Well, good morning, everyone. Welcome to day one of the Jefferies New York Healthcare Conference. My name's Dave Stanton. I'm part of the Jefferies Australian Healthcare Research Team. Delighted to be hosting this fireside chat with Chris and Rishah from Telex. So, lots to get through, gents. Perhaps we could start Chris' question for you. Telex has been around for a decade now and commercialising its products globally. Can you talk about your competitive positioning and what you see as the requirements to be or how do you become successful in the space?

Thanks, David. First of all, appreciate the opportunity and thanks to the audience for joining. I think there's three things that are kind of unique about Telix. The first is we have a great product pipeline, but I think central to the pipeline is this Theranostic concept. And, you know, we've been able to monetize the precision medicine I mean, what you would sort of commonly call diagnostics, but I think there's a lot more to it than just diagnostic medicine. We can talk more about that if you want. But to commercialize the precision medicine side of the business and to build the relationship with that referral physician is so important. And, you know, radiopharmaceuticals are unique. I sort of scratch my head at companies that are developing radiopharma, but don't leverage the fact that when you inject an isotope into a patient, you get a homing signal that tells you where the drug is, and you should use that information. So I think that the commitment that for every target that we develop a therapeutic drug for, that we develop a companion imaging agent for, it's strange to say it out loud, but it's almost a unique position in our industry, especially these days with a lot of new entrants into the space. The second thing is we made the decision, which was not a controversy-free decision at the time. to build our own commercial team. And for us, commercial team is not just SG&A, and it's a significant investment annually, but it's really about building an asset for the company that gets operating leverage as we start to roll more and more products out the door. Selling a radiopharmaceutical is not like selling a regular drug. You don't just toss a viol or a blister pack in a package insert and say, have at you. you know you have to it's about how you inject a patient how you manage clinical risk how you calibrate a camera how you infuse a patient how you recover waste these are all things that you have to think about when you're a radiopharma company and and in fact truthfully when we think about radiopharmaceuticals in practical operational terms you're not really selling a drug you're selling a service it's a significant service component to it which then leads to the third thing that I think is unique about Telix is that we made the decision and I think it's the correct decision and we look at some of our aspirational peers like Novartis that you know it seems like every other week they're announcing a new manufacturing facility we also about five years ago six years ago now 2020 we launched an internal initiative around global supply chain and manufacturing verticality we now have over 50 manufacturing locations around the globe nuclear pharmacies clinical material production scale-up GMP facilities isotope production facilities and whilst we we will not verticalize every aspect of manufacturing it's a strategic you know there are things that we will do and there's things that we will not do we have really I mean we don't we have infrastructure without peer as a company and those assets are becoming harder and harder to obtain the licensing requirements of setting up radio pharmaceutical manufacturing our multi-year processes you can't wake up on the eve of a phase three product launch and decide oh I'm gonna manufacture my drug at scale you have to sort of be ready three four years in advance so just to summarize you know it's pipeline with the Theranostics focus the commitment to the commercial team and and being the face you know being the the face of the customer not handing that over to somebody else or being very selective about who we do it with and then really that integrated vertical integration supply chain and manufacturing understood and and to go into that in a little bit more detail and in particularly in the in the psma diagnostic space um you've got you've got the first company that commercialized two psma targeted imaging agents you know how would you how would you talk about how you're thinking about growth opportunities within that psma franchise right so i mean psma is a solved problem now it's a mature market we've had seven approvals uh you know in the psma space right so it's a kind of a diminishing return um we have about a 40 market share we launched about six months behind lantheus uh did um he did a fantastic job of of creating the industry we have consistently taken a couple of percent market share every quarter for the last 15 quarters and we believe I think as our as our competition believes that there is a great remaining growth opportunity in prostate imaging the markets growing at 5 to 7 percent a year as urologists get more you know excited and more confident around what PSMA imaging can really do I think what we've seen particularly in the last two years is the urologist actually stepping up and taking real direct interest in scanning patients you know instead of referring to an IDTF where the revenue goes somewhere else or referring a patient to a tertiary referral cancer center where the patient may not come back there's really an opportunity there to build service into the clinical offering and so we see more and more PET scanners in the hands of urologists and And I think that's a trend that will continue as well as continue to grow the market. And then it's indication expansion. So we have just a trial that I don't think there's very few things in my career that have been more exciting than the bypass biopsy trial. This is about bringing PET imaging into frontline cancer diagnosis. It took us over a year to negotiate with the agency the protocol for this trial. And where it gets us to is, you know, every year over a million men in America have a prostate biopsy. Eighty percent of those biopsies are not added value. And so it's a lot of morbidity and cost for no benefit. So what bypass does, it does not aim to eliminate tissue. Tissue is important. When you have a cancer diagnosis, you need tissue. But what it does is by looking at the combination utility of MRI, PIRADS, and PET, You can determine whether or not there's any value in giving a man a biopsy or whether surveillance is a better option or whether a more localized biopsy instead of, you know, doing a template and with all the joy that that entails, taking a much more localized approach. That has two enormous consequences for Telix. The first is that it more than doubles the addressable market for prostate cancer imaging. So it's an enormous tailwind. And then the second thing it does is we believe that whoever scans first wins. As a prostate cancer patient goes through their journey, and it's a decadal journey, right, we know that they're going to get scanned time and time again. And we think that there's real merit, particularly as informatics and AI and longitudinal assessment of disease and predictive factors come into PET imaging, that there will be an advantage You're going to want to choose your product, scan that patient, and then the follow-on scans should be consistent so that you have that intrapatient comparison. You're really doing apples to apples over a function of time. So just to summarize, that's a huge amount of tailwinds, I think, for the sector. I'm excited to see what is going to happen. We see new targets coming along as well. So PSMA imaging and prostate imaging in general has got just a very bright scientific and clinical future.

