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

Good morning, and welcome to the enGene Therapeutics call to discuss the non-muscle invasive bladder cancer market. [Operator Instructions] As a reminder, this call is being recorded, and a replay will be made available on the enGene 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 our call to discuss new insights to the non-muscle-invasive bladder cancer market. Joining me on the call this morning are Ron Cooper, our Chief Executive Officer; Amy Pott, our Chief Global Commercialization Officer. I'm pleased to welcome Dr. Neal Shore, Medical Director for the START Cancer Research. 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. Securities Laws. These statements include, but are not limited to, our current expectations regarding the potential benefits of detalimogene, the efficacy, safety and product profile of detalimogene, timing of clinical data and regulatory submission, prospects for regulatory approval of detalimogene, projections of market opportunity and market share, the anticipated market acceptance of detalimogene, if approved, our current views on end market research on the non-muscle invasive bladder cancer market, implications or takeaways from our market research, estimates, projections or forecasts of payer coverage of therapy, our expectations regarding how health care providers may use detalimogene or similar products. They involve risks, uncertainties and assumptions that are difficult to predict and may not prove to be accurate. Results may vary. These statements should be considered only in conjunction with the information in our filings made with Canadian and American securities regulators, including the Risk Factors section of our annual report on Form 10-K. At this time, I'll turn the call over to Ron Cooper, enGene's President and CEO. Ron?

Great. Thanks, Lauren, and thank you all for joining us this morning. We're really excited to discuss how our views of the high-risk BCG-unresponsive NMIBC market have evolved with the e-market research we've conducted over the past months where we use multiple product profiles. We're also very pleased that Dr. Neal Shore could join us today to provide his expertise. Welcome, Dr. Shore. Before turning it over to Amy, I will provide a short overview. Our product candidate, detalimogene is the only novel nonviral gene therapy being developed for NMIBC. It is administered intravascularly to the bladder where it delivers plasma DNA encoding 3 genes that activate the RIG-I pathway and drive expression of IL-12, synergistic stimulating both the innate and adaptive immune responses. We are currently studying detalimogene in the ongoing Phase II LEGEND trial, which includes a pivotal cohort with high-risk BCG-unresponsive NMIBC with carcinoma in situ or assist patients. We'll also discuss the new detalimogene plus surfactant cohort, where we expect enhanced CR any time, durability and convenience. And the BCG-unresponsive papillary only disease cohort, where we expect to achieve NCCN guideline includes. We believe the -- we believe NMIBC is transforming into a rapidly growing market as more therapies become available, creating additional opportunities for patient sequencing and expanding treatable patient population. In May of this year, we shared interim pivotal core data on detalimogene without surfactant during a plenary session at the American Urological Association Annual Meeting. Only 55% of patients experienced treatment-related adverse events, most of which were mild of which only 2.4 were associated dose interruptions or discontinuations, respectively. For the primary endpoint, detalimogene without surfactant had an anytime fixed response rate of 54%, which fall solidly within the range of approved products. Duration of response equal to or greater than 12 months, the key secondary endpoint is still maturing. Landmark CR at 12-month KM estimate of 25% is similar to a silerdron-and approved product. As Amy and Dr. Shore will discuss, we leave detalimogene's overall efficacy, tolerability and hem profile as the only nonviral gene therapy may provide the unique and desirable profile for integration across a number of community urology practice settings. Importantly, our nonvolatile approach also utilizes readily available low-cost components that support scalable manufacturing and simplified storage and handling. Notably, we have completed our PPQ or FDA validation batches, FDA, CDRP, Chemistry, Manufacturing and Controls Development and Readiness Pilot Program designation supports BLA readiness. Importantly, we also see an opportunity to further enhance the profile of detalimogene through the addition of a surfactant bladder rinse. In preclinical models, both murine and NHP, this approach has demonstrated an eight- to tenfold increase in IL-12 expression. We believe that a surfactant bladder rinse will enhance the efficacy of detalimogene without compromising the tolling profile. In addition, the use of a surfactant rinse is anticipated to reduce the bladder dwell time of detalimogene from 60 to 30 minutes, further reducing burden on patients who frequently suffer incontinence and bladder spasms. Looking ahead, we anticipate mature DRP data will be later this year, planned to meet with the FDA and initiate a filing by the end of the year. Importantly, we remain well funded with $285 million. To summarize, we see 4 important themes. A growing NMIBC market supported by increased sequencing. Two, a differentiated nonviral platform designed for community adoption. Three, a promising clinical profile to date. And four, the potential opportunity to further enhance that profile through the addition of surfactant. I'd now like to turn the call over to Amy Pott, our Chief Global Commercialization Officer, to take you through our market research findings. Amy?

