Frankis Almaguel: Yep.
Phillip Koo: Tell us about the methodology of how you calculate dosimetry in the ECLIPSE trial.
Frankis Almaguel: So the idea is we know where the radiation is going and we're able to detect those gamma radiation from a specific area. And we have specific software that'll tell us, will give us a dedicated level number from each location. So basically we can tell which area is receiving what amount of this radiation.
Phillip Koo: So Frankis, tell us a little bit about the methodology regarding how dosimetry calculations were performed in the ECLIPSE trial.
Frankis Almaguel: So basically we had a sub study of patients that we went ahead and did dosimetry. We selected 26 patients from the whole ECLIPSE trial and we did multi-point SPECT/CTs to calculate and have all the maximum data to know where was that radiation going to. To more normal tissues and give us an idea of how safe this is.
Phillip Koo: Great. So when we talk about dosimetry, we talk about radiation exposure and healthy tissues. Oftentimes the discussion focuses on renal exposure. And that obviously is very key and we're learning more about potential renal toxicities with some of these therapies. What was some of the important findings that we learned about renal exposure in the ECLIPSE trial?
Frankis Almaguel: So the data shows that our dosimetry going to the kidneys is comparable to the studies which have been done before and telling us that it was safe to move forward and do the number of treatments that have been supported in the past. So we didn't have that evidence before. And having this dosimetry study, this sub-study allowed us to show that it was safe to have the right, the dose that we were planning and the number of treatments that were planned. And that is very important because it really affects the way the patients respond. Because if you under dose and you decrease the number of treatments, then you can understand how outcomes can change.
Phillip Koo: I think it's important for listeners to know obviously the goal is to be able to maximize delivery of dose while keeping it safe. So there was an interesting modification of the trial due to learnings regarding radiation exposure to the kidneys. Can you tell us quickly about what that was?
Frankis Almaguel: Having this dosimetry data allowed us to increase from four treatments to six treatments. And that is really important because we understand for this patient population where the options after available are not as abundant. And having the right number of treatments did actually make a difference. And we expect that this is something that we want to learn more in the future that having the right number of treatments and the right dose delivered at each time not only is safe, but it's also able to increase the positive outcomes of these patients for this therapy.
Phillip Koo: I think that's a fascinating point that the trial was able to adjust based on the safety data, the exposure data, the dosimetry data, to then understand that we could give more doses and still keep the patient safe. So I think that's really wonderful. How will this information be used by the FDA to assess this drug? Frankis Almaguel: So it's a very good point. We have to make sure we follow the guidelines and the regulations that we have. And the FDA trying to make sure that the trials are done in a safe manner, have some specific points. "Hey, we want this to be safe." So they have some numbers that we have to work around. I don't want to give too much details, but having this dosimetry study gave us the assurance and the security that this therapy was safe.
The key organs like the kidneys and bone marrow were receiving very small amounts compared to the amounts that were getting to the tumors and really allowed us to move forward actually to help our patients. Because actually halfway through the trial, we had to say, "Hey, we have the data. We can increase it to six cycles." And you'd be surprised how many of these patients were so eager to get back to this. And as you know, the right patient for the right medication at the right time with the right dose is something that, when you put it together, it's a work of art. And kudos to all those behind the scenes making these sub-study and these actions happen. It involves a lot of people. And with radiopharmaceuticals, as you know, we have great medications. We have a lot of things to move forward, but the idea is, we're excited.
Phillip Koo: I like that. Right patient, right time, right dose. And I think those are some key points we could walk away with. So Jason, first off, congratulations on being one of the investigators of the ECLIPSE trial, which I think is so important to increase access and options for patients with metastatic CRPC. So tell us a little bit about some of the unique changes that were able to be executed in the middle of the trial based on some of this dosimetry data.
Jason Hafron: Yeah. I think the biggest change is that they had essentially what we would call an adaptive strategy, but per regulatory requirements, they start off with four doses. Once they saw good safety data, they expanded to six. So I mean, that's some FDA regulatory requirements, but as a clinician, I think it'll be, pending approval, that'll be very helpful in managing patients because it gives us a potential option to see what patients did after four. Do we need to go to the full six? So it's kind of like in a backwards way, an example of adaptive dosing, which I think is everyone's trying to figure out how many doses, how much dosimetry do these patients need.
