Telix Pharmaceuticals Limited ($TLX)

Thank you for joining us today. I'm Robert Burns, the Managing Director and Senior Biotech Analyst at H.C. Wainwright. I'm joined today by Chris Behrenbruch, the CEO of Telix; and David Cade, the CMO of Telix. Gentlemen, thank you for joining us today.

Thanks very much. Good to see you, Robbie.

Awesome. So why don't we just dive in?

For those who may be unfamiliar with Telix, can you give us a brief overview of the company and give us a recap of your 2025 earnings that led to a strong year-over-year growth as well as the disease areas that you're focused on?

Yes. Thanks. So we're a fully vertically integrated radiopharma company specializing in oncology. We have a portfolio of focus in urologic oncology and neuro-oncology in particular. We are a commercial stage company. This past year, we did just over $800 million in sales, primarily around our U.S. prostate cancer imaging franchise. That's our -- we have two approved FDA-approved products in that space and very active product portfolio on the therapy trials, which I'm sure we'll get to at some point as well. But in terms of commercial performance, we've just put out our guidance for 2026, targeting the mid-900s in revenue. And really reflective of, I think, a very solid growth in the prostate cancer imaging space globally, but particularly the U.S. as well as the launch of our second prostate cancer product, which got passed through in October of last year. So that's putting a fair bit of momentum into our commercial operations as well. So I'll pause there. Hopefully, that's a good snapshot.

Yes. No, it definitely was. I sort of wanted to hone in a little more on the revenue guidance that you provided. So I know it's around $950 million to $970 million in revenue for 2026, with roughly a 25% growth in the Precision Medicine business unit. When we think about the growth opportunities for the PSMA franchise, where do you see significant upside for that agent as well as the new launches in brain and kidney cancer, specifically Pixclara and Zircaix.

Well, our guidance doesn't include any unapproved products. So it's -- so when we get approval for Pixclara, which we've just resubmitted just this past week and Zircaix is not too far behind. As you recall, we had a CRL for both of those programs last year. Then we will revise our guidance accordingly. We still expect to resubmit Zircaix obviously this year and hopefully launch it this year as well. That product has a breakthrough designation. So pending the review of the CMC issues we had with the FDA. We expect to get that program back on track. For the prostate cancer area, I would say there's sort of three drivers for the business. First of all, there is the inherent growth still in PSMA. We think that's 5% to 7% a year based on the fact that there's still white spaces in the market. There's still referral urologists that are getting up to speed on the value of PSMA. It may surprise you to know it. But CTs and bone scans are still prescribed and obviously, practice of medicine has changed. And maybe David can elucidate a little bit more how that practice is changing. We also see urologists taking more and more of a front line interest in PSMA imaging. So we're seeing -- I think in the steady state, call it, 3 to 5 years out, you're going to see 25% to 30% of the market for PSMA imaging actually directly controlled by urology. I think that's an emerging sort of category of PET scan or user/owner/stakeholder. And I think the second tailwind on the PSMA landscape is really around having a second product that's got passed through. Gozellix is a very innovative product. It offers some real clinical and distribution benefits. And by having a product segmentation strategy or market segmentation strategy for prostate cancer. We really target commercial and hops payers very differently. And I think that gives us a commercial advantage that will translate into revenue. And then I think the third one is we have a significant Phase III trial running this year, which is the BiPASS biopsy study. This is an opportunity to significantly grow the TAM, the BiPASS study stands on the shoulders obviously, of great work that's been done in academia, particularly the PRIMARY2 study that was recently presented. We actually wanted to take that study to the FDA -- actually took that study to the FDA for -- sorry?

We lost you for a second there.

I'm really sorry. Can you hear me now?

Yes.

Well, let's continue. I'll continue for a second, and then we'll just pause and do an audio catch-up. But basically, the PRIMARY2 study, we actually took that study to the FDA, and it does require some tweaks for it to be a label indicating study. So -- but there's a very important education process that's going on in the process of executing that study. And I think that builds further momentum into where prostate cancer imaging can be used. So I'll pause there. Hopefully, you've got some of that. But yes, there's a lot of -- there's a lot to look forward to in prostate cancer imaging in '26.

