Okay, welcome everyone. We're in the home stretch here. I'm very pleased to welcome CG Oncology for what should be a very interesting and exciting discussion about [cretostimogene grenadenorepvec], which is making its way towards registration now. By the way, I'm Josh Schimmer from the Cantor Biotech Equity Research Team. I'm pleased to be joined from CG Oncology by Arthur Kuan, Chief Executive Officer and Chairman, and Ambaw Bellete, President and Chief Operating Officer. Gentlemen, welcome. Let's set the stage, telling us where CRIDO is now in its evolution towards becoming a leading treatment for NMIBC.
Thanks, Josh. Very happy to be here. Just to set the stage, we are about to file our first BLA in the BCG-unresponsive, high-risk, non-muscle invasive bladder cancer indication. This is an indication that probably addresses 25,000 patients in the U.S. What we've shared this morning is our 24-month CR data. This is landmark data at 24 months in all treated patients, and we achieved a 41.8% complete response rate. 46/ 110 patients achieved the CR, which is very exciting. This means that up to 42% of patients after treatment can still preserve their bladders out to two years. In context, Keytruda has a 40% CR rate at three months. That just gives you a sense of what that 42% really means. We're very excited about that. All of our efforts right now are investing in additional development work to expand the indication for CRIDO.
With that, we just finished enrollment in our second phase III trial. It's a trial that is going after intermediate-risk NMIBC patients. These are typically BCG-naive patients. These patients continue to recur, and our aim is to prevent that recurrence as a first-line adjuvant therapy. We're very excited that we enrolled this trial in less than two years, 10 months ahead of our own internal projections, which is very exciting. This is going to be the largest North American trial in this space. The benefit of this trial is we don't have to do any genetic testing, and we also include the patient type who are high grade in that trial as well, which most of our competitors do not. This is going to give us the broadest label in the IR setting. We're very excited about that as well.
All right, excellent. You're putting the finishing touches on the BLA application. What have been the gating steps and what's left to be done?
Yeah, so there are a couple of things. I'll start off first. We have previously been saying we want to optimize our label in all ways possible. The first thing is we wanted to wait for additional durability data, which today is another kind of step towards that. The FDA wants data from the first CR, and they want to see how long does that CR last. So DOR data. What we shared today is landmark data at two years. That information, of course, will be submitted. Another really important data that's coming up year-end is our two-step versus five-step. For context, [cretostimogene grenadenorepvec] imaging initially was instilled in a five-step process, which included two saline washes, a DDM rinse, a DDM dwell, and [cretostimogene grenadenorepvec] dwell. DDM is our transduction agent that allows the virus to infect the bladder more efficiently.
With the new two-step process, we're removing the two saline and one DDM rinse, just going straight with a DDM dwell and a CRIDO dwell. This will cut down the administration time by 15 - 20 minutes, which for a lot of high-volume centers, the 20-minute savings is a lot of time. We anticipate sharing those results in December this year.
Maybe take us through what happens to a patient with the two-step process when they come in. What do they have to undergo, and what physician or nursing time is required?
Sure. Thank you, Josh. From a two-step process, this means that DDM dwell, the transduction agent, will be for about 15 minutes. A patient is placed on the bed, a soft catheter is placed onto the patient. For about 15 minutes, DDM will dwell. There will be the release of the DDM followed by CRIDO imaging for about 45 minutes -1 hour, and the release of that, and then they go home. That's basically the procedure, all in about 1 hour -1 .15 hours in the office.
Is it uncomfortable at any point, and if so, for how long?
No, it's not, because this is actually very similar to the procedure that they have undergone for BCG. BCG is six weekly intravesical doses of BCG that's given in the same type of manner. In fact, from a safety profile perspective, [cretostimogene grenadenorepvec] appears to be safer than what they've undergone with BCG.
Do you expect that you'll be able to get any of the 24-month data on the label?
We expect to file with the data that we released this morning. It will be a review issue and discussion with the agency. We believe that this is the most robust data and best disease data within this class. This is actual CR that we're sharing as well. We hope to have that in the label.
We have seen some fairly significant leadership change and change again at CBER that I think has kind of called into question where regulatory hurdles are now for various indications. How are you kind of feeling about new CBER leadership and the implications for CRIDO?
