Pedro Barata: Neeraj, such a pleasure to be here with you. Thank you for the opportunity again.
Neeraj Agarwal: So first of all, congratulations on the oral presentation at the ASCO 2026 meeting, where you presented a novel radioligand therapy based on antibody targeting of PSMA receptor in prostate cancer. I thought data were very well received. Could you tell us more about the mechanism of action of this new radioligand therapy, and then you can walk us through the rest of the data you presented?
Pedro Barata: Absolutely, Neeraj. Thank you for the opportunity. It's great. And so maybe to facilitate, I'm going to pull up slides and walk through the story for our group... for our audience today. Okay. So just going to... Neeraj, if that's okay, I'm going to walk through the safety and dosimetry of TLX591 that's known as lutetium-177 rosopatamab tetraxetan. So this TLX591, along with standard of care of either ARPI or docetaxel for patients who progress on prior ARPI, also known as metastatic CRPC or APMR according to the new designation by PCW Group 4. I'll stick with PCW Group 3 designation, mCRPC.
So what is this? So great point, Neeraj, the opportunity to explain. So it's actually not radioligand therapy. This is an antibody-based construct. PSMA is the target. Lutetium-177 is the payload, and it's antibody-based construct. Therefore, it is a large molecule. Preclinical data have flight around 5.6 days. It is given in a fixed dose of 76 millicurie times two, 14 days apart, two weeks apart. And it has an uptake in the liver, as you see there, as fecal excretion. So, unique characteristics for this radiopharmaceutical construct, if you will.
So, following monotherapy clinical data, Phase I is called SELECT (ProstACT SELECT). The study here had the goal of understanding the added value of TLX591 on top of standard of care for patients who progress on prior ARPI. And as you know, there are regional differences in US ARPI switched. It is still the most common management. In the rest of the world, docetaxel is the most frequent therapy used. So this trial respects the regional differences around the world between the provider and the patient to define what is really their standard of care for... in the context of CRPC.
And so the trial was designed in a very pragmatic approach like I explained. You really have two-part study. The first part focused on safety and dosimetry is what I'm presenting briefly the data today. And then you have the part two, which is a larger randomized perspective portion. So today basically patients allocated to part one were assigned to TLX591 with either abiraterone, enzalutamide, or followed by docetaxel. So here you'll see the CONSORT diagram. Basically, 57 patients were considered for the study. Ultimately, 36 patients enrolled.
The reasons for exclusion were mainly due to imaging or organ function. I should say an important definition for the imaging. Patients must have had positive PSMA or at least one lesion who had a TLR tumor over liver ratio of two or higher and could not have negative lesions. So ultimately, 36 patients enroll in the study, 11 with abiraterone, 11 with enzalutamide, and then followed by docetaxel. Every... All the patients were able to receive the two doses of TLX591 and then they embark on the therapy they were on that I described. This is really a population slightly older, 77 meaning age.
Most patients received prior ARPI in the CRPC setting. They basically one quarter received docetaxel for hormone-sensitive disease, and they had more visual disease than one would expect, around 36% or so. So here's the safety data. We basically broke it down by hematologic and non-hematologic signal. The non-hematologic were basically minor, grade ones, grade twos, commonly fatigue, nausea, dry mouth. We did not recognize major significant side effects, and there were no toxic deaths or grade fives. Hematologic events were frequent, often thrombocytopenia, neutropenia, and lymphopenia.
I should say there's no bleeding events that occur. And also, there was one episode of febrile neutropenia. We actually look at the amount of blood projects needed, and there were single digits of blood transfusion, single digits of growth factors used, and 14% of platelet transfusion. I should highlight, actually, the platelet kinetics to show the transit nature of that profile. You can see here the dip, which is pretty consistent across the three cohorts of abi, enza, and docetaxel with TLX591. You see the dip happening at 43 days and then a recovery to grade one or better around two weeks later, 14 days later.
And that was pretty consistent across cohorts, which really shows you that transient nature of that cytopenia, if you will. The other aspect, we are able to show the low radiation exposure to the different organs, really below the safety limits for reference in this graph. I would get your eye on the kidney drug exposure or dose exposure, as well as salivary gland. And I should also note this is really aligned with what we know from TLX591 monotherapy profile in prior clinical experience like the SELECT (ProstACT SELECT) Phase I trial. And this is just an example of a patient who is allocated to abiraterone with TLX591.
This patient received... was enrolled in the study, and you can see here the SPECT data. Look at the baseline. You see the salivary glands on the baseline PET scan, and then you don't see that uptake, which really matches what we see on the dosimetry data. And then you see the SPECT CT over time, all the way to 15 days following one dose of TLX591. You can clearly see that tumor retention across time, if you will. So, basically, at the time of cutoff, most patients were alive and on the study. We do see the safety and tolerability profile of TLX591 in the different cohorts with standard of care.
We see low salivary gland and kidney radiation exposure, and we see this sustained tumor retention in the SPECT data through day 15 following administration of TLX591. So really, this feasibility demonstrated in this part one, and the ability to integrate this with standard of care allows us to proceed... to pursue further investigation in the large randomized Phase II or part two portion of the ProstACT global study that is actually currently ongoing in some parts of the world right now. And so we'll see what happens once we're able to leverage that part two.
I will spend a second to thank the patients and the families, and the network supports for being able to participate in the study so far, as well as our co-investigators. Neeraj, you are senior PI on the study play a major role in leading the charge here. Thank you for that. And of course, recognizing the role of the sponsor, Telix, for sponsoring this big effort, right. Close to 500 patients plus around the globe. So thank you, and we'll see what happens in this larger portion of the trial. And thank you for the attention.
