Great. Thanks, everyone. Name's Etzer Darout , Senior Biotech Analyst at Barclays. My pleasure to have enGene with us this morning, CEO Ron Cooper. Ron, maybe if you can just give us an introduction of enGene for those that are less familiar with the story, and then we take it from there.
Well, enGene is, you know, a unique company with unique technology at a actually a really unique time, right? Our technology is called the DDX platform. It's a proprietary sugar platform that we developed ourselves over many years. The lead asset from our platform is a product called detalimogene, which we're developing for non-muscle invasive bladder cancer.
Mm-hmm.
We are right in the middle of an open label pivotal study, so it's an exciting time. Detalimogene itself is a non-viral gene therapy, so that confers a lot of benefits, very unique. This year is a pretty exciting year for us, in that, you know, first up, in Q2 this year, in the spring of this year, we plan a data update at an upcoming scientific conference.
Mm-hmm.
In the second half of this year, we plan to share the long-term data, 12-month data for our pivotal study, which is fully enrolled, so we'll have the final results of our pivotal study. We have a planned filing of the BLA, and we expect an approval in 2027. You wrap that up, the company then has cash that's, you know, over $300 million. We have cash in the second part of 2028.
Mm-hmm.
That's why I said it's a unique company.
Mm.
unique technology at a very unique time.
Right. Awesome. Great. Thank you for that. Based on our conversation with KOLs, non-muscle invasive bladder cancer feels potentially larger, I think, than I think the market assumes. Certainly higher unmet need. Maybe if you can comment on sort of the disconnect, if you will, between sort of how the market views this opportunity and sort of how key opinion leaders are talking about it.
Yeah. This is a market that's undergoing a lot of transformation. Now, you know, the first misnomer is that, you know, people are very focused in on, you know, breast and lung as big cancers. But first of all, bladder cancer is number six, so it's a top 10 cancer, right? It's pretty large.
Mm.
NMIBC within that is around 740,000 in the U.S., so that's quite large as well.
Right.
What people are not quite understanding with the transformation that's occurring is when you think about NMIBC, traditionally, if you were diagnosed with that, the only real treatments that you had were BCG and removal of the bladder. Urologists said, "Ooh, you have cancer. If you fail BCG, we're going to take your bladder out," right?
Right.
Increasingly though, it's understood that NMIBC is a slow progressing disease, so progresses about 20% over 10 years and maybe even lower than that. Now all of a sudden the treatment paradigm is changing.
Mm-hmm.
with this slow progression, there were no treatments, right? Now there are a number of new treatments that have been approved and that are in the pipeline to be approved. What's going to fundamentally change is products are going to be sequenced after each other because these products, you know, they have. They kind of wear out a year later, right?
Mm.
There are recurrence rates anywhere from you know, 60%-80%, right? Quite significant.
Right.
They will be sequenced. The patients don't progress, but they recur. The analogy that I would use for this is a little bit like the multiple myeloma market, right? When Revlimid was launched, it was a billion-dollar market. You add 12 plus new products, it's a 20-plus billion-dollar market as products are being sequenced.
Mm.
I think the same thing is going to happen here. You know, the bladder cancer market's about a $2 billion market. It's projected to be a $20 billion plus because of the reasons I just talked about.
Right. With that, can you just highlight, obviously it's a sort of a space where competition is growing. If you can highlight detalimogene's differentiation relative to what we sort of see from other molecules and maybe also describe the mechanism of action and how that relates to the differentiation here.
Well, first of all, as I said, we're the only non-viral gene therapy, so by itself it is super differentiated and super unique, and that confers a lot of interesting benefits. I think the way to think about that, first of all, is let's flip it around from the customer perspective. The majority of the patients are with community urologists. When you ask community urologists what do they want, what do they need, obviously they need products that have efficacy. They need products that are highly tolerable. 'Cause, you know, these patients are generally, and this is underappreciated, are 75-80-year-old smoking men with comorbidities. It's tough to get them on treatments.
Mm-hmm.
You know, they don't really want to bother with this sort of slow cancer, so tolerability is important. The third thing that's important are some of the non-clinical benefits, how easy it slides into their practice. Does it consume resources? When you think of detalimogene, it's probably the only product that delivers all three, right?
Mm.
Our preliminary data shows that we have a CR rate that's very competitive, good efficacy. We have probably best-in-class tolerability, very low discontinuation, very low treatment interruptions. In particular, community urologists, because we have a non-viral approach, our product can be stored in a regular freezer for many years, in the regular fridge for many months. There's no special handling. If you compare this to some of the other products, right, that require special handling, that require pre-washes, that require decontamination of rooms, that require hoods, right, that require procedure rooms, right? We don't have any of those things, right?
