Christopher Pieczonka: Yeah, thanks Sam.
Sam Chang: We're at the AUA 2026 and we're going to talk a little bit about a presentation you have on MoonRISe-2, which I'll let you kind of explain the mechanism of action of this kind of unique intravesical drug-releasing system with a medication based on looking at FGFR mutations. So why don't you take it away, Chris?
Christopher Pieczonka: Yeah, thanks Sam. I think as background for the viewing audience, when we first took the study on, I actually thought it was stupid, and I thought it was stupid because it's an ablative state.
Sam Chang: Don't mince words.
Christopher Pieczonka: Yeah.
Sam Chang: Tell me what you honestly think.
Christopher Pieczonka: I think the reason for that is surgeons operate and we remove things. And this is a very different concept because it's an ablative therapy. It's not adjuvant therapy, it's truly ablative in nature. So the MoonRISe-2 study built on a platform of an intravesical drug-releasing system, and there are a variety of SunRISe studies that now have an FDA-approved product in BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ with or without papillary disease. This is a different animal. So this uses an erdafitinib intravesical drug-releasing system. So the medicine that's in the intravesical drug-releasing system is different and the device is actually different as well. So this device releases erdafitinib and the device is put in place over a three-month interval rather than a three-week interval. So different than what's currently approved on the market.
As background, this is an expansion of the phase-one study that was done first-in-human for ablative therapy with this particular disease state. And as you know, we're looking in the intermediate-risk bladder cancer patients. There is an FDA-approved product, UGN-102, currently. So there is an FDA-approved product in the disease space. This is to build on that knowledge. And essentially the study saw to enroll patients who had recurrent low-grade intermediate-risk bladder cancer. They had to have greater than or equal to one risk factor according to the International Bladder Cancer Group. Those are things like maybe a solitary large tumor of three centimeters, recurrence within a year.
Sam Chang: Multiple tumors.
Christopher Pieczonka: Four, five, factors for that. And importantly, you had to have... It was an ablative therapy, so if you went and you had cystoscope the patient, you knew the patient had bladder cancer, maybe they got a resection seven months ago, it's a six month scope, you re-scope them and there's another tumor there, that would potentially qualify the patient for the study. So the thing is that you wouldn't remove the tumor there. And so I think this is a paradigm shift because for a lot of docs, maybe some offices are capable of doing a, we'd call it a bite and a burn. You would maybe fulgurate, maybe biopsy. And so in this particular case, you'd either leave the entire tumor behind or you would de-bulk the tumor and then leave sort of a marker lesion. Again, for the purposes of protocol.
Then the patients ended up essentially going into the clinical protocol, and the clinical protocol would allow them to be able to have this intravesical drug-releasing system of erdafitinib, and I'll describe that in a minute, to be given to them in a controlled fashion versus a randomized therapy, which would be considered sort of the standard of care. In this particular case, these intermediate-risk bladder cancer patients, we don't really know what to do with them. People give them BCG, might give them intravesical therapy. No one really knows. It's really not as clean cut that if you have a patient who has carcinoma in situ and it's your first time seeing them, those patients are getting BCG and there's a pathway there. In either case, what would end up happening is that you would place this particular device every three months, remove it, put a new one in and you do that a total of four times. So it would be over...
Sam Chang: It's one year time period.
Christopher Pieczonka: ... a course of a year. And the background on this is that... What I didn't tell you is all these patients who came into the clinical protocol, the concept is that something like 70% of these patients are going to be FGFR mutated. So like upper tract disease, the patients who have intermediate-risk bladder cancer have a predisposition to be FGFR mutated. As a consequence for that, that's something that we are exploring using erdafitinib. So erdafitinib is currently an FDA-approved pan FGFR inhibitor that's used in metastatic urothelial carcinoma for patients who've failed prior therapy. And it has benefit, but it's pretty toxic when given orally. Patients can get a variety of eye problems. Phosphate can become a real problem in these patients. It's not the easiest therapy to use. And so as a consequence for that, as Johnson & Johnson has looked to develop this product, they sought to essentially put that formulation of erdafitinib in their intravesical drug-releasing system.
So really what we're looking to do is to target these patients who are FGFR3 mutated in particular. So we did testing on these patients, they had to be FGFR either two or three mutated, but the vast, vast majority of these patients are FGFR3 mutated. And the thought would be that the erdafitinib going in on a sort of a minute-by-minute basis with a very prolonged and retained consistent delivery time would ablate tumor. So that's the background for the study. And the background for the study is because something like 60% of these patients continue to recur, around 20% will progress. And so this is a disease that in the abstract looks benign, and the gestalt can be a real problem for patients.