Thanks, Ron, and welcome, everybody. We have conducted extensive market research over these past few months, where we've tested a range of efficacy profiles, payer dynamics and practice considerations when considering therapies for high-risk, BCG-unresponsive NMIBC patients. Our market research supports and informs assumptions we will share with you today. The depth and breadth of this market research is as good as anything I've delivered from my days in big pharma and is a robust mix of qualitative and quantitative research. To give you a sense of our extensive approach, over the period of 6 months, we've conducted multiple waves of market research, including over 65 urologists and uro-oncologist interviews, 15 payer interviews to 100 urologists and uro-oncologist surveys and analyzed over 2,000 patient claims. We've also conducted over 20 clinical literature reviews with the aim to capture emerging and future trends that will impact the NMIBC market. On the next slide, these are some evolving topics. We would like to make sure you have insights on as we think about the high-risk BCG-unresponsive NMIBC market. The first 3 assumptions in any market model for NMIBC are pretty straightforward. Most of the literature and claims data would align on the first 3 inputs and annual incidence of about 90,000 new cases of bladder cancer each year, 80% of those being NMIBC and drilling down to about 30% of these cases falling into the high-risk category. Where there is some ambiguity is around the last 4 categories, including the size of the potential population who have CIS and papillary only, BCG-unresponsive classification, market share and pricing dynamics. Today, we will share the insights we've gleaned that are helping to inform our view around these dynamic market assumptions. Slide 10 here is 2 separate subcategories of high-risk disease, including CIS and papillary only, although the 2 can occur concomitantly. While papillary is typically resected by a TURBT and then treated with BCG in fifth setting. CIS is multifocal in nature and difficult to treat surgically. In the next slide, when we're reviewing patient profiles of high-risk patients, it's important to understand clinical guidance as to how to treat high-risk patients. Treatment algorithms within clinical guidelines assist represent a wide range of patients, and it's clear that papillary patients are clinically managed and reimbursed like CIS patients. The NCCN guidelines have set consensus treatment standards for CIS patients with categories within the guideline. 2A category reflects NCCN consensus that the treatment recommendations are based on appropriate evidence for both CIS and papillary only. It is also important to note that all our interview payers indicated that they would cover BCG unresponsive therapies broadly with a 2A plus recommendation. The detalimogene LEGEND study includes a cohort of papillary only patients. Should we receive FDA approval on our pivotal cohort, we would plan to submit for inclusion of NCCN guidelines. Bottom line, our market research indicates that the addressable BCG unresponsive population is larger than many believe. In the next slide, NMIBC represents a unique market, where currently approved therapies and others in clinical trials, but there is no one therapy that treats all patients and practices. In our HCP insights and other published basin patients, there is a clear desire to avoid radical cystectomy. All our urologist interviews stated that they would aim to sequence patients through 3 or 4 lines of therapy before performing a radical cystectomy. Here, we have captured an illustration of how patients could sequence through 3 or 4 lines of therapy and the compounding effect this will have on the eligible pool of patients. Currently, community urologists have few viable treatment options, but with the advent of next-generation products like detalimogene, sequencing will drive growth at the prevalent population. This pattern has been observed in numerous therapeutic categories where innovation expanded the overall market rather than simply redistributing checks. As new treatment options come available in diseases such as multiple non-myeloma, multiple sclerosis and depression, more patients ultimately receive treatment and remain on therapy longer. It is well accepted that most patients with high-risk NMIBC are treated in community setting. However, through our market research insights, we've gained much deeper insights into different breadth of choice and practice needs. Our finding is also real that there is a slight difference in prevalence and incident rate with estimated 75% of incident NMIBC patients seeking care in their community versus 80% of prevalent NMIBC patients. Through our new market research insights, we have dug deeper into the choice drivers for small and large private practice and have characterized these practices into 4 different categories, practices that are resource limited, practices that battle workflow and logistical constraints, practices that prioritize economics and practices of clinical excellence. This has allowed us sharpen our view of the percentage number of patients in the community. Here, we consume in further and understand patients that are being treated