RB/E2F1 pathway. On the right-hand side, as you'll see, upon selective viral killing, it's going to release cytokines as well as tumor-associated antigens, and hopefully lead to a priming of an antitumor immune response that we believe actually translates into the long tail that we're seeing in our clinical studies. Credo is actually given via a catheter that fits seamlessly into a urologist's workflow right now. That's one of the key points. It performs the same way that BCG is given right now. There's no retraining or education on that part. We do a transduction agent treatment called DDM, about 15 minutes, and then Credo is administered shortly thereafter. The patient could dwell in the clinic in the waiting room or also go home, right?
It's actually a very seamless procedure that does not require you to change the current practice workflow. In the next few slides, I'll talk about a couple trials that we've been conducting, and some of them already have data. This BOND-003 trial has a couple cohorts. Cohort C currently is the first cohort that we plan to submit to the FDA. This is the BCG arm responsive CIS cohort. In this cohort, we've already shown some data. As you can see here, the CR rate at any time in over 110 patients is 75.5%. What's remarkable here is the actual observed CR rate at 12 months is 46.4%.
Then if you look at it from 12 months to 24 months, basically 90% of patients with a CR at 12 months remain in a CR at 2 years. That is something that none of our competitors have been able to show, right? If you look at the far right- hand, Keytruda only has a 9% CR rate at 2 years. We believe when we approach patients and physicians with this data, coupled with the fact that we don't have any grade 3 adverse events related to the drug, this is a very compelling profile for patients who want to save their bladders. This is data from our cohort P of the BOND-003 trial. This is going after patients that have papillary disease without CIS.
These tumors are resected at baseline, and then we give Credo as an adjuvant therapy. As you can see here, Credo, you know, although it's still early, it's still trending in the right direction. We're going to have data on this later this year to show additional 12-month data and beyond. This population will ultimately be used for guideline submission, and we can talk about that later. We're, you know, very encouraged to see that Credo can also be used as an adjuvant therapy. PIVOT-006, I think this has been a key focus for a lot of folks. This is a trial designed in the IR adjuvant setting. As I've mentioned, there currently is no FDA-approved therapy in the adjuvant setting for IR disease. We followed the AUA/SUO guidelines.
What's differentiating about this trial is, we're the only company that includes the high-grade Ta less than 3 centimeter solitary lesions in our trial. More on that later, that's a key differentiation for you to remember. The endpoint here is recurrence-free survival. Here's just a summary of how this design compares against some of our competitors' trial design. As you can see on the left-hand side, you know, Credo in PIVOT-006 design, we cover newly diagnosed patients, recurrent patients, high-grade Ta patients, and this is given as an adjuvant therapy, right? Because these patients have a visible lesion in the bladder, and urologists are surgeons, they want to resect that tumor. We believe PIVOT-006 really addresses, you know, many of the concerns that the FDA has or the urologists have.
This is the ideal trial that we believe, you know, needs to be run in this space. Also, we don't have any restrictions with FGFR wild type or mutants at all. This is another trial that we've started last year, and there will be data coming out first half of this year as well. Essentially, we're trying to look at the combination potential of Credo with another intravesically delivered agent. In the past, you may recall, we've already done Credo plus Pembro, and that boosted our response rate by about 10% absolute delta. However, as you know, Pembro is not something that urologists would give on a day-to-day basis.
In light of that, we're looking for two agents that could be given at the urologist's office, gemcitabine, based on our preclinical data, has shown a lot of synergy with Credo. With this trial, you can expect some early data coming out first half of this year, and hopefully could then inform us on what to do next. Within the CORE-008 trial, we tested Credo in a BCG-naive population called cohort A. In this population, I think the goal is to demonstrate that Credo can also work in the BCG-naive setting. We, of course, understand that BCG works really well in a naive setting. Here it's really encouraging to see, for example, in the optimized installation cohort of patients, we saw an 88% complete response rate.