Phillip Koo: So you've treated a lot of these patients, you've managed a lot of these patients, you've seen some adverse events and had to deal with those. And what does having that dosimetry mean to you as the person taking care of these types of patients?
Jason Hafron: Yeah. I think as a urologist, as this space is evolving, we need to understand dosing schedules and dosimetry, which are two different things. And the way that I look at dosimetry is kind of like pharmacokinetics, how a drug performs in the body, what's its concentration? And that's essentially what dosimetry is, is how much dose is going to the tumor and how much dose is going to normal tissue. So it's that balance of efficacy and toxicity, which is really important as a urologist using these drugs to help explain to our patients, to participate in multidisciplinary and converse with our radoncs and our nuke med guys is that as urologists, we have to really understand the importance of dosimetry, specifically the concept of it.
Phillip Koo: I think it's really interesting and cool to see dosimetry now being incorporated into the urology space. Before it was limited to nuke med and radiation oncology. So what words of advice do you have for urologists and med-oncs out there that will have to think about this moving forward?
Jason Hafron: Yeah. I think there's that balance. I think the concept of this tumor sink that, where is the dose going? If you have large bulky disease and the Australians showed some nice papers on it, a lot of that dose might be going to the tumor, or is it going to the tumor? But also when you look at the ECLIPSE trial, the dosimetry data really stands out because not only did they show that they had safe doses, renal is like the limiting organ for determining safety, but when you look at the data that was presented is that we're seeing less dose in the lacrimal glands and the salivary glands and a pretty good percentage difference when you compare it to the previous agents tested in this field. So I'm very excited to see if this dosimetry data pans out. Do we see clinical differences? That data is forthcoming, but it's always nice to see competition, to see new therapeutic options in this space, which is growing. The other thing that's interesting too at this ASCO 2026 is, I counted in my book, there was 67 abstract presentations on lutetium.
Phillip Koo: Wow.
Jason Hafron: So it was a huge, huge area and big area of discussion for this ASCO 2026.
Phillip Koo: I think that continues to be really exciting. I remember PSA was a hot topic and this still is sort of under that PSMA umbrella and seeing that increase in focus, continued sustained focus on the therapeutics I think is really exciting. Dosimetry to me is sort of part of precision medicine. Precision medicine is a very large umbrella. Tell us more about what you see, how the future will evolve when it comes to these therapies and making it more precise.
Jason Hafron: Yeah. And I think that's the key is precision medicine. Right now we use populational standards. Everyone's getting six doses, 7.4 gigabecquerels. That's where we started, but where we need to get to is, like you said, is precision medicine. Is 7.4 the number? Is that getting enough dose to the tumor? And then why do we have six? Can we stop at two? Can we stop at four? That's why ECLIPSE trial is exciting is because we are seeing dosimetry differences between these agents. Can we use that when we're deciding on how to manage these patients and how to console our patients?
Phillip Koo: I think this is a key point that a lot of physicians will need to start realizing is all these different PSMA therapeutics, they're different, just as like the enzalutamides are different from the apalutamides versus darolutamide. These therapeutics are going to have subtle differences too, that have differences in biodistribution.
Jason Hafron: Yeah, there's definitely a lot of nuances and we're just starting to learn about it. I think the other big area is the PSMA PET scan. There's so much information in that PET scan that we're not utilizing. SUV mean, total tumor volume, things like that, that I'm now looking as the PET imaging is no longer just a radiographic image. It's really a biomarker telling us the activity of the disease, the location of the disease, so that we can tailor, to your point, these therapies to get the right dose to the right patient.
Phillip Koo: Well, congratulations to Jason, Frankis, both of you and the entire study team for ECLIPSE. I think it's really charting a new step forward for the entire field. So thank you all.
Jason Hafron: Yeah, my pleasure.