Welcome to H.C. Wainwright's 20th Annual Global Investment Conference. I am Ananda Ghosh , Senior Biotech Analyst at Wainwright. Today, we are very pleased to host Ron Cooper, CEO of enGene Therapeutics, for our company presentation series. Ron, welcome.
Well, great. Thank you very much for the opportunity to be here. This is a particularly special time for enGene Therapeutics. You're catching us at a moment of where the company's going to transition very quickly, so I'm looking forward to sharing that information with you today. As you'd expect, I'm going to be making some forward-looking statements during today's presentation. Let me begin with just a large overview. First of all, our lead clinical asset, detalimogene, we consider this to be a next-gen therapy for NMIBC. There's a couple points I'd like to make first of all before going into the presentation. The first point is, I think it's underappreciated the unmet medical need, particularly with community urologists, and that the advent of new agents is not going to be something where one agent is going to win.
In fact, as we talk to urologists, sequencing is going to become even more prevalent, and that population, the TAM, is going to increase. Therefore, the market is going to get larger. What we're excited about with detalimogene is we have a clinical profile that is emerging quite nicely. With a 54% complete response rate at any time, this is in line with already approved products. With a tolerability profile that's trending towards best-in-class, we think that detalimogene is going to be an important part of sequencing and managing NMIBC patients. An attribute that's really important and often overlooked when it comes to community urologists is how products fit into their practice flow. The beauty of detalimogene is that it is stored in either a regular freezer or refrigerator. It is easily transported, and it fits so nicely into the practice setting.
Now, with a 54% CR any time, as we said, we're in the range of the approved products. But we've always, at enGene, looked to see how could we make detalimogene even better and even more convenient for patients. We're delighted that we just recently have completed the safety run-in of a new cohort of patients combining detalimogene with a surfactant bladder rinse. That has the potential to not only improve efficacy and durability, but reduce dwell time from 60 minutes to 30 minutes. The net would be a better efficacious product, but also a product that's more convenient for patients. As I said at the very beginning, you're catching us at really an exciting time.
We're sitting with $266 million in cash. In the next quarter, we plan an update on our pivotal data set, where we'll share some more of our data that's maturing, particularly from a durability standpoint. We've said that we have a meeting with the FDA, a pre-BLA meeting, and we plan to initiate the filing by the end of this year. As I said before, you're catching us at a particularly special time for enGene. Why are we excited about detalimogene, and what's exciting about this non-viral approach? It actually addresses some of the shortcomings of the viral gene therapies in that we can deliver, in this case, three big genes. We can redose the product, and because we use four readily available ingredients, the cost of goods for our product is actually one of the lowest.
Being non-viral, it also reduces the cost of handling and the like. Let me spend a few minutes talking a little bit about NMIBC. First of all, non-muscle invasive bladder cancer. NMIBC represents the largest majority of bladder cancer diagnosis. Bladder cancer is the sixth biggest cancer in the United States, and you see when you get down to the funnel, the actual incident population's about 20,000, some say as high as 40,000. NMIBC is characterized by CIS, carcinoma in situ, which is all over the bladder, so you can't cut those out. You need to use intravesical therapy to get to that. Patients may or may not have growth tumors, papillary tumors, which you see here. In general, these patients present with blood in their urine.
The one thing, while this is cancer and it's a very serious cancer, it is a slow progressing cancer, about a 20% progression over a 10-year timeframe. The treatment consideration is different. Also when you consider the average patient age is around mid-70s. What usually occurs is these patients are started on BCG. Many of you are aware that BCG has had a chronic shortage, so it's sometimes difficult to get BCG, but it is an effective therapy. However, after a couple of years, there's about a 50% recurrence. Standard of care right now is to use some of the new therapies or IV chemo, and there's some limitations with all of the agents that are there I'll talk about shortly. The ultimate treatment for bladder NMIBC is actually, when I say ultimate, 100% CR is removal of the bladder.
Sounds simple, but this is a very long surgery with very high mortality, very high morbidity. Patients in general want to avoid this. Where are these patients? When you look across the U.S., the majority of the patients are in the community, about 75%-80% of that. The treatment considerations in the community are different from academic centers. You see here from this market research, what are these community urologists looking for? They're looking for the perfect balance of tolerability, efficacy, and ease of use, how the product moves into their practice flow.
And now what's interesting as well, when you look across this community group, there's even a subgroup of the community where I would say about 40% of them through our market research, where they have a characteristic of where the profile of detalimogene is uniquely differentiated. What is happening in these practices? They have limited resources. They have workflow challenges. They have economic challenges. The unique aspects of detalimogene, which I'll talk about shortly, fit in very nicely. Let's give a little background. What is detalimogene? Detalimogene, as I said, is a non-viral gene therapy. What we do is we take a simple generic plasmid, we put two RIG-I genes and IL-12 in that. That is the lyophilized powder, which is mixed with water and instilled in the bladder, which you see here in the last graph.
