Cgcology Inc Aktie

Hi, everyone. My name is Sean Laaman. I'm the Head of U.S. Mid-cap Biotech Equity Research here at Morgan Stanley, and welcome to our Global Healthcare Conference.

Before we begin, to make you aware of some important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions on that, please reach out to your Morgan Stanley sales representative.

With that, we have the pleasure now to welcome from CG Oncology, the CEO, Arthur Kuan. Welcome, and thank you for your time today, Arthur.

Thanks for having me.

Yes. Maybe you could do me a favor and ask me -- answer my macro questions. The first one is the rise of China-originated innovation. And, if at all, how does that change your competitive positioning or thoughts around R&D or thoughts around business development?

Yes. Certainly, based on what we've seen coming out of China, it is something to be respected, and I don't think we should take it lightly. So more broadly, I think we think a lot about when it comes to U.S. innovation, what is the competitive advantage. I still think that being close to the U.S. market, being close to the providers and patients, that in and of itself, I think, continues to be something that could be differentiated in terms of the rate and speed of innovation, making sure that we're well set up for clinical development and clinical operations that's fit for purpose in the U.S. population is also very critical.

Sure. Now moving on to AI. So have you or are you implementing AI adoption within your business? And have you seen it or can you give a description of something that's changed, whether it's on the cost front, a decision, maybe a PoS assumption?

Sure. So I think we're, first of all, definitely embracing AI in all aspects of our operations. Moving beyond sort of the meeting minute summary and e-mail summaries, I think we're now asking every function within the company, from finance to accounting to CMC, to clinical development to really break down their existing workflows and work streams because in order to give AI the right context, you first really need to figure out and dissect your current work stream.

And so it's basically a process of being very honest and auditing your own workflow, right? How ideas come to be, how ideas are vetted. And the more descriptive you can be, the better it is to train your AI agent or teams of AI agents. So directionally, I think the near-term gain is going to come from productivity increase and more of an efficiency gain, right, in the first step.

Sure. And last one before we dig into CG specific, but which policy variable? Is it FDA, Medicare negotiation, MFN, tariffs, global pricing matters most to your economics?

Yes. So I would say in that list, the one that is still up in the air remains to be the MFN. I think we're watching that very closely and looking at what the bigger companies are doing with their negotiations there. But certainly, that has an impact on how you think about, for example, EU pricing.

Sure. And now we'll get on to CG. Thank you, Arthur. I appreciate it. Let's start with the BLA for creto and where it stands. So you've been submitting on a rolling basis and guided to completion in the fourth quarter with the CMC module as the final piece. What's actually left? And coming out of your manufacturing-focused alignment with the FDA, how much submission risk do you think is truly behind you?

Sure. So from a CMC perspective, one of the most important things that the FDA wants to see in the module before we submit is can you prove that the process is reproducible? Is it robust enough? Is it repeatable? Do you have full control over different aspects of your process? One of the things that many companies do during this phase is they figure out new improvements to their process such that they get a higher yield, for example, or they learn that, hey, the clinical opportunity is a lot bigger than what their scale could support. So certain tweaks are made.

I'm happy to share that our process that led to all the clinical GMP products that enabled our clinical trials is a process that we intend to launch commercially, right? So all the experiments that we had performed to characterize the process to validate the process have already been completed. And I'm also very happy to share that, at least just based on the data that we're seeing, it does point to the fact that creto has a very robust process, meaning you can really stress test that -- stress the process to kind of a wide ranging of conditions and still be able to generate the same product that we're using. So that's the good news.

And so where we are in the process is simply in this data generation and compilation of those reports and then fitting them into the Module 3 for submission. There's a lot of authoring and writing and QC that needs to happen. A separate work stream that I also need to mention is around inspection readiness, which is a key aspect prior to getting a potential approval. That's one where upon submission, the FDA could send a team of inspectors to your facilities and to your partner facilities to perform a pretty thorough inspection. And our approach there has been we have engaged several ex FDA inspectors to help prepare our sites for that inspection. And that work stream has been going really well.

