Good morning, and welcome to the enGene Therapeutics call to discuss the non-muscle invasive bladder cancer market. At this time, all attendees are in a listen-only mode, and a question-and-answer session will follow the formal presentation. 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, and we're 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. and Canadian 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, timing of 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 and 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 therapies, our expectations regarding how healthcare providers may use detalimogene, or sequencing of 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 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. Thanks, Lauren. 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 in-depth 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 perspective. Welcome, Dr. Shore. Before turning it over to Amy, I will provide a short overview. Our product candidate, detalimogene, is the only novel non-viral gene therapy being developed for NMIBC. It is administered intravesically to the bladder, where it delivers plasma DNA encoding three genes that activate the RIG-I pathway and drive expression of IL-12, synergistically 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 CIS patients. We'll also discuss the new detalimogene plus surfactant cohort, where we expect enhanced CR anytime, durability, and convenience, and the BCG-unresponsive papillary only disease cohort, where we expect to achieve NCCN guideline inclusion. We believe NMIBC is transforming into a rapidly growing market as more therapies become available, creating additional opportunities for patient sequencing and expanding the treatable patient population. In May of this year, we shared interim pivotal core data on detalimogene without surfactant during a preliminary session at the American Urological Association annual meeting. Only 55% of patients experienced a treatment-related adverse event, most of which were mild, of which only 2.4% were associated with dose interruptions or discontinuations, respectively.
For the primary endpoint, detalimogene without surfactant had an anytime complete response rate of 54%, which falls solidly within the range of approved products. Duration of response equal to or greater than 12 months, the key secondary endpoint, is still maturing. A landmark CR at 12 months KM estimate of 25% is similar to ADSTILADRIN, an approved product. As Amy and Dr. Shore will discuss, we believe detalimogene's overall efficacy, tolerability, and handling profile as the only non-viral gene therapy may provide a unique and desirable profile for integration across a number of community urology practice settings. Importantly, our non-viral 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 and the FDA CDRP, Chemistry, Manufacturing, and Control 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 may enhance the efficacy of detalimogene without compromising the tolerability 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 spasm. Looking ahead, we anticipate mature durability data will be available later this year, plan 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 four important themes. A growing NMIBC market supported by increased sequencing.
Two, a differentiated non-viral platform designed for community adoption. Three, a promising clinical profile to date. Four, the potential opportunity to further enhance that profile through the addition of surfactant. I would 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 have 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 have 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 six months, we have conducted multiple waves of market research, including over 65 urologist and uro-oncologist interviews, 15 payer interviews, 200 urologist and uro-oncologist surveys, and analyzed over 2,000 patient claims. We have 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, we can see these are some evolving topics that we would like to make sure we have insights on as we think about the high-risk BCG-unresponsive NMIBC market. The first three assumptions in any market model for NMIBC are pretty straightforward. Most of the literature and claims data would align on the first three inputs. An 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 four 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 have gleaned that are helping to inform our views around these dynamic market assumptions.
Slide 10 here reviews the two separate subcategories of high-risk disease, including CIS and papillary only, although the two can occur concomitantly. While papillary is typically resected via TURBT and then treated with BCG in the high-risk setting, CIS is multifocal in nature and difficult to treat surgically. In the next slide, when we are reviewing patient profiles of high-risk patients, it is important to understand clinical guidance as to how to treat high-risk patients. Treatment algorithms within clinical guidelines for CIS represent a wide range of patients, and it is clear that papillary-only 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 interviewed payers indicated that they would cover BCG-unresponsive therapies broadly with a 2A+ 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. There are currently approved therapies and others in clinical trial, but there is no one therapy that suits all patients and practices. In our HCP market insights and other published surveys from patients, there is a clear desire to avoid radical cystectomy. All our urologists interviewed stated that they would aim to sequence patients through three or four lines of therapy before performing a radical cystectomy.