So one of the things I'm curious about is if the BiPASS study actually succeeds, what does that mean for the market expansion potentially in terms of the number of scans that you might be eligible to garner?

Yes. Dave, why don't you have a chat about the clinical consequence and maybe what that means in TAM.

Yes, sure. Robbie, it's a very important question, and it was really brought to us by our clinicians themselves. Essentially in the United States, we just focused on the U.S., there's north of 1 million biopsies done for the -- to try to establish the diagnosis of prostate cancer a year. And I emphasize the word try because a very significant proportion of those somewhere between 750,000, maybe 800,000 of those don't yield tissue that can be decisively ruled by a histopathologist either being prostate cancer. So the yield from the biopsy is low. And as a consequence, there's a very significant number, maybe 250,000 men that actually decline a prostate biopsy when they probably should. So there's a lot to improve. Now the way it's usually done is with an MRI scan. And I won't bore you with all the details, but the MRI scan is scoreboard according to a 5-point scan, which is called the PI-RADS system, 1, 2, 3, 4, 5 where 1 is a very normal scan. Typically, we don't get a lot of PI-RADS 1s in the men that we -- in the age group that we expect to have prostate cancer. That's like a very normal scan. PI-RADS 5 is prostate cancer. So there's an area in the middle PI-RADS 2, 3 and 4, particularly PI-RADS 2 and 3, which is a very significant group where the MRI is unresolved. It doesn't indicate to the urologist where to biopsy from. So we typically end up doing what we call a template biopsy, which is sort of a row 4, 4, 4, 4, 4 so basically somewhere between 12 and 20, maybe 12 and 24 needle cores for the biopsy, and even yet it doesn't yield the results. So what there is a huge opportunity to do and the results of this study in this BiPASS study are already showing us is that with the Gallium PSMA PET scan added to the MRI it can either direct using that imaging where the biopsy should be taken. So instead of doing 24 core biopsies. It can be image-guided and 1 needle core can be taken. Or on the other hand, if the Gallium PSMA PET scan is negative, no biopsy needs to be taken at all, and the patient can be reassured and put on to active surveillance where their PSAs monitored and they come back and are simply non-invasively scanned at a later date, 6 or 12 months' time. So for lay people, and this is not a lay audience, but for the lay people, I explain it this the one and done or none and done, which is a major deescalation of what we typically do today, which is very unsatisfying with that low yield of diagnosis. So you can see with that utility that opportunity is very significant, as Chris described, and that's probably an explanation of why this BiPASS trial is enrolling so rapidly, possibly even ahead of plan, which, as you know, doesn't happen with trials all that often.

Yes. So just to summarize, we're talking about sort of an estimated 750,000 to 800,000 scans with -- at the way that, that clinical evolution takes place. And then what it also does is it affords the question to be asked in the future, should PET follow MR or, in fact, should PET lead MR, and that will be something that will come out as there's more experience with clinical practice and combining the two modalities.

Yes. At least for me, as a male, it seems like I would definitely prefer to have the added on diagnostic imaging rather than having to take these numerous core biopsy samples, which are frankly onerous.

Yes. Well, and also it's just a cost. I think it's a cost issue. I mean if you look at the health economics of replacing biopsy, not just the cost of biopsy and the practice demands but also the morbidity issues associated with it. It's going to clearly save the health care money -- health care system money. And as you know, it does patients care about this. And in fact, it's hard to know the exact number, of course, because it's an estimate, and literature varies fairly widely. But there's estimated to be 200,000 to 250,000 men that simply don't participate in the process because just don't want stuff near their nether regions. And if we can -- I'm putting that as diplomatically as I can. And so I think that if we can make patient compliance better and patient engagement better, that's going to have a big consequence on detection rates. So I think it's very positive.

