Welcome to our next fireside chat. I'm Robert Burns. I'm Managing Director and Senior Biotech Analyst at H.C. Wainwright. I am joined today by the CEO of Telix and the division head of Precision Medicine from Telix. Gentlemen, thank you for joining us today.
Pleasure.
Thank you.
So from a high-level overview, given that the interest in the radiopharma space has been increasing, and while it's not fully there yet, maybe provide an overview of the company and its pipeline for our less well-educated radiopharma enthusiasts.
Well, thank you. First of all, appreciate the opportunity to be here. We're a fully vertically integrated, theranostic radiopharmaceutical company. I think most people know this amalgamation of diagnostics and therapeutics. What that means is that for every target that we develop, we develop both an imaging product and therapeutic drug. We think that this is an important thing to do given the nature of this class of therapeutics. It's sort of a shame to inject radiation into a patient and then not see where it goes, and be able to optimize the patient management process accordingly. And we've built a pretty vibrant business commercializing the imaging products in advance. They tend to have a more streamlined regulatory process for the most part.
Yeah.
Present speed bumps, except our recent speed bumps accepted, but we've commercialized the imaging business this year. We'll do about $1 billion in sales of our imaging products, mostly our prostate cancer imaging product, although we did just get approval in brain cancer as well. That cash generation really fuels our R&D engine. I think we have the most vibrant therapeutics pipeline in the industry, including a bunch of late-stage trials. We have three phase III trials currently recruiting. We've been able to finance a pretty formidable R&D engine off the precision medicine business. We don't just see it as a necessity of radiopharma.
Yeah.
We see it as very much our bank account for
Yeah
funding the R&D. Today, we have two major focus areas, and we have some rare disease areas that we dabble in, but our major focus areas are in urology and neuro-oncology. I think maybe this last comment is really on the supply chain and manufacturing. I think that the street and the market knows that radiopharma companies were making just-in-time products. They have short shelf lives. They have lots of distribution challenges. Over the last, well, really over the last five years, since about 2020, we've very systematically built a lot of infrastructure globally.
We have our own radiopharmacy distribution network in the U.S. We have our own manufacturing facilities in Europe and Japan and Australia. We feel that we've built the isotope manufacturing supply chain and distribution to deliver our products. Last year, we delivered about 3 million patient doses, so this is now a commercially scaled activity. I'll pause there, but hopefully that gives you a bit of color.
Yeah, no, that's great. Before we hop into the pipeline, the recent FDA approval, and the infrastructure, maybe talk to us a little bit about your guidance a little more. I saw in your last Q that you revised, modified the guidance for 2026 more towards the upper end of that spectrum. What do you think is pushing that change, and do you think that there's more potential for you to revise it higher?
Well, guidance is guidance. We had a very strong first half. I guess if you flatline the first half, you get to our guidance.
Okay.
Last year, I think in the environment that we're in right now, there's not a lot of value in kind of casual guidance adjustments. We're sticking to our guidance for the year, but clearly the company is tracking in a positive direction. I think we'll just leave it at that.
Okay. Why don't we focus on your precision medicine portfolio first? I think this is going to be more directed towards you. Obviously, on Sunday, we saw the FDA approval of Pixclara, which is going to be the first PET imaging agent for glioma ever. Maybe talk to us a little bit about that market opportunity, how you see the launch curve going over the next several quarters, just so people can orient themselves within this market. Because typically, there really has been nothing there for patients from the radioimaging perspective. For modeling's sake,
Sure
talk to us a little bit about that.
Sure. Well, we've characterized it as not as large of an opportunity as PSMA, but that doesn't mean it's lacking in importance, right? It's important for patients, number one. We chose that indication because it really met one of the highest unmet needs, which is really figuring out as quick as you can whether or not you're getting treatment-related response or actual progression in the tumor so you can get to the next therapy as fast as possible. We chose that as kind of the lead-in indication. It's great for patients, but for Telix, it also gives us that third product now. We're a two-product company right now. As of Monday, we're a three-product company. As I would characterize that, what it enables us to do, remember, those scans are read by the nuclear medicine physician, and we have a great relationship already in that space.