Here, we have captured an illustration of how patients could sequence through three or four 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 of the prevalent population. This pattern has been observed in numerous therapeutic categories where innovation expanded the overall market rather than simply redistributing share. As new treatment options become available in diseases such as multiple myeloma, multiple sclerosis, and depression, more patients ultimately receive treatment and remained on therapy longer. It is well accepted that most patients with high-risk NMIBC are treated in community settings. However, through our market research insights, we've gained much deeper insights into different drivers of choice and practice needs.
Our findings also reveal that there is a slight difference in prevalence and incident rates with an estimated 75% of incident NMIBC patients seeking care in the 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 practices and have characterized these practices into four different categories: practices that are resource-limited, practices that battle with workflow and logistical constraints, practices that prioritize economics, and practices of clinical excellence. This has allowed us to sharpen our view of the percentage number of patients in the community. Here we can zoom in further and understand how patients 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 four distinct segments, of which three express meaningful preference towards adoption of a product such as detalimogene, where its efficacy profile, ease of use, and tolerability is uniquely well-suited. First, we have resource-limited practice where adoption of novel therapies is limited by cash concern. Second, workflow-constrained practices where uptake of viral therapies is limited due to infrastructure or logistical challenges of administration. Third, economic-focused practices where net cost recovery in consideration with efficacy drives adoption. Fourth, clinical excellence practices. Dr. Neal Shore, who'll be providing insights later, runs a 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 ADSTILADRIN-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 bill to acquire NMIBC therapies.
While economic-focused practices are keen to integrate novel therapies, the potential to provide a therapy that balances efficacy, tolerability, and ease of use to workflow-constrained 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. The ability to address these concerns will be an important factor. We believe it's key to note that there are a range of factors taken into consideration when pricing a product. When thinking about efficacy, there are multiple measures, including complete response as well as durability. Safety is, of course, important. INLEXZO , for instance, launched at a higher price point than ANKTIVA despite having less durability.
As noted on the slide, we've repeatedly seen similar pricing dynamics in the highly competitive I-O 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, WAC, 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, assuming NCCN guideline category of 2A. Importantly, private practice urologists clearly indicated that the net cost recovery is critical for building practice infrastructure and capacity. Generating a positive net recovery and efficient practice economics, particularly in a buy and bill marketplace, is both important and common across multiple therapy areas, not just urology.
On slide nine, we have an illustrative example of net sales for an approved NMIBC 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 algorithms for CIS patients could represent 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 would be willing to sequence and try up to three to four lines of therapy to avoid radical cystectomy.
This will create a compounding effect on the eligible patient 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, workflow-constrained, and economic-focused 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 therapies has moved up and allows private practices to build towards net cost recovery and efficient practice economics, as well as the important ability to offer patients bladder-sparing 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 GU 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 of 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-oncologist and investigator, educator, and an author. When you think about what happens in a typical community urologic practice, these patients with high-risk NMIBC, they usually present in their mid-70s when they become BCG unresponsive.
Not that long ago, once a patient did recur after BCG, particularly with high-risk NMIBC, the shortages have really relegated us to just treating this population now. The conversation really shifted very quickly to radical cystectomy, which is pretty commonplace outside the U.S. and even was historically the U.S. perspective. That really is 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 a 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 pretty obvious to all on this call, that has these risks of morbidity and mortality, especially if they're not having bladder voiding dysfunction in the setting of non-muscle invasive disease.
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. 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, if with appropriate monitoring, into the single-digit percentages, which gives us an opportunity to intervene with additional therapies and potentially preserve the bladder longer.
What I've seen change 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. We're moving to a world where patients were quickly referred 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 heretofore they were very rapidly shifted off to academic medical centers.
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 their non-muscle invasive bladder cancer. At the same time, the treatment landscape is becoming therapeutically more complicated, more crowded, thanks to all the recent approvals. Most community urologists are not strictly focused on bladder cancer. They have other GU oncology and non-oncologic focuses. They're managing the full spectrum of oncologic and non-oncologic disease while caring for a high volume of patients.
