Good afternoon, everyone, and welcome back to the Leerink Global Healthcare Conference 2025. This afternoon, we're joined by the enGene management team, including CEO Ron Cooper, as well as CMO Raj Pruthi. Thank you so much for your time. Thank you for being with us. So maybe for the people who are not very familiar with the story, can you give us a little bit of an overview of the company, its history, and its current focus?
Yeah, so the company's name is enGene, and it's a company that's focused in on non-viral genetic medicines. We have a proprietary platform called the DDX platform, Dually Derivatized Oligochitosan platform, where it's a proprietary technology where we've been able to transfect mucosal layers with our genetic material. We have a very robust platform. The company was actually started in Canada, and we still have very strong Canadian roots. From that platform, we've been able to translate our lead product, detalimogene voraplasmid. That product we're developing for non-muscle invasive bladder cancer, particularly patients with CIS resistant to BCG for its first indication, but it has potential to be used in many other areas, other GU cancers as well. We're excited to be in a pivotal program. We expect to finish enrollment with the pivotal program this year, give a little data update later this year.
Next year, we expect top-line data and the submission of BLA and hopefully an approval in 2027. We're a company that's well capitalized. We have $273 million of cash. Cash gets us into 2027. We feel that we're in great shape as an organization as we have a product that could really make a big difference in patients with NMIBC. We're in a period of where we're just executing on the trial, looking forward to sharing data and advancing this product into clinicians' armamentarium.
All right. Maybe can you tell us a little more about non-muscle invasive bladder cancer, how it's treated so far, the patient journey, but also how did it become your first indication? What do you see there that makes genetic medicine the right approach for that?
When you start looking at NMIBC, it's actually the current treatment is pretty poor, right? These patients are generally, the average age is around mid-70s, mostly male, mostly male. It's a disease that has a 20% progression over a 10-year time frame. It's cancer, and it's very serious cancer. You do have some time, right? This is not metastatic fourth-line lung cancer or whatever the case may be. Different. The second thing that's different is that most of these patients are managed by community urologists. About 70%-80% of urologists are in the community. That's where these patients are. Currently, after they're diagnosed, they are treated with a product called BCG, right? I think many of you know the BCG is a very old product. One of the problems with BCG is it's very difficult to make.
Unfortunately, it's been backward for almost a decade. It's very spotty. Some places have BCG, some places have no BCG whatsoever. It's a bit of a catch can over the catch can. Sometimes they put a little bit of intravascular chemo. There are a few other new agents that have been approved. None of these agents really fit the need for what treating urologists have. They either have too much AEs or they're too difficult to administer. Eventually, the patient lands up having their bladder removed. A radical cystectomy is the removal of the bladder, but it's really a terrible outcome, right? Anytime you're taking an organ out of somebody, that's not a good thing, right? On top of it, it's a long surgery, sometimes long, six to eight hours, has a high mortality rate, as high as 10%.
It has really bad morbidity as well because you land up with an ostomy and you generally lose sexual function because the prostate is removed. Right now, the treatment paradigm is really poor. That is why the FDA, I think, has come forward with new guidance, draft guidance to say, look, if you do 100 patients, open label study, you can get an approval. They reiterated that draft guidance in August of last year. I think the future for these NMIBC patients is really a lot better.
Obviously, as you mentioned, this is a non-trivial surgery. There is definitely an appetite for non-surgical treatment options. You mentioned that BCG has been something that has been kind of like the standard of care for many, many years now. There has been a shortage. How should we think about resolution of the shortage? How do you think that would impact the market as a whole and the opportunity for those newer non-surgical options?
Let me answer the second part of the question first. First of all, it'll be good to have more BCG because it's an effective agent, it's relatively inexpensive. The more BCG patients there are, the more patients there are in the prevalent pool. What we believe is this market is going to go from an incident-based market to an explosion of a prevalent-based market. BCG is an important part of that. Why do I believe that to be the case? I think a good example is in the enrollment of our LEGEND pivotal cohort. We have U.S. sites, and we now have Canadian, European, and Asian sites. What's interesting is ex-U.S., they use other strains of BCG. There's no BCG shortage.
What we see is the time frame between getting a site up and going and patients coming in much faster in the ex-U.S. countries. Why? There are just more patients who've been exposed to BCG and need a therapy. I think that's a good example of why I believe that having more BCG is going to be good for patients and actually really good for the market overall. As to the resolution of that, that's difficult for me to answer because I'm not the manufacturer of it. I would say that it's very difficult to make, very difficult. I know that there's only one supplier in the U.S., and that manufacturer is putting together a new plant. Hopefully there'll be something there. They're also looking at ways of bringing some other strains into the country. Between the two of those things, I'm hopeful.
That being said, this proliferation of new agents in NMIBC will be really great for patients.
