Cgcology Inc Aktie

All right. Good afternoon, everyone, and thanks for joining us here at the Goldman Sachs Global Healthcare Conference. Thrilled to be joined on stage today with Arthur from CG Oncology, Chief Executive Officer. I'm going to turn it to you first to just kind of introduce the company and talk about what you think about as key value drivers over the next 12 to 24 months.

Sure. So we're a company that's laser-focused on developing our oncolytic immunotherapy, cretostimogene, for patients with both intermediate risk as well as high-risk non-muscle-invasive bladder cancer. And we have a number of catalysts coming up. Most importantly, we have a Phase III randomized controlled trial called PIVOT-006. Its results will come in the coming months. Shortly thereafter, we are guiding to complete our [indiscernible] setting. And really towards the back half of this year, there will be additional data around durability of our product in the BCG unresponsive setting as well as when we combine it with gemcitabine, additional durability updates will be available as well.

Great. So maybe let's start kind of at the highest level. As you look at the non-muscle-invasive bladder cancer category, can you talk about how you see the unmet need and how patients are kind of stratified within that indication?

Sure. So in general, bladder cancer is split into both non-muscle-invasive bladder cancer, which is about 80% of the opportunity and 20% are in the muscle-invasive category, of which that contains some metastatic patients. The bulk of the opportunity is still in NMIBC. Within NMIBC, we see 70% of that being the target population that we're going after. So that's in the intermediate risk category as well as the high-risk category. And the risk categories are just a way to describe the likelihood of progression into a higher-grade disease or eventually muscle-invasive disease.

Okay. Great. And then as you think about kind of the unmet need and how patients are treated today, what are the goal -- like what do you think is the kind of goal for new therapies entering the market and particularly cretostimogene?

Sure. So we'll start with high risk. Within high risk, the standard of care for frontline patients who are BCG naive is BCG. And so following BCG therapy, you fall into this BCG unresponsive category or BCG-exposed category, right? We'll just start with BCG unresponsive. The goal of therapy here is to prevent radical cystectomy. That's the ultimate treatment objective, which is so that patients can keep their bladders as long as possible. And so there are a couple of approved therapies now. I still think our target product profile represents really the strongest profile in that category. And in terms of BCG exposed, this is an emerging category that really based on the FDA definition of unresponsive, we think it's a bit stringent.

It does kind of leave and carve out this population that's neither naive nor unresponsive that we're seeing as an emerging kind of category that the agency has also recognized as an important bucket of patients. In terms of intermediate risk, the goal is to prevent multiple recurrent TURBTs, transurethral resection of bladder tumor, right? And that's a procedure where the urologists have to go in and resect the tumor in the OR. And oftentimes, these tumors continue to recur to the point where the bladder has been scraped so many times, sometimes it's also less functional than before.

Okay. Great. So maybe let's drill down into the BCG unresponsive category because it's the most advanced of your development programs. Maybe just remind us of the drug's profile. You mentioned it being potentially best in category and the clinical data to date that you've shared.

Sure. So in BCG unresponsive NMIBC in the CIS cohort or the carcinoma in situ cohort, we have shown a greater than 75% CR rate, closer to 76% complete response rate at any time. And at 12 months from a landmark analysis standpoint, we've shown a 46% complete response rate. Most notably, if you go from 12 months to 24 months landmark, cretostimogene as a monotherapy still had a 42% complete response rate. So you'll notice that there is a tail from 12 to 24 months, and we continue to highlight that as one of our key differentiations versus others. And that's really driven by the MOA and of the oncolytic immunotherapy that we think is causing that long tail that you typically don't see with chemotherapeutic approaches.

Great. And you mentioned, obviously, that one of the differentiating features is that duration. Can you contextualize that duration of response versus what we've seen from many of the other programs in development or approved?

Sure. So when we think about the different ways to kind of cut that data. But if you just take sort of this landmark analysis at 2 years, right? So KEYTRUDA has a 9% complete response rate at 2 years. Nadofaragene, another product is probably in the 20% range. And then ANKTIVA is in the kind of 20% range. We don't know yet what TAR-200 has shown at 2 years, but hopefully, we get to see that at some point.

Great. In addition to the clinical data, one of the things we hear a lot is that patient experience really matters, physician experience really matters in administering these products. How does the delivery of cretostimogene compare to some of the other agents in the category? And could you talk about kind of the infrastructure requirements that would be necessary for a physician's practice to administer the product?

Sure. So we've made a lot of improvements over the delivery as well as the storage conditions of cretostimogene. One of the things that we heard from our customers directly is that, hey, not everyone has an ultra-low freezer. These are freezers that are minus 60 to minus 80. So we developed this new storage condition that allows us to take a product out of the freezer and put it into a regular fridge at 2 to 8 Celsius, which is a regular fridge. And in that condition, the product can stay stable from 4 to 6 weeks, right? So that is an amount of time that we believe is necessary for this product to not have that as a barrier. Other than that, this product does not require any change of workflow. If the site can administer BCG, it typically flows right into that workflow without any retraining that's required.

One of the things we've heard is kind of the dwell time consideration. So maybe you could talk about the amount of time a patient will be spending in a prescriber's practice versus some of the other workflows that are out there.

Yes. So from a standard of care of BCG, for example, is up to -- on label requires a 2-hour dwell time. In practice, people only dwell for maybe an hour. And really, after the first visit, typically in the second visit, they get instilled BCG, which doesn't take long, maybe less than 10 minutes, and then they would just go home and void at home. So we envision that currently in the clinical trial setting, the dwell time is roughly 15 minutes with DDM, a transduction agent that we use before we give credo. And credo is probably up to 45 minutes an hour dwell time, right? So all in, an hour and 15 minutes. And after that, they could go home or they -- typically, right now, they're staying in the waiting room, right, which opens up that space for the second patient to come in. In the future, of course, we could envision a case where the dwell could be done outside of the clinic, right, which is kind of more in line with how BCG is done.

Right. In terms of like the specific subgroups within BCG unresponsive and maybe CIS, papillary-only, any mixed patients, I guess, are there any particular populations where you think the profile of credo is particularly differentiated?

I think that's a great question. So our BOND-003 pivotal trial, we had the highest in the kind of most heavily pretreated population. So unlike other competitors, we have a lot of patients with prior chemo in addition to failing 2 courses of BCG and so I'm referring to patients who failed gem or Gem/Doce. And even in that category of patients, credo continues to show a very consistent response rate. And so that is a data that we're certainly going to lean into as we think about the launch and profiling different accounts, both academic and [indiscernible] large urology group practice sites. That's certainly one aspect that I think is quite unique.

Okay. So then as physicians look at, they now have a couple of therapeutic options that they can pick from. How do you think they're going to pick which products they'll use? And are there any -- like what portion of patients then do you think will see credo at some point during their course of treatment?

Yes. I think ultimately, they care a lot about safety and efficacy, and that's kind of the base case. And then whether it requires a lot of modifications or changes to their work durations are sort of the bare minimum that they think about. Therapies, you can look at the 1-year landmark. And it's easy to see that greater than 60% of those patients and perhaps even more, some therapies up to 80% would have recurrence within the first year. So in those instances, it's not going to be a situation where the site just sticks with one therapy and they only use that one therapy. So there certainly will be a sequencing play here. Of course, I think the target product profile, the durability will all play a role here. In terms of -- there are some sites who just are really accustomed to giving chemotherapy. And if we have data that shows even after that, credo could still work really well. That's also another consideration for us because certainly, you don't want to give more chemo after initial chemo.

So you're now on track, I think, for a filing in the fourth quarter of the year. Could you maybe provide some additional color on your confidence that you've satisfied the regulatory requirements that you need to kind of satisfy for a filing, both with respect to the clinical data, which we've just discussed, but also the manufacturing piece?

Yes. So on May 8, when we put out the press release, this was in the context of having a prior FDA alignment meeting. And in that meeting, it was entirely manufacturing focused, and we discussed expectations and alignment on what needs to go into the content of our CMC package. So coming out of that meeting, we felt like all the questions we had were clarified. So we know what needs to be in there from a drafting standpoint and content standpoint. So that workflow continues to be ongoing. And of course, we have a separate work stream that we continue to discuss with investors that we care a lot about inspection readiness.

So this really goes hand-in-hand with the content that we're putting in. Essentially, after we've completed the filing, we do anticipate the FDA to come and inspect all of our manufacturing partners. And we're putting a particular emphasis and focus on the site that we acquired last year. This is the fill and finish site. And so we're doing a lot of preparation work on that. And so that work is ongoing, and we feel like from now until that's going to be sufficient time for us to get them ready.

The area that you focused on has been the site that you acquired, which is primarily, I think, focused on fill and finish. But one of the more traditional areas of manufacturing challenges is maybe not the right word, but is on manufacturing an oncolytic virus. What's your level of confidence that you've satisfied the requirements on that piece of the manufacturing process?

Yes. So we're very confident that there's alignment with the FDA in terms of what tests we need to use for analytical release. Thankfully, we only have one transgene. So it's very easy to develop an assay that looks at that. So that work has already been completed. In terms of the yield and scale that we currently have, it really from an initial launch standpoint, we believe that covers the early years of launch. So there's no changes that would be necessary there. So in general, I think we're very much aligned on the virus manufacturing component.

Okay. Great. Maybe as you think about filing and then preparing for a go-to-market in the next year, how are you thinking about price in the market with the eye to the broader development strategy that you guys are engaged in?

Yes. Pricing is an interesting topic. We've not provided formal guidance on this. But when you think about pricing, safety and efficacy plays a huge role as well as the benchmark of approved therapies, right? And so -- in general, I think in terms of kind of the ranges, on the low end, it's about $260,000 for 1 year, high end $700,000 for 1 year. I think directionally, we'd probably be on the right end of that spectrum. But again, a lot of it still depends on how our intermediate risk data will read out because it's all linked. It's 1 product for 2 different indications.

So how -- let's say that PIVOT-006 does work. What are kind of the important considerations in terms of pricing differential across the 2 markets?

Yes. So first of all, I would say we've already done the dose deescalation when you go from a high-risk disease, which is 30 doses over 3 years. With intermediate risk disease, we cap it at 1 year or 14 doses. So we're aligning on total length of therapy being half of what it's used in high risk. Of course, there's always the first year kind of treatment total cost consideration as well that will be very important to look at as well.

Okay. Great. And are there good kind of pricing analogs for the intermediate risk setting that we should keep in mind?

Well, not yet because no one has done a randomized controlled trial in the adjuvant setting as broad as we are doing, right? Competitors have so far priced in the ablative setting.

How are you thinking about sizing your commercial infrastructure? And what can you share regarding sort of the physician targeting efforts that you need to take on?

Sure. So when we look at kind of launch analogs in the space, I think everyone sort of comes out to be around the 50 to 75 field force range. I would say, based on our own internal analysis, we're in that range as well. And it's really largely due to the concentration of customers, right? The key accounts, roughly 300 network sites, they cover about 80% of all the business opportunities. So when we think about that, just in those accounts, it's roughly a 50-50 split between academic and community urology, largely private equity-backed LUGPA groups.

And a lot of it has to do with the BCG shortage and that compounds over time because if you don't have patients who need BCG, it's hard for you to order BCG. So that issue have basically led to sites referring patients to sites that have flow and have access to BCG. So it kind of compounds over time. So when we think about that split, we think about what is the current practice pattern that they're already doing? Is it Gem, Gem-Doce? Is it any of the branded products? So we're setting the post -- pre and post J-code dynamics there as well.

Okay. Great. And in terms of like other launches in NMIBC, there's a couple that have happened recently. I guess what have you watched and observed in terms of how they've done and things that you would then apply to your own commercial strategy?

Yes. So I would say the -- obviously, the most recent launch is INLEXZO, and we're tracking them very closely. I think reimbursement confidence continues to be a key thing that we look for. Which are the sites that are the early adopters who are waiting on the sidelines for a J-code, right? That information, I think, is very helpful for us to study. And now we have not only the INLEXZO data, we also have ANKTIVA and nadofaragene data. So that's going to help better inform our kind of initial targeting strategies.

So a lot of our profiling work of these key accounts have already begun last year, and we're going to continue to do so into the potential launch next year. And really, the focus is to really figure out like what were the hurdles and what were the experiences that weren't so good or were really good and how can we make sure we apply those learnings to our launch. And really, I think just ensuring our customers that, hey, we're here to partner with them in terms of reimbursement confidence, having the right field reimbursement support, I think it's going to be a very important thing to do.

You mentioned earlier that you've done a lot of things to make the product profile more physician and patient friendly. But I think sometimes there had been like a gap in what physicians were aware of that you guys had made progress against. As you look at the educational gap that you still need to overcome, are there specific areas where you think people agreeing to drive a better understanding of that TPP?

Yes. I think it's -- of course, some of the improvements that we made in the storage condition may have been -- has been like broadly disseminated. So that's certainly an area of focus. I would say in the coming months, once we have the data for PIVOT-006, I think that's also another area that will be kind of a new piece of information that these doctors haven't necessarily been exposed to before, right?

You mentioned this at the top that you're developing cretostimogene in combinations as well, including in the same setting. Maybe you could talk about the role that those combination programs play within the context of your broader development strategy.

Sure. So on one hand, in the intermediate risk category, we are already at the most upstream and top of the funnel in terms of patient flow, right? These are BCG-naive newly diagnosed or recurrent IR patients, right? So PIVOT-006 covers that patient segment. In terms of high risk, BCG-naive patients, they all get BCG and then they flow into exposed or unresponsive. We have our pivotal program, that's the first BLA that covers BCG unresponsive. Now what about the BCG-exposed patient population. In our own clinical trial experience, we had to turn away many patients who don't fit the unresponsive criteria.

So we believe this category of patients is emerging. And currently, there is no on-label therapies for those patients. So our current strategy is both with mono and combination of credo and credo gemcitabine to see if there's any added benefit of credo gem in the exposed category. The early data that we've shown at AUA, which is in the CIS population, right? These are patients that don't get a TURBT. We saw about a 90% to 92% complete response rate at 6 months. So it's early, but definitely encouraging. We're waiting to see what happens in 9 months and 12 months. If that continues to be durable, I think it certainly helps us think through a pathway in the exposed category. And in which case, some randomization would be necessary, so then we can get the TaT1 patients who are BCG exposed on label as well.

Can you talk about the different segments of this population and where you might be able to pursue a guideline strategy versus a registrational strategy?