As more therapies become available, it becomes increasingly difficult to stay current on the nuances of every product, the different MOAs, the different side effect profiles, the resources required, pending J-codes, et cetera, and reimbursement. Physicians, in my opinion, will naturally gravitate towards therapies that they understand well, including their administrative teams that have simpler administration profiles, less scheduling toxicity, time toxicity for patients, and what's going to be least disruptive to their practice flows or what some people call the throughput. When it comes to adopting new therapies in community practice, I think we have really three types of toxicities. I've sort of mentioned them. There's the logistical toxicity, the personnel toxicity. How many medical assistants do you have? Do you need to have an RN to administer? Can it be done by an LPN? What is the requirement for a physician oversight?
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 GU oncology. 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. Many of these really vary on a state-by-state basis and regulation regarding preparation and administration. That also has to be understood on a state, a local investigation. Personnel toxicity is equally important. 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 healthcare community competing for their services, no longer just working in the hospital and in a physician's office. 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. 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. 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 GU oncology. 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. From a practice standpoint, room utilization in the clinic, the physician's time, the nursing time, allied personnel, LPNs, MAs, and the patient throughput are really critical considerations right now in this field. We're all learning contemporaneously. 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. I think that's going to be really interesting to see, and we're certainly hopeful that it has comparable, if not even improved efficacy.
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. 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. Of course, physicians and 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.
The lifestyle and impact all become important parts of the shared decision-making process. Shared decision-making is now the standard of which we have to have this very important conversation with patients and their caregivers. 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 could present multiple options to a patient, but ultimately, it's the patient who must decide which treatment best fits their goals, lifestyle, family, and tolerance for risk and burden. How risk-averse or risk-seeking are they?
Yet 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 and our academic centers. That is ultimately the goal, the North Star for what we do. When I review the data on detalimogene to date, what stands out is the overall profile, so taken completely in context. 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 toward the level of efficacy we have seen with other approved therapies. For example, ADSTILADRIN, while potentially also offering a very safe and tolerable profile with limited schedule of events. 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. If we can determine with ease whether a patient is responding early or not, and it is well-tolerated, that is 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, we can always switch to something else. I think that is a really big, interesting, dynamic, and developing field, this area of sequencing, prior to saying, "Okay, I am throwing in the towel, and I am proceeding to radical cystectomy." My goal as a practitioner, as a prescriber, is to help patients and their families avoid or delay cystectomy whenever it is safe and appropriate.
It does 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 was already said, 80%-85% of this is going on in community practice. I will just conclude and say that what I have seen so far, detalimogene has very strong potential to be a compelling option for these patients with high-risk NMIBC. With that, I would like to hand it back to you, Ron.
Oh, great. Thanks, Dr. Shore, for sharing your perspectives. In summary, we hope that today's event has provided you with greater insight into the NMIBC market. I would like to close by highlighting our belief that the BCG unresponsive market is larger than many believe. That there currently is minimal sequencing in community practices. The advent of viable new therapies will drive sequencing and drive up the prevalent population. There are different types of community practices where the detalimogene profile is uniquely suited, even with varying efficacy profiles. There is 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 net 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. With that, I'd now like to open up the call for questions.
Great. Thank you, Ron. Yes, we'll be conducting a question-and-answer session with our speakers. To our analysts that are joining us live, please use the raise hand feature under the reactions button on your Zoom to indicate that you have a question. Please hold for a brief moment. Our first question comes from Maury Raycroft at Jefferies. Please go ahead, Maury.
Hi. Great. Thanks for hosting this event. Thanks for taking my questions. Maybe just starting off with one for Dr. Shore. Dr. Shore, given the similar efficacy profiles we've seen with ADSTILADRIN and detalimogene, can you discuss what percentage of your patients currently get ADSTILADRIN versus other approved treatment options as a reference point?
