Thank you very much. It's a delight to be here, and I'm grateful for this opportunity to speak about enGene, which is a non-viral genetic medicines company that's at a very important stage in our life cycle. I'm looking forward to sharing more about that, you know, with all of you. Again, thank you to the conference organizers for this opportunity. As you will expect, I'm going to be making some forward-looking statements during today's presentation. Let me just set a little bit of background before I go into our discussion today. I think the first thing that we are very excited about is that we are at the precipice of a fundamental change in the management of non-muscle invasive bladder cancer.
When you speak to the practicing urologists, they've been so frustrated not having much new technology for these patients that have a very serious but slow-burn disease. We believe that this market is going to go from an incident-based market to a prevalent-based market, analogous to what happened when REVLIMID was launched for multiple myeloma. At that time, that was a $1 billion, approximately a $1 billion market. With the advent of a dozen or more agents, the multiple myeloma market is a $20 billion market and beyond. Pretty exciting for patients, but transformational as to where the market will be. The second thing is that our product, detalimogene voraplasmid, which we're developing for non-muscle invasive bladder cancer, is really designed for urologists in that it's a nice combination of, what we believe, terrific efficacy, great tolerability, and ease of use.
As I said, we're also finding ourselves in a special time here at enGene. You know, this is really a transformational timeframe because we're now coming into a time point of where, you know, later this year, we will provide, you know, an update on the pivotal cohort. Next year, mid-2026, we anticipate top-line data and the filing of the BLA, and then, of course, a potential approval and launch in 2027. This is sort of the time, you know, for enGene. Let me begin by, you know, speaking a little bit about, you know, bladder cancer itself. There are really two forms of bladder cancer: non-muscle invasive bladder cancer and then muscle invasive bladder cancer. The majority of the patients are non-muscle invasive bladder cancer.
You can see from this slide, it is a highly prevalent disease in the U.S., about, you know, 730,000 patients, but every year, 65,000 new patients come in. The problem with these patients, if you see in this particular slide, is this CIS aspect, so the carcinoma in situ. Think about that as multifocal around the bladder itself. Urologists often will cut things out. You see when you get into things like TA disease or papillary or intrapapillary tumors, these are often resected and patients go on. Because CIS is multifocal, it requires intravesical therapy. Now, when we think about different forms of cancer, you know, you think about there are big markets, you know, breast, prostate, and the like. In fact, bladder cancer is a top 10 cancer. It is number six. Actually, it is one of the most costly cancers to manage.
Now, how does this management occur, right? Unlike second-line lung cancer and the like, where, you know, you've got to move very quickly, the first thing to note with NMIBC is it's a slow-progressing disease. We estimate around 20% progression over a 10-year timeframe. The other thing to note about this, while it is cancer, it is really not oncologist cancer. It is the domain of the urologist and, in particular, the community urologists, where the majority of patients are managed there. Currently, the way they're managed is after being diagnosed, they are given BCG or chemo, and then they go through a number of options, you know, that are available. What we're trying to do with these patients, though, is have them avoid removal of their bladder or radical cystectomy. Why do we want to avoid that?
First of all, I think we all like to keep our organs as long as possible, right? Secondarily, both the morbidity and mortality with this surgery is pretty significant. You know, up to 10% mortality rate for a very long surgery. Even after a successful surgery, patients land up in the ostomy and they pretty much lose sexual function. These are usually males around the mid-70s, so this is not really a great outcome, you know, for them. What do they have in terms of medical treatments, you know, instead of avoiding this surgery? As I said before, you know, there's a product called BCG, which many of you are familiar with. It's actually a pretty effective product, but unfortunately, it's been backordered for almost a decade now. It's very spotty for availability, you know, within the U.S.
Physicians then have turned to other options because they're trying to cobble together something. Many of them provide patients intravesical chemotherapy, again, with mixed results and not really a lot of data supporting what they're doing. The FDA has approved three new agents for these patients, and it really has helped these patients. Each of these agents pose some challenges for these patients sitting in the community urologist. As we know, Keytruda is a beautiful product that saves so many patients, so many cancers. Part of the challenge of Keytruda in these patients is, one, you know, the administration, you know, these practices do not have the infusion facilities. Two, the AEs are really difficult for them to manage.