Good question. Obviously, the FDA has gone through, as you stated, a number of changes, including Vinay Prasad being in and Vinay Prasad being out and coming back in. I do have to say where this is different is that there's a specific FDA guidance, the 2018 guidance from the agency around the use of single-arm trials for review and approval for the BCG-unresponsive indication. There have been three approved agents under that particular guidance. TAR-200, which has an upcoming approval now, is also going to be following on that same guidance. I think there is a preponderance of good evidence across other therapeutic approvals, review and approvals that gives us continued confidence that really that regulatory pathway is the law of the land, so to speak, from a regulatory standpoint.
From a regulatory perspective, to be able to drop those washing steps from 5-2 , what did you have to show, and was that in collaboration with the FDA?
Yeah, that is in collaboration with the FDA. Our CORE-008 cohort A, which is the trial that Arthur mentioned, that we'll have data from in December at the Society of Urologic Oncology meeting. What we're going to show is really a two-step versus five-step process from a safety and efficacy standpoint. That's in alignment with the agency of what data that we expect to show. I also want to make a point to the fact that our PIVOT-006 trial, which is in the intermediate-risk trial that enrollment was just completed, 360+ patients within that trial that included only the two-step process. All of our other trials have only included the two-step process as part of the trial execution perspective. We feel comfortable with really the direction that we're heading with the two-step versus five-step process.
Is there kind of some threshold response that you need to show with the two-step in the data that you're going to be showing and submitting?
It's mainly on the confidence interval, 95% confidence interval. There is confirmation from the FDA we do not need to run a non-inferiority trial to prove that.
CMC is something else that comes up a lot in talking to investors, again, given some uncertainty around regulatory evaluation. I know it's something you've been working very long and very hard at, maybe give us a status update. You're confident that the CMC component will pass muster on the first go with the FDA?
Sure, happy to take that. From a CMC perspective, I want to just first stress we have brought in the best people to help solve this problem. Swapnil Bhargava, who's not here today, he's our Chief Technical Officer. He came from [Compugen], AbCellera, and he has led four ADC products through the BLA process, including post-approval changes. Having him here in the leadership role, we've also surrounded him with ex-Big Pharma Head of CMCs to advise him. They've gone through 50+ BLAs. Some individuals have done that. Starting from there, we have assessed all the CRLs that have occurred in the NMIBC space. A lot of them have to do with CMC. A lot of them have to do with process changes, site changes, changing the scale. Oftentimes, there are also pre-approval inspection failures, which really has to do more with the quality management systems, facilities, utilities.
When we look at that and we assess CRIDO's situation, number one , I just want to reiterate, we are not changing the sites of manufacturing from our phase III to commercial. It's going to be the same site that supplied CRIDO for the phase III. That will also be the site that supplies for our commercial products. We're not changing the process. It's a very high-yielding and robust process. If you think about the MOA itself, this is a replication competent adenovector. It makes more copies of itself. By definition and by default, it's very high-yielding. Yield is not an issue for us. In fact, from a capacity perspective, at the current scale, we can do about 40,000 - 50,000 vials a year without scaling up. I just want to put that number out there. We're very confident in our current process and scale.
Removing those kind of obvious pitfalls that would lead to CRLs, we're ultra-focused on the other aspects, the pre-approval inspections. These are like SOPs. Did you follow the SOP? If you deviated from your SOP, did you document it, correct it? These are things that are often overlooked, and they could lead to a [Form 483] in CRL. Our team is ultra-focused on that. I'm pleased to say that our CDMO, which is U.S.-based, that makes CRIDO, has recently been inspected by CBER this year with no [Form 483s]. There's some assurance that the facility and the quality management system has already been looked at. The CRIDO process has not, but really, there's already some part of it that has been inspected by FDA.
The other aspect is we just recently announced that we acquired a fill and finish facility that fills CRIDO into vials. They have also been recently inspected by the FDA with no [Form 483s] , and our team was assisting them as well. We are focused on making sure that we can invest in the right infrastructure improvements and upgrades to ensure that they are ready for prime time when the update comes. On that front, we are doing multiple mock pre-approval inspections. We have hired ex-FDA reviewers and inspectors to really look at these plans very carefully from multiple angles, and we want to hear the real feedback so that we can correct them and improve those processes in real time.