All right. There has been increasing competitiveness in the space. I think this is an admitted need that is well recognized. As you mentioned, regulators are willing and eager to bring solutions about for patients. In terms of looking at the non-surgical options currently available and in development, how differentiated is your approach? What do you think are some of the factors that make detalimogene differentiated from others?
I think it's differentiated in multiple ways, right? I think, so first off, what do physicians need? They need products that are highly effective. They need products that patients will take. They need products that fit into their practice, right, that have a low barrier to usage. From an efficacy perspective, we put out some preliminary data last year where we showed a 71% CR rate at any time, very competitive, right? From a tolerability perspective, we have no AEs above level two, right, treatment-related AEs, right? Most of our AEs are reversible. They're mostly associated with catheterization. When we talk to our investigators, they effectively say the patients don't even know. It's almost like sailing. Good from a patient perspective. Second check. The third part is barrier to usage. You think about these are community urologists.
Their practices are very busy. They're moving more and more to private equity. They're becoming more like ophthalmologists, more like dermatologists, right? They're entrepreneurial in nature, right? It is a huge advantage for us in that our product, first of all, is a lyophilized cake powder. It can be handled easily, right? There are no special storage requirements that are required. No special nurses to handle stuff. No special equipment like hoods. No special bleaching or anything like that, or no decontamination. Very easy. It is not a device that has to be inserted multiple times. In fact, given that our product, and we're already manufacturing at scale, we probably will have the lowest cost of goods of all of the new products. We'll be able to put it into all of the community practices.
Literally, the individual in the practice can pull it out of the fridge or freezer. The patient's got an hour. The physician will say, "Here, my staff will take care of this." That urologist will go into another room and do other procedures. After an hour, they might wave to that patient and say, "See you next time." It just slides in so nicely with their current practice. Also remember, sources of revenue for these urology practices, it used to be surgical procedures. Increasingly, these are not great sources of revenue. It was procedures within the practice, but they take up a lot of practice space. They have not had a lot of bill and buy in urology practices, but this bill and buy opportunity can be really attractive for them.
If I think of how we differentiate, this is a product that'll be efficacious, well tolerated, and have the absolute lowest barrier to usage.
If I could comment on that, I think Ron brings up an important point that these patients are taken care of generally in the community. I spent a career in academic medicine, but it's really not in the patient's best interest to have to travel two, three, four hours. For that community urologist, they don't want to lose that patient. I think to have an agent that you can deliver in your community, keep that patient there. Again, they're older. They have to rely on their daughters or granddaughters to drive them in. If they're within their community, that's really a very patient-centric approach.
To get to the patients, obviously, we have to make it through the clinic first. Maybe can you give us an overview of the LEGEND study, the design? You have mentioned a little bit of the initial data. If we can have a review of that.
Sure. LEGEND is the use of detalimogene in high-risk non-muscle invasive bladder cancer. The first cohort is cohort one, which is our pivotal cohort, which is for high-risk BCG-unresponsive non-muscle invasive bladder cancer with CIS. And these patients, there's FDA guidance, as Ron mentioned, for a pathway to regulatory approval. So that's cohort number one, our pivotal cohort. We also have several other cohorts that are important. Cohort 2A is for BCG-naive patients. The intent of that is in areas where there's BCG shortage or no BCG. And they're pockets that have not had BCG for five, six, seven years. I had an email from someone this morning from Emory in Atlanta. They don't have BCG. So this is a not uncommon situation. So that's 2A. 2B is BCG-exposed. So they got a little BCG and not anymore.
Cohort three is high-risk non-muscle invasive papillary-only disease. Others have shown, and the goal of all of this is to create clinical data, clinical evidence for the urologists, and maybe it's NCCN guidelines for them to use it. In fact, for papillary-only, that was done with ADSTILADRIN, with only 47 patients. We're going to develop that clinical background for them, evidence for use.
All right. Going back to that initial cohort of CIS patients where the development path is, or at least the regulatory path is a little clearer there. Back in September, you showed initial data that showed it was 47% complete response rate at six months, right? Since then, you've made a couple of amendments to the study design as a whole. Can you talk a little bit about those amendments and what you hope to see moving forward for the study?
Yeah, great. Great question. We had, I'll highlight maybe three of the probably most important or impactful aspects of the amendment. They're really related to how we manage and who we bring into the study. The first is patients with T1 disease. That's the stage T1. These patients have NMIBC, but they're a high-risk group. They're starting to grow a little bit into the wall of the bladder. Definitely more difficult to treat, more difficult to respond to therapy. Before, if you came in and you had a T1 tumor, we would enroll you in the study. Now, what we'd ask you to do is go back to the operating room and have, I would scrape out that area where you had the previous T1 disease. The reason for that, that's important to do is that rescraping is in and of itself therapeutic.
