Shreyas Joshi: Thank you so much, Dr. Kamat. My pleasure to help share some of this data. We presented at the Southeastern Section AUA meeting in Puerto Rico this March, and so looking forward to discussing this data with you. This is some of the first results from CORE-008 Cohort A. This was a phase 2 study of cretostimogene in patients with high-risk BCG-naive, non-muscle-invasive bladder cancer. Obviously, I'm not going to go into this too much, but there is some unmet need for patients who would otherwise receive BCG. There's not only BCG shortages that are ongoing, but there are some patients who simply don't tolerate BCG or have other needs that preclude them from getting BCG. Also, we know that BCG isn't always effective in all patients, and so there is a space for other treatment options that could be effective for these patients. And so this is the study schema for the CORE-008 trial.
I'm not going to focus on the cohorts B and CX, which are also interesting cohorts. I'm going to focus over here on cohort A, which is really the BCG-naive cohort of patients with any high-risk disease with CIS, and then looking at their first evaluation and any time to event. This is the protocol that the patients underwent. As we know with BCG, cretostimogene followed the same sort of protocol, which allowed for re-induction for patients who had persistent high-grade TA or CIS at three months. They were actually randomized in this trial to two separate arms. One was a five-step protocol, meaning detergent was used, as well as saline washes in a five-step process in order to deliver the drug. They simplified this to a two-step process that didn't require all those saline washes, and they wanted to see, was this just as effective, was this just as tolerated? And also to look at the efficacy of both of the arms in this naive population. The treatments were given three, six, nine, 12 as would be expected, and biopsies were clinically indicated at 12 months.
The baseline characteristics of the cohort was as expected, as part of the larger cohort of patients that underwent the cretostimogene trials, they were majority male, majority White, majority greater than 65 years old. All patients were, for this trial, enrolled in the United States. And looking at this red box is just highlighting the demographics and baseline characteristics of the original administration group, which is the five-step protocol versus the optimized administration group, which is the two-step protocol. Both were evenly distributed, 27 patients in each, and they were well-balanced among all the various categories. And here's really the main crux of the data, which is that this is early follow-up, median follow-up of only 4.6 months. What we found was that there was an 83.7% CR at any time in this early cohort of patients. And this seemed to be pretty consistent between the original administration protocol, the five-step, and the two-step protocol, which is the optimized administration, with potentially a small signal showing that we'll see with the bigger numbers if the optimized administration actually has better efficacy. This was consistent among many of the subgroups, including patients who had prior intravesical chemotherapies.
And this is obviously early data, smaller numbers, but really exciting, looking forward to seeing how this data matures moving forward. And then of course, what are we looking for, as well, is the safety and tolerability, we know from the previous cohort C for the cretostimogene, that it is very well tolerated. And we see this as well in the BCG-naive cohort, both with the five-step and the two-step cohorts that are very well tolerated, no Grade-3-or-greater treatment-related adverse events. This is exciting data, early data, showing that cretostimogene appears to have some efficacy in the BCG-naive patient population and can be used, I think, in the patients that potentially can't receive BCG for some other reasons, or in clinics where BCG shortage really limits access to early treatment for patients with high-risk non-muscle-invasive bladder cancer.
Ashish Kamat: Great. Thanks, Shreyas, for that presentation. Pretty much every agent that's being studied in bladder cancer, or at least non-muscle-invasive bladder cancer, started out in the BCG-unresponsive space, and now is making its way into earlier disease states with the BCG-exposed, the BCG-naive, some of them also going into intermediate-risk bladder cancer. I want to pick your brains a little bit on your thought process as to what do you think is the value of data that come out in the BCG-naive space, but doesn't compare to BCG? How would you, in your practice, evaluate that?
Shreyas Joshi: I find this very, very difficult, of course. And some of this, obviously these were mostly patients with CIS and so they required some intravesical therapy, but in my view, it's going to be very hard to determine how many of these patients are in early CR because there was a good TURBT. And I think that outside of comparing head-to-head with BCG, we're never really going to easily know the answer. What I think that this gives us a signal for, however, is that maybe not head-to-head against BCG, but at least in lieu of BCG for patients who absolutely can't be getting BCG, in my practice, I'll be honest, I'm of course, going to reach for the BCG first because I think it's got effectiveness and it's tolerated. And we have great results with that, we have long-term results from that and we can get patients through it. And I think when we move these more and more expensive drugs earlier into the pipeline, I think we just have to be careful in reaching for them first because we know that BCG works and we want to use what works, upfront.
Ashish Kamat: Yeah. I mean, it's great to see the efficacy. I mean, to actually see a CR rate in excess of 80%, which is great, because if you hadn't seen that, then that would be troublesome.
Shreyas Joshi: Right.
Ashish Kamat: And sometimes folks will say, "Well, the drug is working in the BCG-unresponsive space probably because there was some priming with the exposure to BCG," so I'm encouraged by the data. The other thing that is really intriguing, leaving aside the comparator arm, but looking at the two-step versus the five-step, because I think that makes it more patient-friendly, makes it more palatable to clinics and flows. Could you share with us a little bit, your thoughts about the whole shift from the five-step saline detergent to the two-step?
Shreyas Joshi: Yeah, I think that it is a positive shift. I think that in an academic setting, sure, and especially in a research setting, we can do these five different steps and utilize a room in a research setting. But I think that when this comes to real clinics, I think you're not going to be able to hold a room for that amount of time and put patients through all that. That's just a lot to go through. And I think simplifying it to that two-step process is going to make this a lot more accessible and a lot more palatable to both patients and providers.
Ashish Kamat: Great. Shreyas, thank you so much for taking the time.
Shreyas Joshi: Thank you.