enGene Therapeutics Inc. (ENGN) Earnings Call Transcript & Summary

Good morning, and welcome to the enGene Therapeutics webinar to discuss the preclinical work supporting its lead investigational candidate Deltalimogene Voraplasmid with Surfactant as well to discuss clinical case studies. [Operator Instructions]. As a reminder, this call is being recorded, and a replay will be made available on the Engen website following the conclusion of the event. I'd now like to turn the call over to Lauren Hopfer, Executive Director of Investor Relations at enGene Therapeutics. Please go ahead, Lauren.

Thank you. Good morning, everyone, and thank you for joining. With me on today's call are Ron Cooper, Chief Executive Officer; Anthony Chung, Inge's Co-Founder, and we're pleased to welcome Dr. Suzanne Merrill and David Cohn of Colorado urology. Before we begin, I would like to remind you that during our prepared remarks and Q&A session to follow, we may make forward-looking statements for purposes of U.S. and Canadian securities laws. These statements include, but are not limited to, our current expectations regarding the potential benefits of detalimogene voraplasmin or detalimogene, the efficacy, safety -- the product profile of detalimogene, the potential impacts of incorporating a surfactant bladder rents prior to treatment with detalimogene, timing of clinical data, timing of regulatory submission prospects for regulatory approval of detalimogene projections of market opportunity or market share, the anticipated market acceptance of detalimogene, if approved, our current views on market research in the non-muscle invasive bladder cancer space, implications or takeaways from our market research, estimates, projections or forecasts of payer coverage of therapies our expectations regarding how health care providers may use data limit gene or sequencing of products. They involve risks and uncertainties and assumptions that are difficult to predict and may not prove to be accurate. These statements should be only considered in conjunction with information in our filings made with the Canadian American securities regulators, including our Risk Factors section of our annual report on Form 10-K. At this time, I will turn the call over to Ron Cooper, enGene's President and CEO. Ron?

Great. Well, thanks, Lauren, and thank you all for joining us this morning. You're on Slide 3 is an overview of this morning's agenda. So before we begin the formal presentation, I'll start by reiterating that we believe the antiiBC market is fundamentally changing, as next-generation medicines lead the different needs of community urologists and that dental imaging is uniquely suited to address the combined efficacy, tolerability and logistical challenges of community urologists. First, we believe that the NMIBC market is still immature. And that the advent of more options for patients will drive an increase in the prevalent population through increased sequencing of therapies to grow the overall market. and create room for multiple therapies. This is not going to be a winner-take-all market. Second, we believe that dental imaging's clinical profile to date is compelling. Our most recent interim data update for Legends pivotal cohort, which is studying dental imaging without a surfactant was in May of this year. While our long-term durability data is still immature, with immediate follow-up of just 5.5 months for all patients -- we're encouraged that our study's primary endpoint, complete response at any time was 54% within the range of products already approved for this indication. Even more encouraging was Detalimogene tolerability profile which we believe is trending towards best-in-class. Rates of treatment-related adverse events leading to dose interruption or discontinuation or only 2.4%, respectively. Third, Data image was designed with our nonviral DDX technology, which uses low-cost, readily available components, supporting both scalable manufacturing and simplified storage analytic, which makes it viable for all practices and should allow for broad adoption in any practice setting. Fourth, thinking about life cycle management through the incorporation of surfactant bladder rents. Our preclinical data suggests that this approach may improve both the efficacy of data imaging and reduced dwell time. We remain well funded to accomplish all upcoming milestones and through potential approval in 2027. Now before handing it over to our community urology experts, I'd like to review highlights for market research that give insights into the new dynamics impacting the NMIBC market. First, with the next-gen therapies, we believe the community urology market will begin to unlock and that the prevalent market should grow with increased sequencing. We also outlined the evolving pricing dynamics over the course of several years and that the most recently approved products launching in the range of $500 to $700,000 per year and with little payer pushback at this time. Importantly, 40% of patients being treated in community practice that are either resource limited work for constraint or economics focus. These practices are looking to balance efficacy, safety resources and economics when making treatment recommendation. Now given these constraints, there's continued need for new bladder sparing treatments and dental imaging as a next-gen product has the potential to unlock these segments as a workflow friendly option. I'll share with you market research highlights, but there's nothing better than hearing from physicians around the frontline treating these patients Dr. Con and Dr. Suzanne Merrill. With that, I'll turn it over to Dr. Melancon to introduce themselves their practice and review illustrative patient cases.