I would certainly agree with you that -- why don't we move on to your therapeutics pipeline now? So you recently reported initial data from Part 1 of the ProstACT Global trial, which is our Phase III trial, mCRPC. Can you provide an overview of that trial design? And remind us what you reported in terms of safety as well as dosimetry and what impact that has on Part 2?

Sure. Look, when we took the protocol to regulators, not all regulators had the same viewpoint on it. We had a number of sophisticated regulators that were quite okay based on the data that we had of going straight into ProstACT Global, which is a randomized Phase III trial across 3 different treatment cohort. So it's a standard of care plus versus a standard of care alone randomized study. The 3 different treatment arms are enzalutamide, abiraterone and docetaxel combinations. And we've selected those because those RP switches and taxane reflect sort of consistent global standard practice in first and second-line metastatic prostate cancer. When we went to the agency, they felt that we were a little bit light on the combos with the RPs comparatively. And we went in with a view that enzalutamide and abiraterone are a class, and we had some data to support that assertion, but the FDA wanted to see a bit more. And that's where the genesis of the Part 1 study came out. So it's really to reinforce that there's no particular delta between the different treatment arms, particularly the RPs. I mean we had some combination data with docetaxel. We showed that it was tolerable in combination with docetaxel, but we had -- we were a bit lighter on than the FDA wanted with the RPs. And so that's why we've done this additional study. We've, as you know, just put the results out. Maybe I'll make an initial comment, and then David, if you want to chime on anything. But the purpose of the study, as you know, was safety and dosimetry. We were really looking on a cross-cohort basis. There's always been a lot of speculation around the asset, around safety and particularly hematologic AEs. And what we hope that the data shows sort of fairly definitively is that these are well-tolerated treatments. The 591 layers very nicely on top of those different combinations. What the data shows is that we do have hematologic toxicities. It's the main toxicity associated with it, but it's transient and self-limiting and reverses very rapidly even when the adverse event is a higher grade adverse event. And that's counterbalanced by the fact that the patient-centric AEs are very benign because we don't have salivary gland, exocrine gland uptake. We don't have renal excretion. And so we think on the balance that it represents a very compelling risk benefit. That's what's demonstrated in the safety data. And now we'll be taking that combined with the dosimetry, which is, again, very favorable, particularly compared to current solutions that are in routine clinical use. We'll take that to the agency with the expectation that we'll be able to move to Part 2 and dose patients into Part 2 in the United States in the fairly near future.

Awesome. One of the things I'm sort of curious about as well, what are the next steps in terms of opening up enrollment within the U.S.

Yes. So I mean we did recruit patients in Part 1 in the U.S. So we do have sites that are sort of in the program. We will, of course, be adding a bunch more that are particularly focused on the Part 2. It is a global study. So we have regulatory approval, I think, now in 7 or 8 countries. We are actively recruiting patients in Canada, Australia and New Zealand. We've got U.K. just coming online. So we are rolling out the program globally. I expect that we'll get U.S. patients subject, of course, to what the agency says into the study around midyear, maybe early Q3. We expect about 20% of the study to be recruited in the U.S. And yes, obviously, it's critically important to get U.S. patient experience for the study. So yes, it's a high-priority study. We're really pleased with the data. I think it sort of finally benchmarks once and for all the profile of the drug. And unfortunately, when we deal with targeted radiation, cytopenias are a common side effect, but the fact that the management of those AEs are so straightforward that was the clinical experience gives us a pretty clear platform for discussion with the agency. I don't know, David, do you want to add anything just from a medical perspective?