That was a remarkably convincing answer to a question that's really hard to give a remarkably convincing answer to. Thank you for the details of sharing all that. It's amazing. Can we move to shipping and handling and what the requirements are likely to be upon approval?
Yeah, I mean, I think we've already announced 2 - 8 degrees up to 4 weeks from a stability standpoint. What we anticipate from a shipping and handling perspective, this is very similar to BCG. It's a BSL-2 status from a setup perspective, from a prep and administration perspective. Maybe I can give you an example of a patient coming in next week and kind of how that process would work, and that usually gives some good insight to what will happen. Let's say the patient is coming in next week on Wednesday. They will be delivered on a just-in-time basis on Monday or Tuesday of next week. The facility can leave it within the box for 3 - 5 days, meaning they don't have to take it out of the box.
If they have a normal refrigerator, they can take it out of the box and put it at 2 - 8 degrees for up to 4 weeks. If they have a - 60 freezer, they can also take it out of the box and put it in their freezer. There will be at least 3 different options on the way they will handle it. Really, when the patient arrives, what they would do normally, most sites would do a UA, which is a urinalysis of the patient, make sure that the patient doesn't have any active infections that are happening with the patient, and then prep the product and administer the product similar to what I stated earlier, 15 minutes of initial DDM dwell via soft catheter, followed by 45 minutes -1 hour of the CRIDO imaging dwell, and the patient leaves the office.
That's kind of from soup to nuts.
Any fridge will do? Does it have to be a special requirement for a normal BSL-2?
No, as long as it's a fridge that has 2 - 8 degrees for up to 4 weeks for the normal fridge perspective.
They can even go buy a little fridge.
You can. Yeah, those things, you know, today, they're $300 - $400, and most practices actually have it for a variety of other things. This is not something that is new to them or where they've used it.
What precautions in handling the product?
Yeah, similar precautions to what they would do for gemcitabine or BCG as well. Obviously, mask, eye protection, wear under prep, and then take it and administer to a patient.
Do they need a special hood to prepare it?
If they have a hood, they can use a hood. They can do tabletop prep as long as they're gowned and they're wearing eye protection as well.
You've shown the fridge temperature stability now out to six weeks. Is that all?
Up to four weeks.
Up to four weeks. That's all completed. Is there any additional work that needs to be?
Yeah, we are continuing that work to continue to extend that as far as we can.
We are also conducting what is considered to be shipping validation studies. For example, can you ship out to places like Arizona in the summer? Can you ship out to places like Alaska in the winter under your box? How is that being handled? There are multiple site locations where we will ship the product, open up the box, ensure that the box is stable. Those activities are also ongoing as part of our shipping validation activities.
Okay, any other filing work that needs to be done other than what we've talked about?
No, I mean, I think from a clinical perspective, our data, you know, the 24-month data that we shared, the two-step versus five-step process that we've shared, the stability data that we continue to work on, and then the normal CMC-related activities that we are conducting as well as part of that.
Any precision on when you'd expect the BLA filing to complete?
It's hard for us to give kind of that direction today. We intend to look at a rolling submission pathway for our submission strategy in conjunction with the FDA. Once we initiate our submission, which will be in the fourth quarter, we'll give additional guidance to what that roadmap looks like in terms of timeline for that complete submission.
What's the gating item for that final?
Yeah, what I can say is our view on this first submission has now changed a little bit given the 10-month acceleration of our second phase III, because that's a second BLA that's coming back to back. It's really two BLAs in a back-to-back timeframe. Our emphasis is going to be on CMC, to be very frank. All the focus and emphasis is to ensure CMC is ready for prime time.
Okay.
Because we do not want to jeopardize the intermediate-risk drug launch.
Okay, right. I get it. We'll look forward to those updates. Maybe we can turn to cohort P. All the data essentially is presented from the CIS perspective, not the papillary perspective, but patients in [BOND-003], some have papillary lesions. As we're thinking about what to expect as we shift from kind of the CR profile for CIS, how should we be thinking about papillary and cohort P and what metrics to look for?