We call on urology and nuclear med, and now we have a small team that does the neurology business that drops that down into the nuc med department. We see a lot of synergies in that. We think that out of that market opportunity of 20,000+ scans, we will be able to really penetrate into that market because of the way we are set up. That really adds just to the leverage and layering, if you will of that platform inside of Precision Medicine across these nuclear medicine facilities across the U.S.
Yeah. From an internal revenue projection perspective inside Telix, how are you thinking about peak sales for Pixclara?
Well, I don't know if you can go into that.
Kevin mentioned that there's a kind of theoretical TAM, which is a very disciplined, it's a kind of incidence and prevalence, which, in GBM is kind of one pool.
Yeah.
It's 20,000 - 25,000 scans.
Exactly
We also know that imaging is used multiple times in that recurrence journey, and the label's actually quite broad. It gives us a lot of flexibility on how one defines progressing disease.
Yeah
It is kind of a bit of a gray area in GBM, I would say. We expect that 20,000 - 25,000 scans, which is super theoretical, that is a bit dogmatic. It will be used multiple times. Every time there is going to be a change in clinical presentation.
Another scan.
you're going to get a scan. That's how we see the practice outside of the United States. The NCCN guidelines and other guidelines are much broader than our label. We, of course, intend to occupy the. We are doing clinical work to fully occupy the guideline space.
Yeah
But I think there's lots of upside. We think coming out of the gate, there's a couple of hundred million dollars of business in Pixclara. Then, maybe you want to mention our very exciting phase III trial that we have running as well. I think that's critical.
Yeah. You saw in July we announced that we also want to get into the metastatic brain tumor as well.
Yeah
We believe that that's a multiple of four to five times the original indication. Again, it will just slide right into what we're already doing in that nuc med space. We've already got teams calling on the neuro-oncologist, so you'll see a lot of synergies inside of that kind of TAM expansion. We're excited to kind of progress that trial on through enrollment.
Yeah. This is one of the things that I love about Telix, and this sort of leads nicely into the segue to your next imaging product, which is Illuccix and Gozellix. Obviously, we saw that you completed enrollment within the phase III BiPASS trial.
Right.
That's for the detection of prostate cancer. You've been in that space already, but now you're moving up sort of that treatment paradigm here and the diagnostic paradigm. Maybe walk us through the evolution of the diagnostic paradigm across the prostate cancer space. You've also noted that you've aligned with the FDA regarding an NDA pathway here. Maybe give us a little bit more color around what that entails.
Sure. That's a big bite.
Sorry
Let's take it a little bit at a time. First of all, there's 340,000 new prostate cancers diagnosed each year. Each of those require a biopsy. The bigger picture is that there's 800,000 men that undergo biopsy. What you would hear from a urologist if they get a negative biopsy is that, "I can't tell you that you don't have prostate cancer. I can only tell you that I can't find it." That means in a year or two, based on their presentation, they're going to get another biopsy and another biopsy and another biopsy until they rule that out. The reason for that is just because the sensitivity and specificity around biopsy is good, but it's not great.
We think we can do better, and that's what BiPASS is really geared at, is how by adding PSMA PET gallium before the biopsy can actually rule out the need for a biopsy. What happens then is you get a PSMA gallium scan bypass, and maybe you can bypass the biopsy, which is kind of the key part of that, because if you get a negative PSMA scan, if and when the trial is approved, then you would forgo that biopsy, and then you might get put in again a year or two later for another scan. That's really important. The other really important thing is, the dirty little truth is that 200,000 men say no to biopsy.
What happens to those men is we find them later on with either become symptomatic or their PSA is just out of the roof and they have to do something. If you sat down with a urologist, he would tell you how difficult it is to talk a man into a biopsy. The urology field is really getting excited about this as they become more confident in PSMA scans with our existing indications. Now their confidence is strong as they're thinking through the ability to be able to get a man to go ahead and take the BiPASS scan. If it's negative, none and done, and if it's positive, one and done. So there'll be a more precision biopsy done where they focus in on the area where the little red dot is.