Right.
Detalimogene is a really unique product 'cause it provides the efficacy the doctors want, probably best-in-class tolerability. Most of the patients, you know, don't discontinue. Most of the patients don't have treatment interruptions, and probably best-in-class handling and ease of sliding into those practices.
Right. With that, when you think about sort of your go-to-market strategy, and how you plan to sort of reach those community docs, is there any education that needs to go on, given that it's a slow progressing disease? How are you thinking about that?
Well, I think first of all, from a go-to-market strategy, we think about geographies first.
Sure.
In the U.S., you know, we believe that we'll need, you know, 40-60 sales representatives, which is very manageable for a company like ours, so we're ready to go. In Europe, our go-to-market strategy, we're still evaluating. You know, I and a lot of other members of our team have a lot of experience in Europe, and that'll be a financial decision whether we go on our own or whether a partner, and the rest of them we'll partner. You know, within the U.S. itself, how do we think about this? Well, within these, community practices are often organized in what are called LUGPAs, right, which are a collection of practices. But within a LUGPA, there are usually, you know, a handful of doctors that are really focused in on bladder cancer.
We will be targeting them, right? We'll also have to really think differently about our targeting, from a, how the practices work.
Right.
You know, I'll tell you why, right? Because in the U.S., the number one specialty that does buy and bill is oncology, right? Number one. The second one is urology, right? This is a big source of revenue for their practices. When you segment the practices, some practices are very sophisticated in what they do, and they do a lot of buy and bill. Some practices would really like to do that, but right now the technologies that have been, you know, the first generation products are just clunky for community urologists, and detalimogene a next-gen product, so it's really going to slide in well there. There's a third group, you know, that really haven't explored buy and bill and do a lot of referring.
We will be, first of all, targeting the first two groups, but we think we can really activate the community urologists because we have a next gen product that really fits their needs, as I talked about earlier.
Great. Then maybe, sorry, with the registration, as a study, you know, you first announced data in 2024 sort of for LEGEND and sort of the amended protocol for the study. Can you talk about sort of maybe a little bit more around that amendment, what it entailed, and you know, sort of walk us through now then sort of the next data update, and what we can expect from that?
Yeah. The journey for us and our pivotal cohorts, the pivotal study is the LEGEND program . Cohort one is the pivotal cohort. When it was designed, it was designed by a CMO who was an oncologist.
Mm-hmm.
Right? We just realized we're going to be a urology company. We better have some urologists here, right? You know, the team figured that out.
Right.
which is terrific, right? Our urologist said like, "Okay, like, why are you making this harder on yourselves? You're not even applying standard of care for these patients," right?
Mm-hmm.
We had some good data, initial data, in 2024, but then we made three pretty significant protocol changes that brought us in line with standard of care. First one being before patients even got into the study, the T1 patients, so the T1 patients are at higher risk. Standard of care is to resect their T1, that lesion, and then do a second time. We weren't doing the second one. Now they all have to get that second resection. The second thing is as patients got to three months, if you had a little Ta growth, a papillary growth, we said, "You're out of the study." The doctor said, "It's just a little growth. There's nothing happening with CIS.
Can we just cut it out?" Well, that's standard of care, so now we allow them to do that.
Mm-hmm.
The third thing that we do is we ask for biopsies before patients come out. Before, you know, doctors would look and say, "Well, it looks like it's progressing." But sometimes with immunotherapies, you know, the bladder gets red. So it's a much more, you know, objective versus a subjective approach. You take that and you wrap it around the fact that our again, with a different approach of doing the study, you know, we brought in a very strong clinical operations team that if you take those protocol changes mixed with better execution, better follow-up.
Mm-hmm.
you know, there you go. The results that we shared, you know, late last year, are really compelling and much better, you know, frankly. What we're expecting is, you know, a data update at a major congress in the spring of this year that's planned. There, what we hope to do is really focus in on the primary endpoint, which is complete response at any time, so it's, you know, three and six months, yeah, for us. That will be locked in because we have about 125 patients, and most of those patients would have reached their six-month timeframe.
Right.
It's a pretty exciting time.
Good. I guess the obligatory question these days is sort of alignment with the FDA on the protocol change. I guess as well just sort of how are you kind of thinking about, you know, the pivotal readout, and whether or not, again, you and the FDA are aligned with that. Again, also how does that compare to sort of peers, if you will, in terms of their pivotals?