Sure. Happy to. Yes. We're fortunate to have now accessibility to ADSTILADRIN, ANKTIVA, INLEXZO, I'm using the commercial names here, as well as KEYTRUDA for these BCG unresponsive patients, CIS, papillary. We also have several ongoing clinical trials, including detalimogene. I have about 15 partners. We don't mandate one particular protocol. We look at a 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. 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 don't reflex to one versus another. I hope I'm not sounding 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. Then, we meet and we discuss with not just the physicians, the team that's doing the administration, and we also then, too, look at the economics as well as how our patients are experiencing it. I would say right now, 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. I guess difficult to provide 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. Looking now at it, if someone finds one intolerable or there's some other reason not to continue with it, we are 100% sequencing. 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.
Yeah, makes sense.
I think Maury, Dr. Shore is indicating pretty much equal between the approved agents.
Got it. Yeah, makes sense. 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?
Yeah, Maury, it's Amy here. I can take that. So I think, with pricing's 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 really understanding the reimbursement part and the prioritization part. I think once you have those pieces kind of completed, then what we've heard is, around the net cost recovery, is it's the same whether you have a price point at the lower price point or at the higher price point. So, once you've had to get over the hurdles of prior auth, reimbursement, that helps to understand the kind of marketplace. So whilst we haven't got to our pricing yet, I think what we've been able to show is it is an evolving marketplace.
Understood. Okay, thanks for taking my questions.
Thanks for the questions, Maury. Our next question comes from Sean McCutcheon at Raymond James. Please go ahead, Sean.
Hi, guys. Thanks for taking my questions. For Dr. Shore, does the market research that was presented today parallel your view on sequencing and use of three to four novel therapies ahead of radical cystectomy? Can you speak to your experience and preferences, with sequencing and with the currently available therapies? Then separately, have you seen pushback from payers to this end? Thanks.
Thank you. I appreciate that question. Yeah, as a researcher and as a clinician, I find this to be a 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. In our practice, I'll just speak to my three decades of being in this. 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 Ta, G3 or CIS or T1, unless they have a dysfunctional bladder, they're like, "Okay, what else do you have for me, Doc?" I say, "We've got two options.
We've got standard of care therapies, and we have clinical trials." 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 if 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. In the community, they're being performed less and less. Yes, patients will want to have the discussion for further sequencing. That has been the experience. I think that'll 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 bring into accessibility within their clinics. 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. Then you get into that other 85%, which I thought the breakdown of those four groups was frankly brilliant, and we talk about it all the time, and the issues of the real world implementation, workforce issues, the economics, and the efficacy.
I 100% agreed 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.
Maybe just to follow up, have you seen any payer pushback on sequencing of some of the recently approved therapies?
Yeah. Thank you.
Great.
I knew I missed that one on you.
Yeah, go ahead .
Sorry. I personally have not. To say, "Okay, well, then we have to proceed to cystectomy," I have not had a pre-op discussion with any physician from any of the different insurances that we used, including managed Medicare.
I would just add there that of all the payer interviews that we did, there wasn't any kind of pushback. Again, as I highlighted in the presentation, if you're included in the NCCN guidelines at 2A and above, you would get reimbursement.
Understood. Thank you.
Great. Thanks for the question, Sean. Our next question comes from Andres Maldonado at H.C. Wainwright. Please go ahead, Andres.
Hi, guys. Thanks for taking my question and for putting this presentation on. I found it very helpful. Maybe one question for Dr. Shore, and 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? I guess trying to get a sense of beyond efficacy, what seemed to matter most to those committees? If a 2A recommendation was enough to get you 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? Have you identified any maybe imbalances or inefficiencies that detalimogene's package could leverage to get into those guidelines more effectively? Thank you.
Hey, Andres. I think I'll just take that one. Quite frankly, when you look at the products that have been approved and the products to come, we're all following the FDA guidance for how we conduct our trials. There are some subtle differences, inclusion criteria and exclusion criteria, and in the protocols. 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. We would expect, since our approach is similar to those that have been accepted for NCCN guidelines, that we would achieve those guideline inclusion as well.
