Good afternoon, and welcome to the Jefferies Global Healthcare Conference. My name is Shaun Epstein with the Investment Banking team, and it's my great pleasure to introduce Jason Hanson with enGene.
Thank you, Shaun, and thanks for having us. Good afternoon. As Shaun mentioned, I'm Jason Hanson, CEO of enGene, and as usual, today's statements will contain forward-looking statements, so please consult with our securities filings before making any investment decision. So at enGene, our vision is to bring genetic medicines into the mainstream of healthcare, and we achieve that through our proprietary and unique non-viral genetic medicines platform, which is highly differentiated from the rest of the genetic medicines platforms out there. We offer a highly differentiated lead program, which we call EG-70, which is targeting high-risk, non-muscle invasive bladder cancer patients, for patients who've proven to be unresponsive to BCG, the frontline therapy. Our product is wildly differentiated from our viral brethren.
We offer a single-step administration that's easy to use in a community urology clinic, that is incredibly patient-friendly, that has none of the onerous handling and baggage requirements of viral therapies. The profile of EG-70, in terms of mechanism of action, is quite broad and expansive. It's an IO platform. It activates both the innate and the adaptive immune systems in one drug product, really training the body's immune system to durably clear these cancers locally. EG-70 has broad application, not just to genitourinary cancers, but to potential oncological indications throughout the human body. Importantly, we have a non-viral platform here that supports manufacturing at a scale that can support moving genetic medicines into the mainstream for a top 10 disease in terms of incidence and prevalence, like bladder cancer, and it supports ultra-low cost of goods when compared to viral vectors.
We have multiple value inflection points this year, including a mid-2024 interim look at our registrational phase II study for high-risk NMIBC patients, and we're planning on submitting our BLA in the first quarter of 2026. We've already completed our phase I study. The primary endpoint there was safety, and a secondary endpoint was looking at efficacy at 12 weeks. Really pleased to turn up an efficacy rate of 73% CR at any time. All of our phase I endpoints were met, and we are currently enrolling in our registrational phase II study of 100 patients. We plan on reading that out in the middle of the summer in terms of an interim look. Already, though, from a phase I perspective, we're seeing very strong signs of durability in phase I, which we'll dive into in a few slides' time. Importantly, this is very biocompatible platform.
In all of our dose ranging and animal work, we never reached a maximally tolerated dose, and that really allowed us to dose based on optimal dose, without having to worry about difficult reactions to a viral vector or delivery. No ADAs are generated to our platform, and of course, we can reach and dose as far up as we want, as long as it's efficacious. So that's a very privileged position to be in in oncology. We designed our drug product, which we call EG-70, to be extraordinarily easy to use in any urology clinic. It's a lyophilized product. It comes off the manufacturing line as a powder. It's reconstituted in an open bench with water and instilled into the patient's bladder for a 60-minute hold time. The patient voids, and the patient is out of the chair.
These are very busy urological surgeons we're talking about, and they value patient throughput in their clinic. As you'll see, ours is the quickest chair time of any product in this field, even, in fact, quicker than the frontline therapy of BCG. We don't have any BSL-II handling requirements. We do not require -80 cold chain storage, and we do not require retraining all the healthcare staff at these busy urological clinics, which is a huge advantage in terms of efficiency. As I mentioned, we're using our proprietary non-viral platform to achieve these effects. We don't see any untoward immunogenicity in any of our preclinical work or any of our clinical work, where our mechanism supports rapid repeat dosing, and we get very nice transgene excursion of our gene cargos in the bladder locally upon repeat dosing.
The drug is already ready to be manufactured at commercial scale for launch in 2026. We don't have any of the difficult and bespoke manufacturing processes that have bedeviled companies like Ferring with its Adstiladrin. Ours is a synthetic manufacturing process and is eminently scalable, and that's an important pillar that we're relying on to be able to move genetic medicines into the mainstream. As I mentioned, it also comes with the added benefit of having extraordinary low cost of goods. All in all, we have designed this drug product to be the very first script that urologists reach for upon diagnosis of high-risk NMIBC. Looking a little bit into our platform, which we call dually derivatized chitosan, we really have a broad technological edge here.