across these various practice settings, further segmented by their key considerations. Over 40% are balancing a range of complex needs including resources, economics and efficacy. Our research uncovered that within the private community-based practices, there are 4 distinct segments of which 3 express meaningful preference towards adoption of a product such as detalimogene, where its efficacy profile, ease of use and tolerability is uniquely well seated. First, we have resource limited practice where adoption of novel therapies is limited by cash concerns. Second, workflow constraint practices, where uptake of viral therapies is limited due to infrastructure or logistical challenges of administration. Third, economic focus practice where net cost recovery in consideration with efficacy, drives adoption. And fourth, clinical excellence practices. Dr. Neal Shore, who will be providing insights later runs the very sophisticated private practice and represents one of the clinical excellence practices. However, he can also provide insights on the needs and behaviors of all of our segments. Per Slide 14, here is where we illustratively show the feedback from our market research on where we think there would be meaningful market share of detalimogene in approximately half of the market and minimal in the other half. This shows a competitive profile and ability to have share in multiple segments. We tested a range of efficacy profiles from estiliden-like efficacy to lower efficacy. In all cases, the feedback from HCPs collected in our market research leads us to believe that detalimogene's unique profile generated meaningful market share in attractive community practice segments. Here on Slide 16, we can see that with the exception of hospital health systems, 80% of urologists are using buy and build to acquire NMIBC therapies. While economic focus practices are keen to integrate novel therapies, the potential to provide a therapy that balances efficacy, tolerability and ease of use to workflow constraint practices who'd like to utilize buy and bill but can't administer complex therapies will be important to increasing the menu of options they can provide to patients. Likewise, close to 20% of community practices are resource limited and wary of large cash outlays. So the ability to address these concerns will be an important factor. We believe a key to know that there are a range of factors taken into consideration when advising a product. When thinking about efficacy, there are multiple measures including deep response as well as durability. Safety is, of course, important. Katherine's instance launched at a higher price point than Activa despite having less tubes. And as noted on the slide, we've repeatedly limited pricing dynamics in the highly competitive I&I space. Another key dynamic assumption is the payer reimbursement and price benchmarks within the NMIBC market today. The overall benchmark has moved up from an annual wholesale acquisition cost WACC of $220,000 per year to $690,000 per year. Based on our market research, interview with payers, we believe that interviewed payers will cover therapies at parity, a NCCN guideline category of 2A. And importantly, practice urologists clearly indicated the net cost recovery is critical for building practice infrastructure and capacity. Generating a positive net recovery and efficient practice sector on economics, particularly in a bundled marketplace is both important and common across multiple therapeutics, not just neurology. On Slide 9, we have an illustrative example of net sales for an approved IBC product and projected revenue at priority pricing at a new watermark. If an NMIBC therapy is priced at parity with recent benchmarks, only about 10% of the eligible patient pool needs to be on therapy to achieve roughly $1 billion in net sales. In conclusion, with new and emerging market trends in NMIBC BCG unresponsive, it's important to understand some of the dynamic market drivers. To recap, the real-world treatment algorithm for patients to recite a wider range of patients, papillary-only patients are clinically managed and reimbursed like CIS patients. With more therapies becoming available but still high unmet need, HCPs and patients indicate that they'll be willing to sequence and try up to 3 to 4 lines of therapy to avoid radical cystectomy. This will create a common effect on the eligible pool. Understanding the drivers of choice across private practices is key as it demonstrates differential market share by practice type. Our research suggests that relatively few emerging therapies are well positioned across resource limited, constrained and economic focus practices. We believe detalimogene can address these needs and has the potential to become a leading agent in community urology. The benchmark price for NMIBC therapy allows private practices to build towards net cost recovery and efficient practice economics as well as the important ability to offer patients lattice bearing treatment options. We hope you found these new market insights thought provoking. I would like to hand over to Dr. Neal Shore so that he can provide you with his thoughts on our research findings and the realities of managing NMIBC patients in the community. Dr. Shore.