Very good, but you're not just doing diagnostics. You're not just doing prostate cancer. As we know, you're doing brain and kidney cancer imaging as well. Could you talk to us about how you think about growth opportunities there?

Well, so the model we've taken in prostate cancer is a very ambitious one, and I'll let Richard talk about that when we get to the therapy discussions. I'm joined here by Richard Villex, who's CEO of our therapeutics business. So the compelling thing about prostate cancer approach that we've taken is we are going to scan the patient from the time they're suspected of having prostate cancer to the time that we are assessing therapeutic impact of third-line therapy. We support global clinical trials from Big Pharma, where we provide imaging globally to support indication expansion as essentially a longitudinal imaging product for non-radioactive drugs in metastatic prostate cancer. So we see the whole disease continuum. If you think of that wavy line of PSA levels going up and down over the course of a patient journey, we're there from the beginning to the end, right? And prostate cancer is not a single cancer. It evolves into distinct disease characteristics. So we think of hormone-sensitive prostate cancer as a specific area. Obviously, there's pre-intervention, a pre-prostatectomy. Then there's castrate-resistant. And then there's end-of-life palliative because every prostate cancer patient eventually progresses off RLTs, and you're going to need to do something to transition that patient into palliative And there's a role for nuclear medicine to play there as well. And so we see that continuum of care. We take the same approach in renal cancer. We want to be there from an indeterminate lesion detection assessment to active surveillance to surgical staging to then treatment assessment response as patients go to successive lines of therapy. We want to do the same in glioblastoma. Our first entry point is pseudoprogression disease reoccurrence. But, of course, we want to be in primary staging, right? Of course we want to be in CNS-METs from non-CNS primaries. Of course we want to be in leptimingenial disease. So, again, it's about that disease continuum, and imaging paves the way for our understanding of how these targets will play relevancy in the disease management process, whether that's a radiopharmaceutical, whether that's a non-radioactive drug, whether that's external beam radiation. That Theranostic concept is very relevant across a very broad sweep of patients.

Understood. And you've touched on this, but maybe we can go into a little bit more detail, Chris. Your presence in prostate cancer, can you talk about the portfolio and the different pipeline candidates like 591, 597, 592, and 090, and how they're positioned within the prostate cancer treatment journey and landscape?

Well, I think I'll let Richard comment, But maybe just as an open one, I mean, as I said before, these different assets address different diseases. Castrate-resistant prostate cancer is not the same as hormone-sensitive. Palliative care is not the same as front-line biochemical recurrence. So we see distinct disease, distinct market opportunities, and don't believe that a single asset is going to span all of them. And we're really seeing that now with the latest Plavicto data going to earlier lines of therapy, that the risk-benefit profile just isn't there. So maybe, Richard, perhaps you could give a bit more color on the different assets and why we have them.