Sure. So in BCG unresponsive disease, currently, you can only get a label with the CIS containing disease because surgery is not required. And then with TAT1 disease, these are the pure papillary disease. Currently, there isn't any FDA-approved product on label. So that typically would go through an NCCN guideline Compendia listing strategy.

So maybe pivoting now to PIVOT-006 data here in the next couple of months. Maybe first, we could just talk about like cretostimogene as a product and whether there's any key differences between an intermediate risk and a high-risk patient population that would inform the drug's ability to deliver activity.

That's a great question. So from our vantage point, the core principles and MOA of how cretostimogene works is that it responds to a protein called E2F. And this is a protein that's very important during DNA replication. So fundamentally, as long as there's DNA replication or recurrence of new cancer cells, we believe there should be sufficient E2F that will then activate cretostimogene, right? So that's sort of our foundational understanding and our view of that disease space. We certainly don't have data directly in intermediate risk, low-grade patients. So that is -- we're making that assumption that as long as there's recurrence, there's E2F, creto could be active. So that's sort of the baseline. And beyond that, I would say we're treating patients in an adjuvant setting. So the tumor burden is already pretty low. So that's another condition that I think is unique versus a situation where there's a high tumor burden in terms of both tumor masses.

Great. Maybe you could provide some background then on the clinical study of PIVOT-006 and the time lines you've had this trial enrolling, the enrollment time lines have changed, et cetera. So maybe just start there on the background of the trial.

Yes. So we started enrolling in this trial around mid-2024. And then we completed the enrollment of 364 patients in September of 2025. So that is way ahead of schedule. I think, again, this is the first time that anyone has done this in the U.S. So there are more conservative enrollment projections initially at the outset. But yes, this is a one-to-one randomized controlled trial looking at TURBT with or without cretostimogene. And we do stratify for 2 key factors. One is perioperative chemo, which is a single dose of gemcitabine or not and then whether the patient has high-grade or low-grade disease or not. So those are the 2 key stratification factors to make sure the 2 arms are well balanced.

Obviously, the enrollment came in a lot faster than expected, but I think there was some changes over the course of time in terms of the number of patients you were targeting for enrollment. Can you talk through the decision there and maybe what you were seeing that you felt comfortable moving down?

Yes. So before the study started, we initially wanted to see if we can build in an interim efficacy analysis. Upon speaking with the FDA prior to the start of PIVOT-006, they suggested that we just remove the interim efficacy analysis instead just keep it for interim futility and safety analysis. So I can share that the interim futility analysis has been met. So there's -- the trial obviously continued. But there really wasn't any advantage of having that interim efficacy analysis because the trial would have been almost fully enrolled anyway at that point. So there's that change in sample size based on that.

Okay. How do you interpret the faster-than-expected enrollment that you guys saw?

Yes. So we internally view it as just this enthusiasm that a lot of physicians have with a novel therapy for intermediate risk disease, right? There were a lot of skepticism initially going into it. But really, I think the enrollment rate on some months, we saw 30 to 50 patients coming on to the trial. That was certainly surprising to us. And we think it certainly speaks to the totality of the evidence of creto in other settings that have sort of led through into this setting where a lot of physicians want to try it out as well.

You've kind of mentioned this, but this is a bit of a novel program. You're the first to run a study like this in this kind of patient population, particularly the breadth of the patient population. With that background, how did you kind of come up with the key assumptions underpinning the trial size and powering, et cetera?

Yes, for sure. I think initially, the only evidence out there was this older trial done in the U.S. by SWOG that looked at whether adding a single-dose perioperative chemo or not would benefit patients. So this wasn't -- the control arm is basically TURBT plus surveillance control. And in that study, again, it's not the perfect study because they actually had lower risk patients included. They actually also included higher risk patients that in the end of the trial, they found out that those patients actually received BCG. So with those caveats, that trial was sort of this more conservative view of the world that led to the initial design, right, where initially, we had thought it was more of a 70% RFS rate.

That was kind of the outset. After the study had started, we looked at the [indiscernible] ATLAS trial data that came after we've started the trial. And we continue to rethink in a more modern trial, what could a control arm do, right? So when we looked at the total events that's been accruing, it really, from our vantage point, it really matches more of a 50% RFS control that would sort of, in our minds, make more sense based on the newer data that's come out. It's not perfect. The ATLAS control arm is not perfect as in -- it's not the perfect analog for PIVOT-006, but it is much more recent data than the SWOG trial that I cited that was done more than 10 years ago.

Okay. Great. Maybe then as you think about the bar for clinical success and commercial success, how would you define what you need to see with PIVOT-006 to be kind of both clinically and then commercially successful here?

Sure. So from a clinical standpoint, since there is no FDA-approved adjuvant therapy for this very broad patient population that we have enrolled in PIVOT-006, we believe a relative reduction of 30% is what is going to be clinically meaningful. And even before the start of PIVOT-006, we gathered that feedback from many KOLs, but from their vantage point, they just want an approved product, right? So that's sort of the starting position.

Certainly, we're going to learn a lot more about intermediate risk disease from PIVOT-006, a lot of this kind of baseline characteristics, how the control arm. And so I believe we're leading the and understanding of intermediate risk disease. So being that first-mover advantage, it puts us in a position where we get to prime and educate the market about this disease. And once you have an approved product, typically, there are other ways where you can further enhance that, right? And so in another setting such as CX, we've shown that credo and gem could at least in the early time points add additional efficacy on top. So we think it's just the beginning.

One of the questions that we sometimes get is the use of surveillance as a control arm and whether then 30% reduction -- like how reflective is clinical practices is that. So could you just speak about the use of surveillance versus alternatives in this intermediate patient population?

Yes. Again, like that was certainly one of the questions we had as well. But certainly, with the enrollment rate of PIVOT-006, clearly, people were comfortable with putting patients on the surveillance arm. Again, the progression rate for these patients is not as high in general. Certainly, certain subgroups could be higher than others. So we think based on the NCCN guidelines, TURBT alone is still part of standard practice. And that's really the core argument for why this control arm could stand.

Okay. In terms of then your ability to kind of turn around with that data and file it, I guess, what should we anticipate in terms of time lines to filing on the back of PIVOT data.

Yes. So we've been guiding that in 2027 is when we could file the BLA. Currently not narrowing that, but you can imagine a lot of it is just the clinical module. So cleaning the data, doing the right interpretation and writing up that clinical module will be the work that is required and really aligning with the FDA once that data is available, and then we'll formulate that strategy. But in 2027 is the current guidance.

And how do you think then you've got the potential to then be first to market there. I guess, how do you think first-to-market status will inform your ability to drive uptake in the intermediate risk setting?

I think if you think about the indication, it's -- these are all BCG-naive patients, at least the one we've enrolled in PIVOT-006, right? And so it's interesting because, of course, the obvious answer is to go after sites with high volume of BCG because that helps us with the initial unresponsive launch. But then there could also be a lot of sites that don't have access to BCG, right? So that's another interesting avenue that we can open up as well. So in the end, the good thing is the same physician treats both unresponsive and intermediate risk disease. So I think there's a lot of overlap and synergy where if we can bring to the customer, the HCP, hey, we've got 2 indications now versus just 1. I think that really would kind of open up the topics that we get to engage them on.

Could you speak then to the operating leverage you could get across those launches in terms of whether you would need to invest more into commercial infrastructure?

Yes. So based on our current math, it's still probably in that 75 field force range. However, perhaps on additional kind of medical engagement like MSLs, that could be an area where we can continue to double down on.

Okay. Great. Maybe then in terms of this is a good segue to cash position. I guess can you remind us where your current balance sheet stands? And then what activities from the clinical and then commercial perspective are embedded within that runway guidance?

Sure. So currently, we -- on May 8, we reported we have about over $1 billion on the balance sheet with no debt, and that runway gives us a runway of through 2029. So we're currently covered for all those activities that we described.

Okay. And then I guess, as you shift to making money, as you think about capital allocation priorities in that context, anything that you would think about from a business development perspective?

So first and foremost, I think internally, we're very focused on life cycle management. We view that cretostimogene has a very long tail. We think this is a product that's very hard to genericize or have a biosimilar competitor. But certainly, we want to continue to lengthen that and make sure that we can protect this long tail that we see in this product, right? So that's really the core near-term focus for us.

Okay. Great. I think that brings us basically to time. So with that, thank you so much, Arthur, for joining us. Thanks to everyone who joined us here and on the webcast.

Thank you.

My name is Alec Stranahan. I'm a senior biotech analyst here at Bank of America covering CG Oncology. And thanks for joining us for the session with CG and for joining the 2026 BofA Healthcare Conference. I'm pleased to be joined by Arthur Kuan, the Chairman and Chief Executive Officer of CG; and Ambaw Bellete, President and Chief Operating Officer. Thanks for being here, guys.

Thank you.

Thanks for having us.

Yes. Great. Well, maybe just to tee up the conversation, Arthur, you guys had an update with your 1Q last week. Maybe you can just sort of run through at a high level sort of what was new from that and sort of what investors should be paying attention to over the next few months?

Sure. So as many of you know, we've initiated our rolling BLA submission for our first indication last year. And this year, we're basically committing to complete the BLA submission by the fourth quarter of this year. And this is in the BCG-unresponsive high-risk NIBC space. So that's one of the key highlights of narrowing that guidance.

And the second update, the guidance remains the same that we anticipate that in the first half of this year, our top line data from the PIVOT-006 trial could potentially be available. We do continue to emphasize that it is an event-based trial. So it's always hard to pinpoint exactly when that will occur. But as of now, we continue to maintain that guidance.

And just later this week, we're also very pleased to present data from our Cohort CX trial. This is a trial that's studying creto plus gemcitabine in a combination in BCG-exposed as well as BCG-unresponsive patients. We have reasons to believe that the combination could potentially be additive. And some of the early cut of that data is now available on the abstract. But at AUA, we're going to be presenting the full data set of the early initial responses.

So for that, I think we can talk more about that later, but I think that's definitely one to look out for. As in the past, we've already shown that creto on its own can really have a robust response rate, both in CR as well as duration of response. But now adding on another intravesical agent that urologists are highly familiar with, we think that could potentially have a benefit to kind of shifting paradigm.

Okay. Obviously, a lot going on with the company and a lot of different subtypes within non-muscle invasive bladder cancer. I guess when you think about the PIVOT top line, the Cohort CX from CORE-008, the rolling BLA on track for completion this year. I guess, how do you sort of manage sequencing of those readouts against the BLA completion? Just thinking if you've got the intermediate risk data in hand, would a strong result here maybe change the way that you approach your submission in the unresponsive setting?

Yes. So as we've shared previously, both of those BLAs will have a lot of shared modules. For example, the manufacturing module will be shared across those 2 BLAs. Our current plan is still -- it's still to complete the first BLA before sequentially filing a second BLA on PIVOT-006. And we've also previously stated that we do need to wait for the 12-month response rate for all patients in PIVOT-006. And then there's, of course, the data cleanup, writing up the modules and preparing the package. So as of now, we still anticipate that the PIVOT-006 BLA will be completed in 2027.

Okay. Okay. Maybe we can go one by one, just on the BOND-003 BLA. This is in the high-risk BCG refractory population. I guess in terms of what's left on the rolling submission and sort of how we pair this with FDA's new CMC flexibility guidance. I think you said in the past that this could maybe affect your sort of time line calculus. I guess where do the remaining gating items sit? Is it sort of on the facility inspection readiness, the CMC package or anything about the clinical data itself?

Sure. So I think it's important to note that because creto has breakthrough therapy designation, BTD, it does allow us to have more frequent interactions with the agency. I think the press release from the FDA in January suggests that there is this willingness and openness for the FDA to rethink about manufacturing requirements for sponsors in the cell and gene therapy category, right? So that's more of a general kind of broad-based audience.

I think in our recent communications with the FDA, we basically got the alignment and clarity that's specific and relevant to our program. And with that, we're able to narrow down our BLA completion timing. And you pointed out facility inspection readiness activities. That continues to be a key focus for us. In the CGT space, there's been a lot of manufacturing-related kind of inspection issues. We're ultra focused on that, especially around the facility that we just acquired last year that specializes in fill and finish. That's an area that we put a lot of attention to. But now that we have visibility into what is necessary, we believe everything is going on track and according to plan.

Okay. So the alignment with the FDA, would you say -- would you characterize that as kind of in line with your expectations and what you were already kind of working towards? Or were there additional or less obligations from those?

Yes. I can't go into the play by play, but in general, it's an alignment that provided more clarity for us. And so I think it's overall very helpful.

Okay. And maybe when you think about the competitive landscape in the high-risk BCG-unresponsive, your 24-month landmark CR data and kind of the durability piece is best-in-class from what we've seen versus J&J and enGene and others. I guess what do you expect based on the INLEXZO label would be the on-label sort of efficacy metrics? I think they had 12 months kind of CR rate there. And do you think that would make a competitive label for you? And how would you sort of position that vis-a-vis the long-term data that you've acquired from a commercial rollout perspective?

Yes. So last year, when that label became available, referring to the INLEXZO label, I think at the time of the initiation of our rolling BLA submission, we've already guided that we want to have a differentiated label on what could be a more durable response since we have that benefit given our MOA that could potentially lead to a longer tail, and we've really shown that.

So I think anything beyond that 12-month durability label that INLEXZO has will be a great upside for us. And I do think that in the commercial setting, that's going to play a role because we have something that the physicians and patients ultimately really care about, right, which is that durability. So that's a key component. Of course, beyond that, I think our strength in our AE profile continues to be a differentiation overall, which we can get into more details later.

Yes. Yes. Well, maybe we can talk about sort of the commercial build-out. When does this fall into place? I think you've described in the past maybe 75 field reps could cover 300 urology network sites, which is the majority of the volumes potentially. I guess how does this sort of compare against what J&J is building out for INLEXZO? And is there, maybe, an advantage to having them build out the initial market and having you come in a year or so later?

Yes. I mean -- it's a good question. I think the way we see it is we've really tracked all the launches within this space, not just the INLEXZO launch. And we've really seen where they've hit the mark in terms of physicians and patients, where perhaps there's still some questions outstanding. I think them really coming into the marketplace, we've seen how they've rolled out into the marketplace, how they've engaged accounts, which accounts they've engaged, where they're being successful, where they're not being successful?