Yes. We took a lot of patient input into the design of the trial, a lot of FDA input into the design of the trial. I think fundamentally, the Part 1 results do demonstrate the feasibility of integrating TLX511 with a contemporary backbone of different global standards of care as mentioned, just what the prevailing practice in the United States, which is predominantly RP Switch, but also outside of the United States, both Europe and in Asia, which is primarily moving from an RP to docetaxel. So it really is, as the name of the study says a global trial. So we would see -- should the trial meet its primary endpoint, it would lead to simultaneous filings, not just in the United States and Europe, but ultimately Japan, China, South Korea and so forth. So that's why we designed it that way. I think it's a very pragmatic trial. And as Chris mentioned, the next step is to take those data. They're exactly what the FDA asked for, and we'll take it back and present it to the FDA seeking an IND amendment to start to put U.S. patients into Part 2, which is already enrolling elsewhere.

So talking about Part 2 of the trial, what is the sort of enrollment trend that you're currently seeing for that portion of the trial?

Yes. I mean I can initially comment. So the trial is certainly picking up steam compared to the Part 1 study. The Part 1 study took a long time because it was a very technical study. It required a lot of SPECT Imaging, a lot of patient visits. So we had limited it to -- because of its technically demanding nature, we had limited to a number -- limited number of sites. Now we've added, of course, a lot more sites for the Part 2. And so that's a natural accelerator. Also, the protocol in Part 2 is just much more streamlined. There's a single time point PET imaging for patient selection. It's much more like a clinical treatment protocol for conventional PSMA RLT therapy. So we do expect to see a pickup. And obviously, having some data out as well from Part 1 is quite motivating, I think, for investigators to kind of get on with the study with a sort of clear understanding of what they're dealing with and how they manage patients going forward. So we've seen good pickup. The goal this year is we have based on an event-driven process, obviously, on 25% of events, so around 80 patients. We expect to report out a futility, an interim futility. We've discussed that with a number of regulators, but particularly with the FDA. We don't have -- obviously, because it is event-driven, we don't know when that's exactly going to drop, but we would imagine sometime around Q4 or Q1 next year. And that will be the next sort of milestone on the study as far as the Part 2 randomization goes.

Well, I'm certainly looking forward to that data. One of the other questions I also have, I note that you also have TLX592, which is -- which utilizes an alpha emitter versus the beta for 591. How are you thinking about the sequencing of those 2 agents within your portfolio and the treatment paradigm specifically?

Yes. Look, we're exploring a number of things on alpha. We haven't locked down finally what our PSMA strategy is really going to be in alpha. 592 is a fairly very early-stage asset. We have done some human studies with 592, but they were done with PET imaging as a surrogate. As you know, actinium is quite tough to image in humans. It can be done, but it's not sort of that straightforward. So what we did is we did targeting and biodistribution studies with PET -- with copper 64 as a surrogate, not that we have the intention to develop it commercially, but to get a sense in a benign way of really what the pharmacology of that agent is like, and that looks quite promising. So we are getting ready now to do the first-in-human actinium studies with that agent. We're starting off in very late-stage patients that have typically progressed on lutetium therapy. So that's where we'll get initial clinical experience with that. But the value proposition of 592 is really twofold. First of all, it doesn't have exocrine gland uptake. So one of the real challenges with small molecule delivery of alphas has been salivary and lacrimal gland ablation and not typically transient, usually fairly -- well, more serious, I would say, in terms of grade than what we typically see with a beta emitter. And then secondly, we've had discontinuations of programs recently for renal toxicity with renally excreted alphas. Again, that will vary from program to program. But generally speaking, alphas don't have much business ending up in your kidneys. The liver is a far more radio-resistant organ. And so the attraction of 592, it's somewhat derived from 591, hence, the sort of naming convention is that it is also hepatically excreted like 591. It has very little renal excretion. And so the expectation is that it's a better suited moiety for targeting alpha emitters. And I guess we'll find that out in due course. We, of course, we dabble in small molecules. I mean we want to understand the field. We have a fairly active R&D program looking at alpha emitters with small molecules as well because, of course, the advantage with smaller formats, and we look at small molecules, we look at small proteins. We have a protein engineering team in Los Angeles that looks at smaller formats. Of course, the advantage is that as we move into earlier lines of therapy, and I think the sweet spot for alpha is honestly not treating late-stage advanced bulky cancers. It's not really what the radiobiology of alpha is optimal for. I think if we -- I think alpha will have its sweet spot one day in targeting that very low burden of disease in the early metastatic, perhaps even hormone-sensitive space, that's where alphas will be fantastic. And then tumor penetration is really going to matter. But also those patients are going to live for a very, very long time. And so we've got to be confident that when we're parking an alpha emitter, particularly with respect to clearance organ that we are not creating something that's going to be a major downstream multiyear risk for the patient. And I think that's where the field has quite a bit of evolution to still undertake.