Thank you, Ron. I'm Dr. Suzanne Merrill, and it's a pleasure to be with you today. Following my fellowship in urologic oncology at the Mayo Clinic, I spent 6 years in academic medicine as an associate professor of Urologic Oncology and as Residency Program Director at Penn State Hershey Medical Center. I then transitioned to private practice at Colorado Urology just over 5 years ago. I'd like to take this opportunity to tell you a little bit more about my practice before diving into a case study discussing the real-world management of non-muscle invasive bladder cancer. With my background, I have unique insights into the differences in academic and community urology. Colorado Urology is a large group practice in Denver. We are part of a larger national group, which is commonly called a LUPA -- this has multiple practice sites across our nation and employees over 220 providers. At Colorado Urology, we have over 30 rollout areas, which collectively serve close to 130,000 patients -- our practice is structured similarly to other lupus across the nation. However, there are still many smaller independent community practices that are different from our organization. Many such large practices have provider champions for specific urologic disease states, and I lead our Colorado bladder cancer program. where we look to offer patients access to the most cutting-edge bladder cancer treatments as well as clinical trials, which I will let Dr. Cahn, our Director of Clinical Research, tell you a bit more about that.

David? Thanks, Suzanne. Well, I completed my residency in urology at Montero Medical Center, and I did a fellowship in Colorado Urology and been in private practice since 1919, '98. In 2000, I founded Foothills Urology, which ultimately became Colorado Urology. I've always had a passion for clinical research, and I have the pleasure of leading our practices clinical trial program. At present, we have 7 -- I'm sorry, 38 active trials -- and I have served that as an investigator or I've served as the PI on more than 7 trials in my career. What we look forward to speaking to is the often long ambertisan patient journey and the continued need for additional free or additional therapies in the BCG unresponsive space. With that, I'd like to turn to our patient case studies to shed some light on the various treatments and lifestyle considerations impacting treatment decision. Let me turn it back over to you, Suzanne.

Sorry to interrupt. We're having a technical difficulty, so we're going to go off the air while we figure that out. -- all right. Sorry, guys, we're off the air. We're having a technical difficulty with our players. So sincere apologies and we'll be going live again shortly.

Okay. So where should I pick it up?

Right from where you left off, I believe, Ron and Lauren, we want to completely start over. What didn't work the slides or the audio or what -- so the -- our webcast player, we're having difficulty streaming this zoom there. So my recommendation is maybe we start from the top if that's okay with you guys. I know it's not

So people couldn't get in the meeting or they couldn't hear or they couldn't see the slides. Well, what couldn't they get.

They couldn't hear or see the slides. It said we're not live yet, so they didn't hear anything.

I think we have to start from top.

Yes. Sorry about that.

Okay. All right. That's about I guess we'll just have to run

Are we good?

Yes, yes. Yes, it's it's live now. Sorry about that.

So do we have to go all the way from the very topic like our safe harbor and everything?

Yes, because no one heard that, unfortunately, besides our analysts.

Okay. So -- so when you start, can you apologize to folks where a technical difficulty and say that we're going to restart?

Yes, absolutely. All right.