We're taking all of that and actually incorporating it into our launch strategy. Our launch team has been in place really for a while now. And our team of -- our field medical team, for example, has been out there engaging and having scientific dialogue and exchange with our future commercial customers really now 18-plus months now already, and we'll continue to do that and as we head into the road to launch.

The second piece I would say is we also have a team of health system directors that are calling on the network leadership, for example, at those network sites that you mentioned that are engaged and having dialogue and really doing a lot of account profiling activities and understanding the nuances of really the buying process in itself. So that's what we're learning. Also, the buy-and-bill confidence is increasing. We've seen it with every incremental launch, that buy-and-bill confidence of customers that are ever increasing. That really bodes well when we're coming into that launch into that same similar space.

And really from a footprint perspective, setup perspective, we continue to evaluate the data on really what's the optimal go-to-market strategy, and that continues to inform us of what we're seeing out there. And we know who the first movers are as well, who are the first centers to actually get on board? Those will be the first mover places that we will go after. And also, I think really identifying the types of patients that are the first initial patients. Are they newly diagnosed? Are there patients that are being switched from other therapies and so on? What are those types of patients?

Because of cretostimogene's clinical data and safety profile, we think all of those are potential eligible patients. The first right after BCG, the patient that may have failed TAR-200, the patient that may have failed gem or gem-doce, the patient that may have failed pembrolizumab. Those are all patients that will be eligible patients for cretostimogene.

I guess when you think about the targeted rollout, you obviously -- for a label, it's expected that you'd have to step through BCG. Does that limit the potential prescriber set that you think about regional versus academic? And is there any, I guess, logistical considerations, especially when we think about kind of the exposed population as a TAM expander?

Yes. I mean I would say the following. I don't think -- whether it's in large academic setting or in the community setting that, that really is a differentiated approach. And we think their eligible patients, eligible patients in the community will be able to go after in a similar fashion in the academic setting. In fact, some of the first movers were really more in the community setting just because they don't have the hurdle rate of a formulary, for example, getting through the various committees at a hospital. Therefore, they tend to be the first movers in new therapies and that would be a target place for us to go after.

Mind you also, a lot of them have already gained clinical experience with cretostimogene, for example, in the intermediate risk trial, in the Cohort CX trial or even in the BOND-003 trial or even in our expanded access program trial, we've targeted really the top centers around the country for this deployment just because they see the patients that we're going after for those trials in itself. That by in itself really creates an opportunity because there's already a pent-up demand already existing within those centers and facilities and also clinical experience on how to adapt it into their clinical practice and armamentarium of treatment for their patients.

Okay. Great. That makes a lot of sense. And maybe we can just touch on the safety differentiation versus TAR-200 or INLEXZO, which requires repeated cytoscope-based instrumentation. It's pretty invasive. We hear about pressure on the bladder from the pretzel. How does this sort of translate into a real-world competitive advantage for creto? And I guess how are you framing that contrast in your physician discussions?

Yes. I mean I think in terms of the physician dialogue and discussion is TAR-200 procedure is a cystoscopic procedure that actually patients have to undergo every 3 months. They're having to actually increase the number of cystoscopic examinations they're having to undergo. That's an invasive procedure.

So there's the pain from that procedure. There's the actual throughput of the account, the ability to actually do those types of procedures is an important element of the adoption of this type of therapy within the practice versus cretostimogene, which is very similar to the BCG experience that went through. It's intravesically delivered by a nurse or a medical assistant. It is done in a room that doesn't require special equipment. You need a catheter that is placed into the patient's bladder, DDM followed by cretostimogene for about an hour -- 45 minutes to an hour.

So it's truly a differentiated procedure versus an interventional procedure that may require a physician to actually administer the procedure, which in many cases, it does, especially the removal. So there are 2 aspects of this that you have to consider. So it's not just the placement, but the subsequent removal requires kind of that 2 steps. You're going in, grasping into a patient's bladder that's under local anesthesia, using a grasping device to grasp the old device out of a patient's bladder, pull that out and put a new one in.

So there's 2 times that you're going in and out of that patient's bladder itself. So that -- and then you need a full kind of setup, camera system setup and those type of things to do it. So the requirement even to conduct the procedure in itself, that's an aspect of kind of one of the hurdle rates in terms of that procedure.

Okay. I guess 2 potential points of pushback that I've heard is that with the pretzel, the physicians get to bill for the procedure as well versus creto. So that's one. And then the second is around the logistics of getting creto to patients. Is this still sort of just in time? How do you think about 5-step versus 2-step on the initial label?

Sure. Again, good question. So just getting back into the practice economics that you mentioned earlier, most of the economics on these products are on the drug side of the equation. Most of really what a practice earns is really the ASP plus 6 or ASP plus 4.3 depending on the setting or what they would get from their private payers. That's where most of the economics is.

In terms of actual admin, the admin side of the picture, when you're looking at total reimbursement, so there's admin, there's drug and there's final reimbursement. So that's how reimbursement would work in this particular setting. When you're looking at the admin part, you're looking at about $100 differential potentially in many instances. Again, most of the economics is on the drug. TAR-200 is $690,000 per year or $69,000 a dose plus 6%. That's where the economics is. It's not on the $100 or $150. So that's on that aspect of it.

In terms of the actual in-practice adoption. So from a process of adoption perspective, we intend to deliver on a just-in-time basis to centers, but there's a lot of flexibility with that. So once you receive the box, you can put it in a normal refrigerator for 4 weeks plus, okay, a normal refrigerator. You can leave it in the box until the patient comes for up to 5 days and then take it out of the box. It takes about 15 to 20 minutes to prep and administer to a patient. So really, it does give you a lot of flexibility.

And then the 2-step process, which we've shown data on the 2-step versus 5-step process, we think that, that is going to be the process that's going to be in practice. We aim to have it in our label, but we know that majority of patients to date have actually undergone the 2-step process versus the 5-step process. For example, all of the patients in Cohort CX, all of the patients in PIVOT-006, all underwent a 2-step process versus a 5-step process. So there's a tremendous amount of body of clinical experience in the adoption of the 2-step process within the clinical practice setting.

Okay. Great. Well, I want to shift gears. I'm going to pivot to PIVOT-006. This is your intermediate risk NMIBC Phase III. First randomized Phase III in this setting. It enrolled nearly 9 months ahead of schedule with topline expected and reiterated for the first half, so in the coming months. What, I guess, constitutes a clinically meaningful result here? What is sort of the minimum RFS bar versus the results that lets you describe creto as kind of standard of care in this setting?

Sure. So just to paint the picture, there currently is no FDA-approved therapy as an adjuvant for patients with IR and MIBC really in the U.S. right now. And based on our conversations with physicians, really, we've been very consistent that a 30% relative risk reduction is sort of the clinically meaningful minimum bar. We've not said too much about our own kind of internal expectations. But that's what we've been telling investors that, that is a number to -- minimally that we would have to achieve. And again, once you have an approved product in this space, it's really our chance to then shape and build that market, right? This is a chance where we're going to be at least 18 to 24 months ahead of the next competitor. So that really unlocks a huge population that's going to be on label.

Okay. And I guess how is the event rate sort of been tracking against your expectations? And what does that sort of tell you about the control arm? And is there, maybe, a good historical comparator? Obviously, cross-trial comparisons carry their own caveats. But in terms of control arm, is it like the SWOG study or ATLAS that you think about?

Yes. When it comes to the control arm, we get that question a lot. I think the hard part is no one has really enrolled the AUA SCO definition of IR and MIBC. I think we're one of the few companies who are the first to do this. So we can only find proxies out there. And we've been pointing to the ATLAS, which is the UroGen ATLAS trial that had a control arm with just TURBT. Again, it's not perfect because they didn't allow for a single-dose perioperative chemo. So -- and again, they've enrolled primarily ex U.S. So with those caveats, I think we're kind of maintaining our kind of view on this that the control should be in that 50% range around 12 to 15 months would be our expectation. But again, there are a lot of caveats to that.

Yes. I think they had some difference in enrollment between like the P1 and this patient...

And they excluded the high-grade patients as well, which we have in our trial.

Yes. Maybe a little bit more aggressive patient group as well.

Just on the surface of it because they went for a low-grade IR ex U.S. I think in a U.S. population that includes high-grade IR patients, that could potentially be different.

Okay. And I guess, have you guys given much thought in terms of how you're going to update the market once the study does read out? Would it be sort of a top line with a medical meeting for the full data?

Yes. So I think, again, because it's event driven, obviously, once we're ready to present that information, we'll probably disclose it. Should it fall around a conference, that will be great. If not, there will be a stand-alone release on that. And certainly, investors can expect the primary endpoint be reported. Beyond that, at least the median length of follow-up on these patients.

Okay. And you said even with the top line in hand, you'll -- it will obviously be 12-month RFS that you'll be submitting on. So even if you step through the event gating...

12-month will come later.

Yes, it might be actually a few months later where we see the step through?

Correct.

Okay. Okay. And then when you think about the sequential BLAs, how are you thinking about the pricing framework in intermediate risk versus BCG-unresponsive? I guess there could be maybe different dosing schedules as well?

That is true. So in BCG-unresponsive disease, it's about 30 doses across 3 years. So 18 in the first year and obviously, second year and third year. So that's in the BCG-unresponsive setting. In the intermediate risk setting, it's 14 doses, just 1 year worth of therapy. The pricing will be based on a per dose basis. This is an ASP product. So we really are not looking at it. We're looking at it as a per dose per indication, I would say, but not really as a totality for one indication, it's going to be X price and Y price. On a dose basis itself, it will be inherently lower intermediate risk versus BCG-unresponsive disease, I would say.

Okay. Okay. That's helpful. I want to ask now about your upcoming presentations at AUA, Cohort CX. This is sort of your entry into the larger BCG-exposed population. What should we sort of expect the AUA in terms of patient number, follow-up, any sort of framing to provide?

Yes. So that study enrolled a little bit north of 50 patients. And initially, we set out to enroll just the BCG-exposed patients, but we ended up with some patients who are also BCG-unresponsive. We'll probably not be breaking that out, but we will be commenting on the responses in those 2 categories.

And really, one of the objectives of the study is to figure out whether creto plus gem should be given concurrently or sequentially, right? So there will be more color on that beyond what the abstract has shown. I think one of the key things, of course, is to look at the CIS data, which looks at complete response rate at early time points. That information will be shared later this week.

And once we have that information, I think it's helpful to think about how does that kind of fit into this landscape? Can we put that into the right context. Our view is that the exposed market is 50,000 patients, which is roughly twice as large as our initial label. And so that is a population that currently has nothing on the label right now, right? So I think following that data as well as long-term durability results, which I mean, call it, 12 months from the initial data, that's going to be available later in the year. But once we have that full picture, I think that's a direction that's very exciting for us to think about.

Okay. And I guess what sort of efficacy signal would give you conviction, assuming that you would need to run a larger randomized Phase III in this setting. I think that's what J&J is doing as well, I guess. What would you want to see to make that commitment? And I guess, how do you think about gemcitabine as the combination partner versus other agents?

Yes. I think gem is something that water soluble and urologists are highly familiar with it, giving it as monotherapy, right? I think when we think about the bar for success in this category, first of all, when you think about BCG-exposed and BCG-unresponsive, it's a very fine line between the 2, right? One of them is the recurrence within 12 months of your last BCG dose or after 12 months of your last BCG dose.

So you can see that the cut was made somewhat arbitrarily, right? So we do think about kind of on the worst case is, you got to definitely be better than the agents in the BCG-unresponsive monotherapy setting, right? That's one way to think about it. But we do think that having 2 agents that could be given intravesically is really the key advantage here. And with J&J's drug, there's only currently a monotherapy potential. So they're really testing a longer duration gem versus gem in their trial. I think we have an opportunity to test a combination approach, which hopefully will show a better response.

Yes. And I guess on the topic of combinations, we've seen some, I guess, mixed data for the IO combination in terms of not really moving the needle as much as people would have thought in terms of efficacy. How do you think about the creto-pembro potential combo? In which setting would that be most apt for?

Sure. So this was a study called CORE-001. We tested this in 35 patients. And what you can see at the time, we didn't know how good creto mono was going to be, right? So the combo showed about a 50% or so 2-year CR rate, which is excellent. But now that we have creto mono data in hand, creto itself can do 42% at 2 years. So pembro -- again, pembro on its own has about a 9% CR rate at 2 years, right? So you can see that it's roughly additive, but then you carry all the systemic side effects with pembrolizumab.

So I think when it comes to an immune checkpoint inhibitor for this patient population, the bar is very high, right? So some other big pharma have tested PD-1 plus BCG. Some have met its endpoint, some haven't. But then, for example, Pfizer has decided not to pursue their filing with that combination, right? So the bar is definitely high when it comes to a checkpoint, which is why we want to stay focused on just assets that could be combined and given intravesically in the urology clinic.

Yes. Okay. That makes sense. Maybe in the last minute or so, I want to sort of end on resources at the company's disposal. How you sort of scale manufacturing both in the U.S. and how you're going to approach the European infrastructure as well? Do you want to do that yourself or partner? What's sort of the calculus around sort of the capital allocation strategy?

Sure. So when it comes to manufacturing, we previously have mentioned that at our current scale and capacity, we can supply up to 50,000 vials of creto a year right now. But we have been making plans and investments in this space really since the time of our IPO. So that progress is ongoing, and it's going really well. And the goal is eventually to scale that up 10x, right? So once we get there, I think building on the fact that creto is -- we have a process that's highly robust and scalable.

So that allows us to move this pretty rapidly around kind of different manufacturing network sites, right, that we're continuing to invest in expanding into. So we continue to think about how we can supply a larger market, which we're about to unlock, hopefully, with the intermediate risk trial.

Yes. Perfect. Well, I think with that, we're right at time. So we'll have to end it there. I look forward to unpacking this more at our dinner tonight. But Arthur, Ambaw, thank you so much for the great discussion, and thanks, everyone, for attending. Thank you.

Thank you.

Thank you for having us.

Good morning, everyone. Thanks for joining us for another session at the 44th JPMorgan Healthcare Conference. I'm Brian Cheng. I'm one of the Senior Biotech Analysts here at the firm. On stage, we have CG Oncology. I will now pass the mic to their CEO, Arthur Kuan for a short presentation followed by a live audience Q&A. Arthur, welcome. The stage is yours.