Yes. When you think about the alpha emitter space, obviously, you have actinium as well as 212PB or lead. There are a few players within the lead space. Obviously, ARTBIO is one of them, advanced cell prospective therapeutics. How are you thinking about the utilization of lead specifically with the small molecule components?

I mean, look, there is a sort of a heuristic in radiopharma that your pharmacologic half-life and your radio biological half-life should sort of somehow be similar. Of course, we also ignore that heuristic quite often. I mean lutetium PSMA products that are out there today in commercial use or even in late development are obviously violate that. You have a small molecule that has some hours of resonance time and then you put lutetium on it, which has a multi-day half-life. So we're obviously -- we're not very dogmatic about it in practical reality. I think that the challenge with the short half-life alpha emitters is really when you're dealing typically with a small molecule, you're dealing with something that's under the threshold of first pass renal clearance. You have to manage the design of your molecule very carefully around kidney metabolism. And if your alphas end up in sort of prolonged glomerular retention, you're not going to really have a great outcome for the patient. And so you want those decay events to happen quickly with a small molecule because typically, it's not targeting a lesion for very long before it gets washed out. But on the other hand, you also want to make sure that those events are not taking place in your kidney. So we've had -- we've seen in the last few months, we've seen discontinuations of programs because that balance between imparted energy to the tumor and excretion is not really balanced.

No, I completely agree with you there. When we think about the mCRPC space more broadly, obviously, there are a few other modalities that are targeting PSMA. T cell engagers are a great example of that. We've seen data from GenX as well as Amgen. How are you thinking about the deployment or physician preference for a radiotherapy over a T cell engager...

Yes. I think it's a really important question. And I sometimes feel that the nuclear medicine community, we sort of ignore these questions at our peril. So part of the answer to that is how we've tackled 591, which is really -- because it's a short duration of treatment, it's much more appealing for a medical oncologist to refer a patient. They're not handing over a patient to an authorized prescriber in nuclear medicine or radiation oncology for 40 weeks of therapy, right? So it's more -- and in fact, if you look at the global design, what we're trying to do is really layer 591 on top of kind of routine standard of care so that the patient management dynamic sort of status quo. And we've seen nuclear medicine products fail in the past because there hasn't been parking clinical efficacy aside, there hasn't been adequate motivation for a referral physician to just hand over a patient to another specialty. So I think that is particularly in the U.S. context, I think that is a real kind of just practical challenge. And yes, we forget, and you're quite right to raise it, we forget kind of ignorantly that MedOnc has a lot of opportunities to prescribe innovative new drugs to patients. There's a lot coming down the pathway. You made a couple of great examples. We're seeing next-generation androgens. We're seeing PARPs. We're seeing all kinds of other things impact standard of care in prostate cancer. And I think that the short answer to your question is really that radiation is incredibly valuable as a pillar of therapy of durable treatment response in metastatic prostate cancer. And you have to think about radiopharmaceuticals as the sort of migration from a box from traditional linac-based approaches to systemic approaches, but it's really the evolution of radiation oncology. And I think that managing prostate cancer, as we all know, it's about therapeutic drugs, it's about surgery and it's about radiation. And so I think that PSMA-targeted radiopharmaceuticals have a very natural role alongside potentially other immunomodulatory strategies in prostate cancer. So I think they're actually complementary. We see radiation as a driver of immune response in all kinds of cancers. We haven't seen a lot of success stories on the immunology front in prostate cancer so far on the immuno-oncology. And so I actually think that radiation can drive more success in this space. But yes, there's a lot to think about as the field evolves.

