Sarah Psutka: Well, thanks, Ashish. And thanks so much today for giving us a moment to just talk about this extended access program, which I think is actually a very important opportunity, that it's important for our community to be aware of. With the ever-increasing number of options available to patients who have BCG-unresponsive non-muscle-invasive bladder cancer, we're really left with a critical question in terms of, how do we start thinking about sequencing these agents, how do these agents play in the real world, given that we've seen the results that we've seen in the single-arm clinical trials that have led to approval of other agents, and will likely lead to the approval of the agent that we're going to talk about. This is an extended access program that is really looking at this novel agent, cretostimogene grenadenorepvec, in the real-world setting in the pre-approval space.
And so I'll explain a little bit more about that. But essentially, this is an oncolytic immunotherapy. So this is a gene therapy. It is replicative that stands in distinction, for example, compared to nadofaragene firadenovec, which is a non-replicative gene therapy. This agent selectively replicates and lyses cancer cells. And in doing so, not only is toxic to the cell itself, but also essentially elaborates in immune response against further bladder tumors. And I'll highlight that in a second. The BOND-003 trial looked at the efficacy of this agent in high-risk BCG-unresponsive non-muscle-invasive bladder cancer with CIS, with or without papillary disease, and demonstrated an impressive 76% complete response rate at any time, with a duration of response that exceeded two years. And I think, I'm sure Ashish you feel as excited as I do about the fact that, in a world where we used to have very short opportunities to trial a new agent, and essentially fairly limited durations of action, we're now moving into this world where a number of agents are breaching that two-year time period, and that's pretty darn exciting, because we're talking about giving patients a durable opportunity for disease control in what was otherwise a space where people didn't have that kind of longevity with each of the agents we had available to us.
And the other thing that I think is important to know about cretostimogene, that is very well-tolerated, with a very limited significant adverse event profile. So, this drug has been granted the US FDA Fast Track and Breakthrough Therapy Designations. And we anticipate that likely within the next year or so, there will be FDA approval, hopefully, to bring this drug to everyone. But in the setting of not having that approval yet, an expanded access program is essentially a pathway that allows patients to access a likely beneficial investigational treatment before they're approved. But one of the reasons I got involved with this program, and one of the things that I'm excited about is that it's actually evaluating the real-world performance of this drug within the confines of an expanded access program in a very generalizable real-world patient population. So, it also allows us to begin to collect data about how this drug performs in patients who couldn't have gotten on the trial because they wouldn't have met criteria. And I'll explain more about the extremely, I would say, rational and eligibility criteria for this.
The other thing I'm excited about is it's going to collect a lot of patient-reported outcome data, which I think is going to help us to understand potential the treatment burden and what the patient experience of receiving this drug looks like in a very carefully characterized way. So again, this is a replicative gene therapy. It enters the target cell and ultimately results in the lysis of that cancer cell. And this essentially elaborates in immune reaction. So you get this dual mechanism of action, and that is without sort of belaboring that, I think helps to explain the CR rate, and supports the biologic response rate that we are seeing here. But let's talk a little bit about the EAP. So, this again is looking at patients who meet the FDA definition for BCG-unresponsive non-muscle-invasive bladder cancer. So this is a carcinoma in situ with or without papillary disease that's recurred after patients have received at least five of the first six initial induction BCG therapeutic instillations, with at least two of three maintenance cycles. This is currently an openly enrolling expanded access program.
I learned that 21 sites are fully open at this point. I know we are working to open this up at the University of Washington. Again, it's a very flexible entry criteria. So, unlike most clinical trials that really restrict around performance status and other comorbidity burden, basically any patient who has BCG-unresponsive non-muscle-invasive bladder cancer, who can't get another therapy, doesn't have access to another therapy, or can't get on another clinical trial because of their comorbidity burden, or their performance status, or any other factors, can potentially be eligible to receive cretostimogene on this study. And importantly, this includes patients who have previously received a different investigational therapy. So it's really a very sort of real-world entry criteria. We say, and this is something you've said many times, once BCG unresponsive, always BCG unresponsive, this really allows us to capture all of the patients who really are running out of options, but are seeking a bladder-sparing solution. And then the induction course is a weekly course of the therapy, which is given once weekly, similar to BCG or gem-doce. Interestingly and importantly, patients who have a partial response are eligible for a second induction who don't achieve a CR after that first six weeks.
And then you can see here what the maintenance dosing looks like. So it's three weekly maintenance dosing quarterly for the first year, and about every six months and year two. The co-primary endpoints for this study are safety in this real-world patient population. And then of course, the critically looking for efficacy, the CR rate at any time is the co-primary endpoint. We're also looking at duration of response, progression-free survival, as well as cystectomy-free survival. And then, really diving into the PROs and the health-related quality of life. And for those, these are validated questionnaires, including the EORTC, QLQ and MIBC24, which is a non-muscle-invasive bladder cancer specific, very granular health-related quality of life. But we're also looking at things like treatment utilities, how the patients feel about the utility of this therapy in combination with the actual efficacy assessment. So here again is just a quick look at the study administration schedule, which is essentially what I just discussed. But again, critical and I would think important study points. One, partial responses are able to receive continued dosing of cretostimogene the discretion of the investigator and be re-induced, unless they have a high-grade T1 recurrence. And then maintenance is as detailed. And again, the surveillance is real world practice, but it's meant to be as guided by the AUA guidelines.