Yeah.
That's what they go for.
Yeah, that definitely sounds more ideal from at least from a man's perspective, than what the current standard diagnostic paradigm is. Maybe walk us through what the design of that trial is. I know at least from my perspective, the odds here seem relatively de-risked considering what we've seen in other trials. So maybe talk a little bit about that as well.
Well, I would put it simply that it is really in the, that the trial itself is standard of care except you put a PSMA PET right in the middle.
Yeah.
It is rising PSA, MRI, and then intent to biopsy. So if the physician has intended to give a biopsy, then the patient would get a BiPASS PSMA PET gallium scan, and then they would go on to biopsy. That way, we have a source of truth.
Y eah. And you are correct. We actually took the primary data and then the primary two protocol. We took it some years ago. It is the benefit of having some Aussie roots. And we have a very vibrant nuclear medicine community.
Yeah.
And we actually took that protocol to the FDA and said, "Could we get a label for this?" And their view was that it was not designed. It was a hypothesis testing study. It was not really designed to be a registration study. So you should really think of BiPASS as primary three.
Yeah.
It was designed and sort of evangelized by the folks that did primary one and primary two. We really get the benefit of the data that's already out there, which I think is going to influence practice guidelines very quickly.
I certainly agree with you there.
Can I add one more thing on that?
Yeah.
Because we see this as transformative for men and transformative for Telix. When you think about the opportunity here to move before the biopsy, pre-biopsy, or before the snap, we call it. If you're before the biopsy, the opportunity for redistributing the rest of the scans that would come downstream in a patient's journey become pretty obvious in terms of, well, if you've got a BiPASS, you no longer need initial staging. You've already got staging. If you see more about multifocal or unifocal disease, then the physicians we talk to on the advisory board tell us they'll do better surgery.
Yeah.
That better surgery could create a diminishing biochemical recurrence. Overall, by moving upstream, we create this baseline with BiPASS, then we believe from a commercial perspective, the transformative nature of this for us is then the scan's sticky.
Yeah.
You have a baseline scan with our product. They are going to want to see it throughout the patient's life, so they always know what the first one was. That is a million, 1.2 type market that we are talking about. So a million times anything is a lot.
No, it is definitely going to be a lot there.
I mean, you asked a question about the NDA. So now in that pre-biopsy setting, this is not a staging, restaging indication. We took the view, and the FDA supported the view, that this is not a label adjacency.
Yeah.
This is a whole. I do not know. I am trying to think of what is a. Like BOTOX, you have cosmetic indications, you have neuro indications.
Yeah
You have continence indications. We decided that we wanted to wrap a new NDA around this so that we have the ability to. And there are some things that we plan for this product that are a little different.
Okay.
It does reference Illuccix and Gozellix, but we have a slightly different vision on how the product will be incarnated.
Okay.
What that means is that we get the opportunity to position it differently, distinctly brand it, and also from a distribution and partnership relationship, it is really a carved out space.
Okay.
As you will be aware, we own our own nuclear pharmacy network.
Yeah.
We have been very selective about who our best partners are going forward, and we want to retool a little bit our distribution strategy as well. One of the things you will have seen in our half-year results is that RLS, for example, our in-house pharmacy network went from being the fifth largest distribution network that we use in the United States to the second largest.
Yeah.
The margin impact of running our products through our own distribution and select partners like Cardinal Health, that has a very big consequence for our company in terms of-
Yeah
cash generation. BiPASS is an opportunity to really rethink that.
Okay. Perfect there. Why don't we shift gears a little bit? Well, actually, before we shift gears, when do you think that we might start to see initial data from BiPASS?
Do you want to answer that or I can. Look, we've recruited a trial.
Yeah.
We're now in a six-month observation period. So really, the trial will read out around the end of next year or early next year. Maybe you'll see, I don't know, late-breaking ASCO GU type of thing.
Awesome.
Really, I think practically speaking, it's early in the new year.
Okay. Perfect.
Yeah.