Thank you, Brian. Good morning, everyone. So at CG Oncology, we're laser-focused on one mission, and that is we're developing a bladder-sparing therapeutic for patients afflicted with bladder cancer. And to do that, we've deployed a very focused strategy to address what we believe to be 150,000 patient per year market in the United States. So as you can see here, the incidence of bladder cancer in the U.S. is about 85,000 patients a year.

And the prevalence is a number that's over 700,000 patients. 75% of those patients are non-muscle invasive. And the hallmark of this disease is that recurrences are very often and oftentimes it leads to progression and ultimately metastatic disease. So our strategy is to focus on the non-muscle invasive bladder cancer segment.

And within that, we've double-clicked into the intermediate risk as well as the high-risk population. So you can see we've invested in across the board in IR as well as HR. And in it, we have 2 pivotal Phase III trials, one that's about to read out in the next first half of this year.

And then our BOND-003 trial, which is a Phase III monotherapy single-arm pivotal trial, that's already read out, and we're providing additional updates. That program is currently under a BLA process, which we'll provide more updates on. But as you can see, this strategy leads to what we believe is a stepwise pathway towards our TAM expansion. Starting on the very left-hand side, we're looking at 25,000 patients in our initial addressable market in the BCG unresponsive segment. And first half of this year, we expect to report data from the PIVOT-006 trial.

That will then add another 50,000 patients to our TAM. Also in the first half of this year in CORE-008 Cohort CX, this is a combination cohort of creto plus gemcitabine. That data is expected to come out in the first half of this year in the BCG-exposed opportunity.

These are some near-term expansion opportunities that we believe to be low-hanging fruits for us. So just a quick review of what we accomplished in 2025. We were able to execute on all these key data sets that also led to the initiation of our BLA filing. Our PIVOT-006 trial, which is our intermediate risk trial was also completed.

We enrolled that trial nearly 9 months ahead of schedule. Looking ahead to 2026, I'll just highlight a few key areas for focus -- for investors to focus on. The first one really is we are set to complete the BLA submission for our first BCG unresponsive indication. And from a data catalyst perspective, the first one on the top, CORE-008 Cohort CX, this is in the BCG-exposed category.

We expect to read out the first results in this setting in the first half of this year. So we're looking at cretostimogene plus gemcitabine in combination. And moving to the bottom here, we've also announced last week that the first -- in the first half of this year, we'll be reporting the top line data in PIVOT-006.

So this is a very exciting opportunity. And with that, we're also guiding that we'll complete the BLA submission for the intermediate risk population in 2027. So just to go over the patient journey for bladder cancer patients, specifically in non-muscle invasive bladder cancer. As you can see here, when you first get diagnosed, you go through a series of testing and you go through a series of TURBT.

And then you go into this every 3- to 6-month cycle of surveillance and treatment. So really, what we're looking at here is a chronic disease that continues to recur. And within NMIBC, there are 3 risk categories, but we're focused on the highest unmet need, which are high risk as well as intermediate risk.

Within high risk, you've got BCG as well as other intravesical chemo, radical cystectomy, and there are a couple of FDA-approved agents now. But as you'll see later, our product profile really stands out among all those therapies. In the middle here, I want to point your attention to intermediate risk disease is characterized by multiple recurrences and these patients are really burdened by the amount of TURBTs that they have to go through.

So even intravesical BCG, which is not FDA approved, is no longer recommended by guidelines due to the BCG shortage. So we're trying to position creto in this setting as the first-line adjuvant therapy for intermediate risk disease. Speaking about our MOA, we believe this is really the cornerstone to all of the great efficacy and safety data that we're seeing.

So creto is an oncolytic immunotherapy. It has a dual mechanism of action. On one hand of the equation, on the left side, it selectively replicates and kills cancer cells. On the right-hand side, upon selective viral lysis it's going to trigger a very potent antitumor immune response.

It secrete GM-CSF, which is a transgene that we carry inside creto as well as you're going to see a lot of tumor-associated or tumor-specific antigens that gets released and that then leads to a very powerful priming of the immune system, which we then could show you in our clinical data, we're seeing a very beautiful long tail. And that kind of tail in the response rates can only be seen within immunotherapy. Creto is given intravesically directly into the bladder.

And this fits right within the standard practice. It's given the same way as BCG, which is the standard of care. And very importantly, this procedure can be done by a medical assistant without an MD's involvement. Creto is dwelled inside the bladder after we first pretreated with a DDM transduction agent, which removes all the GAG layer that protects the bladder transiently and then we'll give cretostimogene shortly thereafter.

So it's a very simple procedure and process, and this really fits right into the current practice. This is the first pivotal trial that we ran. It was -- we reported out results at various time points last year. But very importantly, this trial was designed in accordance with the FDA guidance, which really defined what they mean by BCG unresponsive disease.

In a nutshell, you have to fail 5 doses of BCG induction plus 2 doses of maintenance and recur within a 12-month period. So with that, we reported a 75.5% complete response rate in over 110 patients. This is really the largest data set in this population. And if you look at on the right-hand side, these are landmark CR rate analysis. These are complete responses.

At 12 months, looking at the observed CR rate, we're sitting at 46.4%. And at 24 months, it's nearly 42%. And you'll notice that at the bottom here, most of the patients did not progress to muscle invasive disease. So at 96.4% progression-free from MIBC, this is really the highest PFS rate that we've seen in this category.

Here in this bar graph, you can also see clearly how we rank up against other agents that are approved at a 24-month landmark. So creto on the left-hand side, sitting at 42% really remains the category winner. On the very far right, you have KEYTRUDA, pembrolizumab, despite being an anti-PD-1 immunotherapy, in this setting, really, it's only shown a 9% complete response rate at 2 years.

On the right-hand side, I want to point to the second bullet point here. And this is really the long tail that I was speaking to. 90% of patients remain in CR when they have achieved a CR rate at 12 months. So if you have a CR rate at 12 months, there's a 90% chance that you're still going to be in a CR at 2 years. And that is very powerful. And that is a key kind of messaging that we've been telling physicians, and that's resonated really well.

And on the bottom right here, this is also a very unique feature with our oncolytic immunotherapy where you've not seen any grade 3 side effects that's of significance. And this is one of the key differentiations that we have over chemotherapeutic approaches.

Now in the TAT1 subset of patients, these are papillary lesions that are resected by surgery, and then we're giving creto as an adjuvant therapy. So we're looking for the prevention of future recurrences. Even in this setting, we're seeing that out to 9 months, we're still sitting at about 80% event-free survival rate. And that really compares quite favorably to the other agents that have already been approved.

And 2 of them that have made it on to NCCN guidelines are sitting around about a 50% RFS at 12 months. And since our results are at 80% at 9 months, we think we're still trending in the right direction. Moving ahead, this pivotal trial called PIVOT-006 is being studied in a Phase III trial in over 364 patients, 1:1 randomized. One arm receives TURBT plus cretostimogene.

The other arm received TURBT plus surveillance, and we're looking at RFS as a primary endpoint. And so this is the study that we designed in accordance with the AUA-SUO guidelines that includes the broadest range of patients within the intermediate risk category. And of note, again, this is an adjuvant trial, which really fits right into the standard of care.

Here's a chart that may help folks understand how we're positioned in the intermediate risk market. Certainly, there is an approved agent, but it's in the chemoablative setting. We're very much positioned in the adjuvant setting, right? So that's one point of differentiation. And even within the adjuvant setting, you can see that we're covering the entire spectrum of IR patients, including the high-grade TA lesions that are less than 3 CM that are solitary.

This is something that our competitors have not included in their design, but this is a very important category of patients that we believe could be up to 30% of the IR population. So when you take a look at the entire pie, that opportunity set is likely a 50,000 per year opportunity for CG. Moving on, so CORE-008 is a multi-cohort study. Here on this slide, I'm talking about the Cohort CX, which is a combination cohort of creto plus gemcitabine. And we're focused on this population called the BCG-exposed population.

Essentially, these are patients who are neither BCG naive nor unresponsive. This is sort of this in-between patient population that is growing, right? So there's a very large prevalence of these patients out there that unfortunately don't fit inside the tight and stringent FDA definition of BCG unresponsive disease. So with this design, we're trying to design a trial where we're adding gemcitabine on top of creto in 2 different schedules.

One is concurrent, one is sequential, and we'll be looking at high-grade EFS as a primary endpoint, including both CIS patients as well as TAT1 patients. These are the other 2 cohorts for CORE-008. One of the cohorts, Cohort A is in the BCG-naive population, and we're looking at complete response rates in that setting. We've shown some results last year at SUO. So this was done in about 49 patients. And the initial overall complete response rate was 83.7%.

These are BCG-naive CIS patients. And if you can look at the right-hand side, the primary objective of this study was to actually test 2 different administration schedules of cretostimogene, right? So in the original 5-step administration, we saw a 79.2% response rate. In the optimized administration, we saw an 88% complete response rate. Of note, again, it's very consistent. The safety, 0% Grade 3 AEs, no treatment-related discontinuations have been very consistent with what we've seen before with our other trials. And just to double-click into what we mean by treatment optimization in terms of dosing. From a 5-step process, we've then trimmed down some of the washes that were necessary to make it very simple and streamlined for the prescribers. So all we're doing right now is DDM dwell followed by creto dwell.

So this saves about 25% of the time or about 15 to 25 minutes for the site and really just creates a more seamless experience, especially for high-volume BCG centers that see a lot of these patients. That time savings could really help them a lot. This slide, we're trying to highlight the importance of what an HCP would consider kind of their key criteria for prescribing and treating the BCG unresponsive NMIBC population.

And this was done in 100 U.S. HCPs, a mix of academic as well as [indiscernible] community centers. And really, the #1 thing that they look for is duration of response, which really means can this drug work for me and how long would it last, right? So you can see at the top 2 is provide CR, provides DOR, efficacy, right? These patients are thinking about should they remove their bladders.

So the first thing they care about is will it work for me, right? So it makes sense that this is one of the most important criteria. And of course, safety and tolerability comes next because these patients have a median age of about 72, sometimes in their 80s, and they really do care about side effects quite a bit. They still have a very good life, and they do want to have a great quality of life as they consider these therapies. And the fourth one here, which is equally important, ultimately, the goal here is to prevent radical cystectomy.

So as you can see here, this is also ranked very high in our own survey. So from a launch perspective, we're currently in the prelaunch mode. And all of this is driven by data. We've been heavily investing into data being a fast follower to this marketplace, we get the luxury of studying what others have done, and we get -- really understand what the key accounts are doing in terms of how they're adopting new therapies, who are the key decision-makers.

So from a field organization standpoint, we have already hired our key commercial leaders. And highlighted here is, ultimately, we just need about 75 field force to help us execute the strategy. And the reason is that in our target urology network market, 300 network sites will do about 70% of all volume in terms of BCG as well as TURBT. And so that allows us to run a very lean and capital-efficient model to address this market on our own.

And at the bottom here, just to give you a sense of how concentrated this is, just 10 network urology centers do about 10% of nation's volume. So this is really a hyper-concentrated business. And seeing that we have already invested in so many clinical trials across intermediate risk and high risk, we know these key accounts very well. We've been engaging in prelaunch activities.

We've been engaging in clinical research so that they could get an early use of cretostimogene, and we're collecting very valuable feedback, right, as we continue to prime the market and get ready for launch. So in summary, I hope I've shown you that cretostimogene has already shown that we have the best-in-disease efficacy in BCG unresponsive CIS cohort as well as the cohort P cohort in the TAT1 population.

And we have some early data in BCG naive as well. So in the middle here, just as important is the best-in-disease safety and tolerability, a very important metric when HCPs think about treating these patients. On the right-hand side, just as a reminder, this therapy is granted breakthrough therapy as well as fast track.

And currently, from a manufacturing standpoint, we have a capacity up to 50,000 vials a year. And this product can be stored at frozen. So that's a key advantage that we have where we can start to build inventory into the launch. And as I mentioned here, we do anticipate a lot of demand in the future. And so as such, we've been continuously investing in scale up.

The goal here, of course, is to try to scale up at least 10x based on what we have here. And last, but not least, at the bottom, you can see we believe all the successes that we're seeing really has to do with the key and unique differentiated MOA that we have, right, this dual MOA that allows for a selective oncolysis direct killing plus a very potent antitumor immune response. So last, but not least, I just want to remind everybody that PIVOT-006 as well as Cohort CX are 2 of the near-term first half catalysts that investors can expect this year. And with that, I'm happy to take any questions.

Let's start the Q&A. For those who are in the audience, if you have any questions, feel free to raise your hand. For those joining us virtually, you can submit questions on the portal. Thanks for joining us. So very exciting development out of the gate in the new year, especially coming from the fact that you pulled forward your intermediate risk readout, the PIVOT-6 data by 9 months ahead of schedule. That's what you said. What really attributed to the acceleration? And maybe we'll start there first.

Yes. I mean I think what attributed to that is really the fast enrollment that we got for the trial at some months throughout 2025 and earlier even into 2024, we were running 30 and 40 patients per month in terms of enrollment. Secondly, really on the back of the clinical data that we were presenting on the podium at various scientific conferences, we saw such a continued interest from the physician investigator community, along with patients as well that wanted to be on this trial as well.

So that keen interest is really one of the driving forces in terms of where we are at this stage. Secondly, in terms of our data as well, I would say that really our patients, as Arthur indicated, in the trial are per AUA/SUO guidelines. That's the broadest set of patients within intermediate risk NMIBC. And that's really the patients that really ended up being enrolled in the trial, including patients that are high grade less than 3 centimeters as well. So that's an element of really what the design of the trial was.

Can you remind us if this study is an event-driven end point has an event-driven endpoint. And what is the trigger for the top line?

Yes. This is an event-based trial. And once we reached a number of events, then it will be unblinded and studied.

Okay. With that said, does this acceleration in terms of time line. When you look at that acceleration, does that have any potential color in terms of your expectations of the performance of the control arm versus the active arm? And also, can you just talk about your level of confidence now given that the trial time line pulled forward by 9 months?

Yes. So first of all, I think PIVOT-006 is the first prospectively designed modern and intermediaries trial that is run in the adjuvant setting that includes a TURBT control with active surveillance. We've not seen a modern trial of this size done in recent years. So across all of the IR subtype of patients, right? So that's number one.