Great. Thank you. Maybe one quick one for Dr. Shore. Obviously, the sentiment is to avoid bladder cystectomy. 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 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.
Yeah, I really appreciate that question. Look, one of my partners is a fellowship-trained surgical oncologist, and he's trained to do radical cystectomy, robotic-assisted, both with traditional ileal conduit and continent diversion. There are many of these surgical uro-oncologists who are out there. I got into urology, frankly, because of my desire and love for doing cystectomies. When I was a medical student at Duke University, and I did a clerkship at MD Anderson Cancer Center, I found myself in that room all the time. That said, even in high-volume centers, there are some challenges. To your question, I have great respect for my colleagues who have great results. There's always the possibility and likely scenario that the surgical oncologist can list to their patients, "Oh, I saw too many patients who didn't get the right treatment, the non-surgical treatment at the right time.
Too much BCG, too much mitomycin followed by another chemotherapy, or so on and so on, or delays in follow-up, and then they showed up." There's a certain, to your point, the DNA, the perspective of patients who might have not had optimal experience. I don't want to lose the emphasis that these patients need to be followed and monitored very rigorously by physicians who understand the different therapies and the different options, and they need to have the team and the discussion with the patients. I think that could be part of that, and not to overly simplify it, but there's the old expression, when you have a hammer more and more things tend to look like a nail.
I don't mean to say that in any kind of disparaging way, but if you're really good at doing something and you know that you can get good results, I can understand that philosophy. I think it's not unreasonable, and that's why the shared decision-making conversation with an experienced cystectomist versus somebody who's really well-schooled as well in understanding all of these new novel therapies is going to be the state of the art right now.
Thank you very much.
Thanks for the questions, Andres. Our next question comes from Lili Nsongo at Leerink. Please go ahead, Lili.
Hi, thank you for taking the question. Maybe a question for Dr. Shore. As it was stated in the slide, BCG unresponsiveness, that has been quite difficult to estimate. I was wondering, how do you define unresponsiveness in your own practice? What portion of your patients does that represent, and how much BCG supply constraints have constrained your practice this year?
Yeah. I had the privilege of being part of the FDA workshop, gosh, several years ago, where we came up with this more codified definition of unresponsiveness, which is largely the 5 + 2 or the 6 + 6 in repeat induction after CIS. We are very good about recognizing that. That said, I wouldn't say that all of my colleagues have followed that. Even within my own practice, and regionally and nationally, we still see many patients who may not get the five of six induction, who may not get the two of three maintenance, and then they just stop for whatever reason. They didn't want to have a cystoscopy, maybe there was a BCG shortage, they were moving, et cetera.
It's been more than 12 months since they've had their BCG, so it's almost as if they get rediagnosed, then they're really starting from scratch. The BCG shortage has been vexing. We have been impacted by it. It's always somewhat unpredictable. Certain different parts of the country, whether it's southeast versus Midwest, Northeast, West, not everybody is hit at the same time. There is supposedly going to be a new plant coming online maybe by the end of the year or early next year, who knows, that'll have greater production capacity. We have been hearing that for some time. We all look forward to that. Additionally, we're hopefully getting other BCGs potentially approved, whether it's the Tokyo strain or the recombinant strains from the Serum Institute. I think that will certainly help. Split dosing. Some folks have done that.
We've not been very successful in doing that from a throughput standpoint.
Thank you. Maybe a follow-up on data interpretation, or I guess in comparing treatment options when just thinking of efficacy. My question is, how much weight do you put on CR rate compared to DOR and duration of response? Also, how much weight do you give progression to muscle invasive versus recurrence?
The progression rate to muscle invasion is very important. All therapies, we certainly look to make sure that they can delay that progression, delay the need for cystectomy, and do so in a way that doesn't result in metastatic disease. Again, that goes back to my comments about the importance of strict monitoring with these patients. I think that the different CR rates are a wonderful debate that we do in the community. We have a Bladder Cancer Academy that this'll be our 15th year we do that. We have panels and we discuss in a very realistic, real world experience, how do different providers describe this to patients to exactly your question. Are you just going to have the scientific clinical CR at six months, 12 months duration of response?