Sure. And have there been any learnings from what we observed with ADSTILADRIN and ANKTIVA that you've been able to use as learnings to somewhat derisk the process?

Yes. So with respect to, for example, ADCETRIS, I think that's an example where there was a process change, even a scale change. And there was also a certain inspection-related issues that came up. With respect to ANKTIVA, I think what's public is there was a pre-approval inspection, which again, deals with more of the inspection aspect of the risks. And so from our vantage point, knowing that those risks have already occurred, we definitely can't ignore them. And so we've really doubled down, if not tripled down on resourcing to ensure we are really pressure testing our CDMO sites as well as the sites that we now control the fill and finish facility.

Sure. Thank you, Arthur. And on scale, you said clinical and commercial are the same process, locked and agreed with the FDA. Can you remind us of what your current capacity is for the first year or years with frozen storage?

Sure. So the current process can generate up to 50,000 vials of cretostimogene. And we have said that we can store these vials in minus 60 degrees up to 4 years. So it's actually -- from that vantage point, we have the runway, I should say, to take care of the early years of launch. Certainly, our view is the longer term would require a much higher number of vials. So in parallel to this work stream, we have continued to invest in a scaled-up process. That would not be the part of the initial BLA, but it will be ready in a couple of years, just in time for that additional ramp in the future.

Sure. And maybe try and put that, how many patients does that cover in the early years? And do you need any process changes before broader indications?

Yes. So if you were to just assume, for example, at least in the -- for example, the BCG-unresponsive indication, a patient could use up to 18 doses or 20 doses a year, right? You just divide that, you get around 2,500 patients, right?

Sure. Got you. And on the commercial build, can you share more detail around your launch prep?

Sure. So from a launch readiness perspective, our key focus is on account profiling. Certainly, there's a lot of other work streams that take place. But one of the most important ones is account profiling. And so we do that in a few ways. One is just gathering field insights by sending our team members to the key accounts. And we sort of target these accounts oftentimes by how many patients they see, and you can reference that against their BCG usage data. And now that there are a couple of branded products in the market, we're also seeing where those activities are taking place.

And so really, the main work that we're trying to do here is we're trying to ask our customers what's their experience been like? What were the hurdles? What were something that was good that we should continue to do and what were things that we should avoid. And so once we do that, there's a target number of accounts that we're going after that do about 80% of the volume by BCG. And so our goal before approval is to make sure we get that picture in place. And so we could really, on the day of approval, really figure out who are the key players that we're going to be calling on early on.

Sure. So creto is an office-based intravesical treatment that fits existing BCG administration. How central is that operational simplicity to your launch pitch? And how are you quantifying it for community urologists deciding between options?

Yes. So through the last couple of months, we've learned that workflow continues to be a very important decision-maker for these practices. They're very busy. They see a lot of patients. And what they really want is something that does not disrupt their workflow and practice patterns, right? So not too surprising, but it's very important to also hear that from our customers directly.

So the fact that creto can be administered by a medical assistant, the same way that BCG is done currently, it really fits into that practice pretty seamlessly. Yes. And now that we have this improved storage condition, so creto can be stored at a regular fridge 2 to 8 Celsius for up to 8 weeks, we think that's a huge advantage over what we had previously.

Okay. We've moved through the manufacturing and some launch questions and maybe now onto the competitive positioning. So J&J's INLEXZO has been on the market for a year now. Has that reshaped or reformed your thinking around the competitive positioning for creto or not?

Yes. Look, I think their early launch data looks really promising, especially around the data around pre and post J-code. I think the key things I look for is around increasing the reimbursement confidence, especially in the large urology group practices, the private equity-owned accounts. So that continues to be quite favorable. I think it helps us understand the market dynamics a little bit better in terms of who might be the early, mid- and late adopters, right? So that continues to drive confidence in our view of the market.

