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Sam Chang: Hello, my name is Sam Chang. I'm a urologist in Nashville, Tennessee, and we are fortunate to have with us Dr. Mark Tyson. Mark is an associate professor at Mayo Scottsdale. Mark and a group of investigators recently published on using the TAR-200 pretzel in patients actually with muscle invasive bladder cancer. And this just came out in a recent Journal of Urology article. So Mark, first of all, thank you for being with us and look forward to giving us a synopsis of that important manuscript.

Mark Tyson: Thank you for having me, Dr. Chang.

Sam Chang: Sam, please call me Sam.

Mark Tyson: Yeah. This is a global phase one for the TAR-200 device. It's a legacy TAR-200 Study 103, a follow on study to Dr. Daneshmand's muscle invasive concept that was published a couple years ago. Essentially, we're trying to understand the safety and tolerability of this device as well as preliminary efficacy in a population of patients who are not otherwise fit or otherwise refuse radical cystectomy or radiation therapy.

Sam Chang: So I remember we enrolled some patients on these. These were not necessarily healthy patients at all.

Mark Tyson: Right.

Sam Chang: They clearly had invasive disease, and so what were the initial findings?

Mark Tyson: Most of the patients had an ECOG status of three or four, to your point, or many of them did. So like you said, a unhealthy population of patients. And a lot of these patients really aren't fit or otherwise ready for curative intent therapy.

Sam Chang: Right.

Mark Tyson: And so this is an alternative for them. And we know that there's a really quite large unmet need in this population. If we look at some of the national data sets, about 25% of patients in this country don't undergo curative intent therapy with muscle invasive bladder cancer. And that's data that's been confirmed in the Swedish databases in the English databases as well. So we know there's a big unmet need here. And so really this is just an alternative for that population. What we found was that largely this device is well tolerated. There's not a whole lot of side effects that prohibit somebody from keeping this device in their bladder.

There are a number of grade one and grade two treatment emergent adverse events like frequency and urgency and nocturia. But if you think about the population, an elderly population, population with muscle invasive bladder cancer that's not having curative intent local therapy, we expect some of those ...

Sam Chang: Some of those symptoms. Absolutely.

Mark Tyson: ... symptoms anyways.

Sam Chang: Symptoms for sure.

Mark Tyson: So yeah, 40% of patients had grade one or grade two treatment emergent adverse events, mostly in the irritated voiding symptom domain, but by and large, well tolerated, only two patients couldn't keep it in their bladder had to be discontinued.

Sam Chang: And how many treatments do they ultimately get in terms of placement of the TAR-200 device?

Mark Tyson: Right.

Sam Chang: Removal, placement, how many in total? Do you remember?

Mark Tyson: So for induction, it's four 21 day cycles. So 84 days was the induction period, and then 90 days later, patients could undergo an optional three maintenance courses. And like you said, it's a 21-day cycle. It's put in through a little stylet catheter, 18 French catheter, and then removed cystoscopically 21 days later as the next device is put in.

Sam Chang: So what were the results in terms of efficacy?

Mark Tyson: So 32% of patients had a complete response, and I would caution that with, we don't have pathologic confirmation of that complete response, but 32% of patients, according to the investigator cystoscopic evaluation, had a complete response than another 8%.

Sam Chang: And I do remember these were patients that didn't necessarily have an attempted complete TUR or anything like that prior. These were just diagnosed with muscle invasive disease, got the treatment, and about a third then had at least clinical CRs from what you're saying.

Mark Tyson: Right. Yeah, about 32% had a complete response cystoscopically, another 8% had a partial response. But I will say this is mostly a population of T2 patients. So a maximal TURBT was attempted for most of these patients.

Sam Chang: Oh, got it. Okay.

Mark Tyson: There was one or two that had clinical stage T3 disease, but most part of the patients had T2 disease.

Sam Chang: And then in terms of this patient cohort follow up, do we have any idea regarding how these patients did then over a period of time?

Mark Tyson: Yeah, so we're still early in the followup. I think the median followup for this study was about 27 months. We need more follow up for sure, long term. There's only four patients at the data cutoff that had completed the protocol completely.

Sam Chang: Okay.

Mark Tyson: I think that's certainly in the future.

Sam Chang: As you look at the tolerability that you mentioned, was there any side effect that seemed to stick out more than others? Or was it the lower urinary tract frequency urgency?

Mark Tyson: Frequency, urgency, nocturia, that sort of irritative voiding symptoms were the most common.

Sam Chang: Right.

Mark Tyson: But one of the things that also sticks out to me too is if you think, as you know with your vast experience in muscle invasive bladder cancer, these patients who go untreated require lots of clot evacs eventually, local progression of their disease. We didn't see a lot of that in this population. Only one patient on study had to have a clot evac and only one patient required a blood transfusion. So even if we don't necessarily know what the counterfactual outcome is for the efficacy data, because it's a single arm open label phase two, at the end of the day, we don't really know what would've happened otherwise in terms of their cancer progression. But we do know that this probably does have some anti-cancer activity by virtue of the fact that many of these patients didn't really progress symptomatically while in study.

Sam Chang: Didn't have those symptoms that you know that many of your muscle invasive bio cancer, the hematuria, the clot retention, those such things you mentioned.

Mark Tyson: Very rare on this study.

Sam Chang: Yeah. Very rarely did you actually see that in the study.

Mark Tyson: Right.

Sam Chang: So based upon these findings, clearly there are now ongoing trials looking at invasive disease and non-invasive disease as the lead investigator of this trial. How did patients tolerate using the stylet, taking it out? How'd they do with that?

Mark Tyson: Pretty well. It's a pretty simple device to place, and I think most patients tolerated the procedure to place it well, and most patients tolerate the procedure to remove it. Like I said, there were a couple of patients that couldn't tolerate the device just in general. I think there might have been two that had to be discontinued because of that, but the rest of the patients were able to tolerate it and the procedure to place it and the procedure remove it, were relatively painless for the patients.

Sam Chang: So whenever I think about this device, I think again, "Okay, what are the next steps?" There are ongoing cancer trials for sure.

Mark Tyson: Yeah.

Sam Chang: But this device almost begs for other perhaps disease processes to use. What do you think of that as a possibility?

Mark Tyson: Yeah, so the TAR-200 device is being explored in various combinations with IO therapy and BCG, in both the BCG-unresponsive and the BCG-naive population, SunRISe-1 and SunRISe-3. And it's also being studied in various combinations with other therapies for muscle invasive in the SunRISe-2 and SunRISe-4 portfolio. So it's an exciting time to be a TAR-200 investigator. I'm excited to see what those data show, and I think that'll be in the next couple of years.

Sam Chang: Well, that's fantastic. Well, Mark, thank you so much for being here today, and congratulations on the publication ...

Mark Tyson: Thank you.

Sam Chang: ... of the manuscript. And we look forward to future trials and you helping lead the way as you've done.

Mark Tyson: Thank you for having me. I appreciate it.

Sam Chang: Thank you, Mark.

Mark Tyson: All right.