicks. There is a question about the potential sequencing of radioligand therapy between alpha emitters and beta emitters. Acknowledging that we still have a lot of open questions. This is more of kind of your theoretical thoughts on this. For metastatic prostate cancer patients in general, just knowing that PSMA expression and it may change with the background therapy, what are your thoughts on sequencing the two types of therapies? Yeah. There's another question I've just seen in the chat, which I think is also relevant to this question of how you might combine a beta-emitter, which gives good crossfire effect for the macroscopic disease, and particularly those large tumors, which are more likely to be heterogeneous. The path length of the particle becomes critical to giving high radiation to those areas at the same time as treating the microscopic disease with an alpha. Rather than sequencing, I'm actually much more attracted to the idea of using them simultaneously. We know that the expression in any given tumor is always highest with the first cycle of treatment we get because we kill some of the cells that most highly express the target. If we can use that initial uptake, the high biodistribution and high target-to-background ratio that we get through a phenomenon called tumor sink effect, we can minimize off-target toxicity and maximize the radiation dose. Giving a beta-emitting radionuclide like lutetium J591 with an alpha at the same time for that first cycle of treatment, assuming that we can do that safely, and that's an unknown question at this stage, we might have to reduce the activity. An important, I guess I'd always harp on this, the dose that you measure in the dose calibrator in millicuries or megabecquerels or gigabecquerels is not the dose that anything sees. The dose that we see is measured in gray. That's a function of the biodistribution and the bioavailability of the agent. We get much better radiation dose delivery for any given administered activity if the burden of disease is high and the expression of the target is high. Giving the two together will treat potentially the heterogeneous large tumors with lower penetrance of monoclonal antibodies and the small metastases with the alpha emitter. Okay. That's great. Thank you. Dr. Cade, there's a question about ProstACT Global and what led to the choice of second-line therapy patients rather than focusing on post-taxane patients. Thanks, Pamela. I think the original premise was that the early development of the asset had demonstrated sufficient safety and encouraging therapeutic effect in patients that had had multiple prior treatments. We felt that this is in the early days. This is before PSMA-4 and some of the studies in early line treatments. We felt that the asset had earned its right through demonstrated safety and efficacy signals, earned its right to be evaluated as an earlier option. One of the problems with having to require a patient to have to be exposed to chemotherapy is if they're asymptomatic, which they often are, chemotherapy is often undesirable. We felt that there should not be a requirement to a patient to have to have received chemotherapy in a docetaxel or equivalent and experience those side effects before getting access to a radioligand therapy that really doesn't have many side effects that the patient feels. These are just lab tests, blood tests that the patient wouldn't be aware of if you didn't tell them the blood results. I'd love to get the comments from Dr. Agarwal or Dr. Hicks, maybe on this topic of why would we not have to put a patient through the chemotherapy regimen before offering them a radioligand therapy. It seems cruel in a way to do that. Yeah. I mean, there's a very simple pragmatic question is that taxanes are myelotoxic agents. You reduce your bone marrow reserves, and giving a second potentially myelotoxic agent after that would give you a higher risk of blood toxicity. It is an advantage not to have that. As well as that, there's a whole range of patients, and Dr. Agarwal can talk to this, who really just simply aren't suitable for taxane chemotherapy. I agree with you. The acceptability of taxane is very low despite showing almost one year or more overall survival benefit in metastatic hormone-sensitive prostate cancer, the earlier phase of disease. The use of taxane happened in up to 10% of patients with metastatic hormone-sensitive prostate cancer in the US. If you look at the castration-resistant prostate cancer setting, and I'd like to remind me, myself, and everybody else here that taxanes were approved in 2004, and there was no data to use taxane after ARPI therapy in those days. Even now, we don't have any data to support taxane after ARPI. Regardless of that, this is a therapy which is available for the last 20 years now. If you look at the real-world use of taxane, it consistently remains less than 30%. Less than one-third of our patients are receiving taxane even in the real-world setting. Basically, I want to repeat what Dr. Hicks said just now. It's not really desired by the patients. It's not doctor's fault, I think. This is how our patients—and by the way, I tell my patients, they are the boss. My job is to tell them, give them about the data, talk about different therapy options. They decide. It is not a very well-desired therapy. As you said, Dr. Hicks just now, giving taxane before these therapies may actually compromise not only the safety, but efficacy of these novel drugs like TLX591. We are planning to give two doses of TLX591. We are not excluding patients from receiving docetaxel