Hi, good afternoon, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stifel, and very glad to have with us presenting from enGene, the CEO, Ron Cooper. Ron's going to give us an overview of the company. There may be some time at the end for some Q&A. I think all of you are aware of the function within the Zoom that allows you to ask questions. We will get those answered as deemed appropriate. Ron, I'm going to turn it over to you, and thanks for participating today.
Great. Thanks very much, Stephen, for that warm welcome. Thanks to Stifel for the opportunity to present enGene today. Look, we're in a very exciting time for enGene. Where our science at working with non-viral genetic medicines? They're starting to become a reality as we get closer and closer to top-line data and hopefully approval as well. As you'd expect, I'm going to be making some forward-looking statements during today's discussion. Before diving into non-muscle invasive bladder cancer and the opportunity that we have with detalimogene voraplasmid, let me just give you a quick overview. First of all, our lead product is detalimogene voraplasmid, a plasmid that we're developing for non-muscle invasive bladder cancer. We really believe that this is a medicine that could be the cornerstone for community urologists to use just because of the design of the product, really designed for the practices.
Now, why are we excited about this opportunity? I think the first thing is we're at the beginning of a new age for the management of NMIBC. Previously, very few agents being used, now multiple agents in development or being recently approved. We really believe that this marketplace is going to convert from an incident-based patient population that's lost to follow-up to much more of a treated prevalent population. The analogy I would use there is the multiple myeloma market was about $1 billion when Revlimid was launched. With Revlimid and a dozen other agents, that's now over $20 billion, as that became much more of a prevalence-based market. Similarly, right now, we estimate the bladder cancer market's about $2 billion. We expect the same sort of explosive change. Really great for patients and a wonderful opportunity for all of these agents that are being developed.
If you look at detalimogene voraplasmid itself, and I'll get into more details, but we've shown terrific efficacy, terrific tolerability, and the barrier to usage for this product is really low, really low. It's going to fit into the urology practices quite nicely. As I said, we're in an exciting stage for a company. We're a clinical stage company that's hopefully getting close to approval. It's an exciting year for us as we expect to complete enrollment in our pivotal cohort, provide a data look later this year in the second half of this year, and then next year, top-line data with a BLA filing, and we anticipate a potential launch in 2027. This all wrapped around the fact that we have just a little bit below $275 million of cash. We're well capitalized.
We have sufficient cash into 2027, which should allow us to get past data, and as you can see, the filing as well. enGene is in really good shape and in an exciting time. Now, let me back up a little bit and talk a little bit about the disease itself. Non-muscle invasive bladder cancer is the biggest part of bladder cancer, about 75%-80% of it. The disease itself, non-muscle invasive bladder cancer, is a very serious disease. However, it is a slow-progressing disease. These patients progress at about 20% over a 10-year timeframe. Unfortunately, though, if they do progress to muscle invasive or metastatic disease, it is really bad. The treatments are bad, and the prognosis is bad. When you look at non-muscle invasive bladder cancer itself, if you look at the chart on the right here, the real problem is this carcinoma in situ, this CIS part.
They're almost like plaques, multifocal plaques all around the bladder. They're a real problem. At the same time, that could be combined with some growths into the bladder lumen, a Ta disease, or T1, which is starting to get in, getting closer and closer to the muscle as well. The T1 patients do worse. Hold on to that point as we talk about that further. If you think about bladder cancer itself, folks are very focused on breast and prostate and lung, but actually, bladder cancer is a highly prevalent disease and top 10 cancer. It's expensive to manage as well, as you can see here, over $6 billion in the US. How are these patients treated? Most of these patients are diagnosed with community urologists.
They receive a product called BCG, which has been in back over for over a decade in the US. The doctors try a bunch of different things to try and cobble them together. Many patients are actually lost to follow-up. Inevitably, they land up getting their bladders removed if the disease progresses to avoid the progression to muscle invasive disease or metastatic disease. I think a couple of things that are different here for people to think about. Yes, it's cancer, but it's not oncologist cancer, normally managed by the urologist. Yes, it's urologist, but most of these patients are managed in the community where the choice drivers and decisions are different. Yes, it's cancer, but NMIBC is a slow, slow-progressing cancer. The treatment choices are different. These doctors want to avoid radical cystectomy for a number of reasons.