We're able to unlock mucosal tissues in the human body that have essentially remained white space and open them up for application to genetic medicines for the first time. These include compartments, of course, like the bladder, which is easily accessible, but also the GI tract, the nasopharynx, cholangiocarcinoma in the biliary duct tree. There are mucosal interfaces throughout the human body that are easily accessible, that have interesting oncological indications, and we believe EG-70 is well suited to address all of them. Our pipeline is shaping up as follows: Our lead program is EG-70, targeting high-risk non-muscle invasive bladder cancer patients. Again, for patients who failed the full induction and maintenance course of BCG, we've received Fast Track designation.
We're turning up extraordinary efficacy of 73% complete response rate at any time, and we're currently in the midst of enrolling our 100-patient phase II, and we expect to submit the BLA here in 2026. At FDA's behest, we've also enrolled what we're calling a BCG-naïve cohort of patients to see how the drug performs in that frontline setting. This is really an important application to expand the total addressable market for EG-70. Those data are following the lead indication data by about a quarter or two, and we've committed to the street to announce an additional oncology indication for EG-70 this year, which we're extraordinarily excited about.
We also continue to leverage our expertise in transfecting mucosal tissues by pursuing a program in partnership with the CF Foundation to unlock the lung, an important mucosal compartment in the human body that LNPs and viral vectors just aren't well suited to transfect. Diving a bit into our lead indication, this is a multibillion-dollar market with a high unmet medical need. There are many new incidences of these cases every year. Of course, as you all know, there's a BCG shortage, so the first-line therapy itself is in a strict shortage and rationing situation. AUA guidelines determine that these available BCG needs to be directed to first-line cases, creating quite a shortage for patients who need this drug to prevent removal of the bladder. And you'll see that's a key theme throughout this disease state.
Patients do not want to go to radical cystectomy and have their bladder removed. This is an invasive procedure for these elderly patients. It has a high morbidity rate. There's a very high degree of readmission to the hospital after these surgeries are performed. Many people cannot withstand the surgery. There's a definite incidence of suicide and depression among these patients, and the quality of life deteriorates quite rapidly. So the punchline here is patients will do everything they can to keep their bladder. In fact, there's only 10,000 radical cystectomies performed in the U.S. every year across every indication, which, as you'll see, means that this market really should be measured in terms of prevalence, not incidence, because these patients are keeping their bladders basically at all costs until the risk of metastasis is so high, they're left with no alternative.
But as you'll see, that's only at the end of a very long cycle where a urologist has many opportunities, many bites at the apple, so to speak, to treat the disease and arrest its progression. And by and large, these patients are seen in community urology clinics. This is non-muscle invasive bladder cancer. It's technically superficial bladder cancer until the tumor invades the muscle wall. Generally, 70%-80% of these patients are treated in a community setting, which is important to keep in mind. EG-70 itself has been designed from the ground up to be fit for purpose in these community urology clinics. We're delivering both RIG-I to activate the innate immune system and IL-12 to activate the adaptive immune system in the bladder environment locally. This is very an exciting mechanism of action, it is unique amongst the competitive set here.
It is a true IO mechanism of action. It is a T cell-dependent mechanism, and it is antigen-specific, but we're seeing very durable, important progress in these patients that really proves out the case here. As you'll see, there are, of course, other modalities on the market. There are viral approaches with different mechanisms of action. There are gemcitabine approaches with medical devices that essentially provide continuous chemotherapy, and I think you'll see that urologists will basically use all of these orthogonal modalities to try to arrest the progression of this cancer long before a patient ever sees a radical cystectomy. If you look at across the attributes for what would make for a successful product in a community urology clinic, we believe we've satisfied all of them.
We don't have a device that needs to be inserted into the bladder and removed every three weeks the way TAR-200 does, plus we have a very novel IO mechanism of action. We don't require -80 cold chain storage. We do not have to wash the bladder or apply any mucolytic agent, which extends chair time for the patient, which drives busy entrepreneurial surgeons crazy because they want to get these patients through the practice as quick as possible. We do not have to apply BSL-II containment provisions to this product. It's a powder. It can be done directly on a desktop, so you don't have to retrain the caregivers and doctors. In addition, we're non-viral, which means the body won't be generating ADAs to the drug product that you're delivering many times every 12 weeks.