Our first case involves an 82-year-old male, name Walter, a retired veteran who moved into an apartment down the street from his daughter and 3 grandchildren after his wife passed Walter is a long-term smoker with the history of peripheral vascular disease, coronary artery disease COPD and atrial fibrillation, who experiences urinary frequency and urgency, which are currently managed with MiraBETRIC. His cardiologist has prescribed him Eliquis Walter's initial presentation starts in January of 2022, where he develops gross hematuria or blood in the urine, and is urine cytology was found to be positive with a normal CT scan. Using cystoscopy, we saw diffuse erythema, which means severe redness within his bladder. And thus, we performed a TRBT, which pathology confirmed multifocal carcinoma in situ. As as a standard for NMIBC with CIS, Walter began BCG induction. With traffic though, this is a 45-minute drive to and from the office for him and his daughter, who accompanies him and present significant scheduling and child care challenges for the family. Following induction, we find persistence of CIS and reinduction with BCG is recommended. Well, there does respond following reinduction and enters into a maintenance period with BCG for 1 year. However, in July of 2023, at a quarterly surveillance appointment, we see a papillary lesion and another TRBThas performed with past conforming CIS plus high-grade Ta papillary disease. Based on this, Walter is now considered BCG unresponsive high-risk in IDC. At this time, given his more advanced age, continued health challenges with COPD and heart disease, Walter is a poor candidate for cystectomy. At this time, only KEYTRUDA has been approved for BCG unresponsive CIS, for which potential side effects could be significant and difficult to manage for him and his caregiver. While at Stiladren was approved in 2022, it did not yet have its J-code, which met reimbursement would be a challenge. And although resolved in recent years, manufacturing issues ultimately made this drug initially widely unavailable for commercial use. So we settled on treating Walter with Jim Dose, which is successful, and he undergoes monthly maintenance for the next year. His next recurrence is in September of 2024. A -- with cystoscopy, we see a lesion and then perform RBT again with pathology confirming CIS plus high-grade TA disease. Walter is now 85 years old. His health is continuing to decline. And after his last recurrence, he's moved in with his daughter and grandchildren. With his ongoing comorbidities, he's not a candidate for cystectomy and now is developing worsening urinary urgency and incontinence. At this point, both he and his daughter are looking for something that's going to offer a less frequent dosing and be overall more tolerable with his declining bladder function. At this time, the treatment discussion moves to 1 which requires balancing his multi-recurrent disease, his age, comorbidities and bladder symptoms. Since we have already used sequential gemcitabine and docetaxel, we would not recommend treatment with additional chemotherapy due to a similar mechanism of action. -- nor would we recommend other available agents due to their frequent dosing schedule on account of is poor bladder function. Now that he is sharing a bathroom with 4 other people, his daughter feels uncomfortable with clinical trials or products involving viral agents due to the need for urine bleaching as well as the need to do separate loads of laundry for fathers close for a period of time after exposure to such agents. If data imaging were available as an option, it would be attractive alternative for the following reasons. First, being a nonviral gene therapy, it would be a different mechanistic approach than what Walter has experienced and has passed. Second, -- in an aging patient with worsening bladder symptoms, we need a treatment that provides both a strong tolerability profile and reasonable chance of achieving a complete response. And finally, given the less intense dosing schedule and lack of post-treatment bleaching or content precautions, data imagine would be an attractive next treatment for Walter. And with that, I'll turn it over to David to review another case.

