Welcome, everyone, to the Piper Sandler Healthcare Conference. My name is Ashleigh Acker. I'm a Biotech Analyst on Allison Bratzel's team here at Piper Sandler. It's my pleasure to introduce our next presenting company, enGene Holdings' Chief Strategy and Operations Officer, Alexander Nichols. Welcome, Alexander.
Thank you. Can you remind me, is it just a 20-minute presentation or 15?
Twenty-five, o kay. The timer just went to—there we go. Thank you. No worries. Okay. 15 it is. Is that—all right. I'll have to move a little faster. Thank you, everybody. I'm delighted to be here. Thank you to the Piper team for the invitation. I'm delighted to be here to present on behalf of enGene. Before we begin, this presentation will contain forward-looking statements, as you might expect. If you're not familiar with the enGene story, we are a really unique kind of company built around a compelling and novel technology platform that we've spent a lot of time developing in-house. It's a non-viral genetic therapy platform. We'll talk more about how that works.
We are developing a lead product called detalimogene voraplasmid, which is a registrational study for a disease called non-muscle invasive bladder cancer, which is a disease that is really poised for transformational growth. It is a disease that has been managed surgically. We are in a period where we are overseeing a transition to a more kind of hybrid medical management, which is a really exciting time and presents a unique growth opportunity and a large market forecast. As we will talk about, detalimogene voraplasmid combines clinical activity with a really strong safety profile and an arguably best-in-class ease-of-use profile. We will have several near-term catalysts on the horizon, including a data update in the second half of 2026, along with the BLA filing and a potential launch in 2027. When most people think about gene therapy, they often think about it in terms of the limitations.
For example, it's known to be able to only deliver small genetic cargoes. It's typically immunogenic. It has been very historically difficult to manufacture. That's been a sticking point oftentimes at review. DDX platform really solves a lot of those problems. Because of the unique aspect of our delivery approach, we can deliver much larger genetic cargoes. It's not immunogenic. We can manufacture this at a really favorable cost of goods and have no specialized handling at the site of care for the clinicians. Now to talk a little bit more about non-muscle invasive bladder cancer. This is an early form of bladder cancer. Bladder cancer is a disease that's highly prevalent within the United States. There's around 730,000 cases per year.
If you start to think about it on an incident basis, there's around 25,000 cases of high-risk non-muscle invasive bladder cancer diagnosed every year. What is high-risk non-muscle invasive bladder cancer? It's a lesion that forms on the inner wall of the bladder. This is facing the lumen of the bladder. It roughly segments into two different kinds of disease. The first shown on the left is carcinoma in situ or CIS. This is a flat lesion, again, on the surface of the bladder that's difficult to remove surgically. There are also papillary lesions, which are finger-like growths out from the surface of the bladder, which are diagnosed as TA or T1, respectively. These are typically cut out surgically. The patient is also given therapy to make sure that it doesn't recur and improve the outcome of that surgery.
The other important thing to appreciate about NMIBC is that it is a disease that is highly recurrent but slow to progress. Over a 10-year time horizon, 20% of patients will progress, which gives you ample opportunity to treat and basically stop the progression of the disease within its tracks. It is also a very common cancer and one of the most expensive to manage on a per-patient basis, costing over $6.5 billion per year. What is the patient journey for someone diagnosed with NMIBC? Historically, the first stop has been a therapy called BCG, which is a live attenuated bacterium. It is actually one of the oldest forms of immunotherapy. It works very well for the majority of patients. There are two major issues. It is in chronic short supply. Most patients will eventually progress on it.
When they progress, the state of affair for a long time has basically been they can get chemotherapy, which is used as a BCG backstop. It doesn't work particularly well. They can go on a clinical study and check out some of the new therapies that are in development. When those options fail, the patient really has no other choice but to have a radical cystectomy, which is the complete surgical removal of the bladder. This also involves a prostatectomy. It is quite life-altering. There is a significant mortality rate. Patients who have it suffer from decreased quality of life. They have sexual dysfunction and often have an ostomy or a stoma bag. It is really not a great option.