Well, thank you very much, Amy, and thank you, Ron. It's a great pleasure to be here this morning to be part of this discussion. I am the Medical Director of Carolina Urologic Research Center and the Head of the Geo-oncology Consortium for START Cancer Research. I'm also an investigator for detalimogene. I've had the privilege of being involved in over 100 different bladder cancer research trials from all the aspects NMIBC through MIBC and metastatic urothelial carcinoma. And I've taken care of these patients throughout the entirety of my career. I'm really pleased to share my perspective today both as a community uro-oncologists and investigator, educator and author. So when you think about what happens in a typical community urologic practice, these patients with high-risk NMIBC, they usually in their mid-70s when they become BCG unresponsive. And not long ago, once a patient didn't recur after BCG typically with high-risk NMIBC, the shortages have really kind of complicated us to just treating this population now. The conversation really shifted very quickly to radical cystectomy which is pretty common place outside the U.S. and even was historically the U.S. perspective. And so that really is the sort of the standard of care in many parts of the world. But a lot's changed because while we recognize that cystectomy is an important option. There's no doubt about it, particularly in high-volume experienced centers, yet there still is obviously major morbidity and a real mortality in the short term. Patients don't really want to undergo a life-changing surgery that should be obvious to all on this call that has these risks of morbidity and mortality especially when -- if they're not having bladder voiding dysfunction in the setting of non-muscle invasive disease. So at the same time, physicians don't want to see their patients progress to muscle invasive bladder cancer, which is a real inflection point in the bladder cancer journey, where they will require more aggressive therapy, perioperative strategies, cystectomy, possible partials, et cetera. So the good news is that non-muscle invasive bladder cancer is often relatively slowly progressing to muscle invasive, although there is a real possibility for it in our high-risk patients. And we've had numerous recent pivotal studies that have shown the rate of progression to muscle-invasive disease can be kept stiff with appropriate monitoring into the single-digit percentages, which gives us an opportunity to intervene with additional therapies and potentially preserve the bladder longer. So what I've seen changed dramatically over the last several years is the emergence of new BCG unresponsive treatment options, which I think has been fantastic for the field and really kudos to all the investigators who've been part of that and really appreciate the FDA's forward thinking in their approval strategy. So we're moving to a world where patients were quickly referral for bladder removal to one where especially in the United States, patients may be sequenced through multiple therapies before considering cystectomy. That is clearly the state-of-the-art right now. I think it's better for patients. It also now allows community urologists, uro-oncologists and medical oncologists to play an increasingly important role in managing these patients, where here before, they were very rapidly shifted off to academic medical centers. And with this increasingly important role, community practices want to do what they can to avoid that referral both because for multiple reasons, convenience for patients, there's always autonomy issues. There are clinical and economic modeling that can be mutually beneficial. Patients prefer to have this. They like this continuity of care. They have a trusting relationship presumably with the patient and the provider team, which has been built over many years of surveying the non-invasive bladder cancer. So at the same time, the treatment landscape is becoming therapeutically more complicated, more crowded, thanks to all the recent approvals. And most community urologists are not strictly focused on bladder cancer. They have other geo-oncology and non-oncologic focuses. So they're managing the full spectrum of oncologic and non-oncologic disease while caring for a high volume of patients. So as more therapies become available, it becomes increasingly difficult to stay current on the nuances of every product, the different MOAs, the side effect profiles, the resources required, pending J codes, et cetera, and reimbursement. So physicians in my opinion, will naturally gravitate toward therapies that they understand well, including their administrative teams that have simple administration profiles, less scheduling toxicity, fine toxicity for patients and what's going to be least disruptive to their practice flows or what some people call the throughput. So when it comes to adopting new therapies in community practice, I think we have really 3 types of toxicities. I've sort of mentioned them, there's the logistic toxicity, the personnel toxicity. How many medical assistants do you have? Do you need to have an RN to administer. Can it be done at LPN? What is the requirement for a physician oversight and then, of course, time toxicity to the patient. More and more I see this not only in high-risk NMIBC but throughout all aspects of geo-oncology. So logistical toxicity includes the storage, the handling, the operational requirements needed to deliver a therapeutic safely and efficiently. For the viral therapies, practices need to consider freezer capabilities, thaw time, sometimes ventilator hood requirements, PPE requirements. And many of these really vary on a state-by-state basis and regulation regarding preparation and administration. So that also has to be understood on a state or local investigation. Personnel toxicity is equally important. So what