Thanks, Suzanne. Our next patient is quite a bit different. 70-year-old newly diagnosed Alberta is an active otherwise healthy former business executive who travels frequently on an advisory board -- he visits family on both the East and West Coast. Albert plays golf and tennis weekly, and he has no significant medical comorbidities. Otherwise, in great health, his diagnosis of bladder cancer is both a shock and viewed as a major inconvenience. That said, Alberta is initially a motivated patient and he wants to address this issue as quickly as possible. Albert's initial presentation in January 2024 was gross material, which is quite typical. You had positive cytology and a cystostaly revealed multifocal lesions. Pathology confirms high-grade TA and MIBC. He immediately begins a BCG induction. During the induction cycle, he misses a family reunion but is relieved to have a complete response. He then undergoes 1 maintenance cycle. At his next disease assessment in July of 2024. He is still in response and decides to discontinue therapy. Alberta is lost to follow up for a year. Once again, in June 2025, Alber presents with blood in his urine and comes into the office. -- we confirm recurrent multifocal high-grade TA disease. Given the time from his last BCG, he is technically classified as BCG exposed. We discuss a few options with him, including cystectomy, which he refuses. As no approved products have NCCN 2a guideline inclusion for papillary-only disease at this time, which presents reimbursement issues, some clinical trials are discussed given my interest in clinical research. He is not interested in these. So we move to discussing Gemdosy and he agrees to this. We begin the induction course, and he really struggles with severe bladder burning, which results in his inability to hold each drug more than 30 minutes. Once Albert moves to the monthly maintenance, it's slightly more manageable and is able to complete 2 maintenance cycles before he recurs again in November 2025, this time with a high-grade TA lesion. At this point, he's eligible once again to undergo BCG, still cystectomy or a clinical trial. He's reluctant. But given his past success and time between exposures, he once again chooses BCG and completes both induction and 2 maintenance cycles, despite once again experiencing burning and difficulty holding BCG for the recommended 2-hour dwell time. Thankfully, this time, he's not lost a follow-up and a TORBT, during routine surveillance in September of this year, we uncover CIS. He's now officially deemed ECG unresponsive. Albert once again refused cystectomy and he's hesitant to begin -- he's hesitant to begin chemo given this experience with gemdosy, but he agrees to elect -- to try and Lexo, given its strong complete response at any time. So we insert the pretzel. About a week later, he calls our office complaining about urinary burning and the sensation of having to urinate frequently, particularly bothersome during his tennis matches -- and he wants a device removed. Our staff counsels him to continue on the therapy and he agrees. But about a week later, he calls back in demands that the pets will be removed. Albert is a very active guy and as NMIBC has recurred but has not progressed. I would like to give him something else but need a viable option. In this case, I'm looking for something that is different, has efficacy and will be convenient for Albert and something that also offers a strong tolerability profile given this difficulty holding BCG and chemotherapy for the recommended dwell times. Based on data limit genes profile to date, if it were available, this would be an attractive choice for Albert. Ultimately, both cases highlight joint decision-making and the need for additional bladder sparing options whether because a patient forgoes radical cystectomy to maintain their current lifestyle because patients are simply a poor candidate for the procedure. Patients are often trying to balance everyday life management of comorbidities and bladder symptoms with a degree of treatment burden and the hope for treatment success. There is certainly no one-size-fits-all option for each patient. And so as clinicians, we are excited by the continued innovation in the high-risk NMIBC space and look forward to the ability to offer our patients additional bladder sparing options.