So with that, we kind of initial -- our initial assumptions was more of a conservative 70% RFS in the control arm. But our recent viewpoints have evolved, and we have looked at the ATLAS trial from a trial done by a competitor. And in that, their control arm sits at about 50% RFS in about 12 to 15 months. So we think that's a good benchmark for us to think about. And in terms of clinical relevance, we would definitely want to achieve at least a 30% relative risk reduction for it to be clinically meaningful.

And from a -- we know we've not done a study in the low-grade disease before. However, PIVOT-006 is looking at recurrent as well as newly diagnosed low-grade patients and -- there's also a cohort of patients that have high-grade disease. And cohort P within BOND-3, half of those patients treated were of high-grade disease, right? So high-grade TA disease.

So we think there's some potential evidence that creto at least can work in adjuvant population, right? And so we definitely want to -- we look forward to seeing those results and sharing that with the investor community.

And as we think about expectation at top line, how much color can we get in terms of the efficacy profile, the safety profile of creto. I feel that we have a really good understanding of safety so far. So how do we think about just how much we will learn in terms of the efficacy and intermediate risk, which we don't really have a good sense of its performance in that setting.

Yes. Again, because no one really knows how the control arm is going to do in this population in a very precise way. I think I encourage people to think about relative risk reduction versus the control arm. And as I mentioned, 30% relative risk reduction would be clinically relevant.

Any questions from the audience? It will be good to kind of just step back a little bit and just think about the opportunity that you see in intermediate risk. Maybe coming from the lens of just how establish that setting is. And I also kind of want to see what's your take about your physician perception about creto in intermediate risk?

Because your first indication is going to be high risk, BCG unresponsive. So how is that -- is there going to be a gap in terms of adoption when the label for intermediate risk gets turned on?

Yes. I mean, maybe I can comment on that question. I think I'll say the following. I think the physician community is really excited about seeing cretostimogene in this subset of patients. In fact, through the end of the trial, when we completed the trial last September, we really were getting calls last minute from investigators wanting to put additional patients onto the trial.

The hallmark of this disease, when you think about it is continued recurrence over and over again. That means they're having to be resected over and over again. And that reduction of that opportunity after doing a complete resection followed by cretostimogene treatment, they feel it would make really an improvement in the lives of patients that have this disease and this disease burden that could result in the thinning of the bladder wall and perhaps even all the way to the perforation of the bladder.

Some of these patients have undergone 5, 10, 15 TURBT procedures. So really bending of that curve is really one of the outlooks about this disease. Recurrence reduction and really is a hallmark and the goal of therapy in this stage. And we feel like that's a unique opportunity for us to really walk into that market and make a potentially meaningful impact.

And Brian, I'll just -- if I can add that prior to the BCG shortage, this population used to be treated with BCG in an adjuvant fashion. So physicians are very much used to giving an immunotherapy after surgery. So we hope to be the first approved immunotherapy in this category in the adjuvant setting.

And also, I'll just add another color where the high-grade TA patients that we have enrolled in this trial upon recurrence, they tend to become this kind of this high-risk feature, right? So certainly, having an option for those patients before they become high risk is also very valuable.

Turning to the high-risk BCG unresponsive setting. What is the latest progress in your rolling BLA submission -- and I think one interesting update this week is really the PIVOT-6, the time line there. Does that have any impact in terms of how you think about the time line for your first BLA that's in place?

Yes. Very good question, Brian. I would say, obviously, we initiated our submission late last year. We are still in that process -- and we look forward to giving an update as to where we are in that process in the not-too-distant future. In terms of really looking at the PIVOT-6 potential data readout and that in terms of that part of it. From a process perspective, what we are focused on is really to submit a derisked package as much as possible. So we are working and really doubling down our efforts in conducting mock inspections of our CDMO network, actually facility upgrades at our facility that we purchased last summer including quality management systems upgrades as well that we're conducting at that facility.

And then retesting again by mock inspections by FDA inspectors that we have hired on to conduct that. We are very well aware of the history within this space, especially within cell and gene therapy being -- CMC being one of the areas of focus and some of the reasons why others have received a CRL in the past.

We would really like to file one and done, and that's the approach that we are taking. Also just last Sunday, actually, I just wanted to highlight some of you may have seen the release from the FDA around clinical flexibility, commercial flexibility and process validation flexibility from the agency, and we look forward to having a dialogue with the agency around what that value could be for us in our filing process.

Does that have a meaningful value in terms of the approach that we are taking in discussion with the agency on that topic. Then I will go back to the PIVOT-6. PIVOT-6 from an approach perspective, it's going to be filed on the heels of this indication. Therefore, and it is a much bigger opportunity. Hence, the reason that we are taking our time to make sure that we are really filing a derisked package in that space. That's what I would say, anything.

Maybe just on the labeling. Your data set is interestingly differentiating on durability of response. And when you look at further time line that is further out, you differentiate on that, right? That's one of the key point, at least. Is that going to be in the label? And I guess how should we think about the label language.

Do you think that your label could somehow have a differentiation there. So that the session when you looked at the label, they say, this is where creto is going to be different compared to other competitors in the space.

Yes. I mean I would comment that we are going to submit a full data package that includes our extended duration of response. What we have seen, and I think we saw it in the package for N-803 that they were able to get their 24-month data into their label, we hope that we will be able to get that information into the label. Secondly, what we have done is actually really highlighted that in our scientific dialogue and exchange with our investigators today and our future commercial customers today.

Really, the audience is well aware and within this particular space, including at the patient level about the value of what that duration of response data is the long-term duration of response. And that's been a focus area on differentiating cretostimogene compared to other therapies within the landscape.

So I think there are probably 3 key hallmarks from a differentiation perspective. One is number one, does it work? We've addressed that. Number two, how long does it work for me? That's the duration of response. We have the highest duration of response compared to any of the other available approved therapies or those that are in clinical research to date.

Number three is safety. What should I expect from a lifestyle perspective? How does this impact me? Really, we have the best-in-disease data in terms of safety as well. So that's really the benchmark upon which we are hopefully to launch cretostimogene into the market.

I believe we have a question from the audience?

Congrats on all the success. It looks like you guys are executing very well. The question I have is, I'm sure you've commented on this in the past -- is you're clearly in a sweet spot for a large pharma company. you're close to approval.

You talked about commercialization. Of course, these big companies have big commercialization infrastructure, et cetera. What is your perspective on a strategic transaction. I guess -- and are you committed to staying independent? Or do you have a stated view on that point? It's sort of an obvious issue to think about.

Yes. I think as I've mentioned here, this is a launch that we believe we can execute very well on our own, and we're well funded into the launch. Our cash balance sheet is very strong. We have, as of Q3, $680 million reported and that's runway into first half of 2028 without including any revenue projections in that guidance, right?

So we've known these sites, both academic and community over the years, and we have a very deep and intimate relationships with many of them.

In one of your slides, you noted, I think one of the later slide, you noted that you're ramping up 10x, and you also gave guidance on while you also provide detail on the current capacity. How should we think about just your path -- your guiding path toward that 10x goal, at the time of launch, near term, how should we think about the capacity then? And also how aggressive do you need to pursue that 10x given that intermediate risk is a much larger market.

Yes. And the way we think about this is we'll get the first approval in BCG unresponsive. That's an area where the reference pricing has already been well established for us on top of inputs that we'll be considering there, but that will be the first approval. And with that, our current capacity and scale is more than enough to address that market multiple years into that launch.

With PIVOT-6 coming on board and the publication of that data there's also potential for guideline inclusion and then, of course, the ultimate label in that setting. Our goal is definitely by the time we have that label and shortly thereafter, we want to be in a position where we could say, "Hey, into that multiple years into that launch, we'll have that scaled up capacity ready to go." But before then, just building inventory, we believe, is sufficient into that launch.

You talk about pricing. There's a -- as a wide range, let's put it that way. Are you surprised by some of your competitors pricing on the high end? And how does that influence your current thinking about where creto can price for high-risk BCG unresponsive?

Yes. I mean I think to the question about that we're surprised about the pricing, I guess, at the latest entrant into the marketplace. Not really, I would say, is the answer. There's a wide range for approved products from $200,000 to $690,000 a year -- and that's for one year's worth of therapy for BCG unresponsive disease. I think the way we view pricing is we view it through probably 5 different areas. One is really around the target product profile what's your efficacy, what's your safety of your product.

Third is really what is our expected length of treatment on the product; fourth, around what is the landscape pricing, which I just mentioned, $200,000 to $690,000 and the fifth around access, access at the physician level, meaning their ability to actually purchase the product or what's that access point is going to look like. And again, followed by from a patient perspective, the co-pay elements of it and also from a payer perspective.

Those are the variables we're looking at. Obviously, we have the best-in-disease profile when you look at efficacy, when you look at safety, our expected LOT, you can give up to 3 years, which is about 30 doses for high-risk BCG unresponsive disease.

And these products are priced per dose because they are J-code Part B products. So that's an element of what we are looking at. So those are the variables in the equation that we're looking at. And the intermediate risk NMIBC area, the dose is 14 doses per year. So that's a little bit of a difference versus over 3 years, so 30 doses for cretostimogene. So those are the variables that we're looking at in our pricing study. The latest entrants into the marketplace establish a new watermark from pricing perspective, and that's going to be part of the equation that we're looking and calculating on.

This is a great slide to just sit on. Maybe just kind of wrap up. Strategically, your to lead indications. When you think about it at a high level, it's really about the book end of NMIBC, right? You have high-risk physician response on this and intermediate risk on this end -- where do the other 2 fall into place, right? I mean they clearly exist. But I remember that there is a conversation with Arthur that BCG exposed is a little bit unclear.

Even in the doctor's eyes, so how do you think about where those 2 opportunities are for the creto franchise? And how do you capture that in the long haul?

Sure. I mean, I would say, obviously, just as you said, on the right-hand side is our first indication in BCG unresponsive disease both from a regulatory approval and also from a compendian lease thing for cohort P followed by 50,000 patients in the PIVOT-6 patient category. And now really, there is an increased understanding and interest by clinicians because of a definition that has been set forth by the IBCG Group, the International Bladder Cancer Group around the defined population of BCG exposed.

Now we are into 10 years now plus of the shortage of BCG. It has created this patient category in which patients have not received full course of BCG. They have received only induction, half dose of BCG through their course. They're 12 months and a day, but before 24 months in their course of treatment.

And this is really this large group of cohort of patients. And we believe there's an opportunity to conduct a randomized trial with a chemo control potentially and that's what we are -- we're going to have the first data and the combination of cretostimogene plus gemcitabine this year and we are going to be following up with the agency and really about creating a potential randomized trial in that subset of patients to access that subset of patients.

Great. Well, thank you so much for being here. I know that is your first time, and great to have you here on stage and see you soon. Thank you.

Thank you again.

Okay. Good morning, everyone, and welcome to Morgan Stanley Global Healthcare Conference. I'm Sean Laaman, Head of U.S. SMID-Cap biotech equity research at the firm. Before we begin, for important disclosures, please see Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have the pleasure of hosting from CG Oncology, CEO, Arthur Kuan; and President and Chief Operating Officer, Ambaw Bellete. Welcome, gentlemen, and thank you for your time today.

Thank you.

Thank you having us.

Yes. What we're doing with all of our companies. We've got some macro questions to begin with, and then we'll dig into the [indiscernible] CG. So first one, with China's rising biotech innovation, how you think about CG Oncology's competitive position here and will this influence your R&D and business development strategy?

Yes. We pay attention to the China landscape very closely. In fact, in 2019, we partnered out cretostimogene to a Chinese pharma called Lepu Biopharma. They're the ones who actually have [indiscernible] for a lot of their global rights to U.S. companies. So I think through that relationship, I think we continue to stay close to the developing landscapes over there. And I think, ultimately, for U.S. companies, we really need to focus on the novel disruptive innovation that serves a large U.S. population that's largely untapped. I think those are opportunities that we want to continue to focus on.

Wonderful, Arthur. And how are you currently leveraging AI or thinking about AI's disruptive potential?

Sure. I can kick us off and Ambaw will comment too. Outside of CG, all I think about is AI, robotics and automation. I think I'll just briefly touch on some of the repetitive tests that we see in our supply chain whether it's testing, filling. Those are the things that we're thinking very closely, about how to leverage today, but we're also thinking about what we could do in the future as well.

Yes. I mean I think one of the other areas that we focused on is how it can be an enabling activity for us internally, how we can increase efficiencies, such as even small things like meetings and how we create notes, follow-up, those types of action steps, document writing, large volume document writing and comparisons for correlation as well. So we're employing those types of activities in addition to how we show up to the customer, really trying to put models into place such as avatars, for example, in physician engagement and how we can utilize key opinion leaders and those kind of aspects of it. So those are some of the areas that we continue to explore to move on.

Thank you, Ambaw. And I guess on the regulatory side, what's been the most impactful? Has it been FDA changes? Is it being concerns around MFN or tariffs. What's been the most impactful?

Yes, I can start, and Arthur can definitely chime in. I would say probably FDA, that's near and dear to us just because our first BLA is going to be submitted to the agency. We are keeping track of all the changes that are happening within the division. We've been really very actively engaged with the agency as well and happy to really see that. Our review team as a whole has been relatively stable compared to other teams. So we're within the CBR organization. And our review team has been relatively stable, so that's an aspect of it. Obviously, there are other pieces, tariffs, macroeconomics. We make cretostimogene in the U.S. from a tariff perspective, we feel very little exposure from that vantage point. From an MFN perspective, obviously, that's a future state, but we're not partnered in Europe nor have we started activities in the European markets and other OCD type of markets right now. So -- but that's something that we will continue to look at, but FDA I would say out of the three.

Wonderful. Thank you. Now to get CG specific. So starting with creto in high-risk BCG-unresponsive NMIBC with CIS or without Ta/T1 disease, which is the population that you intend to file in later this year. You presented the BOND-003 cohort C results at AUA. And then you've had the most recent durability data update last week. Can you remind us of what we saw here, Arthur?

Sure. So just a quick recap. At AUA, we still had 9 patients pending CR assessment. So essentially, we had 34 out of 101, about 33% in valuable for the landmark at 2 years, right, 2 years from the start of treatment. Our Kaplan-Meier projections at 2 years at that time was 42%, so it's had [indiscernible] of those who are CR but not discontinued. And what happened was last Friday, we reported a 42% complete response to that 2 years. This is actually observed. So effectively, we added 9. So 9 out of 9 CRs all converted. And then we have 3 additional CRs who we booked as nonresponders at AUA. And basically, they were a central review adjudication and 2 were in CR who basically discontinued treatment, but stayed on study. So per protocol, they still got followed up and all 3 were [indiscernible]. So very pleased to share with the public that we now have 46 out of 110 patients in the CR at 2 years.

