Late, in terms of helping the profile of detalimogene voraplasmid. Now, those protocol amendments were effectively implemented near the end of last year. As we were enrolling patients, we would like to have a reasonable cohort, reasonable size cohort of patients, at least three to six months' data where you could see the impact of those changes. That's what we're really waiting for. This morning, we shared our guidance that in Q4, we will share that data. We're still working through whether it'll be attached to a medical meeting or independent. More than anything, we just want to make sure we provide incremental information versus our September 2024 data where we showed a 71% CR rate, a good tolerability profile, mostly grade 1 and 2 AEs. We'd like to provide you something incremental for that.
We believe that by having a bit more data with the protocol changes, we'll be able to achieve that.
Got it. How many patients from the new protocol? It sounds like you're trying to optimize as many patients as possible from the new protocol, right? Can you give us a sense of how many patients might we see at this update?
Yeah, the vast majority of the patients will be in the new protocol. You might recall in the September 2024 update that was 21 patients, right? As we announced this morning, we've hit our target enrollment of 100, and we will likely exceed that. The majority of the patients will be, you know, subject to the new protocol, which brings us in line with standard of care, and we believe will help the profile of detalimogene overall.
Got it. Could these, you know, given that you finished the enrollment, when we think about your pace of enrollment, because there is a little some period of time where you continue to enroll under the old protocol, right, after your last readout, before the new protocol can be put in, right? Are the number of patients enrolled in that window actually not very substantial because your enrollment is gathering momentum and more is enrolled later? Can we think about from that angle?
You got it. Exactly. As you know, near the end, there's always a hockey stick in enrollment, and that's a function of having all the sites up and going and the number of patients who are coming in. In the latter months, we have large chunks of patients coming in. In that period where we were transitioning from the old protocol to the new protocol, relatively de minimis numbers. I think the way to think about it is the vast majority of the patients will be subject to standard of care, and we think that that'll really help the profile of detalimogene .
Great. In terms of reporting six months' data versus and/or 12 months' data, could you give us a sense? It feels like 12 months' data is probably only for those patients under the old protocol, right?
Yeah, exactly. If you look at the 21 patients, as you would probably expect, some of those patients will be, there'll be some protocol deviations likely in that. That will even shrink. When you get to the 12 months' data, that becomes a pretty small database, right? We, and it'll be on less than standard of care as well too, right? I think we have to be a little bit careful. We don't want to over-interpret on whatever data that is. I think we're more excited about the fact now that we've hit our target enrollment, got a good bolus of patients that are running through the study. We're pretty excited that over time we'll be sharing more and more data, and obviously, we'll have much more data on a larger bolus of patients who are at standard of care with detalimogene .
Great. Could you talk about the bar for the CR rate? I guess most focus is on six months' CR rate, but if there's anything that you can talk about about 12 months' CR rate, that would be helpful as well.
If you look at what the FDA has approved, I think the bar, if you look at the FDA, the three agents they've approved, it's between around 20% - 40%, right? You might argue, given that these are small studies, how different is that? Is that really, right? If you look at our 71% anytime complete response rate from our September 24 release, I think we feel pretty comfortable about the efficacy of detalimogene and the emerging profile. If you toss on the fact that we've made these protocol changes and these protocol changes bring us more in line with standard of care, we think that's going to help the profile of detalimogene . I think we feel pretty good about our approvability.
Got it. Some of the protocol management will help like a six months CR. Some of them will help also on the anytime CR, right? You will have impact on both the anytime CR and six months CR. Is that a reasonable expectation?
I think just overall, the reality of it is we had one arm behind our back a little bit, and detalimogene performed very well in our September 2024 data updates, right? We've removed that one arm behind our back and aligned our protocol with the standard of care. You would expect within aligning the standard of care that this should help the profile overall, right? I think we're pretty excited to have hit our target enrollment. Now that we have a larger, more substantive bolus of patients, we're looking forward to sharing some data as time goes on.
Got it. Now, if we bring in the ease of use advantage of detalimogene , how much flexibility on CR rate do you think urologists could extend to detalimogene relative to other products?
It's hard to say, right? It's very much dependent upon individual urologists. Obviously, efficacy is important. You're never going to use a drug that doesn't work, right? We would anticipate, given where our CR rate is, that we have an active drug, right? Urologists have more than one thing to talk and think about than efficacy, particularly in the community where the majority of the patients are. They need to look at the frailty of the patient. They need to look at whether they can come into the office 12 weeks in a row for some of the other agents or whether they can come there week one and two, week five and six with detalimogene . They're looking to see how frail the patients are, and do you want to use a product that has a higher AE profile versus a lower AE profile?