Number one, it has a terribly high mortality rate, up to 10%. That's pretty high. Remember, these patients are in their mid-70s. Also, the morbidity associated with the surgery is very high. Patients land up with a urostomy, which is not nice. You lose sexual function usually. The prostate is removed. It is a highly invasive surgery with great morbidity and mortality. Now, the treatment options, unfortunately, are not that much better. Right now, the first-line treatment option is BCG, which I've mentioned to you already. It's been backordered for almost a decade, and very spotty usage within the US. Out of desperation, physicians have been using intravesical chemo, so the gemcitabine or mitomycin. Again, these things are not well-studied, and the efficacy and tolerability are mixed. There have been three products that have been approved since the FDA put on new guidance for NMIBC.
While they've added the armamentarium, they're just not really well-designed for use in the community. Keytruda is an absolutely wonderful product that does so many great things, but it's a systemic agent, and the AE profile is very difficult for patients and for community urologists to manage through. Adstiladrin , viral gene therapy, again, complex handling that goes with it. And Anktiva is a product that requires co-administration of BCG. Given that BCG is backordered, that makes that product a challenge to use as well. That is why we're super excited about the potential of detalimogene voraplasmid. It's really been designed to be the product for the urology community. What have we demonstrated thus far, and why do we think it could be the product? Number one, we demonstrated with early data the terrific efficacy of 71% complete response rate at any time.
Also, from an AE perspective, our early data suggests a really well-tolerated product. In fact, we do not have any AEs that are beyond stage two AEs. The other aspect of it is a very simple product. It is not a virus. It is easily stored. It is easily transported. It is easily handled. The last thing, which is an important aspect in this therapeutic category, because there have been some challenges with manufacturing. We are already manufacturing at scale. Our product actually uses four readily available ingredients. We think we are going to have one of the lowest cost of goods that is very competitive. For those reasons, we really believe that detalimogene voraplasmid should be the cornerstone for management of NMIBC. Now, how does our product work?
Our product, what we do is we take three genes, and we combine it into a plasmid with the secret sauce, which is a proprietary sugar formulation that transports across the bladder lumen and delivers DNA in the form of RIG-I agonists and IL-12. What's great about this is particularly IL-12, known to be a really good anti-cancer agent, but the tolerability has not been great. By administering it intravesically, which you see on the right here, we're able to activate both the innate and adaptive immunity for these patients. Getting back to manufacturing, this cartoon shows you how simple our manufacturing is.
We literally take a plasmid DNA where we have that's our drug substance, combine it with this proprietary sugar polymer, inline mix that, and then on top of an amphiphilic particle, toss in some PEG, and we land up with our drug product, which is a non-viral drug product. Lyophilized products, we take the water out of it. So it's a cake that you just add liquid to. We're already manufacturing at scale. Right now, we manufacture and will continue to do so with water and regular air. There's just no special treatment needed. Now, we're taking our product into the series of studies. What you see here is detalimogene voraplasmid is in the LEGEND study in four different cohorts. The pivotal cohort is in BCG non-responsive patients with CIS. We're looking for about 100 patients. It is an open-label cohort.
We also have a cohort of naive patients to BCG, one where patients have been exposed to BCG, and one with papillary only. At the same time, our platform is a really interesting platform. We continue to develop other compounds for other urological targets. There is lots of value there as well, we hope. The nice thing about having developed this platform is our IP estate is quite strong, where we have protection through at least 2040 and hopefully beyond. Now, the LEGEND pivotal study, as I said, is in BCG-unresponsive high-risk patients with NMIBC and CIS. It is a global study where we have sites up and going in the US, Canada, Europe, and in Asia-Pacific. We are looking for 100 patients open label. These patients get detalimogene voraplasmid at weeks one and two, weeks five and six, rinse-repeat three more times during the year.