do I mean by that? Community practices continue to face physician shortages, particularly in uro-oncology, we see shortages in nurses and nursing turnover. Nursing Services are highly sought by competitive hospital-based centers and other forms of the health care community competing for their services no longer just working in the hospital and in the physician's office. And there's also the limited staff bandwidth for many of the patients or I should say, the personnel who would want to work in practice. So the drug device combinations, for example, which have been highly effective, they require procedure room time, urologic physician involvement and some staff resources to further manage the adverse event profile. Community practices have to carefully evaluate how much additional burden any one of the approved and pending approval therapies such as detalimogene places on already stretched administrative personnel, clinical and workflow concerns. And I mentioned time toxicity. The treatment frequency, the schedule of events that patients have to endure, I am asked this on a repetitive basis now, not just in bladder but also throughout geo-oncology. So the dwell time, the procedure time and the overall time spent in the clinic will have an influence on patient decision-making as well as their experience. So from a practice standpoint, room utilization in the clinic, the physician's time, nursing time, allied personnel, LPNs, MAs and the patient throughput are really critical considerations right now in this field. And we're all learning contemporaneously. So detalimogene features fewer induction doses than traditional BCG and the potential to reduce with their new surfactant protocol dwell time from 60 to 30 minutes. And I think that's going to be really interesting to see and certainly hopeful that it has comparable, if not even improved efficacy. So beyond these toxicities, physicians must also consider economics and reimbursement. We heard a very nice analysis. There's the sort of spectrum between the economics and efficacy. That's just a real-world consideration undoubtedly. So how is the product acquired? What are the cash outlays. What is the net cost recovery. This is where the health economics to the practice bottom line becomes very germane. These questions matter because even though a therapy can be remarkably clinically attractive, if a practice cannot operationalize, it cannot justify it, absorb the financial risk, it can impact adoption. That doesn't seem always fair, but that's just the cold reality of it. And of course, patients must consider the burden placed on the patient, tolerability, visit frequency. I alluded to already post-treatment precautions such as the GU hygiene for bleaching, et cetera, in the home and other additional caregiver and patient instructions. And the lifestyle and impact all become important parts of the shared decision-making process. And shared decision-making is now the standard in which we have to have this very important conversation with patients and their caregivers. So in a world with increasing options, patient provider discussions around treatment goals and options, they continue to burgeon and patients are highly involved in the decision-making process. They're much savvier than they ever were clearly with not only AI and social media, but also it's just the access to information and education. I can present multiple options to a patient, but ultimately, it's the patient who must decide which treatment fits their goals, lifestyle, family and tolerance for risk and burden, how risk averse or risk-seeking are they? If there is still work to be done to always ensure that patients in community settings have access in the same range of options as we see in our tertiary centers, in our academic centers, that's ultimately goal, the north star for what we do. So when I review the data on detalimogene to date, what stands out is the overall profile. So taken completely in context. So we saw at AUA 2026 in May. My colleague and good friend, Ashish Kamat, he presented the efficacy data. The most recent appears to be tracking towards the level of efficacy we've seen with other approved therapies, for example, in adstiladrin, while potentially also offering a very safe and tolerable profile with limited schedule of events. So these attributes to me and my colleagues are going to be very appealing. I think in a disease that generally progresses slowly, if monitored carefully, many will be inclined to use therapies that are going to be better tolerated, easier to incorporate into a busy personnel constrained practice. So if we can determine with ease, whether a patient is responding early or not, then -- and it's well tolerated, that's going to give me a lot of confidence that I can continue in that therapy -- in that patient's bladder cancer journey or if not, go switch to something else. And I think that's a really big interesting dynamic in developing field this area of sequencing prior to saying, okay, I'm throwing in the towel and I'm proceeding to radical cystectomy. So my goal as a practitioner, as a prescriber is to help patients and their families avoid or delay cystectomy whenever it's safe and appropriate. Does it require expertise by all the practices and a team to do it. Patients want to preserve their bladder. They want to maintain their quality of life. They want treatment close to home. The therapies that will be most successful are those that can deliver meaningful efficacy and recognizing that they need to fit into the realities and practicalities of both patients' lives and as already said 80% to 85% of this is going on in community practice. So I'll just conclude and say that what I've seen so far, detalimogene has very strong potential to be a competitive option for these patients with high risk NMIBC. So with that, I'd like to hand it back to you, Ron.