Neeraj Agarwal: Yeah. So thank you for taking the time to give a snapshot of your ASCO 2026 presentation. This is great. So obviously, anytime we talk about lutetium, we think about radioligand therapy. So I'm glad you explained the difference that this is not a traditional small molecule carrying lutetium here. This is a big antibody known as rosopatamab, which is... technically which can carry a larger amount of radioactivity to the prostate cancer cells.
And it is targeting PSMA, which is a validated target as evidenced by approval of Pluvicto or lutetium-177-PSMA-617 in this setting. The other aspect we learned from your presentation was patients need only two doses of TLX591 or antibody carrying the lutetium-177. So the treatment period is abbreviated to pretty much 14 days. So you get first dose, and you get second dose two weeks after, and you are pretty much done with your radiopharmaceutical therapy, and you can go on with your journey with any other medication you like. Is that correct?
Pedro Barata: No, that's right. I think, Neeraj, you're highlighting the characteristics of these molecule that I think are unique and may provide competitive advantages over other options out there. Of course, it's also being explored in the context of standard of care. So it's not being explored as monotherapy, which is also an important difference, right. So the concept is different. The features of the molecule are different.
Of course, at the end of day, we got to see at the end the activity of that approach, but it's certainly a different approach, different characteristics. And we'll see what the impact of the added value of TLX591 is or gives to patients that get to CRPC progressing on prior ARPI. First, to figure it out, how can we include that in the management of patients with advanced disease?
Neeraj Agarwal: So I love the way you said it. T59 or TLX591 antibody carrying lutetium-177 is not a therapy versus other. It is basically added to the standard of care therapy because it can be given over two weeks and then you carry on with your other treatment, whether it is docetaxel or alternate ARPI, which is huge for our patients because you have presented published the real-world data that half of the patients in metastatic prostate cancer setting don't get to see second line of therapy or subsequent line of therapy. And because this is an add-on therapy rather than one therapy versus other, I think this provides a huge advantage to our patients to avail two therapy at the same time instead of having to sequence. Right?
Pedro Barata: Right. No, that's absolutely true. I can see the advantages for where we're presenting this to a patient. And, quite frankly, there may be why it's been relatively easy to offer this in clinical practice. When we offer a clinical study, patients, we go through the logistics and we go through the characteristics of the therapy. And in this case, that has been a plus, right.
The fact that they understand, the patient understand, "I'll get this. Two weeks later, I'm done, and I continue to get with ARPI or consider chemotherapy afterwards." So from that perspective, I do see the potential advantages. Again, we got to see how the efficacy pans out and that balance and see what happens. And we got to wait for part two to really establish the exact role in the disease for sure.
Neeraj Agarwal: And as you said, randomized part two, which is a randomized portion, is already enrolling in many parts of the world in Asia, Australia, and many other countries. So we really hope to see the results of the Phase III trial in the near future.
Now talking... coming to the side effects, it was intriguing to see the organ exposure data and minimal exposure to salivary glands or the kidneys mostly metabolized by the liver frequently excreted. And this is quite unique from the other lutetium therapy, which is approved in the setting. Could you please comment on that?
Pedro Barata: Absolutely. So, as has been pointed out in the past, I mean, when we use radiation delivering in this way, when we clear it in the renal system, of course, there's an amount of radiation that's going to get into the urinary system that may compromise patients in the long run. That has been an important aspect, or as we call it, an adverse event of special interest.
We want to make sure nephrotoxicity does not compromise patients from receiving subsequent treatments, right. And so that is an important aspect. As we saw from the organ radiation exposure, as you said, which has to do with the characteristics of TLX591, that doesn't seem to be a real concern, and that's important or reassuring because, as we know, we need renal function as intact as possible for us to be able to receive other therapies of interest to treat prostate cancer.
Neeraj Agarwal: Especially in leronlimab.
Pedro Barata: Exactly. And so if you reduce the amount of radiation to the organs, you don't predispose them to potential risk in the future. So I think that's a... in that safety aspect, that is very relevant, and that's what we've been seeing so that those imagery data matches the clinical observations. There was no renal failure or renal insufficiency after receiving TLX591 would make us concerned about the dose being considered. These dose actually lower, right.
76 millicurie times two is lower from what we... compared to the amount of radiation that we can deliver with other radiopharmaceutical options out there, which is obviously less radiation if effective, gives you enough room to receive other forms of radiation therapy in the future as well, considering the organs that have a limited amount of radiation they can absorb during lifetime, right. So that is also an aspect of consideration.
In addition to that, I think is relevant low exposure to salivary glands, which matches the clinical observations of the lower Xerostomia, for instance, which is important to patients because it does change the quality of life or can impact quality of life in a dramatic way. And so, from that perspective, the profile of therapies needs to be matching the quality of life that patients perceive them. And I think those characteristics are really well aligned on the safety side from that perspective.
Neeraj Agarwal: Well, such a great presentation, Pedro. Again, thank you for taking the time and really exciting data on this new antibody-carrying Lutetium-177 requiring only two doses and quite acceptable safety profile with relatively low exposure to salivary glands and the kidney, which is, again, exciting for our patients. I'm really hoping to see good results from the ongoing Phase III trial and hopefully another treatment option for our patients in the near future.
Pedro Barata: Right. So let's hope for that. The study's ongoing part two, as you mentioned, Neeraj, and we'll see how it goes. I know it's enrolling well, and I'm hoping as well, and a positive study means good news for patients, so we're all looking forward to it.
Neeraj Agarwal: Thank you.
Pedro Barata: Thank you very much.