The answer to that is no, that is not what happens, is that we do have to talk about how is the therapy administered. Will it be administered intravesically, intravenously, orally? Are there devices related? How much time do you need to be in the clinic? It goes without saying the patients expect that we will take care of their benefits verification and pre-authorization. Then of course, the big question patients ask in addition to the schedule of events for them and the mode of administration is tell me about the safety profile. What can I expect? As a general rule, these are patients in their mid-70s now. Sometimes I think these are the young patients because I see so many high-performance patients in their mid-80s. So they are very much more attuned to the safety profile.
Lili, I would just add, from our market research, it seems that the community urologists are focused on the CR any time, so does the product work or not? Whereas the academics are more focused in the durability part of that. Thanks for your questions.
Great. Thank you, Ron.
Thanks for the questions, Lili. Our next question comes from Yanan Zhu at Wells Fargo. Please go ahead, Yanan. You might be on mute.
Sorry about that. Thanks for taking our questions. For Dr. Shore, I was wondering, when you weigh convenience and of the myriad of factors and toxicities that you highlighted, which is super helpful, including scheduling, personnel, patient time, logistical. Of all of that, if we can aggregate that as the convenience factor, if you weigh that against efficacy, I was just curious on two fronts. One, is there still a minimum efficacy profile that needs to be met? If so, could you articulate what that might be? Ron just mentioned anytime CR as something that a community doctor will focus on. If you can lay out a wholesome efficacy profile for a community practitioner, that would be super helpful. Then I have a follow-up regarding sequencing. Thank you.
Yeah, I think that, look, once a therapy achieves FDA approval and NCCN recognition or AUA or EAU, then it really becomes that shared decision-making moment. I think that certainly, having a CR in the mid 20% range at 12 months, it qualifies for discussion. Certainly, CRs at six months. Also recognizing that you are monitoring these patients. If you decide to move to something else, you can, and that's okay too. For patients, I'll just repeat. There is a segment of patients who are more data-driven. I think it's the minority who are savvy and sophisticated in terms of just looking at trying to do cross-trial comparisons, even though we always caveat that that shouldn't be done until you do the direct comparative prospective study. But that's the minority of the patient population. I'm not saying that they're any less smart or more smart.
They are more driven by the safety, tolerability, and convenience, and making sure, of course, that there is economic accessibility. Ideally, if you have all of those things, great efficacy, tolerability, schedule of events, mode of administration, delivery, then that will enhance the product profile.
Great. That's super helpful. You did talk about sequencing. So I was wondering, in terms of sequencing what therapy to use earlier rather than later, how does our earlier discussion about convenience and efficacy come into that perspective? Or it doesn't really contribute to the ranking, so to speak, or the ranking order in which the patient receive these therapies. For the company, it looks like in a slide deck, you have a hypothetical accretion at each sequence, second line, third line, and at each step, there is a 50% loss. Is that very conservative? I was wondering what went into that. Is that the patient no longer needing therapy and being in long-term response on the prior therapy, or is that because the patient progressed? Just trying to get a sense of, is this number very conservative or it's the best estimate that you currently have?
Thank you.
Why don't you take that, Amy?
Yeah. I think on the question of sequencing, and I think it's the 50% in that slide that you're referring to. I think that is our best estimate. Obviously, with everyone still understanding how these patients will be sequenced in the future, but we've looked at it from a range, and that would be the median range that we would highlight here.
Got it. And when sequencing these therapies, does the convenience, the efficacy factor come in and determine which drug is used first?
Yeah, I think as Dr. Shore indicated, these are holistic discussions with his patients, and I think that's what our market research says to individuals. As you go through the mix of, here's the efficacy profile, here's the tolerability profile, here's the burden of how often you have to be in, here is the post-treatment requirements. That's a holistic decision. That's where the balance comes in. Thanks for the questions, Yanan.