After a year, now they receive the product in just weeks one and two in a maintenance therapy. So even less frequently than BCG in many ways. We're looking at primary endpoints of landmark analysis, a complete response rate at 12 months. Now, last fall, we shared some preliminary data. And you can see here the baseline characteristics are pretty similar to what you'd expect for an antibiotic patients, mostly male. The one thing I'd point out to you is you see here the T1 patients, 14%. That's a little bit higher than most studies, but I'll come back to that. We had 21 patients that we're going to share data with here. The first off, if you look at, as I said, from a tolerability perspective, all AEs are grade two or less. Nobody discontinued. Everything was reversible, mostly consistent with catheterization.
You see here, this database is a little bigger at 42 because this includes all of the cohorts. I think as physicians have been using the product, they say patients do not really notice the product. Really well tolerated. If you compare that to the products that are on the market or that are being developed, you see here that this is a pre-competitive treatment-related AE rate of any grade. When you get to the serious AEs, there is quite a difference between detalimogene voraplasmid and some of the other products that are either being developed or have been approved. What about from an efficacy standpoint, as I shared with you earlier, 71% CR rate at any time, three-month CR rate of 67%, and a 47% six-month CR rate.
If we take some of the patients that have not made it to the six-month, the six-month Kaplan-Meier curve, 51%, which is very competitive with some of the other agents. When we talk to physicians, they say, "What is the CR rate that will get you excited about using these products?" They said, "Of course, we'd like to have a CR rate of 80%-90%. We know none of the agents have a CR rate of that level. We are going to use all of the products." If you kind of look at the data that I shared with you previously, that first group of patients were not being treated in what we consider to be the latest standard for urological patients being managed in NMIBC. We made a number of protocol changes, three of which I would like to highlight here.
The first one being is for the patients that are coming in. Remember the T1 patients, which I said we had a high number of them. Previously, we would cut out that T1 lesion and put them in the study. The standard of care is to do that twice. If they still have T1, not to put them in the study because it's pretty serious. They probably need to be managed differently. If they don't have T1, to put them in the study. The net result for us should be is that the T1 patients should be smaller as a percentage and more like some of the other companies' studies. The second thing that we're going to do is for patients after the three-month timeframe.
Before, if there was a little TA growth, we'd say, "Oh, they've got to come off therapy." Now we say, "You can snip that out and continue them on therapy." It's almost re-inducing those patients. The third thing is patients were permitted to come out of the study if the doctor believed that the disease was continuing. Now we're asking doctors to do biopsies to confirm, in fact, that the cyst continues. Those three changes, we think, will make a material difference. We believe that we've left a lot of efficacy on the table. In fact, as we continue to develop our product, it will improve and be competitive. As I said, as you look now, I believe that our data is very competitive. CR rate of 71%.
You see that with the currently approved agents and new agents, very much in the ballpark. A CR rate of 67%, very similar to what CG Oncology showed for the BOND- 2 study with a similar-ish type of protocol. They made some changes, which boosted up the six-month rate, and we're making some changes as well. That is why we feel pretty confident about our efficacy going forward. If you then pack this all together, what do we think about potential approval? What we're excited about is the FDA put out draft guidance in 2018 saying one study of 100 patients should be sufficient for approval. In the fall of last year, they reiterated that guidance. You can see here, these are the products that they've approved within that guidance. You can see that we're within that range as well.
We feel pretty good about our chances of approval ability. We believe detalimogene voraplasmid really is a special drug because it's practical, because of the efficacy I've shared with you, the great tolerability, and just the ease of use for the urologists and patients. If I unpack that a little bit for you relative to some of the other products, as I said, for doctors, you've got efficacy, you've got tolerability, and nothing should change in their practice in the way that they run their practices. Remember, these urologists, very busy practices, a lot of turnover. With all the other agents, there's some challenges that go with it. If a doctor chooses to use cretostimogene from CG Oncology, very interesting product, except that it requires special handling, requires a minus 80 fridge, cold chain storage. It's an oncolytic virus.
The clinics likely will need a hood. They'll need to decontaminate the room. They'll need a nurse that was willing to handle the virus itself. The patient needs to come in for multiple pre-washes and possibly need to decontaminate afterwards. It is just a higher burden to use that product. The TAR-200, as you know, this is a product that combines gemcitabine, in a pretzel. It is a risk-benefit from an AE perspective. These patients have to come in every three weeks. That takes up clinic time, takes up doctor time, and takes up room time. Adstiladrin , again, like CG Oncology, it is an oncolytic virus as well, has the same sort of complexities in terms of handling, long time from a thaw perspective. All these products will be interesting products and used by urologists.