So that really represents the highest 24-month CR rate, and it tracks really closely with our KM estimate. And I think I want to point out that competitors actual versus KM may not track that closely because some patients who are in CR may discontinue or withdraw from the study due to AEs, right? So this points to cretostimogene's tolerability and also durability, right? In context, KEYTRUDA is 9% at 2 years, nadofaragene is probably in the 19% or lower, right? And then that really kind of helps you frame that, hey, we're at least 2x or more better than the competitor that's already approved on the market.

Sure. Yes, we thought the data was the best possible outcome what he could have had. Can you frame creto's durability, duration of response and safety with what has been observed with approved therapies and competitors in development?

Sure. So for the 3 approved therapies, you see durability from the first CR in the 40% to 50% range. That's across nado, pembro and ANKTIVA. Our current 12-month DoR from the first CR is in the 62% range. Our 24-month DoR from the first CR is in the 60% range. So that gives you an idea of how not only at 12 months but also there's long tail. Once you hit a CR at 12 months, you continue to have a very durable response rate into 24 months. And we're still tracking these patients. They have to come back for follow-ups every 3 to 6 months. So in the near future, potentially, we could provide another update even beyond that time point. Because ultimately, the end goal here is patients don't want to just save their bladders for 3 months. They want to be able to keep their bladders for years. So we're really trying to move the goalpost here.

Awesome. And you expect to initiate the BLA submission in 4Q. What are you planning to include in the submission? And are there any aspects that remain outstanding?

Yes. I'll start off first. So we've guided early on that we are very focused on improving the administration steps of creto at the site level. We used to do a 5-step administration, which takes about 20 minutes more than a 2-step administration. So we discussed with the FDA, our game plan. They said, run a 50-patient trial, you don't have to do a non-inferiority analysis. So we'll be expecting to report those results and submitting that result to the FDA to compare the 2 versus 5 steps. And we're very confident that scientifically, we don't see any reason why there'd be any difference there. But that saving 20 minutes for a high-volume center really means a lot, right? Other aspects include kind of important stability information. And recently, we purchased a fill and finish facility that fills creto into vials. We are heavily investing in that facility and upgrading its infrastructure to make sure they're inspection-ready.

Right. Got you. Thank you. And recent news in the space concerning single-arm studies, how do you think about the FDA's stance here as it relates to your upcoming BLA?

Yes. Maybe I can take on that question. There have been 3 approved products already under that guidance. It was first proclamated in 2018, followed up with another update in 2024 and August of 2024. We also have a pending approval for TAR-200 using the same guidance. So we believe that really the pathway for approval is solid based on already existing precedent of other therapies that have gone through that process. And we'll also -- we'll see another one very soon as well. That should continue to give us confidence about the pathway there. In terms of our regulatory engagement, I would say we've got Breakthrough Therapy designation as well as Fast Track designation. It's part of our filing strategy. We've had multiple interactions with the agency on our submission strategy and really, based on that particular pathway, the single-arm design pathway. So that's why our confidence remains strong vantage point.

Thank you. And I guess sort of prior to new therapies, treatment with BCG then on to cystectomy, but now the availability of new therapies, it may be post failing BCG attempt 2 or 3, then strategies to preserve the bladder. How do you position creto in that dynamic?

Yes. I would say we do see, especially post our best-in-disease data at the last AUA meeting. We've had really a number of interactions with clinicians. And they do see post-BCG for the patients that -- who BCG has failed. We do see 2 or 3 additional lines of therapy in those patients. And our goal has been to make cretostimogene backbone therapy within the space. If you look at our cross-section of our clinical trials, they cover really the gamut of intermediate risk disease, high-risk disease and all points in between, really working to make a backbone therapy as monotherapy and also potentially in the combination area as well.

So earlier this year, for example, we initiated a trial of cretostimogene plus gemcitabine, cohort CX, and that trial is looking at patients that are both BCG exposed as well as BCG-unresponsive patients in that trial, really thereby adding on to the preponderance of evidence, clinical evidence for the management of those patients.

Thank you, Ambaw. And I guess we saw J&J's TAR-200 granted Priority Review by the FDA, I think, in July. Market is assuming that it'll get to market first. How do you think, given different routes of administration and data that you've seen so far, how would you paint the picture of physician and ultimately patient preference if indeed it does get to market first?

Yes. I mean I would say the following things. In the patient physician discussion with their caregiver as well as the patient, the dialogue they have is around probably 3 major things. Does it work for me? Is it going to work? So how efficacious is it? Is it safe? Is there some changes in my lifestyle that I need to experience by taking on this product? And then the last and really very important question is how long is it going to work for me, the durability. Arthur spoke about that durability earlier as well is showing that, for example, if you're in CR at month 12, 9 out of 10 patients would be in CR at month 24. It's really a compelling patient dialogue and discussion that clinicians can have about it. Really patients ultimately do not want to lose their bladder.

The bladder you're born with is the best bladder that you can live with. And we believe that cretostimogene will help to expand that. In terms of TAR-200 coming on to the market, really, their success is actually good. We do believe that their success is a good barometer of what the opportunity is for cretostimogene. And with the best in disease data, the best safety profile and the long duration of response with cretostimogene, we have a unique opportunity to put it in its right place, it's been backbone therapy within this landscape.

And I'll just add a few points to that. I think with the potential of J&J approval in the near term, I think it will tell investors 2 important message. One is that the single-arm trial using CR as an endpoint and DoR as a secondary endpoint, could potentially gain full approval even in this environment. Number two, the pricing information will be very valuable to all investors, including us and I would say, from a competitive perspective, it's actually great to have pharma kind of priming the market for us to drive up reimbursement confidence. That's a key topic that many sites continue to discuss because this is a market that's new to buy and bill. But it doesn't mean that it won't happen. It's just -- it's an early innings. And the last one I'll say is creto is the only asset that's been tested in BCG-unresponsive heavily pretreated with chemo.

So up to 40% of our trial in BOND-003 had prior chemotherapy, including Gem/Doce. We can't say the same for the TAR-200 trial. So we're certainly going to be leaning hard into that because, as you know, many urologists still give a lot of chemotherapy, GEM mono or Gem/Doce. So that is a unique advantage that we're going to have in our data set that they won't.

Yes. And maybe one thing I could also add, you asked about kind of how is this product used. TAR-200, for example, is administered into the patient directly using a cystoscope. So it's actually manipulating the patient's bladder. You're instrumenting the patient's bladder, putting a scope in to deliver the TAR-200 device into the patient's bladder. Up to 8 times the first 6 months and 2 additional times for the rest of that year. So first year, 10 times manipulation of bladder placement and pull out of the bladder. Patients are already anxious about what potentially you could see and also the manipulation of that patient's bladder, it really is done by urologists, the most part, versus cretostimogene which could be administered by a nurse or a medical assistant, the same really method as BCG. What they have undergone for BCG, the 6 weekly installations same similar process for cretostimogene.

So from a workflow perspective, it's something they're used to. It's something that can be easily adapted into their clinical practice, especially with our 2-step process now, therefore efficiency and throughput has also increased.

Got you. Thank you. We touched a little bit on manufacturing early, but what manufacturing and supply considerations should investors have? And how do you think about the launch? Like how will the rollout happen? What volume do you think you can serve out of the gate?

Sure. I'll touch on those. So I think for investors looking into this space, which is an exciting space, there's been a couple kind of CRLs that occurred in our space, right? 3 out of 4 BLA submissions have had CRLs. And if you look at them carefully, they all fall into a few categories, right, within the CMC risk category. Some players have changed the process of making the product from Phase III to commercial, some have changed the site of manufacturing from Phase III to commercial, some have changed the scale because they have yield issues, and again, the fourth category would be a preapproval inspection failure. That largely has to do with quality management systems, SOPs. So quality related, right? So those are the kind of general buckets I would consider from a CMC perspective as it relates to the risk.

And we're focused on, number one, we did not change the site of where we make creto. It's going to be the same site in the U.S. that will supply for the commercial launch. Number two, we did not change the process. We did not change the scale. Because if you think of our cretostimogene, it's a replication competent adenovector. It makes more copies of itself. So yield is never an issue for us, right? So from that vantage point, we're very focused on the last part, which is the inspections. This has to do with upgrading the facilities' quality management systems, making sure they're following and having the right SOPs in place. If they deviate from those, do they correct them, right? These are some of the details that we're really working hard through. We've hired ex-FDA inspectors to help us with that, right?

So from a capacity and scale perspective, as evidenced by how fast we've enrolled in our recent second Phase III in intermediate-risk front-line adjuvant setting. That trial is 10 months ahead of schedule. So I think investors can tell that we do have drug supply. Otherwise, that trial, even if the patients were there, we wouldn't be able to supply them. So at this moment, what we're saying is with the current scale we have, we can do up to 40,000 to 50,000 vials a year. And the beauty about creto is that we can store this at minus 80 -- minus 60 to minus 80, and it could be stable for up to 5 years and more. right? So we can actually build inventory as we anticipate future demand. So with PIVOT-006, our IR trial pulling forward 10 months, we're already thinking about possible strategies to get that on to NCCN sooner and that will be ahead of our competitors by a couple of years.

Got you. And how do you think about the access to physicians during the rollout?

Yes. I mean, I think that's one of the areas where we've made a lot of investments and if I can just give you kind of a look into some of those examples. All of our clinical trials that are currently being deployed out are really in the top centers throughout the country. They're in the top 10 deciles, 9, 7 and 8, that will be our future really most important customer base. One unique piece about this area and this disease state is that there's such a huge concentration of clinicians that manage these patients and really the top 300 centers generating well north of 50-plus percent of the opportunity that exists out of 7,000 plus, for example, centers throughout the country. So that has allowed us to really penetrate and really look into those. We have the team already of medical science liaisons that are already interfacing with those customers, having engaged discussions, scientific exchange discussions already today.

And we've been really driving on those prelaunch activities, both on the field perspective as well as payer perspective as well, learning insights about the patient journey, what's happening to patients vis-a-vis our clinical trials as well as what's happening to other patients on other therapies as well. And really, we've developed a team that is in place, for example, our leadership team, our commercial leadership team has well north of over 60 years of experience in bladder cancer, specifically. So they know the customers, we know the customers. We are actively engaged with them on an ongoing basis, talking about cretostimogene, talking about the landscape and what's happening within that landscape.

In fact, I do believe that's one of our value drivers. Our customer intimacy and engagement, the ability to know where the customers need and what the patient needs. So we're also spending quite a bit of time in understanding and work with advocacy as well as patient groups, patient ambassadors as well to really help and inform our launch strategies.

And just maybe to push a little bit on price. So you mentioned that TAR-200, if they do come to market first, one of the value proposition is that you'll get some insight on price. So could you frame that a little bit more and maybe some expectations on price or think about the goalpost?

Yes. I can start and tackle on that question. Currently, today, if you look at the landscape, the pricing is somewhere between $200,000 in the case of pembrolizumab per year to over $600,000 in the case of ANKTIVA. So that's really the price band. Nadofaragene is somewhere around the mid-$200,000s, so to speak, per year. When we look at this landscape, really, these are the following metrics from a pricing perspective. Number one, what's kind of your target product profile, okay? What's the expected length of treatment that a patient would be on? Those are some of the inputs in there. And the third element of it is really what's the current existing landscape pricing that helps to inform what your pricing could look like and should be. And the next piece is really from an access perspective, both at the patient level as well as the account level, how would they access that particular price.

So I think we look forward to seeing where they will land. But based on what has been publicly available in terms of what's been communicated at least publicly, really of what their targets are for the next coming years in front of us you have 2 drivers, either you penetrate or you have price or you have a combination. So we do believe that those will be the important aspects of how we will evaluate it. We are just kicking off our pricing studies now to really look at the landscape. And that's the formula we're going to be using.

Wonderful. Wonderful. Now some questions on upcoming data. So I believe there's BOND-003 cohort P data is set for Q4. Can you remind us of the early data that you presented at AUA and what do you hope to present in Q4?

Sure. So cohort P is for the papillary cohort or the Ta/T1 BCG-unresponsive cohort. This will not be on our label, but we intend to follow this -- publish this data quickly and get it on NCCN. There's already 2 precedents ahead of us. pembro as well as nado have both made it into NCCN. So their data around 12 months is about 50% or so RFS, right? So these are patients who have completely resected their tumor and the drug is given adjuvantly, right? So from our data sets, we showed about 14 patients worth of data at AUA this year. And the current RFS rate is about 90% at 9 months. So there's obviously more to come later this year. We hope to report a more mature data set later on and hopefully beating the benchmark of what's already out there in the guidance right now.

Wonderful, thank you. And the data in HR BCG-unresponsive patients with Ta/T1 without CIS, otherwise known as papillary disease. Can you remind us how that population differs in terms of both patient market size opportunity from the CIS population with or without papillary tumors?

Yes. And that market is about, in our view, about 60% of the pie, right, the Ta/T1. And then CIS with Ta/T1 is about 40%. So that's certainly a very important segment for us to go after.

And we've also got the Phase II CORE-008 data in BCG-naive patients, what is the patient size and the commercial opportunity there?

Yes. So BCG-naive is probably about 25,000 patients in the U.S. incidence wise. We don't view it from a prevalence perspective because pretty much all of those patients will get some form or dose of BCG. And they all turn into BCG exposed right away, right? And then if you have received 5 plus 2 doses with recurrence within 12 months, you then become BCG-unresponsive. So in our view of the market is BCG-exposed is going to be the largest share of the market in the future, right? So CORE-008, we've got a few cohorts there. Cohort A is where we're going to read out data this year. This is in the BCG-naive high-risk NMIBC cohort. We never intended this to be one where we believe it's going to beat BCG, but it's very important for us to show monotherapy data there.