So here, this extended access program is offering cretostimogene to patients who have CIS containing BCG-unresponsive non-muscle-invasive bladder cancer who can't get access to other drugs or participate in other trials, but are seeking a bladder-sparing option. And essentially, the idea here is for patients who, we have this fairly, I would say, efficacious investigational agent that is likely to undergo regulatory approval in the coming year. This allows physicians to offer this to patients who can't get anything else. We've sort of gone through all this, but as a quick summary, this again is an oncolytic immunotherapy. It is not only thought to be directly toxic to the cancer cells, but also leverages adaptive immune switching. It appears on all of the top level presentations of the original studies to be very effective, and importantly, very well-tolerated with a very, I think, a favorable safety profile. It's something that as an intravesical therapy easily fits into existing clinic workflows. And so it's something that urologists will have quite a bit of a facility to introduce into their clinic. And at this point, we are actively enrolling, as I said, 21 sites have signed on. And what I think is going to be the important potential research deliverable here is that we're actually going to learn a lot about how this drug works in a real-world patient population.
It'll give us some important real-world data that will likely be fairly generalizable in the lead up to regulatory approval. And this is important in terms of also permitting access of another effective and very well-tolerated bladder-sparing therapy to those patients who can't get onto other trials, or access other therapies. And so we were grateful to the SUO for the opportunity to have a little discussion about this work. And I think there was quite a bit of interest regarding the poster during the SUO. And I appreciate Uro Today's opportunity, giving us the opportunity to speak about it here as well.
Ashish Kamat: No, I think it's great, Sarah. I mean, anytime you have an expanded access program, I think it's really good for multiple reasons, which you mentioned. And just before I got on here to have this chat with you, I was going through my email for other reasons. And I recalled an email from Arthur Kwan, the CEO of CG, wasn't known as CG Oncology at that time, but I've known him for many years, more than 10 years, and just hats off to him for everything he's done, especially this with the expanded access program, allowing patients who otherwise may not have access to the drug to actually get drug. So, really very forward-thinking. One quick clarification in case folks listening have that question, which I wanted to ask you. So, this whole thing about partial response and re-induction for non-responders, it's almost the same thing, right? Can you clarify the difference?
Because I know we used to talk about partial response back in the day when we didn't have anything to offer patients because we didn't want them to come off a study. But now that you have re-induction for non-responders and partial responders, other than obviously T1 progression, what is the real difference in this study and between partial responders and non-responders?
Sarah Psutka: So, I think the real difference at that three-month initial evaluation point is whether or not it's the degree of response. So, if carcinoma in situ or high-grade TA persists, but you see a reduction in overall tumor burden, those patients are eligible to receive an additional six induction doses. If a patient, however, does have persistence of high-grade T1, then that patient would be recommended to come off study for obvious reasons. The protocol does recommend that all patients undergo a complete TUR prior to study entry, just as we would ideally undertake for any patient with, again, this degree of BCG-unresponsive non-muscle-invasive bladder cancer with high-grade T1, having a proper re-resection per AUA guidelines. But it's really essentially in the absence of persistence of T1 at that three-month standpoint, there's the option, just as we would consider if you were treating a patient with de novo BCG, you would, per the guidelines, offer them a second induction course. And you and I have talked about this as well. Sometimes a little bit of CIS, you just need more BCG before you move them into that complete response. Hopefully, given the immunologic mechanism of action here, we hope to be able to convert some of those partial responses to full responses by the six-month mark.
Ashish Kamat: Sure. Great. Yeah. No, I just wanted to clarify that the EAP is not condoning doing anything that's unsafe. It is just different terminology, so it can be captured under different, essentially brackets, right? But if it's T1 disease, we consider that unsafe. The EAP also considers it unsafe. So, that's great.
Sarah Psutka: And that patient by study protocol would not actually be eligible to receive further drug, because obviously that's a failure of response at that point. But the other thing I just really wanted to highlight is how thoughtful the company has been about including patient-reported outcomes. And you and I obviously are very invested in learning more about the patient experience, specifically on all of these novel agents, because that's going to be, I think, I would say it's going to be a big factor that's going to help to drive patients towards one of these novel agents versus the other in the absence of comparative data, is what the tolerability of these agents is. So, having not only just an IPSS and not only tracking physician adjudicated AEs, but getting really detailed PRO data here, I think is going to be super helpful.
Ashish Kamat: Yeah, absolutely. Sarah, as always, thank you for taking the time. Always a pleasure.
Sarah Psutka: It's a pleasure. Thanks, Ashish.