All right. Great. Well, thank you -- thank you very much, Dr. Cohn and Dr. Merrill for your comments. Let me turn it over to Anthony, our founder, to talk about Detalimogene and surfactant.

Great. Thank you, Ron. I'm excited today to provide you with a deeper look at what's next for Dell imaging. I'll walk through the scientific rationale for combining delimagene with a surfactant bladder RINs and answer a number of questions we continue to receive I haven't covered in detail until today. I'll walk through this rationale in 3 parts. First, I'll review the scientific rationale for using a surfactant with an intravesical gene therapy. Second, I'll describe how we selected polidocanol and summarize the preclinical evidence supporting its use in clinical development. Finally, I'll discuss how these findings have formed the clinical surfactant cohort that is now underway within LEGEND trial. So let's begin with the scientific rationale. To understand why improved penetration and distribution of dental imaging throughout the bladder may matter, and it's helpful to revisit detalimogene mechanism of action. That lumogene is a nonviral plasma-based gene therapy designed to deliver DNA encoding genes into cells lining the bladder. Together, these components are designed to locally stimulate complementary arms of the immune system. Rig I activation initiate innate immune signaling and support recruitment of NK cells and T cells to the bladder. Local IL-12 expression then promotes TH1 polarization of the indwelling T cells creating a strong antitumor response, cytokine production and potential formation of durable immune memory. Essentially, we are aiming to create a strong adjuvant effect with that limit. Decades of vaccine biology shows that the strength of the adjuvant effect determines whether the immune response is robust and durable. So the question we ask ourselves was straightforward. How do we increase the level of transgene expression from delimagene?? While an intuitive way to increase gene expression would be to administer a higher dose of detalimogene, our Phase I data indicate that the relationship between dose and gene expression is sigmoidal rather than linear. These more dose-response findings are consistent across gene therapies. In terms of dose response, you can see that we observed a substantial increase in urinary IL-12 when the dose increased from 250 to 800 micrograms per milliliter. But when the dose increased further to 2,500 micrograms per milliliter expression appear to plateau. This pattern was also consistent with other preclinical models. It suggests that increasing the dose alone is unlikely to produce a proportional increase in therapeutic gene expression. That is why 800 micrograms per milliliter was selected as a recommended Phase II dose. We also spaced 2 weekly administration in each treatment cycle to help avoid saturating the host transcriptional machinery. So this observation led us to explore a different strategy. We ask instead of giving more drugs, could we increase IL-12 expression by allowing existing dose to reach larger number of receptive cells. Looking at other gene therapies in the NMIBC space, we found meaningful presence for incorporating a surfactant bladder RINs prior to administration of therapeutic agents. As shown here in this slide, preclinical work with viral gene therapies, for example, citoymagene and accelerant, these agents demonstrated relatively limited urothelial transfection without a surfactant pretreatment. After incorporating a surfactant pretreatment, transfection increased substantially and extended across broader portion of the urothelium. Although the specific vectors, payloads and surfactants shown here differ from delimagene, these findings support the broader biological principle that a surfactant can help a gene therapy overcome the urothelial barrier and improve access to target cells. With that reasoning, we move into preclinical development and surfactant selection. Our goal was not to simply identify the agent that produced the largest signal and an experiment. We wanted a surfactant that could ultimately support clinical development and broad commercial use. So we established 3 principal selection criteria. First, the surfactant needed to be commercially available so that we could have immediate and uninterrupted access to supply. Second, it needed to be available as GMP grade material at scale, and added practical costs and in regions where clinical sites would operate. Third, it needed an extensive existing safety database, detalimogene has demonstrated a favorable tolerability profile and we did not want the addition of a surfactant bladder RINs to compromise that important attribute. These requirements narrow the view to agents with both scientific potential and a practical path into clinical and commercial use. Lanoxin 9 was initially selected because it had been widely used for many years as a spermicide agent in contraceptive products. Consequently, it was commercially available and supported by an extensive body of safety data. DDM was used as a benchmark for our preclinical studies. DDM is a non-ionic surfactant used in another investigational bladder gene therapy product. We did not consider using DDM because it has not been widely used clinically, and it is not available as a commercial product. So here you can see the Lanoxin 9 produced gene transfer comparable to DDM. However, we later learned that -- there are supply chain constraints, which make LOXNO9 less attractive for continued development. We then evaluated polydocanol, polidocanol produced a greater increase in gene transfer and offer broader regulatory and commercial access. Based on the totality of these data, including performance, supply, safety history, and development practicality we selected polydoconol for the clinical surfactant RINs program. Polydoconol met each of our core criteria. It also has an established history of clinical and consumer use concentrations well above the 0.25% concentration being evaluated in our bladder RINS cohort. Clinically, Polydoconile has been used at concentrations of 1% to 4% as an intravenous scarrosing agent for conditions such as varicose veins and hemorrhoids. And also, it is also used at approximately 1% concentration in shampoos and other consumer products. So having selected polidocanol, the next question was whether the surfactant RINs could meaningfully improve the performance of denim aging in preclinical models. So in this slide, these images illustrate the effect of the surfactant RINs on tissue penetration in mouse models. Without