Sam Chang: As you control the different variables that may impact recurrence and evaluation and surveillance, you can see how this would become an attractive option for patients avoiding multiple trips for a TURBT, multiple other installations. This is a once every three-month placement, correct? So different from the TAR-200 medication, the Inlexzo™. So is it a similar size device? Is it that...
Christopher Pieczonka: Yeah.
Sam Chang: Okay.
Christopher Pieczonka: The consistency is just ever so slightly different because the drug is different. But for the summit substance, delivery technique, the removal technique would be familiar with anyone who's using the gemcitabine intravesical drug-releasing system. But I wanted to kind of segueing from when I thought that this study was stupid, that was my exact term, into what I think about it now. And so I have my own patient, she's in her late 80s and her family bought her a Tesla so she can still actually have independence.
Sam Chang: I want to be a family member too. I mean, I'll take one.
Christopher Pieczonka: And she can get to and from a variety of places. But the one son lives in Connecticut, the other lives in California, and she had a large recurrence, somebody we just scoped before, and so her going to the operating room for a simple procedure was not so much about the risk for the procedure, it was the social risk for her in the system. So one of the kids would have to come in, have to drive her to the surgery center, et cetera.
Sam Chang: Stay with her overnight, make sure to...
Christopher Pieczonka: Absolutely. And so when we went through this together and I talked to the family and they went through the informed consenting process, it actually really made me think about this in my mind about how powerful that would be because I think as surgeons, we sometimes sort of maybe don't think about what that really means to say, "You're going to the operating room. We're having something done." So it's such a paradigm shift that if it bears fruit long term would be really, really exciting. And the reason that this is going into a dose-expansion cohort is because the preliminary first-in-human studies have been really, really outstanding in terms of the successful ablation.
Sam Chang: And tolerance as well?
Christopher Pieczonka: Tolerance, very much so, but the complete response rate is pushing 90%. I think it's 89% with a durable response. Again, those are the sort of the phase-one, this is the phase-two cohort. The study's fully enrolled at 140 patients. And the things that we're seeing in terms of adverse events are what we have been seeing with the gemcitabine intravesical drug-releasing system. These patients have some, perhaps, dysuria, frequency, the type of local things that we're seeing. You would manage it with standard urologic care, anticholinergic, beta-3 agonists.
Sam Chang: And we don't have the eye issues or the phosphate issues or some of the systemic. Those have been basically eliminated by the intravesical delivery, is that right?
Christopher Pieczonka: I think you hit it right on the head, Sam. So there's essentially no systemic absorption of erda into the system. So those things are just essentially a non-issue, which is really what's so exciting about this. The other thing is that, I would tell you anecdotally, I feel that this is probably better tolerated than the gemcitabine intravesical drug-releasing system if for no other reason that there's less instrumentation that's done. So it's a pretty attractive thing for a patient because they're used to the three-month thing because they're getting scoped every three months. So this is kind of the social burden on the patient coming in and just getting instrumented is actually very attractive.
Sam Chang: It is something that goes actually hand in hand with the normal surveillance schedule that you talk about.
Christopher Pieczonka: Absolutely.
Sam Chang: So when should we expect the readout from MoonRISe-2, Chris?
Christopher Pieczonka: That's a good question. I think it's not going to be this year. I think with where we are with things, we're heading in the right direction, we're fully enrolled, we're getting follow up. I have some of my own patients who are now beyond a year and they say, "What happens next?" And I say, "I don't know. You're blazing the trail." So once we get to that... Because they're really looking at the durability of response post active treatment. So not everybody is at a year yet and then the events will be collected if there's high-grade recurrence or... So there is not a mechanism within the protocol if you had high-grade recurrence to be re-dosed, but we're going to get there pretty quickly. Essentially the study is being done to look at a variety of key secondary endpoints, which would include the complete response rate at three months.
They're looking at duration of response, but the primary endpoint is the complete response. And like I said, I think we'll get there pretty quickly.
Sam Chang: Well, thank you so much for spending some time with us, Chris. We look forward to actually seeing the readout on MoonRISe-2 and seeing again if we have another additional actually paradigm-shifting type of treatment to go from our TURs to ablative therapy, which would really kind of accelerate other options for our patients.
Christopher Pieczonka: And the one thing I'd also say is this is part of a platform. So this is the MoonRISe-2 protocol. And these patients who are coming into this protocol, their FGFR status is known, but it's an all-comer study. So there is a MoonRISe-1, there's a MoonRISe-3, they're looking at different aspects. So the point on this is Johnson & Johnson is continuing to evolve and spending an immense amount of resources to try and help our patients.
Sam Chang: Great. Thanks again, Chris. We appreciate it very much.
Christopher Pieczonka: Thanks, Sam, so much.