It is in response to the lack of great options that the FDA issued guidance back in 2018 that facilitates streamlined development for carcinoma in situ therapeutics because those are the most difficult patient group to treat. This allows for single-arm, open-label studies, again, with the explicit goal of bringing new therapies onto the market. You can see some of the therapies that have come in under this guidance. Actually, the FDA reaffirmed their commitment to it in 2024, again, underscoring the need for new therapies and to create new options for these patients. This is really important. This is a disease that when you look at where the physicians are and the patients are that are being treated, it's really in the community. 67% of urologists are practicing in the community setting.
When you start to ask them, "What are the things that you look for in a therapy?" you can see that, obviously, tolerability is high up there. A little preview: this is one of the strengths of detalimogene. CR rate, the number of patients who respond to the drug, and the durability of that response are high up there as well. You get into many of the very practical aspects, like can you store it without a deep freezer? How expensive is it? How easy is it to use? All those things really matter. It is the holistic profile that will drive adoption, as we've seen. When you also think about the typical urology practice, these are practices that are suffering from staff shortages. There are not enough urologists for the population. They're under revenue pressure due to reduced reimbursements and increased costs.
Their time is really important. Any additional opportunities that you can give them to save time when choosing a therapy really matter. The other thing we know is that procedures are becoming a relatively smaller amount of reimbursement and, sorry, of total practice revenue. Buy and bill is going up. You can see this very clearly over time. If there is a product that can support all of these different things and utilize fewer resources, that, all else held constant, will be a preferred product. This is one of the reasons why we are excited about detalimogene: detalimogene is designed exactly to operate in these sorts of circumstances.
It offers great evidence of efficacy, seen from our data readout so far, a safety profile that has shown generally mild treatment-related adverse events, as well as really strong ease of use, which we'll talk more about in a few minutes. This is actually a picture of detalimogene. It's a lyophilized product. You can mix it with water on an open benchtop. It's very easy for physicians to use. What is detalimogene? It's a non-viral gene therapy. It's actually a nanoparticle, as shown here. In the next slide, I'll tell you what goes into that nanoparticle. Basically, it's designed to interact with the surface of the bladder, be taken up by the cells once instilled directly into the bladder. This is an intravesical therapy.
Once it's inside the bladder cells, it delivers its cargo, which is a single DNA plasmid encoding two double-stranded RNA agonists of an intracellular receptor called RIG-I, as well as a secreted form of IL-12. The RIG-I agonists are designed to stimulate the innate immune system, which is the way that BCG has historically worked. The secreted IL-12 is designed to stimulate the adaptive immune system and promote a robust immune response. These work synergistically to drive a very strong and local immune response that promotes tumor clearance. I'm just keeping an eye on time. I'm going to have to move a little quickly through this. Manufacturing is an advantage for us. This is a relatively straightforward process. You begin with our plasmid DNA. You mix in our proprietary sugar polymer, DDX, which is really the secret sauce behind the technology.
It forms a nanoparticle. You passivate the surface with a PEG molecule. You get this PEGylated nanoparticle here. I'm also pleased to announce that today, enGene was awarded CDRP designation, which is an FDA pilot program that allows us increased correspondence around CMC, which we feel will even further streamline our manufacturing process at review time. It's a great opportunity for us. It's on top of our RMAT designation, which enGene has also received. Now getting to the LEGEND study. As I mentioned, we are running a registrational open-label study in BCG unresponsive patients with carcinoma in situ. We fully enrolled the study recently. It's actually one of the largest cohorts, which we'll talk more about in a minute. We're also looking at it in other NMIBC contexts, including patients who have never seen BCG. These are BCG naive patients and patients who have seen some BCG.
