Ashish Kamat: Zach, it's a pleasure, and honestly, I'm on your side most of the time, so I'm really enjoying being on this side and having you ask me questions.
Zachary Klaassen: This is the hard side, isn't it? I think that first of all, the AUA's done a very good job about having these plenary sessions and having some of these high-level data presented. I know we haven't always had that at the AUA, so it's been a huge draw, and now that we're seeing great data from non-muscle-invasive bladder cancer, almost every meeting we're seeing something. This data you presented was the LEGEND trial, phase-two interim results, detalimogene, and this is a very unique sort of mechanism, so maybe get into the mechanism just before we talk about the results.
Ashish Kamat: Yeah, absolutely, and I think Dave Penson's done a great job, right?
Zachary Klaassen: He has.
Ashish Kamat: Getting this plenary session, the clinical trials in progress, and it's really great to have this at the AUA and not just have to rely on ASCO or ASCO GU or ESMO. There's so much going on in non-muscle-invasive bladder cancer, especially in the BCG-unresponsive space. People are always like, "Well, how many more trials are we going to have? How many more drugs are we going to have?" That's where you've got to really look and see, is there a need for a specific agent? That's where detalimogene comes in. Actually, the mechanism is a plasmid delivery mechanism, so that's separate from bladder cancer or anything else. You can deliver gene therapy without using a virus. It's a plasmid delivery, and what this does is it delivers the genes for IL-12 and also for RIG-I, and essentially three genes, so it's a non-viral delivery, ramps up the innate immune system and also the adaptive immune system.
The advantage is, you're getting sort of the same ramping up of the immune, adaptive/innate, but you don't then have the downsides of a viral gene delivery mechanism, both for the patient from a safety profile, although we know it's relatively safe, but from a practice standpoint, because a lot of folks in the community, a lot of folks in smaller hospitals just don't want to touch gene therapy.
Zachary Klaassen: Sure.
Ashish Kamat: This way they can give gene therapy without having the downside of needing biosafety hoods or level-two safety for the viral delivery.
Zachary Klaassen: Absolutely. What's sort of the dosing schedule? Because, I know we've seen ... The patient population's all kind of the same. We've seen other trials like that. What's the dosing schedule for detalimogene?
Ashish Kamat: Yeah, so the purpose of the genesis of the trial dosing schedule was actually, the scientists really did some elegant work very early on, looked at the data from nadofaragene, which was once every three months, then looked at some of the other data from more intensive treatment regimens, like for example, Creto (Cretostimogene), which is every week, and tried to come up with the minimal dosing required. Right? Sometimes when you go to the minimal, you've got to be a little careful about that, but the dose is, dose weeks one and two, five and six, every 12 weeks. It's very patient-friendly, and the maintenance is only two weekly doses every three months, so it is very patient-friendly, per se, easy for the patients to come in, get the treatment and not be stuck or tied into the doctor's office.
Zachary Klaassen: Let's get into the results. What was the high-level results you presented at AUA?
Ashish Kamat: These were from the BCG-unresponsive cohort, as most of these data are, and it was a cohort of 125 patients, but 22 patients were in the evaluation at 12 months. There's still about half the patients that still need to be evaluated, so interim results, but I'm glad that we were able to present it, because we are able to show 53, 54% complete response rates at any time, and they were durable. 91% of the responses occurred at the evaluation, the first evaluation. A few converted with re-induction, but close to 89, 90% of these patients that had that complete response stayed in a complete response at that nine-month evaluation. As we've seen with multiple drugs in this arena, that tends to drop, right?
Patients really care ... They don't care what happens at three months or six months. They care what happens at 12 months, and even though Kaplan-Meier estimates were put up at 25-ish percent, I just want to caution that I wouldn't pay too much attention to that. It could be higher, could be lower, because we still have half the patients who haven't been evaluated.
Zachary Klaassen: Absolutely. A great summary. Let's fast-forward, assume this gets into our practice. Where do you sort of see this positioning? What patient type would you give this, in sort of clinical practice?
Ashish Kamat: Zach, that's the billion-dollar question, right, because I think it's great that we're going to have multiple options available for patients, right off, there. Let me say, I think this and other drugs will get approved. We'll have multiple options, and we'll be able to tailor it to the patient. If a patient can only come to the office X number of times because they have transport issues, then something like this is something they may prefer. If they're like, "No, just throw the whole kitchen sink at me, I can come twice a day if I have to," then you might choose a drug that has a more intensive regimen, but has higher numbers of efficacy. It might be a toxicity issue. It might be that they're in a rural area where the practitioner cannot have a gene therapy that's a viral delivery and has to rely on this, or gem/doce.
It's hard to say that there's going to be one clear winner. I think this is going to be one arrow in the quiver that we have to offer our patients, and it's going to be essentially personalized.
Zachary Klaassen: Yeah, absolutely. Before we wrap up, I know there's some other sub-platforms under LEGEND. Maybe just talk about BCG-naive, the bladder wash cohort. There's other stuff coming down the pipeline as well.
Ashish Kamat: Yeah. The other stuff and the other pipelines in the LEGEND cohort are essentially ways to improve upon the numbers, right? Because, some of the other drugs, as we know, cretostimogene requires a bladder wash, which is a little bit cumbersome for the patient, so they're trying to go into shortening that rinse. On the other hand, with the LEGEND, detalimogene, there is nothing. We just put it in the bladder. They're now trying to say, "Hey, can we add in a little bit of a rinse or detergent to improve the numbers?" These are all little tweaks in the protocol that all companies are doing. There's no data yet to be able to share with anyone, or at least I don't have any data that's publicly available, and the other cohorts are similar to what everybody's doing, right? Everybody's trying to get approved in the BCG-unresponsive space.
Zachary Klaassen: Find another target.
Ashish Kamat: The market is much huger in the intermediate-risk and the BCG-exposed, so those are the different arms. We don't have data yet to share.
Zachary Klaassen: Awesome. Anything we haven't touched on? Anything before we wrap up?
Ashish Kamat: No, I think chatting with you is always a pleasure.
Zachary Klaassen: Likewise.
Ashish Kamat: We touched upon everything.
Zachary Klaassen: Awesome. Thanks, Ashish.
Ashish Kamat: My pleasure.