If we double-click on what that means in practice for a busy entrepreneurial urological surgeon, that means that EG-70 is essentially the easiest to use and the quickest to use. As I mentioned, a single-step administration, installation into the bladder through an indwelling catheter, bladder hold, void the bladder. The next degree of complexity involves BCG, which is currently the frontline treatment, but is an attenuated bacteria. In that case, the bladder dwell time is 120 minutes, and there's some moderate masking and gowning and urine bleaching required because it is a live bacterium, though, of course, attenuated. But as you move into the more esoteric viral modalities and take a look at Adstiladrin, these products are minus 80. Adstiladrin itself requires a very long thought process, three to 10 hours.
This is a buy and sell busy urological clinic that bears the risk of product spoilage, as well as the risk that many of these elderly patients, many times do not keep their appointments. So they're told for Adstiladrin to show up at 8:00 A.M. for a 2:00 P.M. instillation and bring a book. In addition, there's many KOLs out there who will say they're using Valium suppository for these patients because they're difficult in terms of patient tolerance. They're coordinating with OR beds in their systems to put the patient in Trendelenburg position to relieve pressure on the bladder. They're administering anticholinergic anti-bladder spasm medication, and all in all, this makes for a very burdensome workflow for a busy community urology clinic. Keep in mind that these community urologists are seeing many different types of indications.
They're not just looking at non-muscle invasive bladder cancer patients all day. They see prostate cases, they see kidney stone cases. So the non-muscle invasive bladder cancer patients are a smaller proportion, and they don't want to reengineer their entire workflow for a small proportion of patients. Even CG's product itself, which is a live oncolytic virus, has a number of steps that add to complexity here. They need to pre-wash the bladder. They need to use a DDM to remove the mucus and gag layer from the bladder to expose it to their viral vector. Then they need to wash the bladder out again. Then they need to reinfuse DDM, and then they can finally put in Creto.
and so while we applaud all efforts to serve these patients, it clearly is a more complex work stream and is not necessarily the ideal commercial embodiment you'd like to see for a busy community urology clinic. At enGene, we've followed the FDA guidance to a T on submitting a dossier to treat these high-risk NMIBC patients who've proven to be unresponsive to BCG, and we've designed our study in accordance with all of the requirements. As I mentioned, we finished our phase I, met all of our primary and secondary endpoints, and we're in the midst of our phase II, which is 100 patients.
As you'll see in a few slides' time, we're dosing with different, of course, dosages, but we're also dosing in our phase Phase I, we dosed with different frequency of dosing, so we'll talk into that in a few slides' time. In the phase II, the primary endpoint becomes 12-month CR rate, which is an important endpoint in this disease state. Looking at our phase I data, we're really excited to turn up a 73% complete response rate at any time. Although this study was designed, of course, as a 12-week study, met all of its safety endpoints, as we'll talk about the safety profile here is extraordinary. We also saw encouraging signs of durability in this study, despite the fact that Cycles II, III, and IV were entirely voluntary for patients.
They really only signed up for 12 weeks of therapy. If you focus in and double-click on our recommended phase II dose, which is what we're dosing in our registrational trial, you'll see patients are responding at the 6-month timeframe at a rate of 60% CR, which is statistically as good as the best in class. We're very excited about that because our product comes with amazing features that really make it the ideal product for where these patients are treated, which is the community urology setting. Looking at our biomarkers, which we've measured in some of our patients, we're seeing extraordinary IL-12 excursion locally in the bladder. And what we're trying to do is maximize the exposure of the urothelium of the bladder to IL-12, and that's exactly what we've done here. We see durable expression, we see prolonged expression.
We don't see a dampening in transgene excursion as you add additional product to it, say, four times every 12 weeks, which is what we're calling our prime dosing. So it's exciting in the sense that usually with gene therapy, particularly with a viral delivery mechanism, you do see a dampening in excursions. We don't see that at all, and it really supports the notion that non-viral is gonna win the day here in the long term. Our safety profile is remarkable in the sense that it's remarkably unremarkable. Most of our AEs are Grade one and Grade two, and they're largely consistent with instrumentation of the bladder, which is common to all the products in this category. So we're really excited about this tolerability profile. We're told anecdotally by urologists that patients tolerate this extraordinarily well.
