Joshua Meeks: Wow, more than that. 12-13 years, yeah.
Sam Chang: Wow. So I think we're going to start off, Josh, talking about 3120, a phase-1/2 trial looking at an intervention for patients that were either BCG-unresponsive or BCG-exposed, I think. Is that correct?
Joshua Meeks: So the interesting thing about this, Sam, that's really cool is intravesical ADC. So it's a novel ADC that Merck acquired in their pipeline, and so it's anti-nectin-4, so it's targeting nectin-4, but potentially a different epitope. The preclinical data that was just shown at AACR suggests that... And there may be different groups of patients. It doesn't seem to be the exact same target. And then it's delivering... The payload part is a topoisomerase inhibitor. Again, it's a novel ADC, but the unique part for us as surgeons is the delivery. It's an intravesical delivery, which obviously we're much more comfortable about. We know the data from EV-302, 303, 304, the IV therapy for ADCs, but this is an intravesical.
Sam Chang: And from what you saw... It's obviously early, phase 1/phase 2. Tell me a little bit about the tolerability first.
Joshua Meeks: And that's the major question. That's why it's a phase-1. So it's [inaudible 00:01:49] design. The goal is to enroll 45 patients overall. And again, there's three different doses, and the goal would be to enroll 10, and then it advances on. So part of this challenge, part of the R&D part of this is figuring out how much to give. We don't know where the sweet spot is. We don't know about penetration. So these are all the research questions that are being asked in the phase-1 part of this is, again, tolerability, side effects. Patients are going to get dosed weekly, once a week for six weeks. Then they're going to have an evaluation at 12 weeks, and then if they respond they can go on to get maintenance.
Sam Chang: And with that evaluation, are you going to be able to look at the binding of the agent? Are you going to be looking at... In terms of success... Because you have different levels. You have, how is it going to be integrated and bound? Once it's bound, are they able to deliver the payload? Are they be able to affect changes with the topoisomerase? Those are so many different questions. So I guess obviously safety first, but then the next steps in terms of, okay, are we getting to the point where we want to get to? So tell me a little bit about that.
Joshua Meeks: That's really the scientific end of this is trying to figure out if the payload's hitting and if you can detect when you do... And so part of that is thinking about people who respond and don't respond and how long, when they get exposed, does it actually sit in the bladder aligning for? So these are all the research questions that we're able to work with the Merck team to figure out, how do we best address that? And if the tumor never comes back, then that's perfect. But if not, then the real questions are, well, does the therapy work and it's just not getting there? So I think that's really where the innovation needs to happen. We had done a phase-1 study a long time ago with pembro but didn't have that R&D-
Sam Chang: That sophistication.
Joshua Meeks: Which you need. That's where the collaboration really... The hope is they do that.
Sam Chang: Because you understand, okay, we've got a good target. We think it binds well. We've got a good payload. But then you have other questions just thinking about, is it dwell time? Is it a dosing schedule? All the-
Joshua Meeks: Penetration. Getting the... Yeah.
Sam Chang: Exactly.
Joshua Meeks: Yeah, exactly.
Sam Chang: So what is the dosing schedule in this trial? Is it-
Joshua Meeks: It's, again, once a week for six weeks and then going monthly. So taking a page from what we normally do, but unclear if that's the right regimen.
Sam Chang: Yeah, exactly. Yeah.
Joshua Meeks: But you got to start somewhere.
Sam Chang: Yeah. That's exactly what I was saying.
Joshua Meeks: You can make educated things based on the way our mechanics of our clinics are set up, but maybe you don't need that much. Maybe you need more. But I think those all need to be figured out.
Sam Chang: And then in the future... Obviously this is early. This is proof-of-principle. This is to get safety, tolerability data and to get the science regarding, okay, we're hitting where we need to hit, et cetera. Do you see this... I know we want to get away from systemic, but do you see it in combination with systemic? I know it's focused in non-muscle-invasive. Tell me where you see short-term future and long-term future.
Joshua Meeks: So the key thing about this cohort is that you can either be BCG-naive or BCG-exposed, but they have to have CIS. And I think CIS is still a problem. As we've talked about a bunch, the more you look for it, the more it's there, and realistically we're not really sure about why things respond. I know we have a lot more therapies than before, but we still don't know what works, so having more... And again, I think a lot of our overall bladder cancer is going to be shifting towards NMIBC. The more people are cured for MIBC and metastatic cancer, you're going to have more superficial disease, and that landscape is going to be longer, so having more drugs I see as a benefit.
Sam Chang: Yeah, no, and I really think, and I've talked with you about this before, that these different, newer treatments are really going to alter how we do surgery, how we survey, all those types of things, so very, very important work. Do you have any idea of timeframe in terms of, okay, how enrollment's going to go, et cetera? I hate to put you on the spot regarding that, but it would be a popular study for sure, I would think, but-
Joshua Meeks: So there's already sites across the world opening, including in the US, and so... I don't know exactly today how many patients have been enrolled and treated. We know in other intravesical ADCs, it's pretty easily adopted by our urology sites. The key thing is that sites have to be able to do the translational part, but they're already on that.
Sam Chang: Right. Because you've got to look at serum. You've got tissue. I'm sure you're looking at urine studies as well, clearance, all those things. So as always, Josh, the science behind the different projects you have, the thoughtfulness behind it, we should appreciate very, very much. And so thank you always for your efforts, and look forward to hearing how this progresses in the future.
Joshua Meeks: Thanks, Sam. Exciting time. Exciting project.