I think this just further adds to the body of evidence of what Credo can do as a potential backbone therapy in this setting. Here, you know, as we think about commercial launch, our key leadership team are already in place. We already have a team of MSLs calling on key accounts, really, starting with profiling work. What's important about this slide, I would say this is an indication where it's hyper-concentrated, right? It's really driven by a few factors. The shortage of BCG, right, that compounded over 10 years, enriching all of these key accounts. Another driver is a lot of the private practices are being acquired by private equity group. Cardinal Health is one of the largest owners of LUGPA right now.
Those factors combined makes this a very concentrated business, and Ambaw, President and COO, will further, you know, explain that as well. We're really excited about launching in this setting because, you know, really just 300 accounts would account for more than, you know, 70% of the business that we're talking about. The last slide here, I'll just leave everybody with some of the upcoming catalysts that are coming this year. I think one of the most important things this year is the completion of BLA filing, but as you can see, there are also additional data readouts that are coming, including the top-line data in PIVOT-006, as well as Cohort CX , which is Credo plus gemcitabine in the exposed population, and we've also tested that in the unresponsive population.
With that, Tyler, I'll pass it to you for any Q&A.
Perfect. Thanks very much for that presentation, Arthur. I'm joined here by Ambaw as well. Before we get into the specific indications, though, I just have to follow up. You've got obviously the lead BCG unresponsive HR indication. You got exposed, naive, papillary, intermediate risk, a lot of different indication expansions. You gave the patient numbers, which is obviously very significant. Have you guys ever put that into $ and just talked about the potential market opportunity from a $ perspective, starting with the lead indication and how that expands? I mean, we have pricing now, and if you just multiply that across those patient populations, the TAM becomes ridiculous, right? You know, if you factor in penetration, what are your thoughts on that?
I mean, I would say that really we haven't given any type of direction in terms of what the market opportunity looks like in terms of guidance. I think what we've looked at is, obviously we've got the barometer of what's the pricing within the landscape. It's $200,000–$700,000 a year, for example, in the BCG-unresponsive marketplace. When you look at the opportunity, just the first two indications, let's just focus on that. A few things to have to think about is what are the total number of doses in each of those indications? For example, for cretostimogene and BCG-unresponsive is up to three years, 30 doses over a three-year period. In the intermediate-risk area, it's 14 doses across one year. That's really from a treatment perspective, and it's gonna be price per dose.
You have to look at it from that vantage point. The factors when it comes to pricing, which relates to market opportunity, are really what's kind of your TPP, what's your target product profile for your product? What's your expected length of time on treatment that we expect on average for it? Obviously, you can apply the efficacy factor, so to speak, to cut down that number further down, and really penetration ramp. That's the other piece of that equation. You know, so once we're able to better complete our pricing studies, which are underway now, I think we'll be in a better place to kind of give that look and view.
I think if you look at the latest available product, for example, into that marketplace, I think it set a new watermark, so to speak, on a dose basis, but that's 10 doses per year, for example. We have to look at it. Does it become total cost of, you know, at the year-end, what does that look like? Those are some of the factors that we're looking at. We think the opportunity is large and huge. I think it will settle out really how well each of those therapies penetrate into that landscape and marketplace is kind of our view today. I don't know if you have anything else to add.
How do you think about, retreatment, right? That's another unique angle here, right?
Sure.
These patients don't usually get treated just once. What do you expect with these novel therapies in terms of retreatment over time?
I mean, I would start by. I think BCG-unresponsive disease is different than intermediate-risk disease. We don't have reinduction in an intermediate-risk NMIBC, but we do with Credo in the BCG-unresponsive, you know, landscape and also in the BCG exposed future landscape that we're looking at in the next phase of our trials. I think it's mechanistically, you know, MOA or mechanism of action plays a role, whether or not that would work. We've shown that there is a 50% conversion rate to CR. Those patients that were reinduced, 50% of them converted to a complete response upon reinduction. We see that it works, and it works really the mechanism of action of Credo allows it to work in that manner.
Great. Now we'll get into the BCG-unresponsive high-risk NMIBC lead indication. Question that you've been getting from everyone is: How is the preparation for the BLA going? When might we get the next update? Could you guys submit tomorrow? Where are you at currently?
I mean, I'll start on that. We've already initiated submission. We, you know...