Well, the FDA's been terrific, you know, with us. Now, you know, remember, when you think of the FDA, very rarely do they give guidance in there. They recognized the need in NMIBC, right? You know, the guidance that they originally put out in 2018 and then reiterated draft guidance in 2024 said if you do, you know, 100 patients or so open label, you'll get a complete approval.
Mm-hmm.
What's nice is that a number of products even recently have got that. It's pretty rare in all of the things that they do, and I call that rock solid. We've had a good dialogue with the FDA and, you know, the FDA has provided us a number of important designations. We have Fast Track, we have RMAT, we have CDRP, you know, and I don't think they give those to companies unless they are, you know, they're serious about working with us to bring this product across the line. We've had very constructive dialogue with them. We've shared our preliminary data with them, which has resulted in some of these special designations. You know, I think we feel pretty good about being on track for, you know, working through the filing in the second half of this year.
Yeah. Great. How does the protocol compare to other programs? This BOND-003 program, SunRISe-1, how does the protocol compare to those?
Well, you know, I think, you know, I always caution people to make comparisons, right?
Mm-hmm.
First of all, we do not, you know, have access to their protocols, right?
Mm-hmm.
We don't know for a fact, but from their publicly disclosed information, what you see is many of the changes that we've done seem to be similarly done with them. But I always caution people to compare against these particular, you know, I know it's human nature to compare, but first of all, the patient population, including criteria, are very heterogeneous, right? NMIBC patients are very different. I believe the protocols are different. In these studies of 100 patients or less, right?
Mm-hmm
You can see a lot of swings. I believe that we're roughly aligned with others. Again, I would just caution individuals to make comparisons between the studies, even though it's human nature, 'cause there are different patient populations often and often different protocols.
Great. Yeah. Maybe another change, if you could comment on, is there a meaningful difference or maybe the reason driving the change from, you know, complete response at 12 months to sort of complete response at any time? Is there a meaningful difference there? Maybe what was the motivating factor for that change?
Well, that's just sort of standard discussion. We started in a particular area. We started to talk to the FDA.
Mm-hmm.
The FDA said, "Look, this is the primary endpoint for all the other products that, you know, we've approved. So we would expect us to align." Primary endpoint is CR anytime, and the key secondary endpoint is, you know, duration of response, right?
Right. How, you know, with the potential for sequencing of these different therapies, I guess, how do you see the NMIBC space evolving over time? Where do you think, you know, your program fits into that sort of paradigm?
Well, again, I believe this is a real transformation that's going to occur.
Mm-hmm.
First of all, you have to think about the, you know, the customer groups, right? You think about where are the patients? Over 80% of the patients are in the community, right? About 17% from our market research are in the academic centers.
Mm-hmm.
In the academic centers, you know, these are places where they remove bladders, and they're really focused on efficacy, and they have the resources to use some of these new technologies, right? Some of the newer products that are approved and the products that have come along actually sit very well there. These new next gen products, where we lead with detalimogene, are actually ideal for the community. Right now, most of the new products just don't work very well for the community flow, right? What we see is in the community that patients will be diagnosed, 'cause that's where the patients are. Well, they'll start with BCG if they can get them. A non-viral approach like detalimogene because it's just so easy in their office, right? We'll have a product sitting in the fridge.
You know, it literally, you know, anyone in the practice can take it out of the fridge, mix it with water, regular catheter, instill it into the patient, five or 10 minutes, they're out, right?
Mm-hmm.
That's a lot simpler than a lot of the other technologies. We believe there's going to be a transformation in these with these next gen products, and some of these other newer products will continue to be used in the smaller, you know, specialty area.
Got it. For detalimogene, do you think about opportunities for the program beyond BCG unresponsive NMIBC with CIS? Where else can this program go?
Well, I think what's really exciting about our, first of all, our platform, is our platform can be applied in many areas. Our technology can be applied in many areas. Detalimogene specifically, we've already started a couple of additional cohorts and, you know, patients that are naive to BCG, those that have been exposed to BCG, and those that have papillary only and don't have CIS. Those cohorts are ongoing. We're also looking at some of the other areas, as well. 'Cause one of the nice things about our product is that being a non-viral gene therapy, it's the only one. It being a non-viral product and not being an LNP, the cost of goods in manufacturing this is actually relatively low. So that allows you to go to a wider range of diseases.
Because the handling is a lot easier as well, it also allows you to go to a wider range. The potential for detalimogene outside of its first indication is pretty significant.