There's a product called Adstiladrin, which is, again, a viral gene therapy, again, sort of difficult to give to the patients, complex handling that goes with it. And then there's a product called Anktiva, which requires a combination of BCG. And I've talked already about the shortage of BCG. That provides a challenge unto itself. That is why detalimogene voraplasmid could really be a first-choice agent for these community urologists in particular. Why? We've demonstrated great clinical efficacy, and I'll show that we've had a 71% CR rate at any time. Two, from a tolerability standpoint, the product is really well tolerated. AEs, grade 2 or below, most of the patients say, you know, they don't really notice it. It's almost saline-like in that way. Three, this product is designed for urologists. To administer this product, they do not have to change their practice at all.
It's similar to BCG, in fact, less of a burden than BCG. I think the fourth thing, which is something that gets overlooked in this category, there's been some hiccups in manufacturing and being able to supply product. One of the nice things about having a non-viral gene therapy is that we actually should have a very competitive cost of goods, and we are already manufacturing at scale. We believe that we should be able to fulfill the market needs. Of course, you know, in the event that, you know, when we do our filing next year, you know, we expect to be able to put together a package, you know, that is approvable as well. What is our product, you know, detalimogene voraplasmid? Effectively, what we do is we create these nanoparticles with a drug product.
What's beautiful about our approach is we're able to put a pretty big genetic load in. It's three genes, two RIG-I genes, and IL-12. I think many of you are familiar with IL-12. We know it's a very good anti-cancer agent, but, you know, a very high AE profile. By delivering it intravesically, we get the benefits of that without the baggage. The beauty of this cargo is that we have an impact on both the innate and adaptive immunity. I spoke a little bit about our manufacturing advantage. What's great about detalimogene voraplasmid is we actually use four readily available agents. You see here within this process, what we do is we have a plasmid DNA, right, which is really the drug substance.
The secret sauce is a proprietary sugar, so that's the DDX, which we mix together in an inline manner. Then we create these nanoparticles, throw a little bit of pegylation on it, you know, so that we land up with a non-viral product. The nice thing about this, we are doing this in just regular conditions, so air and water, right? No special handling, you know, no minus 80, no special solvents. As I said, you know, we're well on our way, you know, to be able to manufacture, you know, for, you know, commercial needs. When we think about the development of detalimogene voraplasmid, we have the LEGEND trial, which has four cohorts up and going. The pivotal cohort is in BCG unresponsive patients with CIS, and I'll talk more about that.
We also have three other cohorts: one for patients that are naive to BCG, a second one where patients have had some BCG but do not fulfill the criteria in cohort one, and a third cohort, which is really interesting, of patients who do not have CIS but have papillary only. That data, you know, with other companies has resulted in NCCN guidelines and some usage there as well. The other aspect that is really exciting about our company is that we've developed this DDX platform. It is a robust platform where we've translated detalimogene, but there are a number of other compounds that we're developing. We're really excited about the future. Because we've developed this platform, we own a lot of prior art. Our IP portfolio is really strong, as you see here from the slide, you know, through, you know, 2040.
We feel very good about that. Let's talk more about the LEGEND study. As I said before, this is for BCG-unresponsive high-risk patients, right? This is a study where we have sites up and going here in the U.S., but also ex-U.S. in Europe, Asia-PAC, and Canada as well. We're looking for about 100 patients, an open-label study. What's great about detalimogene voraplasmid is the dosing schedule is even less than BCG. Patients get it week one and two. They take a break, come back, weeks five and six, rinse-repeat three more times that year. Then they go into a maintenance period in years two and three where they get it in week one and two. The endpoint that we have here is a landmark analysis, 12-month CR rate. Here are our baseline demographics. Very, very typical for this patient population.
You can see mostly male, mid-70s. The one thing I would draw your attention to is just the number of T1 patients that we have in this baseline group, double digits, 14%. I want you to hold that thought because I'll come back to that later on. Because remember, T1 patients with CIS are those that probably are at the highest risk. They're the most difficult patients. What do we see first from a tolerability perspective? This is some data that we shared last September. What you see here is, as I indicated earlier, that the adverse events are grade 2 or less. They're mostly attributed to catheterization. Nobody has dropped out of the study because of AEs. We feel that, you know, detalimogene voraplasmid has a very good tolerability profile.