No, I completely agree with you there. Thank you for those insights. Why don't we shift gears now to TLX101, which is currently being evaluated in the IPAX-BrIGHT study, which is a Phase III trial in brain cancer. Can you talk a little bit about how that trial is designed, what the status of it is as well as the market opportunity there?

Dave, do you want to talk about IPAX-BrIGHT, more your wheelhouse?

Yes, sure. Maybe I'll open, Chris, and you can add some comments. But Robbie, IPAX-BrIGHT, as you said, it's a Phase III trial of our Iodine-131 amino acid asset, which is relevant because you need a small molecule to cross the blood-brain barrier. This asset targets the LAT1 large amino acid transporter, which is expressed in glioma tumors. We've got a number of studies that are sort of precedent studies, IPAX-1, IPAX-2, IPAX-Linz, which is an investigator-initiated trial that have demonstrated meaningful tumor control and some extended survival. So I'd caveat that because these are Phase I trials, but survivals from time of diagnosis in the range of 23 to 32 months. So these are meaningful survivals given the median survival is typically the order of 9 to maybe 15 months in that population. Essentially, IPAX-BrIGHT is our Phase III trial. And this study, again, has a Part 1 and Part 2. I won't bore you with all of the detail, Robbie, but Part 1 is a Bayesian design, which aims to optimize the dose of TLX101 and to optimize the dose of Lomustine, which will be the control arm. So there's 2 agents and the FDA requires us and other sponsors to spend a fair bit of time at the front optimizing the dose magnitude and the dose schedule. So that's part 1, optimizing the dose of 101 together with Lomustine and there's a Bayesian design that does that. Once we get to the optimized dose, there will be an expansion cohort. Then we get to the exciting bit, and it's a familiar theme, Part 1 and Part 2 of ProstACT Global, we talked about but IPAX-BrIGHT has a similar schema where Part 2 is a randomized Phase III design where we will randomize patients to the conventional therapy, which is typically Lomustine, that's in the guidelines like NCCN guidelines versus Lomustine, again, which is having 101 layered on top. So the question that is being asked in this trial is can we take a conventional standard of care and add a radioligand therapy on top of that to improve upon the standard of care. And in this setting, it will be overall survival. These patients have a limited duration upon recurrence. This population is patients with recurrent glioblastoma and overall survival is the primary endpoint of this trial.

Can I just make a quick time. We are...

Please.

We've been getting monotherapy data, IPAX-BrIGHT. IPAX-2 study was monotherapy data. We have done a dose escalation study, just to be clear. So we have an idea of what we're targeting in terms of dosing regimen. It's -- as David noted, it's about layering that now on top of standard of care where the extra run-in piece is required. So when we've done prior studies, including quite a bit of compassionate use experience in Europe, patients have typically been receiving whatever standard of care is available, whether it's Temozolomide, Lomustine, adjuvant radiation therapy, additional surgical. I mean it's been the whole heterogeneous hail Mary of recurrent glio research or clinical management. But now it's really about locking that down into a slightly more constrained study. And so that's really what that run-in part of BrIGHT. It's not about to validate dosing because we've done that, but it's about really ensuring that the dosing assumptions that we have on top of standard of care -- on top of a prescribed standard of care hold up as we go into Phase III. So I have to say Dave's team has done a phenomenal job from a KOL engagement perspective. We've got a bunch of sites in Europe now that have been working with the asset for a long time. I've done a lot of patients, had a really positive temperament towards the asset have seen really good disease control and treatment responses even in some cases, which we don't see in this patient population very often. So it's a very gratifying to have so much investigator momentum and interest in the study from top-tier European neuro-oncology sites is very gratifying. And we're really looking forward to rolling this out to U.S. patients this year as well.