What's beautiful about detalimogene, though, is that it has both an impact on the innate and adaptive immune systems. it's a 1/2 punch. As I was talking to you earlier about our components in manufacturing, how is detalimogene made? We take that plasmid. The secret sauce is our proprietary sugar, the DDX, in line mix them, throw a little pegylation on top of that to create nanoparticles. Now, why is this good? Well, first of all, this is a product that is very stable and easy to store and transport. It will probably sit once we complete our discussions with the FDA for years in just a regular freezer, the same one you have at home, and for many months in the fridge. So a clinician or someone in their practice can just reach into the fridge, mix with water, instill with patients.
I'm delighted that we've already completed our FDA validation batches. We're manufacturing at scale. Since we have the CDRP program with the FDA, we have a lot of dialogue, and we feel pretty confident about our filing from that perspective. What is the design of detalimogene? It's designed to be easy for patients and easy for the practice. Easy for patients from what perspective? Very few doses. We give the drug week one and two, week five and six. Very little time in the office. Then there's nothing that occurs afterwards in terms of extra precautions like urine bleaching or the like. For the practice, as I said, most practices have a fridge or a freezer. Many of them don't have an ultra-cold chain storage freezer. It can be administered by anyone, any qualified medical professional.
As I said, there's no decontamination needed within the practice, no hoods required or the like. If you summarize this, detalimogene is the only product that does not have complex shipping or storage, that has a short administration timeframe, that does not have any bacterial or viral decontamination, that doesn't require any post-treatment action, and can be administered by anybody in the practice itself. So where are we studying detalimogene? Our clinical trial is the LEGEND program. Cohort 1 is with BCG unresponsive patients with CIS. One of the bigger programs, 125 patients, and we have some other cohorts as well. But let me go a little bit deeper into Cohort 1, which is detalimogene without a surfactant. Again, it's BCG high-risk patients, a global study that we've put 125 patients on. Primary endpoint, CR anytime.
If you look at the baseline characteristics, they are pretty typical for these patients, mostly male, average age in the 70s. Please note a couple of things here. We actually have a patient population that is highly experienced. Almost 40% of the patients have CIS plus a papillary disease. Even though our study is designed for BCG and detalimogene, we have a high percentage of patients, 25% of the patients that have had a prior treatment. At the recent American Urological Association's meeting, we shared preliminary data. What you see here is a 54% complete response time, again in line with other products. We provided some updates on where we were from a 12-month landmark perspective. You can see here at 13.3%, that seems to be relatively low. However, you see in the bottom there, that has the whole denominator.
It does not have all the numerator. We have 19 patients that are complete responders and potentially two more that are progressing. If you look at the Kaplan-Meier curve, we anticipate a 12-month landmark CR of about 24%, 25%. When you think about your approvability, though, and if you think about what the FDA is looking at, first of all, they are looking at the primary endpoint. Currently we are at 54%, which is in the range of the other products. Where there is some confusion on the street is what is the key secondary endpoint for durability? What it is of 54% of those patients, what percentage of those patients are still responding 12 months and beyond? You can see here, that is roughly 40%-50%, about half the patients.
We are waiting for our data to mature, and we would expect to be within FDA requirements for that. One number that the market is quite focused on is this 12-month CR rate, which I will remind individual is not a number that is an endpoint. It is not a promotable number. Later this year, we will be providing you more information in regards to that. As I said, right now our Kaplan-Meier curve has us looking very much like an ADSTILADRIN type profile for that parameter. Tolerability is absolutely excellent. You see here a pretty low risk of treatment related AEs, 55%. Put it in the context of the approved products and the products in development, that is really competitive. I would draw your attention, though, to the real measure of how well tolerated the product is.
Dose interruptions and dose continuations are very low, 2.4%, and that appears to be trending towards best in class. We would consider ourselves trending towards best in class tolerability. The package that we say for detalimogene is efficacy that is in class, potential best in class tolerability, best in class ease of use and handling. We said to ourselves, we have always wanted to make sure that we could do everything we can to make detalimogene the drug for community urologists. How could we make it even more effective and even more convenient? We have considered using a surfactant bladder rinse for detalimogene. As I said before, detalimogene on its own has really a compelling profile. If we add a surfactant in, what would that look like from a tolerability perspective, and can we improve efficacy?