Finalize.
I think, the next question becomes when is that going to be complete? What we've stated is that we will complete in 2026. We will give better guidance soon as to what that means in terms of, you know, what modules have gone in and really, based on some waiting, so on some additional feedback from the agency around what that timeline would look like. We hope to give some guidance exactly when that would look like over the coming weeks and months ahead.
I think one of the things that we looked at also is. At the beginning of this year, the FDA announced that for cell and gene therapy products, a new greater flexibility in terms of CMC package, data package submission, when it comes to clinical as well as commercial, flexibility and process validation steps of flexibility. We're really in dialogue around the agency of what that truly means for our respective package, and better understanding of that, I think, will allow us to better calibrate and really give further guidance and maybe better triangulate the timelines as well further for the market as well.
Got it. In terms of activities and to complete the BLA submission, it's primarily CMC facility-related process validation. Is that fair to say?
Yeah, I think that is fair to say. I would say so, yeah.
Is it, the manufacturing process seems to have been locked in for quite a while, right? It's primarily what happens after the credo is manufactured.
Mm-hmm.
It's the fill- finish facility and that final step of the manufacturing.
Yes.
Yeah. I mean, just to, you know, give you some color on that.
Yeah.
From a clinical data perspective, it's pretty clear what the FDA is looking for, right? I mean, basically, they're looking for the length of CR lasting at least 12 months from the initial CR, right? It's that kind of detail on a manufacturing standpoint, right? 'Cause obviously, we've made batches and batches of credo.
Mm-hmm.
These are GMP-grade products that we put into patients, you know, reviewed by FDA. We know how to do that. There's just obviously a higher standard when you go from clinical to commercial CMC. A lot of that has to do with exactly what you pointed out. It's around the inspections of the facility, right? You know, I think we now have a component of that within our hands and our control, right? It's the fill finish facility, those are the areas of focus. I believe we've put the right people around the table to help us address these matters.
Got it. Whether it's involving consultants or doing mock inspections or all of the above in terms of finalizing that, you guys are just making sure that you are 200% confident that you're gonna be ready by the time you finalize submission such that you guys are ready to get approved, especially given the upcoming IR data. Is that fair to say?
Yeah.
That's right.
Yeah.
That is. That is true.
Just to add on to that, the IR opportunity, obviously, you know, we now have a lead time relative to TAR-210.
Mm-hmm.
Right? That lead, I think it's pretty exciting, you know, for us to see, we definitely wanna make sure we put enough time since the two filings all share the same CMC package.
Got it. Okay. Besides completing the BLA submission, how are you currently preparing for launch with respect to building a sales team, a commercial team? What's that process like? Where are you at?
Yeah. I mean, I think we've been in pre-launch, really over the past, 15 plus months, now and really all of, you know, heading into 2026 as well. We are right in the midst of that. What we have put in is really are the components of that, pre-launch activity. Our field medical team, for example, has been in the field. Our health systems directors are already in the field, and we're adding on to that team, and they're responsible for profiling the largest value customers around the country.
Again, our national account team is interacting with payers across both regional as well as national payers as well, and continuing to do landscape assessment of what's happening from a payer landscape with all the new available therapies, zero level of controls that are being put in place, utilization management, and so on and so forth. We're building upon that. We have a T-minus plan. T-minus a projected date of plan that we're adding on additional resources such as our field reimbursement staff, our regional business directors, our key account managers as well as part of that build. We're expecting around 75 to 80 individuals that will be part and component of that team to be put together.
We're very fortunate that the team we have already assembled have a tremendous amount of track record within bladder cancer itself, which is rare to get, and we're very fortunate to have hired that team already in place.
The, you know, data is obviously half the battle when it comes to launching a new product, and you guys obviously have great data. I guess in terms of the other half, are there any learnings from past launches in the space or from the J&J launch to date, even though it's still early, that you can elaborate on and that it's impacting your commercial strategy?