When you compare the tolerability and the AE rate of detalimogene voraplasmid to other agents that have either been approved recently or are in investigation right now, you see the treatment-related AE rate of 48%. It's very competitive versus some of the other agents. Probably more importantly, as you start looking at a disease that has a slow level of progression, trying to avoid serious side effects, grade 3 or above, you see that, you know, there's a difference with detalimogene voraplasmid and some of the other agents. What about from an efficacy standpoint? In data that we shared September of last year, you know, we're pretty excited about a 71% CR rate at any time, three-month CR rate of 67%, 47% at six months. If you progress some of those patients at three months, that would be a Kaplan-Meier curve of about 51%.
We were delighted with this data. It was the first time that we showed data with a single dose, a single dosage regimen with detalimogene voraplasmid. In looking at how we were conducting the study, we actually believe that we've left a lot of potential efficacy, you know, on the floor. In fact, our clinical trial was missing some of the standards that the AUA asked and standard of care. We've implemented a number of protocol changes, but three protocol changes that are particularly important. The first one being is before the patients even get into the study, we now will re-resect those patients twice. Removal of that T1, not just one TURBT, but two TURBTs. If they still show T1, they will not get in the study.
That second TURBT is known to have a therapeutic benefit, and it's like four times the benefit. So what do we expect to be the net result of that? The number of T1 patients as a percentage in the study should go down. For the other companies, it's been in the low single digits. Ours was in the high single digits. And that the individuals that have T1 with the double resection should more likely than not be responders as well. So that'll be a good thing. The second change that we've done is after three months, our doctors were saying to us, "Look, CIS does not seem to be, you know, progressing. We've got this little growth, and standard of care is we just snip that out." Previously, we would say, "Well, no, you can't do that.
The patient's got to come out of the study. Now we're allowing them to snip that out and then re-induce the patients. You've seen with other companies, when they've done some re-induction, that has resulted in a material change in efficacy as well. The third change that we've made is before we would allow physicians to take patients out of the study if just on visual inspection it looked like there was progression. That, as you can appreciate, adds a level of subjectivity into things. Now we're making it more objective. We're asking physicians to do a biopsy to confirm if there's progression or not. These three changes we believe are material changes and will have a material impact on our efficacy numbers.
Now, if you compare it to the other agents, I think, as we said, I think we're pretty pleased with what we have with the CR rate any time compared to, you know, the other agents in development or approval. You can see here that our six-month rate compares very similarly to the BOND II study, which CG Oncology conducted with their agent. Very similar. The big change between, you know, BOND -002 and BOND-003 is a material amount of re-induction in patients, which we expect to have as well. I think the logic holds that, you know, we have a good efficacy for our product, but we've handicapped ourselves. We believe that these changes should make a difference and that we really do have a competitive and efficacious product with detalimogene voraplasmid.
Now, you know, there's been a lot of discussion, you know, in the public and what's happening with the FDA and FDA approvals. And we get asked, you know, what is the bar for approval? What is the guidance? You know, I think here are the agents that have been approved under the FDA guidance. We do know that in dialogue with the FDA that they do not issue guidance lightly. The initial guidance for this patient population, the draft guidance for BCG unresponsive patients, was in 2018. They updated the draft guidance last summer as well. And I think that reiterates that the FDA and the patient community says there's still a very high unmet medical need here. So we feel pretty confident about our regular path forward. And our dialogue with the FDA continues to be a very positive and constructive dialogue as well.
What do we land up with and what do we believe that detalimogene voraplasmid is? I think we have a product that is actually a best-in-class product that is really well designed for the urology community. Because what do you get? You get the package of really great efficacy that we've already shown so far. Tolerability where patients say, "Hey, you know, this is not a burdensome experience for us." For the practice itself, slides right in, you know, to these busy urology practices. If you look at it from the optics of the physician itself, you know, how does this compare to some of the agents? What do you get with detalimogene voraplasmid? As I said, efficacy, good tolerability, and ease of use. If you compare this to the CG Oncology product, right? The CG Oncology product is one that is stored at - 80.