Sure. And beyond INLEXZO and the setting now includes a few options, and we've spoken to a bunch of KOLs over the course of the last year, and they're suggesting that patients will cycle through 2 or 3 options. And so where do you think creto might fit in the sequencing? And what's the single most point of differentiation that you could be leaning on?

Sure. So in terms of the patient population that we enrolled in BOND-003 Cohort C, these were heavily pretreated BCG-unresponsive patients, up to 40% of them have had prior chemo. So I think that is really what we intend to go after, like newly diagnosed BCG-unresponsive patients. And I think we have the added benefit of showing that, hey, creto can work just as well even if you had prior chemo, right? Because a lot of the current market is dominated by generic chemotherapy. And so that's a segment where I think we have a unique differentiation.

I think one of the most important differentiation of creto really speaks to its MOA and it's backed up by clinical data. What I'm referring to is the long tail that we're seeing. So if you have a CR at 12 months, there's a 90% chance you have a CR at 2 years. That long tail is not something that's easily repeated by others. And so we think that durable efficacy plus the clean safety profile that we have in conjunction, right, plus the workflow advantage should be something that makes it easy for us to message to the market.

Sure. Makes a ton of sense. I guess on the BCG supply side, that's about to change, I believe, with Merck opening a facility that triples capacity of BCG by the end of this year. So how do you think that might change the way that BCG-naive patients are treated? And do you see any read-through for the BCG-unresponsive therapies that we discussed? And does more available BCG expand the funnel of patients who eventually become unresponsive and reach you? Or does it strengthen BCG's hold on the front line and raise the bar for displacing it?

That's a great question. Yes. So BCG, again, works reasonably well in the frontline BCG-naive setting. So the bar has always been very high to tap into that space. Should there be a tripling of BCG supply? Then what could happen is more patients who are currently not receiving the full course of BCG could then receive that. So you're right. I think the dynamics and split between exposed and unresponsive could potentially shift, right? Because our current view is that the unresponsive market is 25,000 patients. And in the exposed population, it's about 50,000 patients. So there could be potentially a shift there should there be a tripling of supply, right?

I think when it comes to the intermediate-risk opportunity, it's still pretty wide open. 10 years ago, those patients would have received BCG. However, practice patterns have changed, guidelines have changed. So being potentially first in that adjuvant setting there, I think we really -- even if BCG were to come back, having an improved product in that setting, I think we'll still be in a very good position.

Fantastic. Thank you, Arthur. Moving on to BOND-003 and the high-risk data package. So the BOND-003 Cohort data showed 75.5% complete response at any time and a median duration of response of around 28 months. And you've highlighted that 90% of 12-month responders remain in response at 24 months. Mouthful. As you talk to investors and physicians, which of those numbers do you think best capture the differentiation? And how do you frame durability against the competing profiles?

Yes. So if you just look at what's -- I think the 12-month CR rate is usually something that people care about because it's something very intuitive that, hey, I start treatment today, am I going to have my bladder in 12 months, right? So there's that number. And I think what's often surprising is that durable tail that I talked about from 12 to 24 months, that 90% durable response during that period, I think it's quite surprising. And I think it's also differentiating.

Sure. And on the label you're filing for the CIS population with or without papillary disease, help us bridge to the papillary only and the BCG-naive data sets. With Cohort B showing high-grade event-free survival in low 80s at 9 months and CORE-008 Cohort A at 88% complete response in BCG-naive. How do those cohorts factor into your life cycle and label expansion strategy? What's the timing? And how does the BCG supply outlook shape how you position creto in the naive setting as a BCG alternative, a combination or a therapy for patients who can still access BCG?

Great. Yes. So I'll start with the BCG-unresponsive papillary patients. This has been a population that typically would not be for BLA approval. Most competitors have gone on to the NCCN compendia listing, and they are being reimbursed based on that. Obviously, there is a competitor who has a PDUFA date for that population in January. So we'll be watching that pretty closely. But we'll have the 12-month results end of the year for that cohort, and we intend to publish it at a peer-reviewed journal to just get the necessary steps ready.