Yeah, exactly. So as you mentioned, we have different assets depending on the patient population that we want to address. And recently, we have disclosed a new generation peptide asset named the 597 that we, Louise by the way, disclosed these results a month ago at the IPCS Congress, so where she was treating patients, and the dosimetry data were exceptional, so that's something that we are extremely proud of, but I can come back on that in a minute, perhaps.

Okay. Yeah, so perhaps we could dive into that a little bit more detail. You know, what was the encouraging data for you in that 597 trial?

So, as I was just mentioning, so Louise Emmett disclosed recently this data at our Congress in Lugano, and we identified that this compound has what I call a therapeutic window, which is amazing. It's mainly because of the very low salivary tumour uptake and also very low kidney uptake, which confer to the molecule the capabilities to have what we call a load dose, which is 8.5 GbA as a dose that we can administer to the patients, versus the 7.4, which is the empiric way of treatment with the first generation of PSMA compounds. So here we can provide three doses in two weeks, which is amazing, because until now, it was completely impossible to administer this amount of radioactivity with a PSMA compound. So to make a long story short, this compound will be a game changer, especially for patients, as you mentioned, where the quality of life is important. So we would position this compound as a first indication, probably in the hormonosensitive setting, where, by the way, we just obtained the clearance from one center in Australia to run a phase two trial in this hormonosensitive setting with this compound. And in parallel, we have also the 591, which is under the phase three trial, post-aglobal, that we position in the MCRPC setting, first and second line.

And if I can add to that, I think one thing that's good to remember, when you're dealing with very bulky late-stage disease, a macromolecule and a beta-admitter where you have a large protein sink is a very credible way of pretty assertively treating a patient. When you get into a low disease burden, where tissue penetration matters much more, in part really much more localized energy matters much more, you know, that's where the alpha emitters, I think, are going to really come into their own, so, you know, we are, of course, lutetium is a great workhorse, lutetium has, you know, broad potential across the continuum of disease, but what we're really hopeful for, and that's reflected in our R&D pipeline on the alpha side, is really that eventually we'll see alpha emitters get used in that low burden of disease, and I genuinely believe beta emitters will never, in my opinion, based on the data I've seen, give curative intent in early metastatic patients. I don't think that's likely, but I do believe that there's a possibility. If we can keep renal excretion out of it, you know, alphas don't belong in your kidneys ever. If we can keep salivary glands, extracrine glands in general out of it, I think alphas can provide that curative intent in early metastatic setting, I think particularly when we combine it with good imaging and probably external beam radiation. You know, I think that we forget kind of at our peril that standard of care in that early metastatic setting includes external beam radiation. And how wonderful to be able to do combined dosimetry where you're combining endoradiotherapy with external beam radiation. That's going to give you a super durable response. So I think the prostate cancer landscape is really transforming. And to Richard's very good point, quality of life is we've shifted the needle a lot on prostate cancer. Now we need to focus not just on therapeutic outcomes, but quality of life as well. And I think that what we saw at ASCO this year was really a very big focus on, okay, we're getting durable responses, we're improving survival, but now what shape are we leaving our patients in when we've finished treating them, and that's a pretty interesting question to solve.

And you've announced recently a collaboration with Regeneron on co-developing and co-commercializing and some next-gen candidates. Can you give us some highlights from the announcement and what you're hoping to achieve over the longer term with this one?

Well, Richard, I think that was your baby, so why don't you... You did a great job at closing that deal, so would you want to...

Yeah, thank you. So, yeah, we approached Regeneron, and after a good discussion, we decided that we can you know that Regeneron is really extremely well-known in oncology for having a platform for developing antibody drug conjugate. So they wanted to develop and try to test some compounds with radiopharmaceutical activity. So now it's what we call the radioactive ADC, if I can call it like that. So we have a contract with four compounds. that we have to develop jointly with them and then with the option to have four additional compounds. So I would say that we are surfing on the wave of the ADC, which is, as everybody knows in the room, probably a hundred billion dollar market by the end of 2030. So it's normal from a lifecycle management perspective and also exploratory perspective to test radioactivity with ADC. So we are paving the way with, I would say, our two first antibiotic compounds, the 591 that we just talked a minute ago, but also with the gerantuximab compound that we named the 250 compound. So it was a natural path for us to work with Regeneron on this study.