I can reduce your or improve your recurrence-free survival fourfold just by doing the rescraping, irrespective of treatment. That is important to set that patient up for success in the trial. The other aspect of re-resecting the T1 is if you are T1 on re-resection or worse, you actually do not enter the trial. Really choosing the patients who are going to benefit most with detalimogene. The second part of the amendment that is important is if you are now on trial and at three months we are surveying you and I see you have a little growth of tumor, a Ta tumor. In the past, you would have come off study. Now we say, okay, there is just a small Ta tumor. That is a surgical disease. I am going to go in there and just snip that out.
I could do it in the office or in the operating room and then re-induce you or keep you on study. That re-induction paradigm is a very common one we've done with BCG. Other studies have done it. I heard from investigators saying, "My patient's doing really well. It's just this little small thing. Why can't I remove him and keep him on study?" Now you can. The third element of the protocol amendments is we're much more objective in how we assess responses. It might be at three, six, nine months, you come in for your surveillance cystoscopy and then say, "Ron does a cystoscopy and looks in and says, 'That's a little red area.'" I've been practicing for 30 years. I know CIS when I see CIS and can call that CIS.
I may look in and say, "That's a little red area in the bladder and you've had immunotherapy." If you do a cystoscopy three months after BCG, for example, it'll look like a bomb went off in there. There's patchy red everywhere. What we've done now is if you're going to make the call that it's recurrence, you have to biopsy that. I mean, that's just good clinical medicine and it's part of a trial. Those are the three main buckets. To come back to what is the impact of that, I think each of these scientifically, but otherwise is going to have a meaningful impact to keep patients on study and actually to improve the CR rates. I think what we saw in September was really kind of the floor.
All right. Can you tell us a little more in terms of how does the study compare to the ongoing studies from other modalities or competitors?
The first two things I mentioned, the T1 re-resection and re-induction, has been the format for, for example, CG. In CG, in their BOND-002, they did not re-induce. In BOND-003, they did re-induce. In fact, they saw better CR rates. That is what gives me optimism for that.
Okay. Can you give us kind of a sense of progression of enrollment, site activation, patient interest?
Site activation and enrollment have been fantastic. I think there's a lot of reasons for that. I think at some point you get a critical mass and kind of interest and sites and awareness of who, what enGene and what detalimogene is. We're now in North America, EU, Asia PAC. There's a lot of interest in that. I think these other cohorts I mentioned, BCG naive, for example, has garnered interest for investigators who want to get their patients, give them an option if they don't have BCG. We're really excited with how enrollment's going.
I would just add as well is that Raj, before coming to enGene, was the head of a couple of different academic institutions in urology, right? And is on the guidelines, is very much ensconced in this community as well. Our previous CMO did not have the same sort of experience, had more of an oncology background. Having Raj very much in touch with that community, plus with his insights in adapting our protocol really to becoming more of sort of standard practice for urology, that combination with getting sites up and going has really left us quite optimistic on where enrollment's going to be.
As enrollment is progressing, we're going to have an update from the program in the second half of this year. Can you maybe give us a little bit of detail on what to expect for each of the cohorts?
Yeah, I think it's still work in progress for us, right? The data that we presented to you last September was the first time that we presented the same dose, the same dosage regimen, and the same patient population. I think we're pretty excited that we showed terrific efficacy and great tolerability. We want to make sure that we're providing you some new information, right? That new information will be probably a greater n, probably a longer amount of time on therapy, but also some patients that are within the new cohort, right? It's an open label study. We can see the data coming in. We can see enrollment. Until we're comfortable that we're going to be able to provide you something that's incremental, we're really not going to be able to give you a lot more detail on that.
Suffice to say, we're really aiming to provide you something more than last September.
All right. We'll exercise some patience then.
Thank you for that.
As you mentioned, regulators in the U.S. are again eager to move forward and kind of make the regulatory path clear for those non-surgical approaches. How should we think about the regulatory path for the specific cohorts, so the high-risk CIS? How should we think about the regulatory path outside of the U.S.?
I think two things to think about. One, you see some of the other companies in the space have made filings ex-U.S. That makes us confident that that is possible. We have been very focused on the U.S., but we started to open dialogue with authorities ex-U.S. Thus far, the feedback has been encouraging. We look forward to pursuing that. We really believe there is a significant ex-U.S. opportunity for detalimogene .
Again, this cohort, the path is very clear. What are some of the next steps you anticipate for the additional cohorts? Beyond the high-risk cyst patients.
Yeah. As Raj was saying, the reason we've started these cohorts is to provide the medical community more information. We know that detalimogene is a product that can be used in multiple places for multiple. The potential is quite high. Right now, there's some need with the BCG shortage. The two cohorts, BCG naive and BCG exposed, that fulfills a need, right? Until the BCG shortage is resolved, it could be a therapeutic option. As Raj has indicated, the fourth cohort, the papillary-only, there's precedence to say that with a relatively small open label data set, you can get NCCN guidelines. Normally that's associated with reimbursement as well. I think we're pretty excited about the additional cohorts.