It requires cold chain storage. You know, there may be a dropship opportunity, but it is an oncolytic virus. And it is a potent oncolytic virus. If you look at the only other oncolytic virus that's approved in the marketplace, it requires special biosafety handling. For these patients, you know, they will require multiple pre-washes. Then they'll have the treatment itself. Likely they will need to bleach their urine as well. Very effective, interesting product, but a challenge for urologists that are particularly in the community setting. You compare that to the J&J product, TAR-200, which is gemcitabine, you know, in a plastic device, right? The first thing the physician has to do is look at the risk-benefit between, you know, the efficacy and the potential for serious side effects.
You know, these patients are going to have to come in every three weeks. It begins with a firm catheter. Then three weeks later, the patient has to come in. They need a procedure room to use another catheter with a grabber catheter to remove the device, put a new device in. It is a different burden for both the practice and for the patient. At Adstiladrin, you know, a product that, as you know, is approved, but it requires a good chunk of time for thawing. It also requires pre-medication. This is a virus as well. The logistics of this for the practice and for the physician can be a challenge. Now, if you take this, you know, from a patient optic perspective, what does it look like from a patient perspective?
For detalimogene voraplasmid in the clinical trial, you know, there are no pre-washes. They're there for an hour, and there are no actions afterwards. They come in week one and two, week five or six. You know, in real life, they will go home. It is a short administration of probably five to ten minutes. They'll say to the patient, "Go back, you know, go home, hold for an hour, void, and you don't have to do anything." The nice thing about it is detalimogene voraplasmid will likely be administered by the support staff within the practice. That practicing urologist can go on and do other procedures and do other things, right? Whereas for the patient experience, you know, if they are prescribed the CG Oncology product, you know, they've got to come in. There's four pre-washes that they will have to do.
There's the whole time. And given that it's an active virus, you know, there's probably going to be a bleaching requirement. And as I've articulated with the TAR-200, it's every three weeks that they have to come in. And with Adstiladrin, it's again an active virus. They're going to be in the clinic for a while, and they're going to have to bleach, you know, their urine as well. So if you package this all together for both the urologists and for the patients, and considering that these urologists are in the community, detalimogene voraplasmid actually brings them the best combination of really terrific efficacy, tolerability, and slides into their practice flow quite nicely. Now, I articulate, you know, this as sort of choices between agents, and it's binary.
Actually, I think what we're really excited about, this is going to be an area that's going to be terrific for patients. The market will go from what I would consider to be an incident-based market to much more of a prevalent-based market. I think as urologists sit down with patients, they'll be able to say to them, "Look, these are multiple agents that are available." As you saw from the data that I shared with you, these agents have somewhere between a 20%-40% 12-month CR rate. By definition, in a year, 60%-80% are going to require a new medicine. The incentive will be both for the patient, because these are generally 75-year-old-ish males, you know, in communities, they'll want to be closer to where they live versus traveling to an academic center.
The incentive is to have medicines that keep them close to the community and also reduces the burden for them. The incentive for the urologist is to obviously satisfy their patients, but also financially, they'll want to keep those patients within their practices. More and more, these practices are moving into a bill-and-buy model, which is a great source of revenue for them. Sequencing these agents will also be great for their patients, but it will also be great for the economics, you know, of their practice, right? Let me just close up, and then I'm happy, you know, to take any questions in the last, you know, four or five minutes. You know, we have a team that's really qualified to commercialize and launch this product.
You know, you might have seen that we've now added a Chief Global Commercial Officer, Commercialization Officer to the organization. We're getting ready to go. Let me just summarize by saying, yeah, it's a special time for our company, enGene. I think we're at the beginning of a fundamental shift in the NMIBC market. I think that detalimogene voraplasmid being unique and highly differentiated with a great efficacy profile, a great tolerability profile, and a lower barrier to use can be an important part of this new treatment paradigm. We're also in a time frame where a lot's going to happen. Data later this year, next year, we anticipate a filing of the BLA, and then we anticipate an approval and launch. I think we're delighted that we have enough capital to get us through, you know, a number of these milestones.
Our guidance says catch into 2027. Based on these inflection points, we should be able to get there. Again, I want to thank you all for your attention today. Thank you for your interest in enGene. I'm happy to take any questions. All right. It doesn't look like there's any questions today. Again, thank you all, you know, for your attention and interest.