Now, if you look at the other viral gene therapies that you see in this slide, in the top, you see the usage without a surfactant. What you see is either no transfection or very little transfection. You add a surfactant, and you see in green there or in the staining that that really does boost transfection. What does that look like from detalimogene? Well, you see in the top left that detalimogene, you actually see pretty good expression indicated by the colors there. But if you add a surfactant, you see an increase in both depth and breadth. If you look to the right there, that's a 10x increase in IL-12 expression. Now, that is in the mouse model. You say, "Well, any other models?" Well, here in the NHP, what you see, again, a 9x increase in expression, but also an improvement in distribution.
We believe that this could make a material impact on the efficacy of the product. The next question is tolerability. From this chart here, you see that there is very little systemic exposure with the surfactant that we're using. We've selected a surfactant, polidocanol. The reason we've selected that is it's widely studied, it's an approved product, has a big safety database, and it's actually used in shampoos at 1%, and we're using a quarter of the dose. As I said, we're up and going with another cohort of patients. The way that it is administered is the patient is catheterized. You put polidocanol in for five minutes, take polidocanol out, put detalimogene in, and instead of having a dwell time of an hour, it's a dwell time of half an hour.
Net saving of 25 minutes approximately for the patient and for the practice. That's a material convenience saving, and as I said, the data would suggest an improvement in IL-12 expression, which should translate into greater efficacy over time. As I said, we've just finished the safety run-in for these patients. We're actively enrolling sites, and we look forward to updating the market as we have more data. Let's close off by talking about how we see this NMIBC market evolve. It's a very exciting time for NMIBC patients and for the providers, because finally there are going to be options. I think the way that we think about this is our market research first says that patients will take three to four, if not more, lines of therapy, sequencing products.
When you survey patients, the vast majority, 90% of them, do not want to have an organ removal, a radical cystectomy. What we see is that right now, many of the newer products are being used in the academic centers because they're a little bit more difficult to use, as I described before. Whereas if you look at the community where 70%-80% of the patients are, right now they get BCG. We see detalimogene being used right after BCG because, A, efficacy, well-tolerated, slides into the practice, but also you will know usually within three months, 90% of the patients respond at that time. If you don't respond, only 3% of the patients progress. It is really ideal at that pace. We anticipate three or four lines of therapy at the community, and then going on to the academics.
In the bottom right, you see an illustration of what we mean about what's going to happen with building this prevalent population. It's not one drug that's going to win, multiple drugs are going to win. If you think in year one, there's 10,000 second-line patients after BCG, about half of those from the durability data that I talked about before will recur. Then they'll need another second-line patient. Then some of those patients will pop in in year two, but you can see how you're creating a compounding effect of more patients in the prevalent pool, therefore, a bigger market overall. I think it's pretty exciting what's happening within the marketplace. I do believe that payers are recognizing that these new technologies can make a really big difference.
From our market research, payers have said to us that, look, if you have NCCN guidelines, you're generally going to be covered because it's serious, it's cancer. You do see, though, that over time the pricing benchmark has changed from roughly $250,000 per patient a year to closer to $700,000. Just doing simple math, to achieve $1 billion of sales, you need roughly about 2,000 patients. Getting back to the treatment-available patient population, you see here in the high-risk BCG unresponsive and exposed patient, that's going to be around 40,000- 75,000 patients, naive patients, incremental on that, intermediate, a little bit bigger. This total patient population is pretty significant. As I've indicated earlier, with these new agents and with sequencing, this market is going to get bigger.
Let me close off by saying, first of all, we have an incredible team here at enGene. This team is really dedicated to making sure that new medicines get to the marketplace, and they've done it multiple times before and have commercialized products before. We're pretty confident this team can get the job done. Just to close up here, what I'd like you to walk away with is that, first of all, this NMIBC market is going to look a lot different in the next five years. The analogy I like to use is the multiple myeloma market, and when REVLIMID was launched. That was a $1 billion market at that point. You add over a dozen agents, a $20 billion market because patients are receiving multiple lines of therapy and sequencing. This is a large market now.
It's only going to get bigger with these new agents. Not one product is going to win. What's exciting about detalimogene is what community urologists tell us that they want is they want the right balance of efficacy, tolerability, and ease of use. Detalimogene is unique. It is the only product that balances all three. Highly differentiated product. On top of that, with the surfactant, like other people have used, we have the potential to improve efficacy and make it even more convenient. A good detalimogene perhaps could get even better with the use of surfactant. In closing, this next couple of quarters are pretty exciting quarters for the company. We will provide an update on the data in Q4 of this year.
We have a pre-BLA meeting with the FDA, and we would like to report on that. Our intention is to initiate our filing by the end of the year. We expect an approval for detalimogene and a platform designation in 2027. You wrap it around, we're sitting with $266 million of cash, enough cash to get us through all those important milestones. This is really an exciting time to be part of the enGene journey, and we're at a point of where a lot is going to happen with detalimogene. I thank you all for your attention. I'm happy to take any questions if there's a bit of time.