And you talked about the BCG-naive data set, the 88% complete response. I will perhaps remind you and the audience here that we actually have a very exciting creto plus gemcitabine combination data that we also shared earlier this year. And that was done in a setting of BCG-exposed and BCG-unresponsive patients. So of 50 patients, we had about 50-50 each in responsive and exposed. The data was very similar. But we had achieved about a 90% event-free survival at 6 months. So very promising.

With that data set, we had an alignment meeting with the FDA around the Phase III concept, which is we want to enable a Phase III trial in the BCG-exposed setting using creto plus gem versus gem. So we got the confirmation. And so pending the 12-month results that we're going to have later this year, we're going to figure out the proper sizing for that study and pursue that potentially early next year. So that would then help us unlock that additional 50,000 patients I spoke about earlier, right? So we're -- I think that's a space that is a very low-hanging fruit that may not have received as much attention recently.

Sure. That's awesome. Moving on to PIVOT-006 in intermediate risk, which is the big near-term catalyst for us. The first randomized registrational trial in intermediate-risk NMIBC has pulled forward roughly a year, top line expected imminently against surveillance control. How do you define a clinically meaningful result? And how much do you want the market focused on the hazard ratio versus the absolute recurrence-free survival split?

Great question. So given the randomized nature of the study, the primary endpoint is recurrence-free survival, and that's going to be expressed in a hazard ratio format, which, again, it really means are you reducing the rate of recurrence, right? So we've been saying, and this is based on our feedback talking with KOLs and physicians that a 30% relative risk reduction would be clinically meaningful. So we think that's -- given that there is no approved product in that category right now, there's a competitor product in the ablative setting. Our position and based on our trial design, we're going after patients who have completed a full TURBT, right?

So I think this is an area where you asked about the hazard ratio versus the 12 months. It's -- from a urologist's perspective, they potentially will not compute the hazard ratio as the same way a regulator would look at it. So they may also want to look at the 12-month landmark numbers.

Sure.

Yes.

Sure. And how do you think about the control arm performance? And does the stronger-than-expected control arm worry you if it compresses the absolute benefit even with a good HR?

That's a great question. Yes. So I think the control arm here, the truth is, I think PIVOT-006 will be the answer to how does the control arm perform. Obviously, ahead of that, we think the best closest proxy would be the ATLAS trial, of which the control arm had a TURBT treatment option. And so that kind of trends in that 50%, 12- to 15-month RFS range in that specific setting, right?

So I think when we talk about hazard ratio, it's always done in a relative risk reduction concept. So as long as we can continue to achieve that, we still think we'll be in a very good shape to demonstrate that we can reduce the number of TURBTs for these patients.

Sure, sure. And the study has enrolled a broad range of intermediate-risk patients. So how should we think about a pooled RFS number across that heterogeneous population? And could subgroup performance end up mattering as much as the headline?

Yes. So the study is not powered by each subgroup. So we definitely have capped certain subgroups, for example, like the high-grade Ta to a certain amount to make sure it's well balanced, right? But across the board, I mean, these are all defined as intermediate-risk patients. So we think ideally, both the newly diagnosed, recurrent, low-grade, high-grade could all be part of it. And that will give us the broadest label versus the competition.

Sure. And how do you think about the intermediate-risk opportunity versus BCG-unresponsive in terms of both addressable patients and market size?

Sure. So this one, intermediate risk is one where you have to go and create the market. I think BCG-unresponsive has a very well-defined market at this point. It's still growing. I think with -- when it comes to intermediate risk, creto could potentially be the first to market, especially in the adjuvant setting. So it's one where we have the responsibility to go and shape that market. In absolute number of patients, it is twice the size of the unresponsive patients, right? So just in terms of like sheer number of patients that are addressable, it is a much larger opportunity.