Thanks, Dr. Shore, for sharing your perspective. So in summary, we hope that today's event has provided you with greater insight into the NMIBC market. I would close by highlighting our belief that the BCG unresponsive market is larger than we believe. Their current animal sequencing and community practices event of viable new therapies will drive sequencing and drive the prevalent population. There are different types of community practices where the detalimogene profile is uniquely suited even with varying efficacy profiles. There's a new price point for these therapies, which is near $700,000 a year. At this price point, a therapy requires only around 2,000 patients in order to generate over $1 billion in revenue. In conclusion, detalimogene's efficacy to date, tolerability and simple handling may provide a unique offering to a large swath of community urologists who are currently limited in viable options that they can integrate into their practices. We look forward to our plans to meet with the FDA later this half and initiating our BLA submission this year with a potential approval and platform designation in 2027. So with that, I'd now like to open the call up for questions.

Great. Thank you, Ron. Yes. We'll be conducting a question-and-answer session with our speakers. [Operator Instructions] So our first question comes from Maury Raycroft at Jefferies.

Maybe just starting off for Dr. Shore. Dr. Shore, given the similar efficacy profiles we've seen with adstiladrin and detalimogene, can you discuss percentage of your patients currently get adstiladrin versus other approved treatment options as a reference point?

Sure, happy to. Yes. So we're fortunate to have now accessibility to adstiladrin, Opdivo, inlexzo, I'm using the commercial names here as well as KEYTRUDA for these BCG unresponsive patients, CIS, CLS, papillary. And we also have several ongoing clinical trials, including detalimogene. I have about 15 partners. We don't mandate one particular protocol. We look at the patient and we say, we have access to these varying therapies, assuming that their insurance/accessibility is not an issue. We describe to them the workflow. We describe to them the time commitment. We describe to them the different adverse event profiles, which each does have. And so it's somewhat evolving because of the recent approvals and getting the J-codes in position. I would say we're using all of them. We try not to be -- we don't reflex to one versus another, and that's probably -- and I'm not -- I hope I'm not sound like I'm avoiding your question is that we like to do clinical trials. We did it in all of these drugs that have been approved I'm certainly optimistic that detalimogene will get approved. And then we meet and we discuss with not just the physicians, the team that's doing the administration. And we also then to look at the economics as well as how our patients are experiencing it. So I would say, right now, we're -- without giving you exact percentages because I honestly don't have them at the tip of my tongue, I would say we're probably almost equivalent in the approved therapies with the exception of using pembrolizumab.

Okay. And so yes, I guess, it's difficult to provide like a reference point percentage of patients at this point.

Well, I would say percentage-wise, 98% will get a BCG unresponsive therapy or clinical trial. And looking now at it, if someone finds one intolerable or there's some other reason not to continue with it, we are 100% sequencing. And that's a really interesting and evolving field. There's not a lot of prospective clinical trials on that. And I do think we'll start to see that going forward.

Yes, makes sense.

I think Maury, Dr. Shore is indicating pretty much equal between the approved agents.

Got it. Yes, makes sense. And then maybe just one other question for the company and maybe for Dr. Shore as well. Just wondering how you characterize the optimal pricing sweet spot for NMIBC drugs, recognizing that while a higher price can drive stronger economics, it can also create some cash flow constraints for certain practices. So how should we think about that, especially relative to detalimogene.

Yes, Maury, it's Amy here. I can take that. So I think with pricing, pricing is always one of the last things that you do. However, I think what we've heard from payers and HCPs is that it's about understanding, really understanding that kind of the reimbursement part and the prior authorization part. And I think once you have those pieces kind of completed, then what we've heard is around the net cost recovery is it it's the same whether you have a price point at a lower price point or at the higher price point. So once you've had to get over the hurdles of prior auths, reimbursement, that helps to kind of understand the kind of marketplace. So whilst we haven't kind of got to our pricing yet, I think what we've been able to show is it is an evolving marketplace.

Our next question comes from Sean McCutcheon at Raymond James.