Yeah, and we've always been targeting agent agnostic, but it does take a lot of, I mean, I think most people in the room appreciate, it takes a lot of R&D resources and clinical resources to develop biologics. And actually, there aren't very many radiopharma companies developing biologics. And the reason for it is historical. Radioligin therapy was traditionally run in mostly European and Australian nuclear medicine departments, where they didn't have the financial capacity to develop biologics. And yet, if you look at radiopharma today, it's actually a book-ended industry. So you have small molecules on one side, and then you have mostly intact IgGs on the other end. And there's very little in the middle. and that's an enormous real estate space to study and so when you think about the things that are really exciting in next generation isotopes like lead to 12 actinium ask the team and you think about some of the half-lives and you think about some of the radio biology of these things that middle real estate is kind of where you want to look you know so I'm excited about some of the things that are coming down the pathway small protein formats novel scaffolds things that have you know middish you know blood half-lives like 12 to 36 hour half-life things that are hepatically excreted rather than renally excreted because those will be better for your alphas so there's a really long way to go so I feel like we've just scratched the surface and to Richard's point you know it's very early days on the Regeneron deal and there's not too much to talk about other than what we put out in the public but for the fact that it It also signals that biologics have got some time in the sun coming up ahead, I think.

And if we move on to brain cancer, you've got that phase three trial for glioblastoma, the IPAX-BRITE trial, that you're doing a combination with lamoustine. So can you talk, too, about how this trial is designed and what's the status? Perhaps that's one for Richard.

Yeah, with pleasure. So IPAX-BRIGHT is our pivotal trial for the one-on-one compound in the treatment of metastatic recurrent glioblastoma. The clinical trial is in fact in two parts. We have a dose optimization with Lomostine. It's part one, followed by the part B where we will use the recommended dose and treat the patients. The clinical trial has already started to recruit in some European and Australian countries. We intend to obviously start the clinical trial in the US a little bit further during the year 2026. So that's exactly what we intend to do with this treatment. I have to confess that it's part of our portfolio, my preferred assets, because we know how debilitating is this disease. There's no additional treatment that has been disclosed during the last 20 years. And on top of that, in Europe, perhaps you don't know, but we can do, some physicians in some countries can do homemade or home-brewed compounds that they can inject to the patients. And we have already some publications and also compassionate use programs that we push at Telix to help some patients. And the results are just striking. So that's something we need to transform in a pivotal trial to obtain a marketing authorization and propose for all the patients across the planet.

And Richard, you've also got another clinical trial in glioblastoma, the IPAX2 trial. That's for newly diagnosed glioblastoma patients. Can you comment on that and how that's going?

Yes, you're right. So IPAX2, we just disclosed at the beginning of the year some preliminary results on IPAX2. it's on early stage patients so why because you know in glioblastoma that one of the first intent of treatment is also the external beam radiation therapy so we decided to associate EBRT plus themosolomide with the one one compound and we received the first result there we will have some additional results coming during the year with the long-term follow-up so that that's It's a phase one study, so we will pursue the development of that. But as you know, when you discuss with the authorities, we need to start the development first in last line, and then we climb the lines to the additional indications. So that's the rationale for the IPEX II study. So more to come on this area.

And Rochelle, you're on the roll, so we may as well stick with the therapeutic side. And moving to renal cell carcinoma, can you provide an overview of the 250 program in clear cell renal cell carcinoma, please?

So the 250 program is what we call also the antibody, the general entuximab compound, which is targeting the CA9 receptor, very well-known in oncology. And our lead indication is in clear cell, renal cell carcinoma. So we have a clinical trial named LUTEON, which is a phase 2-3, which has already started in some European countries. and Australia, we just obtained, beginning of May, the IND clearance to start the clinical trial in US also. So it's, as I was mentioning, a phase 2-3 where we have a dose optimization and validation before starting part 2, which will be the confirmatory phase for the efficacy where we are looking for PFS and OS in order to get the registration for this compound. So, once again, I would say it's an amazing portfolio because, as you mentioned, we have prostate, a phase 3 trial, CCRCC, a phase 3 trial, glioblastoma, a phase 3 trial, so that's a lot.