Yeah. I mean, look, this is the first probably unencumbered launch, as I would say, meaning that the TAR-200 launch is really a full-on market launch without any type of limitation. When you look at it's a great proxy for us to look at, we've been studying that launch very closely. I would tell you in a few areas that are of critical importance the way we view it. Number 1, who's actually prescribing the product first? Who's actually using the product first? Number 2, how are they purchasing or accessing the product? Are they using specialty? Are they buying direct? Who are those customers? How long is it taking academic facilities to get it on their formulary? We've seen a range of 6 to 8 months or longer. How long is that? Are they buying direct?
Are they using an office dispensation? These are all the learning pieces of it. How is decision-making being made in that practice? Meaning if they have 50 person, you know, group, for example, is it 1 or 2 physicians? Is it 5 physicians, and so on? We're learning all of those things and incorporating that into our launch plan.
That's great. Maybe a final question before we get to intermediate risk. On the label, on approval, do you expect any differentiation there relative to TAR-200 or Enlexo?
I think I would say the data that, we've generated from a DOR standpoint, is certainly already, much longer than that, than the TAR-200 label.
Yeah.
As I've mentioned, patients in this, you know, with this disease, they really care about preserving their bladders as long as possible. We're certainly gonna lean into that. What might not be on the label, but it's just as important, is the fact that in the BOND-003 trial, we have patients who have failed prior GEM, prior GEM dosi, right? That's another segment that, you know, Ambaw team, they're definitely gonna, you know, stay focused on because that's a setting where it's gonna be difficult to convince a doc to give more chemo.
I would say really from a strategy perspective, we're looking at it as a first choice opportunity for cretostimogene. That's our message.
Yeah.
Our data shows that we can be that first choice, and that's what we're focused on delivering upon that.
On the durability, you guys have set an impossibly high bar for Enlexo. I look forward to seeing their 2-year data because I'm pretty sure it's gonna be lower than yours. All right, let's move to IR NMIBC.
Sure.
Maybe you could talk about what investors should expect to see from this top-line report that's been experienced an incredible acceleration that we're gonna get by the end of the first half. You know, given the fact that, how do you expect the high-risk data to translate to intermediate risk? Are there any key biological differences in these patient populations? Again, what should we expect?
Sure. I would say, you know, the benchmark in PIVOT-006 has been, one of, you know, kind of just drawn a lot of attention. We've been saying consistently that after we started PIVOT-006, we learned about the ATLAS data, which is, you know, a trial that, of... you know, didn't complete. It was underpowered. We still look at the control arm, and to just, you know, gain some insights as to what that control arm could do, which is just TURBT. You're seeing about, call it 50% RFS at the 15-month range or so, right? You know, we think that might... Obviously, there are many differences between PIVOT-006 and ATLAS, right? Namely that, we enrolled most of our patients from North America.
We also allow for high-grade Ta less than 3 cm to be included. Those are kind of the top differences. You know, we think from a relative risk reduction standpoint, a 30% relative risk reduction is what a lot of clinicians would view clinically meaningful. One of the key features of our trial is we also allowed for a single-dose perioperative chemotherapy. In the U.S., maybe up to 30%-40% of patients are being given a single dose of chemo right now, right? That gets incorporated into PIVOT-006, and obviously, you know, we're stratifying against that variable, so it's well balanced. You know, those are the things that we're currently guiding right now.
Okay. With the, top-line report, we'll likely just get a hazard ratio. Could we get like 3-month rates or 6-month? Should we think about, you know, the different endpoints that will be reported on?
Yeah. The primary endpoint will be available, which is hazard ratio, right? Obviously, we'll also share, you know, you know, the median length of follow-up. As to landmark data, the 12-month landmark data will not be part of this update, but that is a key secondary endpoint, as well as 24-month RFS. Those will be available at a later time point.
Got it. Got it. Okay. In terms of completing the BLA submission with high risk, how soon after do you think you can submit the BLA for intermediate risk? Is it possible they both get submitted together, or do you expect kind of a gap between the two?