And most importantly, we're generating the 2 versus 5-step information for FDA. But from there, we do have Cohort B and CX. B is in BCG-exposed monotherapy. We do want to establish creto as a monotherapy there in about 150 patients. And that is -- that market in BCG-exposed, people have asked us how to think about that market. The way we think about it is if the naive market is 25,000 patients a year, and they all turn into exposed that same year, right? We think it's at least twice of that from an eligibility perspective, right? And from a BCG-unresponsive market, our current view is it's about 25,000 patients that we can address, right? So Cohort B against monotherapy and exposed cohort CX is, as Ambaw mentioned, creto plus gemcitabine in both BCG-exposed and BCG-unresponsive, right? And the motivation there really is we have demonstrated creto plus pembrolizumab as an add-on, could boost our response rate and durability. However, we recognize the issue of pembro being sold to [indiscernible] and creto is staying within the urology practice. We want something that the urologists can administer at the same time together, right?

So gem is something that urologists routinely give. We have preclinical studies that's not published, where we have demonstrated the synergies between gem and creto in the right doses and right combination. So we're very excited about that trial.

Cool. We've seen some recent data in the space from the PD-1 inhibitor sasanlimab. Can you contextualize that for us.

Sure. So that trial, the CREST trial was done in a BCG-naive high-risk population globally. It was sasanlimab plus BCG versus BCG. BCG in the control setting showed about an 85% CR rate in the CIS population. The combo showed about an 89% CR. And then the kind of EFS curve probably only separated at year 3. So really, it did hit its endpoint. However, we do question whether the 4% upfront CR spread is meaningful enough plus all the grade 3 side effects from the 10% to 30% range that you don't get with BCG. There's also a small chance of myocarditis that led to death in one of the arms of that combo. So the risk reward is not entirely clear to us. And as I've mentioned, you're selling this product to different call points, right? Can you convince urologists to give checkpoints that's to be determined.

Wonderful. I guess sort of moving on a little bit, for intermediate-risk NMIBC enrollment, recently completed in the Phase III PIVOT-006 study. Can you remind us of the current treatment landscape for these patients?

Yes. I mean, the current treatment landscape for these patients and intermediate risk by guidelines. So TURBT is really first-line therapy in these patient followed by chemo, 1 dose, single dose chemo from a neoadjuvant perspective as well prior to the operation. So now we've got -- if you look at intermediate-risk NMIBC, there's been a recent approval, for example, in low-grade intermediate risk in lieu of TURBT that requires really a change from a clinician how they manage these types of patients. So -- and again, if you look at it from really a patient population perspective, the largest and broadest patient population is really what's addressed by PIVOT-006, which is based on AUA SUO guidelines, both low-grade intermediate risk and high-grade intermediate risk, less than 3 centimeters, [indiscernible] disease, that's part and parcel of our PIVOT-006 trial. Compared, for example, to the MoonRISe trial, which requires FGFR alterations where the patient has that or not, that's kind of a subset of population that probably cuts that patient population by 25% or so if not higher.

So really, our trial, which really rapidly enrolled over 200-plus patients just this year were enrolled into that trial well 10 months ahead of what we had projected in advance of it really shows the robustness of the data as we were releasing more and more data on cretostimogene in terms of our BOND-003 data that we've been releasing, physician interest, PI interest, patient interest continue to grow. And that's really what facilitated that trial's enrollment so rapidly and so quickly within that landscape. And as Arthur indicated, we intend to really quickly move forward and potentially file for that indication right behind our BCG-unresponsive first indication in advance of that after we publish the data, once you have an FDA approval in your first indication and have a publication get on the NCCN guidelines and then once you have a follow-on product in advance of an FDA approval, once you have a publication a peer review journal, you can seek the addition of that into the NCCN guidelines.

And that's the path that we're going to follow for PIVOT-006. And we think from an opportunity perspective, when you look at that intermediate-risk patient population, we think it's probably around 2x of the BCG-unresponsive marketplace, the 25,000 or so patients that we mentioned earlier. So we think that opportunity is that -- even that much higher for this patient population to access creto.

Got it. And what about muscle invasive bladder cancer? And how are you thinking about creto's potential in that opportunity?

Sure. So in that setting, we've run a trial called CORE-002. This is an IIT trial where we combine creto with nivolumab, giving neoadjuvantly prior to radical cystectomy. So about 6 doses of creto and then 2 doses of nivo and then at week 10 you resect the bladder. And we were looking for a pathological CR, right? So nivo alone in this setting is about 7% PCR. The combo showed about north of 40% PCR. So again, we're obviously looking at the space very carefully because the elephant in the room is EV plus pembro. I think until that kind of works itself out, we're not in a rush to make any moves in that setting right now. But it's good to know we already have some efficacy and safety demonstrated in that setting.

Okay. Great. I have 1 final formal question. But just your cash on hand, your -- where does that give you a runway to, the funding requirements for the launch? When do you hope to get to cash flow positive?

So we currently have about $660 million cash on hand, and we've guided this will be into first half of 2028 in terms of runway. So covering many kind of milestones that we talked about this morning.

Wonderful. And is there any question that I didn't ask or something that I should have asked today?

Comprehensive, yes.

Yes. And you covered a lot of ground. Thank you for the opportunity.

Wonderful. Thank you, gentlemen, for attending.

Thanks for your time.

Take care.

Thank you.

All right. Good morning, good afternoon, everyone. Thanks for joining us here at the Goldman Sachs Healthcare Conference. Thrilled to be joined today by Arthur Kuan from CG Oncology.

And maybe I'll just kick it off with kind of a high-level question. If you could provide an overview of the company, and let's focus on some of the key value drivers over the next 12 to 24 months?

Sure. So Arthur Kuan from CG Oncology. We are in this really exciting and growing market called non-muscle invasive bladder cancer, which is about 75% of all bladder cancer from an instance perspective. And within that, we have a product that addresses both the intermediate risk and high-risk population. And that's about 70% of the 75%. And in numbers terms, we're talking about 50,000 patients instance in the U.S. alone, right?

So it's exciting. We're filing our BLA in the second half of this year. It will be the company's first BLA in the BCG unresponsive high-risk NMIBC population. That's about 15,000 patients a year. There are three products approved in that category, but they've not made any meaningful penetration yet, and we can go into that.

So this is an exciting space where these providers who are urologists have not previously experienced kind of a boom in the buy-and-build set up, but this is their chance to do so. So we're here to really revolutionize and really evolve this whole space and this market will continue to evolve and grow over the next several years. So we're very excited about that.

Awesome. Lots to talk about. Maybe we'll start with some of the data updates that you've had recently. You had a big updated AUA. And maybe you can talk us through some of the key outcomes that you shared at that particular conference? And I think 24-month update was one of the marquee kind of features of the data. So we'll focus on that as well.

Sure. So just to remind everyone, our modality is an oncolytic immunotherapy and it's very important to keep that in mind because ultimately, we believe our MoA is one of the key drivers of the clinical data and outcomes I'm about to share. So in a 110-patient trial called BOND-003, and a specific cohort called Cohort C, we enrolled patients with carcinoma in situ disease that cannot be resected. So the FDA allows us to use complete response as an endpoint, as well as duration of response as a secondary endpoint to assess these patients. And in those patients, we saw a 75.5% complete response at any time that we reported AUA this year. And importantly, these responses are highly durable.

So at 1 year, the KM estimated duration of response is 65% and at 2 years, it's 58%, right? So meaning, if you have a response at any time, your probability of lasting greater than 2 years is north of 50%. And that's really exciting.

When we think about the landmark analysis, right? So regardless of kind of when the CR occurred, but let's say, you started therapy on day-1, at 12 months, over 46% of patients are in a CR. And at 2 years, the data is still reading out fully. But so far, we have 9 more patients who are pending. But excluding those, we're already at 31% to 34% CR rate at 2 years.

And KOLs would tell you, if you hit a 30% CR at 2 years, that's game changing. None of the competitors out there that are approved are even close to kind of that 30% plus mark. So with 9 more CRs pending assessment, and kind of given the long-tailing immunotherapy that we're all accustomed to, we certainly think that, that number could further increase, right?

You kind of alluded to this, and maybe you can contextualize for us how those response rates stack up versus other agents currently on the market or in development in non-muscle invasive bladder cancer?

Sure. Yes. So I'll start with KEYTRUDA's response at 2 years. So KEYTRUDA was the first approved agent in this space in 2020. And at 2 years, they have a 9% complete response rate, with a 13% Grade 3, 4 side effect profile. So it's not surprising that their penetration rate in the space is probably in the low single digits.

And so next to that, we have nadofaragene, which is a gene therapy product, secreting interferon-alpha. They do about 19% at 2 years. And then there's a combination product, IL-15 plus BCG, that's probably in the 24% range, right? So anything north of 30%, I think, psychologically is a big step up, right? So if we can even kind of be on the high end of that kind of 30s range, it would be unheard of.

And then if you couple that number, which this number is also going to go inside the label, it's cystectomy-free survival rate. And there are a couple of ways of doing it, but I think what one of our competitors, J&J who hasn't read out the 2-year data yet, they're reporting CFS rate of about 90% at 1 year in responders. So in contrast, we have 90% CFS rate in responders out to 2 years already. So meaning, if you have a CR, right, there's a 90% chance that you're going to be cystectomy-free out to 2 years, right? And that's also another meaningful endpoint for folks to see.

One of the areas where I think you guys have gotten pushback on the profile of cretostimogene versus some of these other agents is on the like re-induction of the drug. Maybe you can explain what re-induction means and kind of give us some context for why you think it's been not as big of a deal?

Sure. Yes. So re-induction is not something that we came up with. So if you go back to the standard of care for this disease, it is BCG. And BCG is given in this kind of a weekly times 6 fashion. So once a week for 6 weeks, and then you assess whether there's a response not responded. You typically give another course of 6 weekly induction. So that's what we mean by re-induction. And in that re-induction, you can see north of 50%, 60%, 70% response rates in the first-line setting, right?

So it's something that the urologists are very accustomed to, and the patients are also very accustomed to, given the mechanism of action. So I would say, re-induction only works if your MoA supports it. In contrast, chemotherapy, you do not reinduce a patient who has a progress on chemo, right? It's just not part of the modality as well as a standard practice.

So in our case, we adopt a similar approach given our oncolytic immunotherapy MoA. We have seen in Phase II studies where there is a delayed immune response, right? And for some reason, these patients, if you give them another course, 50% of the time they [Technical Difficulty]. And those CRs are actually highly durable. So in the Phase III trial, 28 patients were reinduced and 14 of them converted to a CR. And those CRs are still highly durable and some are even out to 2 years now.

Okay. So for the patients, you mentioned there was a 28, and then 50% of them are kind of getting into a response. For those patients that do need a re-induction, how does their overall first year of treatment compare to the overall first year of treatment for a patient who doesn't need to be re-induced?

Yes. So if you don't need re-induction, your year-1 number of doses is about 15 doses. And if you do need re-induction, then it's 18 doses. So 3 extra. And then year-2 and beyond, we do 6 doses per year.

And it doesn't matter at that point?

Yes.

Okay. In terms of the regulatory filing, how are the re-induced patients incorporated into the overall responder analysis?

Sure. So there is -- the FDA is very clear about this to us as well as to other sponsors. If a patient gets re-induced, meaning their first CR didn't occur at 3 months, but occurred at 6 months, because they were reinduced at 3 months, and we check them up every 3 months. Meaning, the first CR would have occurred at 6 months, the FDA wants us to follow them for at least 12 months. So month-18 from the start of therapy, right? So that's the only way that those patients could be included into the label. So we're doing exactly that, and we're even trying to push boundaries a little bit more to see if there's room to incorporate not just 12 months from the first year, but maybe something beyond that.

Okay. So of those 28 patients, do you have data that you've shared, or can you share on what the, like, landmark looks like at 18 months? Or the duration of response? Whatever makes the most sense.

Yes, I think, hopefully, in kind of future conferences, we can go through those.

Okay. So I think you mentioned this in your initial kind of notes on the company, but you're preparing for a filing in the second half of the year. Talk to us about what are the gating factors that stand between you filing before then?

Sure. So number one, I'll start with the efficacy part. The minimum duration of response that we're looking for is at least 12 months. Certainly, we're trying to push the boundaries to see in this competitive market, how do we get more duration of response data into the label. So potentially 24 months, 18 months, something beyond 12 months. So there's that one aspect.

The other aspect is we have announced that we're trying to simplify the administration process from a previous 5 steps to currently a 2-step process. So to be clear, cretostimogene is a administered via a soft catheter by medical assistant, a urologist or MD does not have to be involved in that process. It's done the same way that BCG has given, so no change to the practice workflow.

Now what we're trying to do is to optimize the turnaround time for the centers. And we used to do kind of 5 steps where you do a saline wash, DDM wash, and then you do a DDM dwell, and DDM is a transduction agent that allows the virus to [Technical Difficulty] tissue. Followed by the DDM dwell, you give creto and dwell after 45 minutes to an hour.

So what we've done now is to eliminate the washing steps because we're avoiding the patient's bladder anyway. And even if you avoid the patient's bladder, you're still going to have a urine that comes into the bladder continuously, right? So we're just going to go straight to the DDM dwell, drain it followed by the creto dwell. The time savings there could be about 20 minutes or so. So I would say, this is one where we believe it's -- it will be nice to have in the label, but we definitely want to push for it because saving 20 minutes of a very high-volume center would actually be pretty meaningful, right? And so we're collecting that data for CORE-008 trial right now.

Okay. So talk to me about the data generation that's required to enable that? What is -- has the agency specified what they're looking to see? And when can you complete this study?

Yes. So in our pre-BLA meeting, we're very clear. We asked the agency, hey, how do we get this 2-step process in there besides BOND-003 Cohort C, which used the 5-step. All other trials have gone to the 2-step process. And they said, hey, show us 50-patient data from CORE-008, which looked at both the 2-step and 5-step. And they're not asking for a kind of randomized controlled study. They just want to look at, in general, like from a confidence interval perspective, safety efficacy is it within the same ballpark.

Okay. So are they looking at both safety and efficacy? And is there a set time point they're looking at it for?

Basically, CR any time. Yes. So we believe we should have that data by the end of this year.

Okay. And so then once you have the data in hand, you're going to be able to submit the filing. Is there anything else on the manufacturing side that needs to be done?

Yes. So one of the things that we're trying to enhance is the experience at the site level, right? So our product is stored at minus 60, which has a tremendous shelf life of up to 5 years. But we recognize that maybe there are some sites that may have access to a freezer. So for those sites and for all these sites, we ship just in time, right? So the just-in-time delivery is something we need to validate, which is ongoing, meaning we ship a minus 60 in the current and the product can remain stable inside that current for up to 5 days. So it gives them some wiggle room there.