Sure, I can take that. At AUA this year, we presented just in 14 patients in the cohort P data that was very preliminary, but the recurrence-free survival or event-free survival rate at that time was 90% at six months, right? In just 14 patients, right? Obviously, the caveat is TURBT was involved, right? You have to take that into consideration. Therefore, the two agents that have made it into NCCN guidelines were [pembrolizumab] as well as [nadofaragene firadenovec], and they've both shown about a 50% RFS at one year in about a 50-patient trial each. That is sort of the benchmark that we're looking for. Obviously, you know, well north of that would be great. We do expect to provide another data readout end of this year. Investors can also look at the CIS plus TAT1 group that were in BOND-003.
Those patients responded just as well as a pure CIS population. That is probably the toughest to treat population of all high-grade, high-risk NMIBC.
It has been hard for some companies to get papillary on the label, and you pointed out all the NCCN guidelines. You can still get access to therapy, but what do you think it is going to take? Is that an objective of yours to get papillary onto the CRIDO label?
Yeah, I would say that at this moment in time, we're focused on guidelines only. You know, if in order to get high-grade, high-risk BCG-unresponsive TAT1 on the label, a sponsor would have to run a randomized controlled trial, and that's very clear.
Maybe we can turn to some commercial considerations, even though we've just kind of scratched the surface of the development programs. It's amazing how you can make so much of one product, and you're taking a number of different really important directions. I do want to talk commercial considerations, and maybe you can frame the unmet need in HR NMIBC and whether there are certain lessons we can glean from some of the other products that have launched into that setting recently.
Thank you for that question. I think there are three approved agents within this category. If you look at the utilization of those three agents in the marketplace, it has not been perhaps as robust because there are ongoing other clinical trials that are being conducted within the same landscape in the same patient population. One thing that we have seen, if you look at it from both an incidence and a prevalence perspective, for example, there's probably around 25,000 or so BCG-unresponsive patients on a yearly basis. When you look at that patient population, there's still an unmet need that exists. There's still BCG shortage that continues to exist in certain pockets of the country. There are also patients who are looking for therapies as well that are going to actually be durable for them.
When you look at duration of response and the fact that, for example, if you make it to one year and you're in complete response on CRIDO's imaging, 9/10 patients will be in complete response at month 24. It's a compelling story. The physician-patient conversation once BCG has failed them is, "Doctor, how long is this going to work for me? Is this safe? Is there lifestyle changes that I need to undertake in order to take on this new product?" The how long factor is a big and important factor for patients. I can't emphasize that enough. We've done a lot of patient research and patient-focused discussions around this. This is part of that discussion that they have with their clinician. We believe CRIDO's imaging fulfills such an important role and caveat within this space that exists within this space.
Really looking at the landscape alone, I think, and speaking with physicians around our data post-AUA, and we will continue to speak to physicians now post this additional data that we released just this morning, we anticipate that conversation is going to be the same. The feedback that we're getting is we see at least two to three lines of therapy post-BCG in BCG-unresponsive patients prior to cystectomy. That's an important aspect of the discussion.
There's an odd dynamic that some of us have noted in talking to specialists about their practice, and it kind of gets to the point of where are these patients? I would have naturally thought you'd speak to a urologist who would say, in part because of how many years it takes to ultimately progress to muscle invasive, they say, "Wow, I've got like hundreds and hundreds of patients who've gone through BCG. They don't yet have MIBC. I can't wait for it to bring the hordes in, right, to get their disease under control." That's not really what we hear. I'm not quite sure why. Where are these, in theory, hundreds of patients? Are they out there?
Have we overestimated the market just from that?
No, I don't think there's an overestimation. Like I said, there's about probably, if you combine, if you look at both prevalence and incidence, you're looking at about 25,000 of those patients. What we have seen in looking at SEER data, Medicare data, and so on, is that there is such a huge concentration of patients in the highest volume centers that see these patients. If you speak to the run-of-the-mill urologists, and there's probably about 7,500 - 8,000 actively practicing urologists, the subset of the majority of patients are being seen by maybe 300 - 500 of those urologists. That's where they're going.
Okay. When you talk to those practices, they tell you about them.
Yeah. I think that's where the majority, if you look at decile 10, for example, which is the top decile that look at these patients, there are 69 facilities that are the top deciles in the country, where 10% of the nation's volume is concentrated in just 69 centers. That's just, you know, one example of the data.
Okay, got it. You're also running a study in the treatment-naive setting. You know, there is a standard of care that's not a bad standard of care in BCG for those who are able to access it. How do you think you can differentiate data-wise in a first-line setting?