It's akin to injecting saline into the bladder. So we're really excited about that notion, and that's quite differentiated with how patients even feel about BCG. BCG itself is a live bacterium. It can be highly irritating, and in fact, estimates are that 18% of patients are actually intolerant to BCG itself, and it can induce bladder spasms. And of course, -80 products can do the same. We've heard that with Adstiladrin, so this is a huge edge in a community setting. Again, looking at our CR rate, comparing it with Credo, Adstiladrin, you can see statistically at the 6-month response rate, which is highly indicative of a 12-month complete response rate, we're statistically right on par with Credo, which we're very excited about. These are exciting durability signs, even in a phase I context, where patients really only signed up for the first cycle.
We've got patients voluntarily agreeing to get Cycles II, III, and IV, and we've got patients that we've followed out well beyond 12 months that are still in response. So we're really excited about making a difference in these patients' lives and elongating the time before they would ever have to think about a radical cystectomy. Importantly, it's interesting and I think important to understand this market, that the urologist quarterbacks the patient journey. From the time that a patient is diagnosed with high-risk NMIBC, generally with hematuria, blood in the urine, or dysuria, difficulty urinating, these patients are seen and quarterbacked and managed by their community urologist, by and large. So this is a multiyear window to treat these patients.
One thing that came out of the recent AUA is a shift in viewing this market from an incidence market, i.e., how many new cases of this disease are happening each year, to realizing that, in fact, patients don't want their bladder out, and the very emergence of intravesical options is prolonging the time for these patients to get therapy. So it's a multiyear journey, and some of our competitors have agreed with this, saying patients generally here will get two-four cycles of different intravesical therapies to try to arrest the progression of the cancer because the radical cystectomy is such a high morbidity event. Which means there's a huge market here when you measure it by prevalence, and that there can be multiple winners here in this market.
So we're really excited about new therapies coming online for these patients, which really expand the entire TAM. For all of the participants in this market, we think, again, because of our ease of use and fantastic data, we'll be the first script that urologists reach for, but we expect that patients will be treated, for example, with TAR-200 at some point if they relapse, which is basically continuous gemcitabine, or even CG0070, which has its own unique mechanism of action in terms of GM-CSF and lysing the tumor. Point is, there's room for multiple swings of the bat here. So the goal here for EG-70 and the LEGEND trial itself is to establish a foundation, a foundation for EG-70 to be the product of choice in the high-risk NMIBC category, which is itself a multi-billion dollar market.
As I mentioned, we'll be doubling that TAM as we're looking at a new cohort of patients that have either been, naive to BCG or partially exposed to BCG. In addition, we think EG-70 is well suited to a number of different oncological indications. I mentioned some of them earlier, but things like UTUC are clearly within the wheelhouse of EG-70. M, MIBC, EG-70 could be an interesting option for those patients as well. Intermediate risk bladder cancer is an important category as well. If you think about risk of progression, we think EG-70 is particularly well suited for intermediate risk bladder cancer patients, where, of course, the risk of progression is even lower than in high risk.
There's a clear and open, basically white space in terms of the clear standard of care, and we think we could really establish a standard of care where EG-70 is an important part of the urologist's armamentarium to treat IR. So that's an important market expansion for us. So we're very excited about building a durable uro-oncology franchise for EG-70. So in summary, we've touched upon the fact that at enGene, we're moving genetic medicines into the mainstream, addressing a top 10 disease in bladder cancer. We have a very differentiated program, non-viral, ultra-low COGS. Of course, that means we can serve these huge markets in high risk and intermediate risk without supply chain disruptions. I would point you to the difficulties Ferring had with making their adenovirus since they've been approved in 2022.
As supportive of the notion that no one should underestimate CMC and the advantages that a synthetic platform like ours provides, basically ultimately scalable manufacturing and ultra-low COGS, particularly as you expand that concentric circle around additional indications in lesser progressed cancer cases. We're also excited, of course, about our interim readout in this year, as well as submitting our BLA in short time frame here and launching this product in 2026. So that concludes the presentation. Happy to address questions if there are any, and really appreciate the opportunity to speak with you today.