We believe that detalimogene voraplasmid with great efficacy, great tolerability, and the lowest barrier to use makes it the most logical product to use first for the doctor. You look at it from a patient perspective. What's great about detalimogene voraplasmid, it's only an hour of chair time. It's a very small volume of drug that they have to keep within the bladder. There's nothing to do before or afterward, no induction period, no need to bleach the urine. Whereas if that patient was to receive Anktiva, that patient would be subject to four pre-washes. So nurse has to come in, out, in, out, in, out. Then you have chair time. Afterwards, urine needs to be bleached. For patients who are taking TAR-200, they need to come back every three weeks, right?
You have the sensation of a piece of plastic within the bladder as you void. Similarly, at Adstiladrin, you're going to have some of the challenges of virus handling. All that being said, though, all these agents, I think, are pretty exciting agents to have. You see here what we actually see occurring. As we talk to the clinicians, they plan on using all of these medicines. What's great about it is they're all different technologies. So detalimogene voraplasmid is the only non-viral genetic medicine. As you can see, there's some recombinant immunotherapies and checkpoint inhibitors. There's some viral gene therapies. Of course, there are some combinations. This is what's going to be an important part of the marketplace. Many of these agents, if you look at the early data, there's 60-80% recurrence rate in a year.
I think doctors are getting very excited about having these new agents and being able to sequence them and to have patients avoid radical cystectomy or moving on to muscle-invasive disease. To close up, just to say that we have the team that's done this before, has executed, and brought products along the line. We are very focused in our execution. Just to close to say that this is a pretty exciting time to be involved with enGene and to be on the journey with us. I think we're at the beginning of just a new period for the management of non-muscle invasive bladder cancer. We just believe this market is going to explode and grow. We have a product that's actually really well-suited to this growth. We are in a period right now with data around the corner, potential filing, and potential launch with insights.
Again, I would like to thank the team from Stifel for this opportunity to share with you our progress here at enGene. I'm happy to take any questions if we have a bit of time. Thanks, Ron. That was great. I guess with respect to the amendments in Cohort 3, are you of the thinking now that the registrational dataset that you could submit to FDA for purposes of a BLA would include both patient data pre-implementation of amendments and post-implementation? Is that something that you guys are still trying to figure out? What does that decision-making process look like for you at this point? Yeah, I think we have to see the data, and we have to be in dialogue with the FDA. My sense is the minority of patients will have been in the old protocol.
It's actually quite common to change your protocol during phase three studies. We just chose to highlight this point a bit more, given just the nature of the disease and the changes. It's highly likely it'll be all together. The majority of the patients are CIS patients. I think we feel pretty confident, though, the complete database will be a competitive database. I know there's been maybe some greater drug development interest within this intermediate risk segment of patients. I think the FDA has given some guidance there recently. I mean, I guess it would seem to me like your product profile is also quite amenable for that intermediate risk patient population. I guess where is that, if at all, on the list of things for you to try to tackle here? Yeah, it certainly is something that we think about.
To your point, the profile of detalimogene voraplasmid with great efficacy, great tolerability, and just easy to handle for those intermediate risks, so by definition, lower-risk patients would actually be a good fit, right? I think one of the two things that we think about, number one, we're very focused on executing here at enGene. We want to make sure we stay close to the nitty-grits of this product across the line. It can be expanded to multiple other forms of bladder cancer, but also other diseases, right? The potential, I think, is really large. We want to be focused. The second thing as we think about IR, what the unmet medical need and how these products fit in, there's some subtleties in that that we want to sort through before we go diving in.
Number one for us, the priority is get the registrational cohort fully enrolled, get the product submitted, and get an approval.
All right. That's all we have for time. Ron, really appreciate it. Best of luck, and looking forward to the updates here in the second half of the year.
Yeah, thanks again, Stephen. Really enjoyed the opportunity to be here. Really grateful.
All right. Take care. Thanks. Bye-bye.