One of the interesting assets that I also find fascinating in your pipeline is CLX250, which is being evaluating clear cell renal cell carcinoma. I'm curious where that -- what's the status of that trial that's ongoing? And from an early standard activation perspective specifically?

Yes. I'll make a few comments and then Dave, perhaps you chime in. I have to tell you this program has been very challenging because of the constant change in standard of care. I mean, kidney cancer moves so fast. And it's actually really gratifying. If you take a step back and look at the field overall, we've made huge strides in kidney cancer over the last decade. It's become a very immunotherapy-centric study. We are seeing new combination therapies evolve that are providing fairly incremental, but steadily in the right direction, survival benefit for patients. And I think the 2 cornerstones today as we see it evolve is really the immunotherapy combinations, whether that includes or doesn't include things like TKIs or cabozantinib or whatever. And then on the other end of the spectrum, we've obviously seen the emergence of belzutifan in the last-line setting. And so what this has done is we've been developing our sort of Phase II strategy around this asset. We've been taking multiple approaches. We've been looking at combo immunotherapies in first and second-line setting and how to layer in kind of more traditional treatments. And we continue to do research in that area. But what we have decided is that there still remains an unmet need in last line rapidly progressing patients. We don't feel that, I mean, belzutifan has emerged as a new standard of care in that setting, but it's not. I don't think it's -- I don't think anyone believes that it's a very overwhelming solution. And so I think whilst it's good to have a new option in that patient setting, and there are a lot of patients that progress off immunotherapies, I think we can do better. What we learned from this initial work that we did in the space is that we can resensitize patients back to immunotherapy to an extent with radiation. And we have some fairly compelling monotherapy data. And so what we have done is we've gone back and said we're going to do a, call it, a VISION trial style study in last-line progressing metastatic patients and then start to work upstream in parallel with the immunotherapy combination. So we have, for example, a study that's open at the moment, that's combining immunotherapy checkpoint inhibitors with targeted radiation that's being run at MD Anderson. So we have these sorts of studies, which are really about preempting and planning a little bit what happens when we move upstream from that monotherapy advanced metastatic signal. So that's the current plan today. That's what the LUTEON trial is designed to do. It's to really -- to look at that last line setting where there really isn't a lot of treatment options. It's a traditional place for nuclear medicine to be. And then once we get that monotherapy efficacy confirmation because we have some pretty nice data that shows disease modification and stabilization in that patient population, progression-free survival, prolongation, then there's an opportunity to move up into the earlier lines with combination immunotherapy. Dave, do you want to add anything?

Yes. Thanks, Chris. Robbie, you'd be familiar with this, but I just want to highlight the need. There are -- we've had a major advance with immunotherapies over the last decade. And those patients who enjoy a response, that's great for them, but it's only -- it's a 30%, maybe 40% of the population that you expose to an immunotherapy agent in advanced kidney cancer that get a response. So there's a large group that when I talk to patients about this, they often say things like what if I blow through and just go straight through because I'm not one of the responders. And they're the ones that are really worried about needing something else. So there is a large subset that end up in the treatment refractory end of the journey very quickly. And that's why we need assets like this to be developed and...

And also why we need the imaging as well. And just the same way as we're seeing PSMA playing a huge role in patient selection and longitudinal patient response assessment in prostate cancer, we already see the same demand for renal cancer. There's no doubt that the Zircaix product, which we still expect to launch this year -- that's the true companion imaging agent to 250. It's actually the same targeting agent. It's actually, we are able to do predictive dosimetry with the zirconium agent for the lutetium product, which is really exciting. That's the first time that we've had that in our portfolio because, as you know, prostate cancer imaging has really centered around small molecule imaging. But with renal cancer, particularly for primary staging, we want to keep the ureters nice and clear. We don't want bladder. We don't want kidney. We don't want anything. Basically, from the belly button downwards, we don't want any -- we don't want to see any of that. And so that's why a hepatically excreted agent very compelling for imaging. But ultimately, that asset is not going to get just used for indeterminate renal masses and primary staging and maybe evaluation of reoccurrence. But ultimately, it's going to get used for looking at treatment response. and to try to determine, as David says, when is the patient really truly progressing and to try to get ahead of that and not subject the patient to prolonged toxicity from immunotherapy if there's something that -- or cabozantinib or belzutifan, if there's something that you can do if you can move them on more quickly and still preserve some capacity to respond.