chemotherapy after that. If you give taxane before, which have literally no established survival benefit after ARPI failure, and you end up compromising the receipt of TLX591, I think I will see that as a bigger problem. Okay. No, thank you for that. On that same note, similar question, but in ProstACT Global in part two, the question is whether patients with prior Pluvicto will be allowed to be enrolled. The question is asking because of the PSMA addition study that will read out later this year, and it might position Pluvicto in the hormone-sensitive setting. Do you have any thoughts on that? Of course. It's possible that Pluvicto may be available in the clinic. At the same time, when PSMA-4 trial was happening, we had cabazitaxel in the clinic. I'm sure they are going to be great to have those many options. Ultimately, it comes down to the patient's wishes if they would like to have a shorter course of therapy where they're not being excluded from other therapies, such as docetaxel, for example, versus going with something which is there, which they can always avail at the time of disease progression. That is the point or comment on Pluvicto approval in pre-chemotherapy space. Yes, that is an option. You have to get six doses, six weeks apart. More cumbersome for many of our patients, especially who are traveling long distances. With all the other aspects we just discussed, side effect profile is very different. Number of doses is very different. Number of radiation doses delivered to the body is different. It will be a discussion between me and my patient as an investigator. I think the patient will choose the right option for themselves. Regarding the PSMA edition trial, we hope the trial is positive and we have that option available. By the time PSMA trial reads out, PSMA edition trial reads out, and assuming it reads out this year, by the time it is FDA-approved and in use, wide use in the community, and by the time those patients are progressing, because we are assuming the drug will be effective when it is going to be approved, we are talking about four or five years of progression-free survival. We will be long done with our trial by then. We should be able to be done with accruing on the TLX591 trial in the next two years at the most. I do not think we will even see those patients who are going to be receiving the Pluvicto in hormone-sensitive setting. By the time they have progressed, we are assuming TLX591 will be available in the clinic. Yeah. The counterargument is that if they've already seen Pluvicto, they'll already have some off-target toxicity potentially to their kidneys and salivary glands. Giving a retreatment with that may exacerbate that problem. Potentially going to a different agent with a different biodistribution may be advantageous as long as the target is still expressed. If the target is expressed less intensely, and that's, again, part of the evolution of castrate-resistant prostate cancer, it tends to lose PSMA. As I pointed out in one of the slides, when the expression is lower, there is a theoretical advantage of a monoclonal antibody. I think that these could be complementary. They'll have different toxicities. If someone has heavy bone marrow infiltration, there could be advantages with still using Pluvicto in that setting compared to using a monoclonal antibody where you're going to get toxicity also from the blood. I think we've still got a lot to learn about the place of this therapy in an environment where there are multiple other therapies. As Professor Agarwal has said, there are many options for patients, but not all of them are suitable depending on age, renal function, pre-existing toxicity, patient preference. They're all important considerations. I'm absolutely confident that this agent will find a place in the treatment of prostate cancer. I'd just like to add, we have four ARPIs available in the clinic. Dr. Jonasch can tell me if I'm wrong. There are more than five TKIs, a wedge of TKIs available in the kidney cancer space. There are so many other IOs available from different companies. There are going to be three different types of actinium, not actinium, lutetium-177-based therapies, Pluvicto, and hopefully two more will be approved. It's great to have options for our patients. I will not worry about the competition or options. I think as a patient, if I'm a patient, I would like to have those options. I think there are so many positive attributes of this drug, as Dr. Hicks just said, non-overlapping toxicities, relatively speaking, less doses, two doses, you are done, and less doses of radiation therapy delivered to the body. I think those are hugely attractive to me. When hopefully we'll be discussing TLX591 as an available option after two years in the clinic, all those will be taken into account when our patients are making a decision. Okay. Thank you. I think we have time maybe for actually, I think we may have to wrap up given that we are right at time. Thank you both of you for sharing your insights with us today. With that, I will hand it back over to Kyahn. Look, I think I just want to say thank you very much, firstly, to our expert speakers for joining us. We really appreciate you taking the time to educate our audience. We've had a lot of great questions coming through. We really appreciate the attention. I think anyone who we didn't get to, I will reach out to you separately to answer your questions. We had a lot there, and we appreciate it. With that, wishing you all a good evening and a good morning. Thank you to our TLX speakers as well for joining us today.