surfactant, detalimogene is concentrated primarily near the luminal surface with the surfactant RINs, the nanoparticles appear to reach cells in the intermediate and basal layers of the urothelium. That distinction is very important because cells closer to the basal laminate are more metabolically and endocytically active. Once the vector enters those cells, their biology may better support nuclear transport and transgene expression and therefore, has the potential to increase both the magnitude and duration of localized gene expression, which may ultimately translate into improved efficacy and durability. The MIRRAN studies provided evidence that this deeper penetration had functional consequences. On the left, the surfactant RINs appears to have broken the sigmoidal response seen with detalimogene alone, having generated a greater than 10-fold increase in localized IL-12 expression and maintain expression for a longer period. On the right, we deliberately use a suboptimal dose of detalimogene to test whether the surfactant could improve biological activity. And you can see here a brief 5-minute bladder RINs restore efficacy in that model. So taken together, these findings suggest that the surfactant is doing more than simply changing distribution is increasing expression of the therapeutic cytokines and improving antitumor activity in preclinical models. The surfactant RINs may also enable a more convenient administration experience. In this preclinical experiment, a 5-minute RINs allowed detalimogene to be administered with a 15-minute dwell time to generate substantially greater IL-12 expression than detalimogene alone with a 60 minutes dwell time in the bladder. Notably, we're not carrying the 15-minute dental imaging dwell time directly into the current clinical study. Instead, we selected 30 minutes to our time to provide an additional margin for patients' potential inability to tolerate holding liquid instilled into the bladder. This is an issue overview by Dr. Cahn in his case study. A shorter dwell ton could be meaningful for patients with irritated or overactive bladder who may find it difficult to retain an intravesical therapy for a full hour, it could also reduce chair time and improve treatment capacity within community urology practices. So next, the biological response we are generating is also relevant to establish bladder cancer treatment. IL-12, interferon gamma and CXCL10 are all important mediators of antitumor immunity within the bladder. And these same targets are upregulated by BCG, which remains to be the standard of care in the high-risk NMIBC setting. BCG established clinical activity provides support for the relevance of this immune access. That imaging is designed to engage the biology through a differentiated, targeted and localized approach via IL-12 expression and rigI activation. These data show that the effect in preclinical models extend beyond the initial increase in IL-12 expression. With the surfactant RINs and a shorter element in dwell time, we have served increased and prolonged expression of IL-12 in murine models. We also observed sustained enhancement of interferon gamma and CXCL10 production. This is very important because it suggests that the surfactant mediated increase in delivery produces a broader and more sustained response across multiple key anticancer biomarkers. An important development objective was to preserve the procedural simplicity of detalimogene. Sub surfactant can interfere with the stability or potency of a subsequently administered drug -- if that occurs here, the surfactant would need to be washed out with saline before detalimogene administration, adding another step to the procedure. Our study show that potential residuals effect on volume in the bladder or catheter at levels of up to 10% did not have any impact whatsoever on detalimogene stability or potency. As a result, the RINs can be removed and detalimogene can be administered through the same catheter without an intervening saving watch. This helps preserve a straightforward single cateterization workflow. We also evaluated whether the surfactant RINs produce local bladder toxicity or systemic exposure. In the mirror model, bladder weight is used as a sensitive marker of inflammation or toxicity. As shown in the figure on the left, latter weight remain unchanged following treatment. We also evaluated plasma DNA and IL-12 levels in plasma and observed no evidence of systemic exposure. Next, we move to validate these findings in nonhuman primates, whose bladder anatomy and biology provides a relevant larger animal model. As shown in the figure on the left, the combination of a 5-minopolydocon RINs followed by a 15-minute detalimogene dwell, produced approximately 9-fold higher mean human IL-12 expression than detalimogene alone with a 60-minute dwell. The proportion of positive tissue samples also increased from 29% to 81%. This suggests improvement in both the magnitude of expression and its distribution across the bladder urothelium. Importantly, we observed no systemic distribution of polidocanol following administration as shown in the figure on the right. The nonhuman primate results, therefore, reinforced the 2 central findings from the Merin work. That is preventing the bladder with polidocanol significantly enhanced localized gene expression in bladder with an encouraging preclinical safety profile. The consistency of these findings across multiple preclinical models gave us the confidence to move into clinical study. In May of this year, we announced the initiation of a new cohort in LEGEND trial evaluating surfactant bladder rents plus detalimogene in patients with BCG unresponsive high-risk NMIBC with carcinoma in situ with or without papillary disease. The clinical procedures uses a single catheterization. -- patient received a 5-minute bladder RINs with 15 milliliters of 0.25% polygonal followed by detalimogene. Detalimogene dwell time has been reduced from 60 minutes to 30 minutes in this cohort of the study. The safety run-in is now complete with no dose-limiting toxicity observed and the efficacy portion is now in progress. The cohort may enroll up to 80 patients and will access and will assess whether the increased gene expression and favorable administration profile seen clinically can be translated into improved clinical activity, durability tolerability and a more convenient patience and practice experience. For the surfactant cohort, specifically, we expect to provide a 6-month complete response update on approximately 20 patients in mid-2027. So with that, I'll turn the call back to Ron.