Thank you for that. One of the things I'm also sort of curious about because I know we're running up on time, so I'm going to make this succinct. When we think 5 years down the road, 5, 10 years for Telix into the earlier-stage pipeline, how are you envisioning the mixture of validated targets versus more novel nuanced targets as well as beta versus alpha emitters? And what do you think is the most underappreciated aspect of Telix?

Well, that's all of us underappreciated our current market cap. I think we're trading at a poultry multiple of our commercial business, but I think you'd be disappointed if the CEO didn't say that. So I'm just meeting my obligations there. But I think at the end of the day, look, I'll be the first to admit. Some of our portfolio has fairly well-trodden targets like everybody does, but we think we're taking a differentiated approach from a pharmacophore perspective. Our focus on biologics is quite unusual, mostly because biologics are harder. But the selectivity and the engineering that you get on a protein gives you all kinds of strategies for PK modification and changing your biodistribution. And so it is more complicated. It takes longer, but it also gives you a lot of really great control and flexibility over where you steer radiation. And I think one of the things when you look at Telix's pipeline, whether you like our targets or you don't like our targets or whatever, is we choose the right radionuclide for the biological problem that we're trying to solve. And I think that, that's really important. So we do have the appetite to say, all right, this is the cancer biology we're dealing with. This is the radiobiological mechanism of action we're hoping to achieve. And here's how we're going to steer it within time and energy constraints, this is how we're going to steer that radioactivity to that -- with that particular goal in mind. Now we are -- as you noted before, we are -- we do work in Lead-212. We do work in actinium. We do work in astatine. If you want to get something across an intact blood-brain barrier, chelators and radio metals are pretty challenging. charge matters. Pretty tough to do, but radiohalogens have lots of potential. So we have, for example, a near-term first-in-human study with an astatinated amino acid, which is for looking at leptomeningeal disease. That's a really beautiful example of where you have a widely disseminated -- relatively small metastases. It could be a great opportunity for an alpha emitter, but you still need to have things that have a more favorable CNS biodistribution. So you need to think about your radio labeling strategy there as well. So those are the sorts of thoughts that we have as we develop the earlier-stage pipeline. Some of our first-generation products were either small molecules that people relatively well understand or antibodies, full-length antibodies. I think that the sweet spot somewhere in the middle where we're dealing with smaller formats potentially that have better tissue penetration, but are still steerable to more radiation-resistant clearance organs. Internalization still matters even with alpha emitters, receptor-mediated internalization is different than binding to the substrate of a receptor and having some transient on-off effect. So I think there's a long way to go. I think what we really see now is the first generation of pharmacophores, and we've been -- we've had some great successes for the field, but there's a lot more that we can do to optimize the pharmacology of radiopharmaceuticals for the types of isotopes that we're interested in delivering to patients. So I think that's the science lens of the company. And fortunately, we're in a great position where through some M&A and through some organic investment, we've been able to build new capacity. And in fact, this year, you will see the beginning of a couple of very novel targeting agents, including with novel targets that will come out and go into first-in-human studies where you'll see the fruits of that labor materialize.

Well, I'm definitely looking forward to all of the innovative science and data that's going to be coming out of Telix, both this year and in the future. Gentlemen, thank you for taking the time to have this insightful discussion with me today.

Yes. Thanks. I'm sorry about the audio. I hope it came through reasonably well, but I always appreciate the opportunity, and you always ask great questions, Robert. So thank you.

Awesome. Take it easy, Chris. Nice to see you again, David.

Thanks, Robert. All right. Bye-bye.