Aaron Hansen: Thank you, Neeraj. It's great to be with you. Thanks for having me.
Neeraj Agarwal: So first of all, congratulations for presenting the novel data from your phase-one trial. What I found very intriguing was the new payload, novel payload and the interesting results. So before we talk about the results and the patient population, why did you do this trial? Why do we need Actinium?
Aaron Hansen: Yeah, it's a good question. So we've obviously seen a lot of success with radioligand treatments when we think of Pluvicto and lutetium. And not every patient responds to that therapy though. Around 30% unfortunately won't. And so as a class of therapy, it's very effective, but we need newer treatments in order to help salvage some of those patients who aren't fortunate enough to have a response to a beta-emitting therapy. And so that's where the origin for this study came from to explore an alpha therapy.
Neeraj Agarwal: Fantastic. So what is the patient population here?
Aaron Hansen: So this is your classic sort of phase-one population of metastatic castration-resistant prostate cancer. These are patients who were typically heavily-pretreated, so they would've progressed on an ARPI and also multiple lines of chemotherapy. In this part of the study that we've presented, there aren't any patients who have had Pluvicto. However, as the study will develop, those patients will also start to be included. So it is a late-line study.
Neeraj Agarwal: So patients had metastatic castration-resistant prostate cancer, or if you go with a new terminology, androgen pathway modulation-resistant prostate cancer, APMR prostate cancer, these patients had multiple lines of therapies in the past. What was the median line of therapy these patients had received?
Aaron Hansen: It was around three.
Neeraj Agarwal: So that's heavily-pretreated patient population. And you treated them with a novel agent. Could you tell more about the novel agent? What is the agent?
Aaron Hansen: So the agent is Actinium-225 FL-020. I'll just call it Actinium-225 for short. It was developed and discovered on a novel technology platform called Uni RDC. And essentially Actinium is the radioactive particle that undergoes decay leading to alpha radiation being emitted. It is chelated to a conjugate that recognizes PSMA. So this agent is specifically designed for patients who have PSMA-positive metastatic prostate cancer. There is another component to the compound where there is a cleavable linker which attaches it to a membrane particle, which sort of increases the weight of it a little bit more. And the idea there is that it will not penetrate into normal tissues like salivary gland and kidneys, as much as what it would preferentially-
Neeraj Agarwal: So making it more specific for prostate cancer?
Aaron Hansen: Correct.
Neeraj Agarwal: Great. So what were the results?
Aaron Hansen: So this was a dose escalation study. It went from one megabecquerel to five megabecquerels with an increase of one megabecquerel for each dose level. It is currently what was reported in the poster was patients up to the five megabecquerel dose. There is a plan to go up to 10. So this is sort of the halfway point at this stage. The objective of this study was to determine the safety and efficacy of this new compound, and also to try to establish ultimately what the recommended phase-two dose will be, and then there'll be an expansion cohort. So we're not yet at that point to be able to declare the RP2D, but of the 15 patients that have been enrolled, we've seen some quite promising data in terms of the safety profile. So there have been no DLTs, or dose-limiting toxicities, at this stage. There have been four SAEs or severe adverse events, but they were not related to Actinium-225. And so it's been shown at this stage to have quite a promising safety profile. A lot of times with Actinium agents, xerostomia is a common adverse event of concern. And in this population of patients, it occurred in six patients, five of them were grade one and reversible. So it wasn't too severe. There was one patient with a grade two xerostomia that did discontinue study for that adverse event. However, the other part to add to that story is that they were also starting to progress as well. So there were a couple of reasons to be taking that patient offstudy.
Neeraj Agarwal: So far it looks like drug seems to be pretty well tolerated, which is definitely great news for our patients if this continues to behave like what we have seen so far and hopefully a bigger trial in the near future, which will potentially provide a new treatment option of Actinium-225 payload being delivered into the prostate cancer cells in a more specific fashion. So we don't see marrow toxicity or salivary gland toxicities we have traditionally seen with other PSMA-targeting agents. Is that a correct conclusion?
Aaron Hansen: Yeah, that's very true. And what was interesting as well from the data that's been reported is that we haven't seen at this stage any major renal toxicity. There was some mild anemia, but there's been no reported thrombocytopenia at this stage. This is still early days, as you correctly point out. We're going to need to get longer-term data on these patients as well in order to really characterize those toxicities like the cytopenias, xerostomia, kidney function. But at this stage, at this snapshot in time, it does look reasonably tolerable and promising.
Neeraj Agarwal: And I can tell you, based on my own experience of drug development, if you don't see a signal in first 15 patients, that's pretty good news actually. If you don't see thrombocytopenia with the Actinium, or if you don't see xerostomia or dryness of the mouth to any severe degree or don't see marrow toxicity, I can tell you we are hopefully looking at seeing more promising data at next GU meeting in 2027.
Aaron Hansen: Absolutely. Can't wait. I think everyone is very excited to see where these alpha therapies are going and Actinium obviously is-
Neeraj Agarwal: Yeah. I personally felt quite excited about this new molecule and the minimal side effects which were initially reported. Well, congratulations, Aaron, for leading this cutting-edge trial, and hopefully you will tell us about more promising data in the near future.
Aaron Hansen: Thank you so much.