Right now, based on our September 2024 data, our AE profile looks pretty good, right? They're also thinking about how much space do I have, and how much space do I use, and how do I utilize it? Do I have access to these particular rooms or not, right? You put that all together. At the end, if you think about it, you're sitting in your community urologist, you're looking at the agents that are available and the new agent, the profile at detalimogene voraplasmid is a pretty attractive profile. As I said, reaching the fridge freezer, five minutes, you're in and out. That is something that's really valuable for the urologists, and particularly where the patients are right now.
Got it. Lastly, on efficacy data, when the data comes out, some investors may be tempted to make cross-file comparisons, right? What are the caveats, and could there be a reasonable way to compare the data?
As you know, in general, we try and avoid comparisons between different studies. I would argue there are three things really to consider in this case. First of all, if the studies were 1,000, 2,000, 5,000 patients, you would say, okay, there might be some differences. These studies are less than 100 patients, 100 patients or less. Even statistically, there's a big swing with a few patients. That's the first point to think about. The second point to think about is, while individuals think all the protocols, we reach to the shelf to get the same protocol, these are confidential documents, and there's just differences in inclusion/exclusion criteria and things that you do. There's differences in the protocols. The third thing to think about is, as I spend more time with NMIBC patients understanding the area, these are heterogeneous patients.
For instance, a patient that comes in first time presenting, has cysts and has one lesion, will get into all of these studies. Also, though, a patient who has had a couple of therapies before, maybe has had a kidney removed, maybe has had some other concomitant diseases, still fits the entry criteria. That's a pretty broad range of patients. I would caution individuals to solely look at the CR rates between these products. In reality, if you start looking at even some of the newer products used in a real-life setting versus in this controlled clinical trial, it's very different. It's very different. Basing your decisions on 100 patients between differences in studies is something that you want to be careful of.
Great. Thanks for that framework of thinking. Obviously, you now completed your enrollment, and I think you guided, you know, you guided for BLA in mid-2026, and that's a 12-month study. Everything lines up well. Can you maybe touch on BLA filing and your confidence to be on track there?
Yeah. We updated our guidance for BLA submission to the second half of 2026. All late breaking news. That's just more as a function of the reality of it is it's very hard to turn off the study right away. There's a lot of interest from the urologists that are in our study. There are patients that are still in the screening process. Getting back to our earlier discussion, I think we'd like to have as many patients in the new protocol as possible. With that, we're pretty excited to say that we're on track to file in the second half of next year. We're ready. If you look at our regulatory and clinical teams, they're very strong. In fact, many of our modules are already written, ready to go. I think one of the big advantages for us is being a non-viral gene therapy.
We use four simple ingredients, and we're already manufacturing at scale. This area has been besieged with manufacturing challenges, and we feel pretty confident in what we're doing from a manufacturing perspective. You put that all together, I think we're on track for the clinical package and the CMC package and our preclinical and the other modules. We're ready to go. We're looking forward to having top-line data and filing quickly thereafter.
Great. That's certainly understandable. Sorry, I missed the breaking news, being in meetings since the morning. Yeah, I think that's totally within a reasonable range for that change. Perhaps in the remaining time, maybe we can talk about some other cohorts in LEGEND. You have cohort two, cohort three, and we are expecting updates from those cohorts also in the second half. Can you talk about what these cohorts are and what is the opportunity associated with the studies?
We think the profile of detalimogene is very interesting, but we also want to provide as much data to treating urologists as possible. We initiated three new cohorts. Cohort 2a is for, again, NMIBC patients with cysts, but are naive patients. Cohort 2b are those that have been exposed to BCG, and both have cysts. Cohort 3 are individuals who have papillary disease only. We're excited that we're actually enrolling patients in those. We're excited that the community really wants to put patients in those. Frankly, these are more to expand the knowledge, right, for the community. The biggest priority is the pivotal cohort, Cohort 1. We're really focused on getting that through and generating that data. The others will follow over time and we'll provide updates as those data sets mature.
Got it. I think we are right on time. I wonder if there's any questions in the audience, Oron. If not, I think we're on time. Thank you, Ron, so much for all the insights and for your time. Looking forward to the data next year. Congrats on completing enrollment for the study.
Thank you, Yan, and to Rachel, for the opportunity to be here and to chat with you. I think at enGene, we're pretty excited about where we are with detalimogene . We're kind of getting into the zone where a lot's going to happen in the next little time. I'm really glad to have the opportunity to share that with you today.
Great. Yeah, I appreciate all the insights and your time. Thank you, Ron.
Thank you.