And beyond that, we've also executed a study that allows us to take the product from minus 60, move it into a fridge, which every single center would have at 2 to 8 Celsius for up to 1 month. So we already have that data. Now it's just about -- we talked to the FDA about how do we get this into the label? They said it's just a matter of executing kind of more lots to show them that, hey, there's a statistical variance and sampling that makes sense. So that's ongoing. And we believe that part to us, it's a low-risk execution, and we just want to make sure we get that done correctly.

Okay. So with all of these things, activities that are ongoing, I guess, what is your level of confidence you'll be able to submit the filing by year-end?

So we think the guidance on initiation will remain on track. We've not requested for rolling yet. But if we do, obviously, we definitely want to leverage everything that's available to us, to optimize the filing efficiency.

Okay. And would you anticipate a priority or standard review?

So we do have BTD. So in the past, agents that have BTD in our space, specifically have received priority review. But obviously, it's something we need to ask.

Okay. Maybe as we think about the commercial opportunity, let's start high level. Can you describe the addressable market as you see it?

Yes. So in the U.S., and I'll mainly focus on incidence. So the incidence in the U.S. is there are 85,000 new patients with bladder cancer diagnosed each year, right? And 75% of those are non-muscle invasive and then 70% of those are, what we believe, we can address, in the intermediate risk and high-risk population.

So our initial on-label claim for the first product would be in the BCG unresponsive category. And there are about 15,000 eligible patients each year that we can address. And there's certainly a lot of kind of patients in between the BCG naive and BCG unresponsive category called BCG exposed. That's a growing number of patients, and that's a number probably well north of 30,000, 40,000, 50,000 patients that are in the BCG-exposed category.

So we have a couple of trials addressing that. And we have a trial addressing BCG-naive high risk that we'll be reading out later this year, CORE-008 Cohort A. And then lastly, on the left-hand side, an intermediate risk, we're going really the most upstream kind of patients. These are either de novo or recurrent intermediate-risk patients who have typically not seen BCG before.

So when we talk about BCG naive, I like to think about are we talking about high risk or intermediate risk? So in the intermediate risk bucket, that's 18,000 new patients coming to the market each year. And these patients live for a very long time. Their progression rate is really low. The issue that we're solving for is actually recurrence. They continue to recur every 3 months, and it's become a real burden for these patients.

The guidelines recommend kind of one dose perioperative chemo and then you kind of observe for recurrence. And if BCG were to be available, you can give BCG. So we have this unique window where there are no BCG currently available in the U.S. to give to the IR patients. So that's why we're able to run our PIVOT-006 trial, which is a randomized Phase III controlled trial against TURBT, right? So it's an adjuvant trial, where one arm gets TURBT, plus creto; the other arm just gets to TURBT. And we're looking for RFS as an end point.

So that trial, we just guided this past quarter that we're 6 to 9 months ahead of our enrollment schedule. So that's really encouraging. We've never seen enrollment rates this fast in any trials in this space. And it's actually one of the market segments that we believe we have a unique advantage in, and I'll explain why. Number one, I mentioned there's this BCG shortage enabling us to enroll in this space. Number two, because of the shortage, all the pharmas with the PD-1 can't really enter the space, because the PD-1 agents need to be an add-on to another agent, such as BCG. So it's really kind of a blue ocean segment for us.

Now the two other players that are in the space. One is obviously UroGen, which they have to lead the lesion behind and allow their chemo gel to ablate the lesion, right? So there's going to be some segment of the market that may prefer that. But we think the majority would prefer resecting the tumor that they can see and giving drug afterwards.

And the other part is -- J&J has an erdafitinib product in a pretzel called TAR-210. They have to do two cuts. First cut is FGFR3 positivity, either by tissue or urine and another cut, they have to exclude high-grade TA lesions, which again, those are patients that we include, and we think it's about 30% of the market that are in the high-grade TA category.

So FGFR3 is probably, per J&J, 70% of the pie. But when you do those two cuts, their target population then shrinks by 50% relative to ours, right? So if we were to get our label, this is going to be the broadest label, no testing required and the safety profile we anticipate to translate over from the unresponsive setting. So that's really our view of like getting to the most upstream of all these patients. And then at the back end, we have the unresponsive label. And so we'll slowly come in between to capture the high-risk naive and high-risk exposed patients.

Let's go back to the unresponsive group because it's going to be the first you get approved in. And so in that population, you mentioned a 15,000-patient incidents. Talk to us about the carcinoma in situ versus papillary pieces of the population. What's the breakdown? And then what's the path to market for each of those groups?

Sure. So the initial on-label claim will be in the carcinoma in situ group. And those patients take up about 40% of the unresponsive market. The remaining 60% are TAT1 or papillary lesions that do not have CIS present. That's [Technical Difficulty] the market. So for CIS, we're going to go for the full approval on label. For TAT1, the FDA has said that to get on the label, you need to run an RCT, which currently is not feasible, because there is no control arm in that setting that will be appropriate.

The strategy there is to go from an NCCN Compendia listing. And what you need to do is show in 50 patients with a 12-month follow-up of RFS, a number that's probably north of 40% at 12 months. We believe that's the path to gain on NCCN for Level 2b evidence. The CIS population will get like Level 2A. But once you're on there, based on our market feedback, the sites are getting reimbursed by payers.

Okay. So talk to us a little bit about the competitive landscape and BCG-unresponsive. So there's a couple of drugs that are already approved. You guys, J&J is expecting to get approval later this year, I think. So talk to us how you expect the market kind of to segment with the available therapies? And also, how are you thinking about sequencing?

Sure. So this market is really interesting because it's partially driven by this compounding BCD shortage issue. So over the years, these sites continue to concentrate. If you're not seeing patients, you're not getting more BCG, you're starting to refer patients out to centers that have BCG and have volume. So kind of just kind of snowballed over time. And so we're really focused on the top accounts, right, in the country, call it, 300 accounts. And we're putting them on our trials. We're calling on them right now ahead of launch. And those are the customers that we're focused on.

So of those, you're probably thinking about half of them are academic and half are large urology group practices that are typically owned by private equity. And our focus is really on both, right? So -- and we can say that because we've involved both kind of provider types on our studies.

And they do behave a little bit differently. The [indiscernible] are very much kind of P&L driven, very much focused on the bottom line. The academic centers, they may have their preferences. Maybe 1/4 of them, they really prefer chemo, such as Gem/Doce combo. For those patients, our approach is to simply lean into our data set, right? We're the only company that has generated data post chemotherapy. And 40% of our patients on BOND-003 have had prior chemo. And of those, maybe 50% of them have had prior Gem/Doce.

And we're showing that response rates are very consistent in these different subgroups. So we're going to lean into that and just, hey, what would you use after Gem/Doce? Is it more chemo or is it immunotherapy, right? So we're going to address those -- that segment, want to build trust with them and let them experience creto.

For the others, we've had working relationships with them for a long time. They've been part of our trial, and they've been innovating with us with new trial designs. So we feel very confident with that. And some of the kind of community-related questions, do you have a hood, do you have a freezer, the academic centers will not have those issues at all. So that segment, we feel very comfortable in.

And even in the community setting, thanks to COVID, many of these centers actually have freezers on site. And if they don't, we're covering a lot of the high-volume centers by BCG volume, by enrolling them into our trials. And if they don't have freezers, we would have addressed that issue during the trial period, right? And actually, to our surprise, like very few centers that are high volume actually would not have a freezer. So that actually is a good setup for us to keep our sales force very focused on these key accounts.

Okay. So you kind of started to allude to this, but there have always been questions around like the infrastructure that a physician or a group practice would need to implement to be ready to offer creto. So can you talk to that, what does the doctor's office need to do in order to get -- to start prescribing cretostimogene?

Yes. So really, the first question we ask is like, hey, do you give BCG right now, right? And that's sort of the first kind of line of questionnaire. And if they do give BCG, that means they know how to prep a BSL Level 2 product safely by protecting their staff. And they have a specific workflow, right, which does not take up a procedure room with the full kind of camera setup where you need to performance a cystoscopy in. So given that existing workflow, we do not need to change that process at all. So typically, a medical assistant will be assigned to this task and administered creto with a soft catheter. And we then focus really on kind of the throughput and how they're going to get reimbursed and all that kind of step-by-step walk through with them.

You mentioned the ability to shave off 20 minutes, but what is that relative to or in terms of -- if I walk in as a patient, how long am I going to be at the doctor's office? When can I leave?

Yes. So currently, it would be about 1 hour and 30 minutes. I think with this new process, it could be potentially down to an hour. And then in the future, post launch, there are centers that give BCG and the patient goes home and dwells at home. Then that would just be administration and leave, right? So that's sort of the long game that we envision.

Obviously, studies would need to be conducted to get to that point. But we currently have the hypothesis that there really is no reason that you need to dwell in the clinic. So once you get creto, you can go home, right? So that's the kind of band state. But for now, it will be 1 hour and 30 minutes, shortening to potentially an hour. In the future, shorter than that.

Okay. In terms of provider economics, I guess, I think you mentioned earlier buy-and-bill and not being kind of new for this market. So how should we think about the provider economics and how that will shape their decision-making?

Yes. So it really comes down to the drug, which is ASP plus 6%. There are administration fees associated with administering creto, which is an intravesical insulation delivery fee. That's, call it, $80 to $100. But really, what they're going to make money off of is going to be from the creto ASP plus 6%, right? And obviously, reimbursement confidence is very important here. And I think with the three approved agents, as well as maybe a fourth, those are all going to continue to drive reimbursement confidence with these providers. It's very important because they've not had to experience kind of a high price tag buy-and-bill model before. So having them being like fully primed and ready by the time we launch is very important.

Okay. Cohort P, which is the papillary population that we talked about earlier, that study is expected later this year. Maybe you can talk about the key endpoints for that group of patients and what the benchmarks are to kind of get to the NCCN Compendia's trend?

Sure. We showed a preliminary kind of the data at AUA this year. So in 24 patients, we have a recurrence-free survival rate of about 90% in 9 months. This is just in 24 patients, so it's little small. The full set, which would be in about, call it, 50 to 55 patients, that's expected to come out probably mid of next year. But later this year, we should have additional data out to 12 months in those earlier patient population.

I would say the benchmark is, for the two agents that made it into the NCCN Guidelines, they're about 40% at 12 months in terms of RFS, right? So I would say, being well north of that would be very important. And we got to publish the paper and then it could then be completed.

What should we look for in terms of other data updates later this year?

Yes. So we're very excited about CORE-008. That study has three cohorts. A, B and CX. Cohort A enrolled patients who were BCG naive, high-risk NMIBC. And that population has been fully enrolled as of April. So we expect to have data on that later this year.

In terms of benchmark, again, AUA, we saw that Pfizer ran a trial with Sasanlimab plus BCG -- versus BCG. And when you look at the BCG control arm, they're probably the most current control arm data in BCG naive using BCG mono. And we saw that they had an 85% CR rate at any time. So 3 and 6 months unique CRs. And at 12 months, they saw about 76% CR at a year, right? So I would say that's probably the benchmark to look at in this population.

It is a high bar, right? So I think we've been very consistent in our view on the market that we actually believe BCG exposed is the opportunity because even in a shortage, these 25,000 BCG-naive patients are getting some BCG. So the minute they get some BCG, they turn into exposed. So we think the exposed market is sort of the lower-hanging fruit. And those two cohorts, B and CX, B is monotherapy creto, CX is creto plus gemcitabine. Those are actively being enrolled right now, and we should expect data probably also next year.

And the bar for exposed is harder to tell. But again, these patients really have BCG. So when you give them more BCG, response rate shouldn't be as robust as the first-line BCG-naive patients. So the bar is certainly lower. And the two data sets there, both mono and combo with gem would help inform us of kind of where we land.

Okay. As you think about commercial launch preparation, maybe talk to us about what you're doing to prepare for a potential approval as soon as next year?

Absolutely. So our commercial leadership team is already in place, like the senior leaders. And we already have a team of MSLs covering all the key regions in the country by BCG sales volume. They're calling on customers every day, new relationships, existing relationships. And we're really profiling these accounts down to like the very kind of detailed level to figure out who's responsible for the [indiscernible] that patient experience and all of that, right? So there's a lot of prep work and relationship building.

On the other hand, if you think about our clinical portfolio, we're addressing really all aspects of IR and HR. And so we've actually geared our kind of trial enrollment towards sites that we believe are going to be key customers for us. And a lot of them are actually private equity-owned [indiscernible] which really helps us open the door because ultimately, they may be doing kind of more of a coordinated purchasing.

Okay. I think you mentioned there's like 300 high-volume sites or maybe the top decile or whatever. I don't know exactly how you define it, but what portion of those are private equity owned and do they...

I think like more than half, I would say, are private equity owned. And again, that number has continued to evolve. I think maybe 10 years ago, it was maybe like 30%, but the roll-up continues to happen amongst the very few players.

Okay. And how many reps would you anticipate needing to kind of service market?

Yes. I mean, we looked at benchmarks and we did our own analysis on kind of accounts, reach and frequency. So based on comps like kind of the 50-60 range is what we'd expect. Yes, so a small footprint.

Okay. Maybe you can talk about the cash position. How -- what is your current runway guidance? And what are the activities embedded within that?

Sure. So as of Q1, we have about $688 million in cash, and we've guided the Street that it's good through first half of 2028, and which would cover all the existing programs I mentioned, including getting to the PIVOT-006, which is one of our most important trials readout as well as our initial launch in BCG-unresponsive.

Okay. And does that include all the commercial preparation and activities that you need to do?

Yes.

Okay. Great. And how do you think about additional sources of capital then?

Obviously, there -- on a small biotech, we can always use more money. But we've been very disciplined in the past 10 years of our company's history. I would say, there's always room to continue to invest in manufacturing capacity, which we have done. I think, we actually invested in one of our drug product providers in the first quarter. So there's that aspect, including like working on next-gen formulation. So what I'm excited about is adeno vector is actually very stable with the right formulation, even at room temperature. So those are work that I see that we can continue to invest in to make that experience even better.

Okay. Great. Is there anything that we haven't talked about today that you think is important to understand?

It's very comprehensive. Yes. Happy to take questions on that.

No one ever wants to ask a question. So it was great to speak with you, Arthur. I really appreciate all the time. Thanks to everyone who joined us here and online. Thank you.

Thank you.