Why don't we shift gears to the therapeutics pipeline? Obviously, there's been a lot of developments within this space. One of them being that you aligned with the FDA regarding ProstACT GLOBAL 2, and that includes the statistical analysis plan as well as trial protocol. Given that, I know that ProstACT GLOBAL 2 has been recruiting outside of the U.S., but you haven't been able to do that yet within the U.S. So talk to me a little bit about when you think you'll be able to get that up and running here.
Yeah. So the Part one was the only regulator that really required it was the FDA.
Yeah.
Everybody else was fine with the trial. We respect that, and that was fine. We elected at the end of the Part one to have an end of Part one meeting with the FDA just for the specific purpose of reviewing that data and getting their agreement that that study component met the objective, and that there was no impediment to us randomizing patients. So the FDA agreed to that, and we've reported that outcome. In a couple of weeks' time, we have a pre-Phase III meeting formally to update and align our IND with the rest of the world.
Okay.
Because in the intervening period of running this little study for the FDA, we actually launched a Phase III trial
Yeah
in seven countries. It's just about protocol harmonization and CMC harmonization. I don't expect that to be problematic. We have many sophisticated regulators that have accepted that package. We got a little bit more procedural work to do. I do expect that we'll get U.S. patients in before the end of the year. Investigators are waiting for it.
Yeah.
It's a really exciting study. Investigators that have experience, including in the U.S. with it, they love it. I think it's a really underappreciated aspect of TLX591. It's a very short treatment duration.
Yeah.
It's a very intense, short, easy to weave into your.
It's so different than Pluvicto.
It's so different than Pluvicto, and from a patient perspective, you slot it in between your ARPIs.
Yeah.
It gives you a break.
Yeah.
That's the ultimate.
That's nice.
That's the ultimate opportunity, rather than having to concurrently run what is effectively 40 weeks of therapy.
Yeah.
The way that we've designed the trial, the flexibility on the standard of care options, I just think it's such a differentiated approach. We're really excited to get U.S. patients into the study. And obviously the FDA has to bless the amendment.
Yeah.
From a clinical data perspective, the part one was a real success.
Yeah, no, I completely agree with you there. How has enrollment been going ex-U.S.? When do you think we might see interim analysis from part two?
Good. Yeah, so it's recruiting well ex-U.S. I think we're live in, maybe as of this week, maybe we're live in eight countries. Canada, U.K., Australia, some Asian countries. We have approval in Japan, China, Singapore as well. So we're really looking at this globally, and frankly, that's part of the opportunity for the asset, given that it is a very straightforward treatment protocol, and there are a lot of countries in the world that don't have access to the current standard of care. I think we really see that as worthwhile
Yeah
globalizing the study from the outset. The U.S. patient recruitment is not on the critical path for interim readout.
Okay.
We've previously indicated we expect to get that interim readout by around the end of this year or early next year. Obviously, it's event driven, so we don't have an exact date for you. We are in really good shape to meet that goal.
Okay.
We are on track with recruitment.
Awesome. One of the things that we noticed last month was that the FDA approved Pluvicto, plus an ARPI in the metastatic hormone-sensitive prostate cancer setting. Obviously, you have TLX597.
Yes.
That is also going into that setting. How is that agent differentiated versus Pluvicto? Talk to me a little bit about why adaptive dosing can be so monumental.
Yeah. So TLX597, and this came out of the blue, so a lot of people are sort of like, "What?
Yeah.
Where did that come from?" We do believe in alphas. I have always said, I think pretty consistently, betas are going to be much better in bulky disease. Antibodies have a super advantage in castrate-resistant disease.
Yeah.
It has been extensively published. The internalization of an antibody means that in low PSMA-expressing disease, as prostate cancer progresses into later stage disease PSMA levels go way down. In fact, when you have advanced, heavily pre-treated disease, it is almost neuroendocrine-like. You could actually take a somatostatin imaging agent and image a prostate cancer patient in advanced castrate-resistant disease, and you will see target expression. Like it is-
Interesting
in fact, there's a recent publication that just came out. The important thing at the outset to know is that prostate cancer is not one disease. There's primary localized disease, has a very distinct biology. There's hormone-sensitive metastatic disease, very different biology. Castrate-resistant disease, really different biology.