Yeah, our first-line high-risk BCG-naive trial will read out later this year in the monotherapy setting. Our view is that BCG as a monotherapy works really well. It's just that there's always been a supply issue, a shortage issue that's been here since the 2010s. The goal there is to first establish monotherapy response, see how single-agent activity is, and then hopefully build upon that. Right? We have demonstrated, unlike other agents, that CRIDO can be the backbone, and we can add on additional therapies. To that front, we have another cohort that's almost fully enrolled called Cohort CX, which is CRIDO plus [gemcitabine], which we're very excited about. We have a lot of preclinical data to show the synergy between these two agents when given in the right sequence and dose level.
That would be another one that's not quite in the first line, but in what we believe to really be as close to the first line as possible. It's in the BCG-exposed population. There are about 26,000 high-risk BCG-naive patients coming to the market every year. Most of them are going to get some dose of BCG, one, five or six, right? They're all going to flow through and become exposed right away. Our focus in the next 3-5 years is actually going to be shifting towards the BCG-exposed population, right? Neither naive nor unresponsive. It's a wide net.
If you're combining with gemcitabine, that would seem to give you kind of that trump card of data, where you're leveraging two mechanisms that, as you point out, may be synergistic. Is that a regimen that you could go against BCG in a treatment-naive setting and feel confident you may be?
That's a great, great point. I think the question with BCG-exposed as an indication is, how do you get a label? Do you need to get a label? Obviously, the control arm should be BCG. That has been the challenge with development in this space. I think more dialogue and more data as they become available would be important to discuss with regulators and KOLs. On that front, we have two trials in the exposed setting. We have [CRIDO Monotherapy] in Cohort B and then Cohort CX, which is CRIDO plus [gemcitabine] in the exposed setting. At least we'll have the mono data and combo data, and then we'll be able to see. There are other cooperative group trials that are running exposed trials right now or about to, using BCG as a control. Hopefully, we'll be able to learn from those experiences as well.
We spent most of 2024 into part of 2025 on the back and forth with TAR-200 and [Johnson & Johnson], and a data set that seemed to really, their data set really fizzled at AUA 2025 while yours really shone. Now you can do something here that they can't, right? Because TAR-200 is gemcitabine and a pretzel, in a device. They can't combine with CRIDO unless they come to you, but you can combine with GEM as you're doing. How are you thinking about that emerging profile and then going from your initial phase II data into another data set that can really start to pull away from TAR-200 even more than I think you've started to do?
Yeah, I mean, I can get started and Arthur can also chime in here. I think I probably would go back to what has been kind of our goal with [cretostimogene grenadenorepvec] and really making it backbone therapy between the intermediate-risk category and the high-risk category and all points in between. If you look at our development programs, they focused in the high-risk disease states. We've conducted our BCG-unresponsive trial, which would be our first indication. We have an ongoing trial in the BCG-naive patient population. We have another trial in the BCG-exposed patient population in addition to the intermediate-risk trial. Some are monotherapy and then some are combination therapy. We've released data already on CRIDO plus [pembrolizumab], for example. We now have an ongoing trial with [cretostimogene grenadenorepvec] plus gemcitabine. A part of our goal is to make [cretostimogene grenadenorepvec] backbone therapy within this space.
That's what some of the unique differences are that we believe we'll be able to bring to market alone. We already have the best-in-disease data when you look at monotherapy, when you look at efficacy, when you look at safety and duration of response perspective. We really are looking forward to bringing that forth into the marketplace. We know that they have an upcoming approval into the marketplace. We'll learn a few things from their launch. We hope that they're successful because we do believe there's a unique opportunity for us to go into that marketplace. We also have a chance to see what their price point will be as well, which will further give us an understanding of what the opportunity is. As you know, this landscape has a wide price band, somewhere from $200,000 - $600,000 per year.
We think that understanding that element will allow us to actually come back into the marketplace with the right price point for us that will incorporate our target product profile, our potential length of treatment on the product in itself, which would be a big determinant for really the overall value of what we think [cretostimogene grenadenorepvec] can be into the future.
I feel like we could literally spend the whole morning talking about [cretostimogene grenadenorepvec] , but we have to call this session to a close. Arthur and Ambaw, thank you so much. Looking forward to the next updates from CG Oncology.