Thanks, Ron.
Great. Our next question comes from Judah Frommer at Morgan Stanley. Please go ahead, Judah.
Yeah. Hi, guys. Thanks for the presentation and for taking the questions. Maybe for both Dr. Shore and the company, maybe just thinking about the 12-month data that we'll get in the back half of the year, anything we should be looking for there that could impact decision-making in clinic post a potential approval? And then how could the surfactant bladder rinse cohort and time to data there impact a potential ramp in the commercial setting? Do you have a sense that docs may be waiting for that surfactant bladder rinse data and potentially an updated protocol, or do you think that conversations are already productive just with the data that's in hand thus far? Thanks.
Yeah. Let me take both of those, Judah. I think that when we gave our presentation earlier this year on the AUA data, what we were saying is the data looks like with a 54% CR rate at any time, that is in the range of approved products. From a durability perspective, Kaplan-Meier said that the 12-month landmark, which is not a secondary endpoint, and it is not a promotable endpoint, we are trending towards the ADSTILADRIN profile. Then the durability is still to come. You see the range of approved products, that is within 40%-50%. I think that when the FDA looks at our total durability package, that we feel that we will be in a fileable zone. Nothing really different than what we shared before.
I think as it relates to the surfactant, because we have selected polidocanol, which is an already approved agent, has a lot of safety data. If you look at the other gene therapies, they have used a surfactant to increase expression. Without a surfactant in preclinical models, they get very little transfection. With the surfactant, they get a boost in transfection. We have seen a pretty significant boost in transfection in our preclinical models, and so we are already up and going with a surfactant cohort. There is a lot of enthusiasm within the medical community, within the research community. The first part of the protocol is a safety run-in, the first time we take it to patients. So we are looking forward to updating the market later on.
But we would anticipate that we will get a detalimogene-only approval sometime in 2027, and then we will supplement that later on with surfactant data.
Thanks.
Great. Thanks for the questions, Judah. Our final question comes from David Dai at UBS. Please go ahead, David.
Great. Thanks for squeezing me in and doing this presentation. Very helpful here. I have two questions for Dr. Shore. The first question, just around, Dr. Shore, are you using all the approved therapies right now? If you can just give some numbers around, let's say, there's 100 patients that are BCG-unresponsive, what percentage of these patients are receiving each of the approved therapies? Secondly, on sequencing, one thing you mentioned is just you're looking to get detalimogene into different sequencing in bladder or BCG-unresponsive patients. How do you envision the detalimogene would fit into the different sequencing in BCG-unresponsive NMIBC patients? Are these going to be second line, third line, or fourth line?
Hi, David. Maybe the first one Dr. Shore answered previously. Just to reiterate, I think his comment was that each patient they have a dialogue with, and in the new therapies, he's been using the products equally. Maybe you want to make a comment about sequencing, Dr. Shore.
Can you put us on the phone?
Yeah, I think that I like the sequencing question. That's evolving. Look, the first of these that came on board was, many years ago now, was the Pembro. As somebody who was embracing IO therapy, I actually used it a fair amount, and that never took hold in the urologic community, I think primarily at the time because of concerns and a requirement for education on immune-related adverse events. That's changing. I was involved with the development of ADSTILADRIN and ANKTIVA, as well as INLEXZO. INLEXZO just most recently in this year got its J-code, that our adoption for that has started to increase significantly. The ANKTIVA we've started to use as well, especially since we've had access to the recombinant BCG.
And then, of course, ADSTILADRIN really because of its early adoption or its early approval and our involvement in the trials was taking sort of the bigger share. I would say that is all sort of to some degree redistributing, and it is an evolutionary process. And we still in some patients will do intravesical chemotherapy as well.
Thank you so much.
All right. I think we wrap it up there, operator.
Yep.
All right. First of all, many thanks, Dr. Shore. Thank you, Amy. Thank you all for joining us. We look forward to providing additional updates later in the second half. Thanks for hanging in a little bit late with us as well. Have a good day.