For Dr. Shore, does the market research that was presented today parallel your view on sequencing and use of 3 to 4 novel therapies ahead of radical cystectomy. And can you speak to your experience and preferences with sequencing and with the currently available therapies. And then separately, have you seen pushback from payers to this end?

Thank you. I appreciate that question. Yes, as a researcher and as a clinician, I find this to be remarkably exciting field. We sometimes say it's a bit of an embarrassment of riches. We went from virtually nothing, radical cystectomy, overutilization of BCG and BCG with some chemotherapy to now having really efficacious novel MOA therapies. And so in our practice, I'll just speak to my 3 decades of being in this when I -- in my most last few years with these approvals, when one BCG unresponsive therapy isn't working. And based upon a repeat biopsy and the patient has persistent high-grade disease, not necessarily muscle invasive, but TAG3 or CIS or T1, they're like, well, unless they have a dysfunctional bladder, they're like, okay, "what else do you have for me, doc?" And I say, we've got 2 options. We've got standard of care therapies, and we have clinical trials. And they're like, okay, I want to hear more about that. Because it's a very morbid procedure to have your bladder removed and have to wear an ostomy and/or have a continent diversion. We have had some trials recently, and I participated in it, which patients can get through that surgery without complication, they actually can do pretty well. That said, it's still obviously one of the biggest life-changing, body changing surgeries that we do. And in the community, they're being performed less and less. So yes, patients will want to have the discussion for further sequencing. And that has been the experience. I think that will continue to be the experience. It's early days. Many of the smaller groups, and there's still a few thousand of them out there in the United States, are learning through our conferences and through educational events to learn how to do or to bring into accessibility within their clinics. And that's where I really think that the surveys that you heard from Amy 100% resonates with my experience. We have tremendous heterogeneity in the clinical workforce. It's a very different world to be part of tertiary academic centers, typically in metropolitan areas, they see 15% of the patient population with bladder cancer and frankly, for all oncology. And then you get into that other 85%, which I thought the breakdown of those 4 groups was frankly, brilliant. And we talk about it all the time, the issues of the real-world implementation, workforce issues, the economics and the efficacy. So I 100% agree with everything that Amy laid out to you. I think that to their credit, they did a very nice job in their interviews and their surveys.

And maybe just to follow up, have you seen any payer pushback on sequencing of some of the recently approved therapies?

Yes. Thank you. I knew I missed that one. Sorry, I personally have not, especially if I -- and if to say, okay, well, then we have to proceed to cystectomy. I have not had a pre-auth discussion with any physician from any of the different insurances that we used, including managed Medicare.

And I would just add there that of all the payer interviews that we did, there wasn't any kind of pushback. And again, as I kind of highlighted in the presentation, if you are included in the NCCN guidelines of 2A and above, you would get reimbursement.

Our next question comes from Andres Maldonado at H.C. Wainwright.

So maybe one question for Dr. Shore. It would be great to get Ron's opinion on it after. As we look at the NCCN guideline inclusions, how different were those data packages submitted to the NCCN guidelines committees across those agents? And I guess trying to get a sense of beyond efficacy, what seemed to matter most to those committees. So if a 2A recommendation was enough to get to the broad payer parity, what are some of the other things outside of the obvious efficacy and safety that those committees weighed across those packages. And have you identified any maybe imbalances or inefficiencies that detalimogene's package could leverage to get into those guidelines more effectively?

Andres, I think I'll just take that one. Quite frankly, when you look at products that have been approved and the products to come, we're all following the FDA guidance for how we conduct our trials. Now there are some subtle differences in inclusion criteria and exclusion criteria and in the protocols. And I think what we've seen from an NCCN perspective, since they're relatively standard, that is what they've used to determine whether inclusion within the guidelines. So we would expect since our approach is similar to those that have been except for NCCN guidelines that we would achieve those guideline inclusion as well.

Great. And maybe one quick one for Dr. Shore. Obviously, the sentiment is to avoid bladder cystectomy. But for those community urologists that tend to perhaps be slightly more aggressive on when they recommend radical cystectomy to a patient. Can you just maybe on a broad level, explain to us kind of what are some of their genetics? What is their phenotype of thinking, which makes them slightly more aggressive. Obviously, preservation is the key here, but we've come across some urologists that just tend to be a little bit more aggressive in that sense. Would love to get your high-level thoughts there.