But also coming in behind the prostate portfolio, which is obviously the most mature, but the PIXClara asset, which has got a PDUFA date of 11th of September, and then Xerchaix, which is the renal cancer imaging product which is just about to get resubmitted our BLA resubmitted after a setback last year on the manufacturing side these two imaging agents I mean they image the targets we treat gerontuximab is actually the same targeting agent as our therapy program in fact with the manufacturing changes we've had to make really the future CMC pathway for the therapeutic is really cross-referencing the diagnostic BLA package and so it gives us a lot of confidence you know we've we've imaged I mean with was their cakes I don't know how many patients we've damaged hundreds hundreds and hundreds of patients and we've had an expanded access program open for for a long time I think we've had a couple hundred patients in the US alone under that expanded access program so that gives us really a lot of confidence in our understanding of the target, what the dosimetry looks like, you know, what the patient profile and disease presentation looks like, and so I think it's, again, you know, I mentioned in the beginning that it's not, we don't call it diagnostic imaging because we don't think that the diagnostic piece is actually all that important. The precision medicine piece is really important. The imaging allows us to run smarter clinical trials. It allows us to do better patient selection. It allows us to measure treatment response assessment. And even in the case of the 250 program, it actually de-risks our regulatory pathway because, you know, that's an example of a kind of a true theranostic pair. So I think that the imaging provides just really profound benefit to the therapy programs. I mean, we always think internally, how do we integrate? What's the imaging going to tell us? What's the edge that we can get out of a therapy program from what we know imaging that target?

Understood. and you've already mentioned that you're agnostic to the targeting agent so a question maybe for both of you you're agnostic to the targeting agent and the isotope can you talk to us about how you think about the development of the next generation candidates that you guys are going to go after so really that's not a fireside chat that's like a bonfire chat conversation with a couple of bottles of whiskey I think or tequila or something.

I think, look, at the end of the day, I've always said it, and it's not a popular sentiment, but I hate platforms. I think that, you know, you say I've got a particular targeting moiety that I like, and all of my biology is going to be based around the limitations of that moiety, or I have a particular isotope that I like, and all of my biology is based around that particular radio biology, just not the way we manage cancer. So when we think about it, in fact, it's one of the reasons why we've started to do some internal innovation around protein engineering is to think about okay what's the what's the bio distribution of the disease we're trying to tackle what are the clearance organ considerations that we are trying to to map into the target product profile you know if we want something that's you know hepatically excreted or really excreted and we make decisions like that you know sometimes it really matters um then then it's cost right like i i'm i keep hearing that oh a terbium will be the next thing to cannibalize lutetium but are you going to really set up a global supply chain for terbium for 10 more uh clinical consequence right and the answer is probably not right so economics plays a big role uh distribution plays a big role um so you know what's your half-life of your product when we did when we dispense a dose of elucic we dispense it from 266 nuclear pharmacies in the United States with a two-hour shelf life that's got a whole supply chain associated with it but actually we made decisions in the chemistry and in the physics of that product that map onto that supply chain infrastructure so that's why we we do take that agnostic approach and as far as studying I mean Richard's team is studying very closely the future of all of the alpha emitters and not all of them but there are many more than what we are looking at but we you know certainly the three frontrunners of astatine actinium and lead to 12 you know we have a really good handle on that we have our own lead generator we make the TCM we are partnerships around actinium that are very advanced in the R&D phase so we We want to understand these isotopes very well so that we can factor them into our economic, clinical, and development decision-making.

Very good. Well, maybe we will get that drink later and talk about it some more. But we're getting the wind-up. We've just got one minute to go. Luke, Richard, perhaps over to you for the last question. So any sort of underappreciated assets that the market's sort of not looking at that they perhaps should be?

Oh, in our portfolio, perhaps, the FAP. I would say we acquired last year a portfolio of FAP's compounds, one for diagnostic and two for therapy. So we are currently developing that also. FAP, as you know, is targeting the tumor microenvironment, and I'm a big fan of this mechanism of action because it's for all resistant cancer where the microenvironment is there and does not authorize the classical therapy to treat the patient. So there's a lot to explore in this dimension with alphas or beta, probably more, because we need to target a bit broader than just the tumor cells. So, yes, that's the fact I would position in our portfolio as something which is not currently valued and that we are developing.

Yeah, that's a great point. so we've got the we've got the wind up now we're gonna have to end it here and thank everyone very much for their time thank you very much team and yeah