I think we would expect a gap. You know, if you look at it, you know, the PIVOT-006 trial, last patient in was last September. You know, 12 months after putting together a data package for submission to the agency, you know, we suspect and what we've guided is that we will file in 2027, you know, based on how data comes in, data cleanup, and readiness for filing. Some elements, as Arthur mentioned earlier, since they share, for example, the CMC data package will be easy. Obviously, those things will be kind of done already that we can utilize, but still preparing the data package and so on. We see that the BCG unresponsive package will be completed, and then, after that, you know, we will file the intermediate risk trial package.
Got it. The longer-term 12-month RFS rate data, the earliest it could come is like at the very end of the year or early next year probably, right?
Somewhere in that category, yeah.
Given that September. Yeah.
You got it. Yeah.
Okay. Just, again, you touched on this briefly with intermediate risk versus high risk.
Mm-hmm.
You know, obviously the market dynamics are a little bit different. Pricing's a little bit different.
Sure.
Difference in doses, you know, and the number of total doses being received by the patient.
Mm-hmm.
You know, it'll be the total cost the patient will be different clearly. It'll be much higher in high risk than intermediate risk. How are you guys thinking about that? Can't really charge a different price per vial, obviously, right?
No. I mean, these are Part B products, so just by the nature, very nature of how these products are priced and reimbursed more than the pricing element of it, we can charge different price points, you know, based on the different disease states. If we had a different NDC number, different product, and so on, yes, but this isn't the case. As I mentioned earlier, you know, there's about 30 doses across, you know, 3 years for BCG unresponsive disease, about 14 doses in the intermediate-risk area for 1 year. So just effectively, you're about half in terms of from a dose intensity perspective and also obviously overall price when you look at it price per dose as well.
Yeah.
It's probably a good way to look at it.
All right. You multiply that with some sort of penetration of the patient numbers. Obviously both large multi-billion dollar potential markets.
Yeah. Sure.
It's fair to say that high risk is probably gonna be a larger opportunity than intermediate risk, right?
I think it's too early for us to kind of give that guidance of which market would be higher than not because, you know, the persistence on therapy is an important determinant of it. You know, we have patients that in our BCG unresponsive state that wanted to continue on therapy. We have some that, you know, at month 36 on forward, they may feel differently. I think, you know, till we see kind of the real-world opportunity, it's really hard for us to delineate and say one is bigger than the other and so on and so forth. You know, from a $25,000 versus $50,000, yes, for sure. How well we penetrate each of those markets, I think will determine the level of how much of an opportunity it is within those segments, is what I would say.
also realize that this is the first adjuvant, you know, branded product within, at launch, within this landscape, and we've got a two-year lead, you know, for many other assets coming into the space. That's a little bit of the nuance and differences versus coming in into the BCG unresponsive marketplace where, you know, our mantra and really approach is first choice for patients with BCG unresponsive disease. That's still, you know, a four-product market already that exists. I think there are nuances to those, and penetration will play a role, number of doses will play a role, and those are kind of some of the variables at stake.
Okay. Fair enough. The Cohort CX data of Credo plus gem that you mentioned.
Mm-hmm.
Can you talk about what sort of data you'll present this year and what you think you need to show in terms of efficacy to move the combination forward?
Sure. In the CX cohort, we've enrolled patients who are both BCG exposed as well as unresponsive. As you know, the definition between exposed and unresponsive is really a very fine line. Right? We expect them to potentially behave, you know, similarly, right? We already have robust unresponsive data. We've shown some data with pembro and Credo combo. All right? That led to, you know, a response rate in the 80s, right? Initially.
Mm-hmm.
Early on, I think we're gonna show data from a first result standpoint, just basically, you know, just an event-free survival number as well as a CR rate number in the CIS population, right? Durability will come after. This is a study that we've enrolled about 50 patients or so.
Okay. You guys also have papillary and BCG naive data later this year. Lots to focus on, but we're out of time. Maybe just to wrap up, we'll ask you both what you believe is the most underappreciated aspect of the CG story by investors right now.
Yeah, look, I mean, there's, it's a long time in the making, but I think we have the benefit of being a fast follower, and we can really learn from what others have fallen short of. You know, we think the initial indication, high-risk BCG-unresponsive continues to be very exciting to us.
Great. With that, Arthur, Ambaw, thank you very much.
Thank you.
Thank you. That was great.