Yeah.
Then end-stage castrate-resistant disease, very different biology again. The bulk of the disease matters. So when we're talking about hormone-sensitive cancers, we're really talking about a low burden of disease, and a macromolecule is not going to be the ideal
Yeah
targeting vector there. A beta emitter is also not going to be the ideal targeting vector there because you're talking about, for the most part, fairly small tumors. So most of your irradiation energy is going to go outside of the tumor.
Alpha is ideal there.
We have two alphas. We have two horses running internally in alpha. We have TLX592, which is a PK-engineered variant of TLX591. It is really about getting actinium out of the body as quickly as possible.
Yeah.
We think that is really important. And it is also a hepatically excreted agent.
That's essential.
We don't want alphas anywhere near your kidneys.
Yeah.
We don't want alphas in your salivary and lacrimal glands. That's the whole strategy around TLX592. But what we wanted to see is, could we engineer a small molecule with a cleavable linker that would have better tissue penetration for very small lesions, and that's why we developed 597. So 597 has a really different chemistry compared to the sort of existing urea motifs that are in that space. But because of the linker design that we've developed, essentially what it does is it leaves a lot more residualization of lutetium, and it doesn't have the same glomerular filtration profile in the kidneys, so we see about a fifth of the kidney dose, and then we see about a similar sort of decrease on salivary glands.
So really, it was originally designed with actinium in mind, and in fact, we still intend to explore that asset with actinium. But when we started to see some of the data come out on the hormone-sensitive side, which look, I think it's a great step forward for patients. We want alternatives to chemotherapy.
Yeah.
We want alternatives to ARPIs. The data is not a slam dunk either.
Yeah.
I think that the long-term quality of life issues, one thing that happens is that as we move into patients that have a lower and lower burden of disease, you are going to see more and more cytopenia, you're going to see more salivary gland impact because there's less of a sink for
Yeah
the radiopharmaceutical. I think that that's kind of evident in the data that we're seeing. So we feel that the current standard of care is really not optimal for the hormone-sensitive space. There's a need to develop pharmacophores that are better suited to that disease profile. That's what 597 is there to do. To start off with, we ran a randomized trial between a standardized Pluvicto dosing schedule versus a dose intensification. The reason why we can do the dose intensification is because we have such low renal, I mean, basically our off-target effects are way lower. We can give the patient much more activity. If there is one thing that we have learned from SPLASH and ECLIPSE, for example, right, is that it is a dose-dependent relationship.
Yeah.
Right? Getting more in is good. The other thing that we have learned about in the hormone-sensitive space, which is just super exciting, like game changer, first dose of PSMA therapy in a good responder typically results in an upregulation of PSMA, and we want to treat into that.
Yeah.
Our dose scheduling is day one, get the flare verified by imaging, of course. Get the day one, then we dose intensify for day three.
Smart.
Day 15. That is actually the bulk of the therapy. If you think about what that looks like, it is the small molecule dosing equivalent of TLX591. We have been doing dose intensification for a long time.
Yeah.
It is just that we haven't done it in the small molecule context.
Yeah.
Follow-on doses after that, every six to eight weeks. Those are just maintenance doses. The bulk of the therapeutic response is in those first few doses.
Yeah.
Think about that from a patient compliance perspective, right? I mean, we see the majority of that treatment response in those first two weeks.
Yeah.
I really would encourage you to think about TLX597, TLX591. They're morally equivalent. It's just that they are optimized for different kind of disease presentation environments.
Yeah. I've always loved that about Telix, is its forward-thinking nature and how to best treat not just an indication, but different settings with an indication. That's exactly what you've done with TLX597 and TLX591. All right? Two different approaches, but optimized for the exact same disease.
Yeah.
Obviously I could talk to you guys, I could talk to you, Chris, all freaking day long about your portfolio, but we've run up on time. But I'll be talking with you later, so thank you, gentlemen.
Yeah. Thanks for the opportunity.
Thank you. Cheers.
Always a pleasure.
Yeah. Thank you.