Right. Thanks very much, Anthony. So in conclusion, we believe that within the growing NMIBC market detalimogene alone may offer a differentiated total product profile that can address the needs of a large quality of private community urology practices with its balance of efficacy, tolerability and a streamlined experience for both patients and practices. At the same time, we're actively investigating future life cycle management and our ability to improve efficacy, mean tolerability and reduce burden to both patients and the urologists with our surfactant bladder rents. We're now approaching important near-term milestones in Q4. We're planning to provide updated data from our pivotal cohort. Our key primary endpoints, CR at any time of is likely not to change significantly. The key secondary endpoint durability after 12 months will still be immature, but we plan to provide an estimate. We expect tolerability to hold even with increased exposures. Additionally, we expect to have the vast majority of 12-month landmark data. And based on the data we presented in May, we expect to have in cost efficacy of best-in-class tolerability, handling, ease of use and cost of goods. Last, we expect to initiate our BLA submission for devalimagine. Next year, we're tracking towards both potential proof for dental imaging as well as a clinical data update midyear on our devalimagine plus surfactant plate range cohort. So it's really an exciting time for Engine and dental imaging. We apologize for the technical challenges. I hope you can stay with us as we open up the call for questions.

Great. Thank you, Ron, and thank you to our speakers. [Operator Instructions]. Our first question comes from Maurice Raycroft of Jefferies.

Great. Thanks for doing this call. The event has been really helpful and thanks for the KOLs as well. Maybe just starting off just how representative are these case studies or what proportion of patients fit this general profile where the KOLs would use dedolimagene. And as the HR NMIBC treatment landscape expands, how do the KOLs rank the available options and which factors drive their preferred treatment choice?

Maybe Dr. Merrill, you want to start with a little bit on how these how these cases generalize to your population and talk through that question. Maybe, David, you could add a few comments on that as well.

Sure thing. So these cases are pretty representative in regards that we see a spectrum of patients from age and comorbidities. So we gave you kind of that spectrum of a younger patient diagnosed with disease still very active in their lifestyle and with their professional life that dealing with intravesical therapies can be a challenge. When they're very frequent dosing and the problems they can pose when they cause symptoms. And then we gave you the other end of the spectrum of the elderly patient as they've been sequenced already through mini therapies and their bladder symptoms are really driving a lot of our choices into that next line as they've already passed the threshold of not being safe to take for cystectomy. In regards to that second question of kind of our ranking of the therapies available for BCG responsive disease. Ultimately, what drives the decision unfortunately, is multiple fold. It has to deal with certainly efficacy, but also very much close knit is what is going to be tolerable for that patient. So involving again, what bladder symptoms they have, any issues with a course traveling to these locations where we can administer these therapies. And then certainly, they're, again, bladder symptoms, et cetera. So a lot of things play into that decision beyond just efficacy of what we use. And so it's really important to have a lot of options as what Ron said, really rings true to us that it is not one drug fits all patients. It's really nice to have a lot of options to really individualize our treatments to that patient's needs.

And if I may add, thank you, Suzanne. And I was going to reference what Ron said as well, it's not just one size fits all. If you think about it, these patients have a disease in their bladder. First line of treatment for most of them now and into the foreseeable future is going to be BCG, which can be very toxic to the bladder. And just as Suzanne said, we're going to be focusing as much on tolerability as efficacy because we're asking these patients with compromised organs to hold these agents in their bladder for efficacy. So the fact that we're able to create -- we have an agent here in detalimogene that potentially is efficacious and well tolerated and now with a shorter dwell time, is quite important. And I can just say anecdotally, my clinical coordinators have noted a difference in the tolerability with this shorter dwell time. So that's -- it's encouraging, and we're very -- we're excited to see what the data shows.

Got it. all really helpful perspective. And maybe just 1 more technical question, and I'll hop back in the queue. You mentioned Sigma dose response relationship. Do you think this surfactant meaningfully increases the effective drug dose delivered to the tumor? And if so, should greater tumor exposure lead to I guess, translate into a proportional improvement in tumor suppression -- or would you expect the benefit to plateau beyond a certain exposure level?

Thank you for the question. This is Anthony. Let me just clarify one point. I just want to make sure that we understand detalimogene doesn't need to get the gene expressed in the tumor cells specifically. You can express it anywhere in the urothelium and the fact that we're trying to achieve would come about. So that's number one. It doesn't need to get to the cells specifically. So the question is whether we expect to see higher, certainly, the preclinical data that we're seeing we're seeing very, very consistent across multiple animal models that the expression of these transient carried b detalimogene, it's all increased in 9 to 10 fold level. So -- and based on the mechanism of action that I review earlier, we do believe that, that would translate into better response. At least we've seen it in animals. And certainly, we need to wait for the data in humans and see how that play out.

I think we're pretty excited to have dealing on its own. We get pretty good expression. And you saw that in the animal models, the addition of polydonnlosurfactad really adds potential in 2 parts, better expression as well as reduced dwell times. So we look forward to getting the clinical data for that. Thanks for the question.

Our next question comes from Lili Nsongo at Leerink.