Shreyas Joshi: Thank you so much, Dr. Kamat, and happy to share this data. We were able to recently present this at the Southeast section meeting in Puerto Rico. And these are the durable 24-month outcomes from the BOND-003 Cohort C study that we're continuing to accrue data from. Just briefly, as we all know, cretostimogene works in a dual pathway, one by replicating within cells and lysing them, but then also by amplifying the antitumor response. And so, the protocol for this was the patients who were BCG-unresponsive and mainly CIS patients. And so they underwent the induction course, they could undergo a repeat induction course if they had some residual high-grade disease, and then they went on maintenance. And of course we were looking at the primary endpoint, which was CR at any time, but then we also looked at the duration of response, which is really what we're going to present today. The patient demographics are what we would expect, and this has been presented before from the Cohort C population, which is predominantly white and male and over the age of 65. About two-thirds of the patients were from the United States. And interestingly, this was a pretty highly pretreated population.
This study started at a time where we didn't really have a lot of other options, and a lot of folks had undergone intravesical chemotherapy, up to 41% of them had undergone previous intravesical chemotherapy, and some had even undergone immunotherapy with systemic pembrolizumab. This data has been presented before, that the anytime CR rate was 75%, but I like looking at this landmark data at 12 months and at 24 months, and looking at the absolute number of patients. So out of the 110, how many were in response? And at 12 months, we have 46%, and at 24 months up to almost 42%. And this is meaningful to me. When I am talking to patients, I want to compare apples to apples as much as I can. And I really like using at least the 12-month data. If I have longer-term data, I love using that as well. And we're starting to get that here with cretostimogene. Looking up at the two-year mark, 96% were free from progression to muscle invasion, and around 84% never underwent radical cystectomy in this 24-month period. This is another way of looking at that data, but I think it does add something, which is that 90% of patients who were in CR at one year maintained that CR at two years. As we know, when we start treating patients with this, there are some that are just simply not going to respond, and those patients are going to fall off relatively early. If I can tell patients that, "Around 46% of patients are going to be in CR 1 year, and if you are in that 46%, there's a very, very good chance, 90% chance that you maintain that CR at two years." And I think that that is a meaningful thing that I can discuss with patients, and that can help them guide their decision-making with regard to what treatment they're going to choose. A few interesting points here, which is what is circled over here, which is these patients who completed treatment, some actually just maintained a very durable CR over 45 months, indicating that there's some sort of innate immunity that it really activated that continues to, I think, control their disease.
The CR rates were consistent, and I like to point this out too, because there were a significant number of patients who were also T1 with CIS, and they also maintained CR rates as well. That is the latest data we have from Cohort C. I think that it adds a meaningful point to discussions with patients when we start having these discussions once cretostimogene is available for commercial use. But even when I'm discussing these patients on clinical trial, it is data that I can now share with them and hopefully guide them in how they're going to continue along their non-muscle-invasive bladder cancer journey.
Ashish Kamat: Yeah, no, thanks, Shreyas. And I think that's a very important point, because we know that these drugs work, we know CG works, and I don't have a crystal ball, but I presume it's going to get approved. But once it gets approved, you have to be able to select the right treatment for the right patient. And patients, like I mentioned earlier, they really care about how long the treatment's going to help them avoid the radical cystectomy, CIS trial data, notwithstanding, patients really would like to prefer to spare their bladder. So with these long-term data, close to 50% of patients at 24 months, what's your sense as to how long would you continue to treat a patient with CG? In your clinical practice once it's available, would you want to give them a holiday and then try to re-challenge them? Any sense as to what you might do in the real world once you have access to it?
Shreyas Joshi: I think that there's going to be competing factors. One is that, one, it is tolerable, patients, it's easy to give, but the second aspect of that, that there's a price tag that's going to come with this, and we have to worry about financial toxicity eventually as well. I think that from a purely biological standpoint, I do want to give them a treatment holiday. I would like to potentially treat at about two years. This isn't defined yet, but stop it, see how their disease responds. There is some sense that some of these patients who are responding really well probably had a little bit more of the favorable biology, that they're going to have good outcomes long-term, and the ones that weren't going to have good outcomes fell off early on that waterfall plot. So I think that's probably how I'm going to approach this, but I would be curious to know in your practice, how are you going to counsel patients about how we maintain gene therapies that activate the immune system? And I don't really know. We're kind of borrowing from what we know from BCG, but I don't know if we know.
Ashish Kamat: Yeah, no, I think that's a point that we are all going to have to wrestle with because we have to balance the cost, not just the drug, but the cost of the healthcare system, the cost of patients, and of course, the financial toxicity of actually visiting the hospital. And I think the longer a patient is without having a recurrence, the more likely it is that whatever recurrence occurs later is less life-threatening. And I tend to use that when I talk to patients, even with BCG, for example, I'm like, "Hey, you've been disease-free for a while, 'cause some patients want to come and get that booster every six months forever," which is something that Norm Lamm and Alvaro Morales used to say should be done. But I think if a patient say, let's assume CG, they're disease-free at 24 months, maybe even 30 months, and then I think giving them a holiday and maybe re-challenging if they recur in a year, two years, five years is very reasonable. But again, that's a data-free zone, so I think that's something that will have to be studied. What's really encouraging from this data is that there is activity, activity is sustained and it's durable, and that's really the message that patients want to hear from us.
Shreyas Joshi: I think what I take away from this is that those who are responding are going to continue to respond. And so we have an early litmus test as to whether or not a patient should stay on the drug, and I think that that's helpful.
Ashish Kamat: Right, absolutely. Thanks so much, Shreyas, for taking the time. Always a pleasure.
Shreyas Joshi: Thank you so much, Dr. Kamat.