Timothy Clinton: Thanks, Dr. Kamat.
Ashish Kamat: So, there's a lot of stuff happening at AUA, there's a lot of early stag trials being read out, and one of them is the poster that you have. So, tell us a little bit about the genesis, the idea, the mechanism, and essentially what you're going to be presenting.
Timothy Clinton: Yeah. So, this is an interim result for the ADVANCE-2 trial, which is an investigation looking at the PROTARA agent called TARA-002. And this is an agent that actually has been around for a little while, but now making its way into the non-muscle-invasive bladder space, and specifically looking at BCG-unresponsive CIS disease, as many of these trials are. And they've partnered with the SUOCTC to provide basically pretty good enrollment numbers, and so this is an early look at some of that data.
Ashish Kamat: And let me ask you there, because again, this agent has been on for so long that people have heard it in different iterations of its name. But share with our audience a little bit about what it is, the bacteria, and how it works.
Timothy Clinton: Yeah. So, TARA-002, as it's going to be called at the moment, you're right, previously had some other names and was largely utilized in Japan for actually some benign indications, but now being utilized in bladder cancer. It is a killed streptococcus pyogenes bacterium, so a similar type concept to BCG, but different in that it's actually a killed bacterium and not just an attenuated bacterium. It does utilize penicillin to help kill the bacterium, and so actually one of the exclusion criteria is for folks who have severe penicillin allergies. But aside from that, it's a very well-tolerated medication, and more importantly, it seems to have some efficacy for unresponsive non-muscle invasive bladder cancer.
Ashish Kamat: Okay. So, tell us about the interim results from ADVANCE.
Timothy Clinton: Yeah, that's the exciting part. So ultimately, they're trying to enroll about 100 patients into this trial, it's a phase-two trial. Thus far, they've enrolled, well, the interim results that they're reading out is about 43 patients. And the exciting number is sort of a complete response rate at any time thus far is right around 68%. So, some promising signal in this interim analysis, and that seems to have some amount of durability. So at six months, which allows for a reinduction, there continues to be about a 65% complete response rate.
Ashish Kamat: And I think that's the number that patients care about, right? Because when we first developed the BCG-unresponsive paradigm, reinduction was not allowed for patients that had persistent disease, and that was because we and the regulatory bodies were all afraid that the patients would have a bad outcome. And we've learned over the years that it is safe to reinduce. And ultimately the patients care about what happens at six months, at 12 months. So, including reinduction, do you have data on patients that achieve that CR at any time, including reinduction, and then the durability? How long is that response?
Timothy Clinton: We do, and I'll just say that there's... So, of the patients who got reinduction, let's say. So, now we're talking about smaller numbers, but thus far of the 15 patients that are valuable, who had repeat induction, eight of them have an ongoing complete response. So, that's been the numbers thus far. But again, it's an interim analysis, so I think as you mentioned, the real question mark that remains as many other drugs is what is that durability? And so, do those patients continue to have sustained responses? And most importantly, and I think one of the more comparable time points is that 12 months CR response rate. And so, we'll wait to see what that reads out at.
Ashish Kamat: Yeah. And again, I appreciate you cautioning that it's small numbers, but I think it's always encouraging when you have the patients that were reinduced having almost similar durability of response to those that achieved at de novo, right?
Timothy Clinton: Exactly.
Ashish Kamat: Because otherwise it could be something to do with the initial quality of your biopsy, even though we think we don't resect all CIS, we know we certainly can, if you go into the blue light and things of that nature. Any data that you can share with us on the adverse event profile?
Timothy Clinton: Yeah. I think that's actually one of the best parts of this agent is actually probably both its ability to be given in the clinic as far as an intravesical agent, it doesn't require any freezing or intricate handling. It's very easily reconstituted and given intravesically, whether it's through a bag or a catheter tip syringe, but it's very well tolerated. So, the adverse events have been about 26% that are treatment-related adverse events, but all Grade 1 or Grade 2, no treatment-related Grade 3 or greater adverse events, which is a great sign but also very similar to a lot of the intravesical agents that we have seen. And so when I talk to patients, I really counsel them, these are patients who have failed BCG or other agents, and I try to explain to them that it should be pretty similar as far as the types of adverse events that they may or may not encounter with this drug.
Ashish Kamat: Yeah, that's great. Again, I remember when we had nothing for these patients, now we have so many agents for these patients, and I think it's just great that we will... Hopefully, I don't know, no crystal ball. But if this gets approved as well based on the interim results and the full study, there'll be more options for our patients. But asking you now to step outside this study a little bit and maybe put on your crystal ball hat, what do you think this, if approved, will fall into the whole, I'm going to choose this for this patient paradigm?
Timothy Clinton: Yeah, you're exactly right, this is the crystal ball and probably the, I don't know, billions of dollar question. We were talking a little bit over lunch, I don't know that I have a great answer. Everybody's going to want to try to compare these single-arm trials and try to make heads and tails of the 12-month CR rate, I think it comes down to a couple of things. So, tolerability is going to be a really important one, right? Is it an intravesical agent? Is it a systemic agent? Is it a device? And I think you have to think about the sequencing of those things, right? Especially right now, this trial is in patients who are pretty heavily pretreated. They've failed multiple lines of therapy, still with CIS in their bladder, but that sort of patient with INLEXZO or something else may not be able to tolerate the device as well because they're so heavily pretreated.
And so, when you're thinking about the sequencing of these drugs and devices now, maybe that device needs to be sooner because you can't quite give it after all of these treatments. Is that the right answer? I don't know. Hopefully, and I think everybody is wishing at some point to develop a biomarker or some sort of test that will allow us to determine who's going to respond best to each one of these different agents that I know you know very, very well.
Ashish Kamat: And I think that biomarker question is something that everybody's working on, and I sure hope that somebody gets there, if it's not me, you, somebody, because we really need that. But I think from a patient perspective, it's great that we have so many choices that we can offer to them. So, again, congratulations and thanks for taking the time.
Timothy Clinton: Thanks so much.