Right. You just talked about sort of manufacturing, and you're participating in the CDRP pilot program. Maybe you can describe what that is and then also sort of, you know, again, as you kinda talked about before, the differentiation detalimogene from just historical NMIBC programs that have sometimes struggled with manufacturing.
Yeah, really great question. Well, first of all, we're very honored the FDA granted us CDRP. You know, it's a pilot program, you know, one of nine companies. It's given on the basis of great innovation, but also clinical data and clinical need. To your point, when you think about in the old days, complete response letters were for clinical reasons. Now they're mostly for manufacturing, and it's been more so in this category.
Mm-hmm.
Effectively what this means, though, rather than, you know, taking Module three, the CMC module, and kinda throwing it over the fence when we file, we actually start engaging in an early dialogue with the FDA. We open the kimono, and we say, "Here's what we're planning." They give us feedback, more of this, little less of that, et cetera, et cetera. That will, you know, significantly reduce the risk of CRLs. Now, we always felt because, A, we've been manufacturing at scale. We're pretty much finished our PPQ batches, our validation batch, so we'll be writing Module three, you know, very soon. Because our product takes readily available ingredients and, you know, it's not a virus, it's not an LNP, you know, we wind up with a product that has relatively low cost of goods.
Because it's not a virus, the handling is a lot easier as well, so makes it very competitive. I think CDRP is a real help for us and, you know, certainly reduces any risk that we might have on the manufacturing front.
Great. What type of feedback have you gotten from key opinion leaders in bladder cancer around detalimogene as well as sort of how it sort of compares to competitors?
Yeah. Well, first off, you know, I actually never consider them to be competitors, right? These are complementary medicines. The reason I say that is, you know, if there was a product that had a twelve-month complete response rate of 80%-90%, that would be a competitor. That would be the number one product that's being used. Most of these products have an anytime CR rate around two-thirds, somewhere in that range. The products have a 12-month rate of 20%-40%, which means patients are going to recur. All these products are going to be used, they're just going to be used in different places and in different sequence.
We just believe that when you think about the needs of the community urologist, the first-gen products, they're not really using very much because they just don't fit their needs. They're just too clunky to use, right? These next-gen products where detalimogene is leading, I think really fits to where the patients are and it's going to transform, be able to start the transformation, you know, of this marketplace.
Yeah. Right. Obviously, for your upcoming data disclosures, if you can just talk through what good looks like in terms of benchmarks or hurdle rates, and you think about sort of what is a good data set, what is not a good data set as you think about sort of these upcoming disclosures.
Well, you know, these are experiments, right? You never know exactly where you're going, where you're going to land up. I think, you know, in our spring conference, right, you know, that's where we'll be focusing on the primary, because most of the 125 patients would have hit the six-month timeframe, right?
Mm-hmm.
If you look at the range of products in that, they range in sort of, you know, 50%-70% range of CR anytime. So, you know, let's see where we end up. You know, we had a CR rate of, you know, 63% anytime in the preliminary. So if we're within that range, I think, you know, that sounds good to me, right?
Yeah.
Then in the second part of the year, you know, we expect to have, you know, the 125 patients, the majority of them, you know, would have reached the 12-month timeframe. Again, it's an experiment, and the range there is 20-40, right? We think we're going to be competitive in both, in both ends.
Mm-hmm.
You know, I think that we feel pretty confident, you know, this being an immunotherapy in our durability, as well.
Yeah. Great analysis. Beyond the CR, right, obviously sometimes you kind of have trade-offs in efficacy, safety, and convenience as well. Just think about other parts of sort of this data set that beyond CRs that you're going to be looking at and trying to educate investors about.
Yeah, that's a very good point. I almost skipped over probably one of the most important things, right, is the tolerability, right? You know, again, think of these patients, 75- 80-year-old smoking comorbid men, right? They don't want to have a hassle, right? If you look in our clinical trials thus far, you know, we have discontinuation rate, you know, in the very low single digits. We have treatment interruption rates very low, where other products are in the 40s and above. The tolerability for us is going to be very competitive, and that's going to be important.
I think what Wall Street is missing is that, particularly for where the patients are in the community, these newer products are just too difficult for them to use to get into their practice flow, costs them too much money and too much resource. Our product is going to differentiate so nicely. It's going to just slide right into the practices. In fact, it's going to be easier than what they've been using in BCG.
Mm-hmm.
That's going to be a big benefit.
Yeah. Great. Oh, looks like we're up on our time. Ron, thank you so much for your time today. Thank you for our listeners and we'll be back soon with our next session.
Great. Appreciate the opportunity. Thank you.