They don't fall under the FDA guidance strictly, but they're still in need of therapeutics, as well as BCG unresponsive patients with papillary-only disease. These are patients who only have that papillary lesion and do not have cysts. We have a very strong IP portfolio with coverage going out to at least 2040. The LEGEND study, again, it's a global single-arm study. These patients are dosed four times in a three-month cycle. That three-month cycle is very standard for this disease. It corresponds to the typical monitoring cadence for a patient. Our primary endpoint is the complete response rate at any time. We're also looking, of course, at the duration of that response. I'm going to show you data from two different patient groups. It corresponds to 125 patients overall, which is our total intention to treat population.
In September of 2024, for those of you who are familiar with the story, we introduced some pretty meaningful protocol amendments that were designed to bring our protocol to the standard of care. We had some protocol that allowed for some heterogeneity in patient treatments that we really wanted to bring up to a consistent level. Thirty-one of those patients are pre-protocol. Ninety-four are post. As you can see here, these are very typical patients who have this disease across both protocol groups, both in terms of BCG doses as best guidance specified, generally older. I think the thing to pay attention to here is that we've had a lot of patients with T1 lesions, which makes them a higher-risk patient group. Keep that in mind as we review the data. They have both kinds of disease, papillary and CIS.
We're very pleased to see that the protocol amendments that we introduced seem to be having a very positive impact on both the data and the durability observed to date. We are pleased to show a six-month complete response rate of 62%, as well as an anytime response rate of 63%. Among those patients, we had four three-month non-CRs convert to CR at six-month assessment during reinduction. For the 23 responders at six months, those who made it out to the nine-month assessment, five of five had a complete response. A really exciting preliminary look at the data. You compare this to the pre-protocol patients, now updated for 31 patients who were treated under the old protocol. You can see that there's really a meaningful difference here. The old protocol had a 41% complete response rate. New protocol is out at 62%.
We have also disclosed that the durability of these pre-protocol patient groups out at 12 months is lower than the historical approvals for other therapies in BCG unresponsive NMIBC. The takeaway is that the protocol differences, the protocol amendments are really having an impact. Just keeping an eye on the time here, the other thing I'll note is that this is a product that patients have tolerated generally well and pay particular attention to the dose interruptions and the dose continuations along with the treatment-related adverse event rate. When a patient goes on this drug, they typically tend to stay on the drug. That is a very favorable number also in terms of the overall tolerability profile. I'm just going to skip ahead here. You can see that it actually fares very favorably as compared to some of the other agents on the market.
Likewise, the data that we've released so far from the complete response rate at any time in six months, you can see these numbers also track very favorably against the competitive landscape of approved and products that are still in development. Now just to close up on the overall product profile of the disease, again, thinking about what some of the other agents in development require of both the patient and the clinician, maybe there's some complex shipping and storage. If you're being treated with a viral gene therapy or a bacterial therapy, there's often enhanced decontamination steps that are required. Maybe the patient has to bleach their urine, which is required of the viral gene therapies. Patients and physicians don't need to worry about that. It's really streamlined and a very simple product to use.
When you think about the future of this disease, the patient's diagnosed with a high-risk disease. They get treated with BCG. We're hoping that this non-viral gene therapy, owing to this combination of efficacy, tolerability, and ease of use, will be one of the first things that physicians reach for, particularly in the community setting. If they have a recurrence of this disease, which we know to happen, they can then progress to an academic referral center where they can be treated with some of the more advanced modalities, like viral gene therapy, for example, which require a more robust facility in terms of decontamination and then patient management after the drug's been given. The future and the market opportunity comes from the ability to sequence patients through multiple agents as opposed to having a much more limited option set that we had before.
We also have a really strong team that's done this before, developing this product. I think I'm going to close there with the caveat that due to a recent fundraise, our runway has been now updated into cash into 2028. That was a little bit of a whirlwind because we had less time than we thought. I thank you all for your attention.