It's going to provide doctors with even more evidence that dental imaging is a very active complement that we use in different areas, and they'll have access to it hopefully as well.
We look forward to the update later this year. I want to talk a little more about your technology platform. Obviously, detalimogene uses your DDX platform. Can you tell us a little more about the platform, how differentiated it is, what you see as the key point for the platform, and where else do you see applications for it?
If you step back on genetic medicines or gene therapies, what are the big challenges with that, right? Challenge number one is genetic load, right? In AAV therapy, there's only so much cargo you can put in, right? Challenge number two is immunogenicity, right? Are you causing lots of other problems? The third one is, particularly for the ex-vivo gene therapies, manufacturing becomes very complicated, very expensive, and the business model doesn't really work. Our team has done a terrific job of designing a platform that actually addresses all of those challenges, right? The first thing, and the way we do that is we focus in on accessing mucosal tissues, right? With our DDX platform, we found a way to transfect genes, get through that mucosal barrier. What does that allow? It allows us to put a big genetic load, right?
We have three genes in detalimogene, RIG-I and IL-12. People know IL-12 pretty well and they know it's a product that comes with a lot of AEs that goes within the safety profile is an issue. By delivering it intravesically through the mucosal layer, we're able to solve that. That is one thing that's solved. The second thing that's solved is we use for detalimogene four readily available ingredients. We do it with water, with regular air, no special handling. That keeps our cost of goods relatively low. If your cost of goods are relatively low, that means you can go to wider diseases. That makes it possible for us to deliver genetic material to any place in the body which has a mucosal layer. Obviously, we're very focused on the GU area.
The potential in GU is quite large, but there are other tissues that we could penetrate as well with our platform.
Thinking specifically about other tissues, can you talk about the body of preclinical data so far? What are the tissues that you've explored and where have you seen encouraging data?
I think it's a little early for me to share that information. One of the things is that we are very focused on dental imaging right now. We're very focused on the clinical work on that. At the same time, we do have an in-house lab, right? In our in-house lab, we're doing some pretty interesting experiments where we hope to make dental imaging even more convenient. We're looking at ways to potentially boost efficacy. We're looking at ways of deploying dental imaging through other GU cancers. We have some other compounds and combinations that could be used in other GU areas, but also we could go to some other tissues as well. Give us a little time to let us cook a little more. Once the cake started to bake a little bit, we'll share a bit more with you.
All right. As the Gen Z would say, we'll let you cook. Obviously, the internal pipeline is cooking. How do you think about potential monetization of the platform through partnerships? Has there been interest there? Are there external capacities that you might benefit from through partnerships?
Yeah, I think again, the short answer is yes, and we'd love to do that. It's a little bit of making sure we're deploying capital the right way and focusing. We're a company that's very focused on dental imaging, very focused on executing our trials, very focused on making sure the preclinical models are completed so we can complete one of the five modules for the FDA. Most of our resources are there, right? We're happy to engage in a partnership if someone's interested in our platform. We've had some preliminary discussions on that. We look very carefully against resource allocation about how much resource that would take for us and what the return is. For us right now, we just see that dental imaging could be a very big product.
We have to make sure that we not only finish the clinical work, but all the work around it so it's very attractive.
I know this is an early question, but is this a product that you intend on taking out to the market alone? Do you think that for global expansion, you would likely look for a commercialization partner? How do you think about it? Granted, it's early.
No, it's not early. No, it's actually not early. We're a pericommercial company, right?
That's true.
If you think about it, if it all goes to plan, we'll be launching.
You're not in the spotlight.
No, no. That's one of the things that's attractive about this business, though. There are a lot of urologists in the U.S., but not all of them do bladder cancer. Of all the things they do, it's not the biggest thing. Often, particularly in these large practices, if there's a practice of 30 doctors, three or four do bladder cancer. Just like Raj was a specialist in bladder cancer. As a result, in the U.S., you probably need somewhere between 40-60 sales representatives. Very manageable for a company like ours and with the opportunity here. I think that's when we step back and think about our go-to-market strategy in the U.S., likely our plan would be to go ourselves.
On the other extreme, in my experience in launching in ex-U.S. countries, ex-Europe, there's too many countries and it's too costly to bring forward a structure there. Probably in those ex-U.S., ex-European countries, a go-to-market strategy would be partnerships. For Europe, it becomes an economic discussion, right? It really becomes, is it better in our hands versus someone else? I was President of Europe for Bristol Myers Squibb. I launched a lot of products there. My previous company, we launched in Europe and it was very successful. We just have to look at the financial models and we'll decide on that. We are already very much thinking about our go-to-market strategy.
All right. I guess we just have a little under a minute. If there are any questions from the audience.