Sure. And assuming that you do have a positive readout, what's the path and timing to a second filing? And could it quickly become a commercial contributor along with the high risk?

Yes. So that's one where what we've been saying is once we have the data, we're going to have to engage the FDA. Certainly, there are different filing considerations here. But I think we'll have a very open dialogue with the FDA because they share a lot of the same parts, right? They share the same nonclinical and CMC modules. The only part that's different is the clinical module, right?

Right. Moving on to some questions around combination in earlier lines and CORE-008 and Cohort CX. What did the combination teach you? And how does it change how you think about positioning monotherapy versus combo as you move into earlier lines?

Yes. So this is a great example where early on in our development plans, we had tested creto plus a systemic checkpoint agent, for example. And the results were additive. But we learned quickly that the urologists would really prefer to keep the patient in their practice, meaning that a pure intravesical combination versus intravesical, one systemic, might be preferable. So here's a case where creto plus gemcitabine, these are 2 orthogonal MOAs coming together. And based on the sequential treatment regimen, which is creto/creto-gem, it seemed to generate really good results versus the concurrent creto-gem.

So we're more likely going to take forward the creto/creto-gem sequential therapy. It's going to be less burdensome for the patient because each visit, there's only one agent that's being administered. And gem, when it's given on its own, it doesn't have a lot of long-term side effects either. And so given the early data, it seems to be additive. And so we await to see the 12-month results. And if it holds up, it's definitely very promising.

Sure, sure. And on the BCG-exposed population, that in-between group that's neither naive nor unresponsive. Why do you believe in that market? How large is it? How do you think about the path to addressing it?

Yes. So conceptually, every year in the U.S., 25,000 new high-risk BCG-naive patients come to the market. They all get some form of BCG even during the shortage, right? Because in fact, BCG should be preserved for these patients. So from there, you then have 2 pools of patients, one who are BCG-exposed, one who are BCG-unresponsive, right?

So in our own experience, we had to turn away a lot of patients who don't fit the FDA definition of BCG-unresponsive, right, which is 5 plus 2 doses of BCG recurrence within 12 months, right? So anything outside of that, this is a really wide net that currently is all off-label. So based on the BCG claims data, we know there are a large number of patients actively on BCG. And we understand that the narrow FDA definition was really meant for a regulatory purpose. So really having this potential label really helps us capture everyone downstream of receivable BCG.

Sure. Moving on to financials and strategy. So you have roughly $1 billion in cash runway through 2029. And you've recently added $500 million through the ATM. With quarterly burn around $80 million and launch spend ramping, like how are you thinking about whether the current position fully funds you to and through launch? And what would prompt you to tap the ATM further?

Yes. So currently, all the programs that I just described, including the BCG-exposed Phase III, they're all covered part of our current cash runway guidance. I think in general, our view on this is any kind of SG&A spend would have to be fit for purpose on where the needs are with respect to commercial as well as R&D. I think you kind of titrate up and down depending on kind of where you are with those activities.

When it comes to R&D, I think we still think there is a number of opportunities that we can potentially tap just with creto and just within bladder cancer, right? So we've already kind of done some of the building blocks with, for example, muscle-invasive bladder cancer, but more work will be done on that. So we remain pretty disciplined with how we're spending capital.

Sure. I guess the #1 inbound I get is when are we getting the PIVOT-006 data? So what's your latest answer to that, Arthur?

Yes. So as recent as August and even at this conference, we're saying that it's in the near term.

Okay. Fair enough. Now I've run out of my questions. Apart from this final one, is there anything that I didn't ask that I should have or any message you'd like to leave investors with?

We just appreciate everyone's support. We have a lot of exciting catalysts coming up. And so I think you've covered all of them.

Okay. Great. Appreciate your time, Arthur, and thanks, everyone, for listening.

Thank you.

Thank you.

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.