Started again. Welcome back, everybody, to the 2025 RBC Global Healthcare Conference. My name is Greg Renza, one of the Biotech Research Analysts here. For our next session, we're pleased to have CG Oncology joining us from the company's President and Chief Operating Officer, Ambaw Bellette. Ambaw, great to see you. Thanks for being here.
Thank you.
A lot to talk about with CG Oncology. Certainly, one of the really interesting stories over the past year-plus coming to the public markets. In addition, a great deal of data generation with your lead program, cretostimogene. Maybe for those who aren't as familiar as we are, maybe a brief introduction, Ambaw, to the company, to CG, an overview of cretostimogene in the non-muscle invasive bladder space.
Sure. Thanks again for the invitation. You know, at CG Oncology, we really are focused and dedicated to patients with urological cancer. Our goal has been really to enable patients to live with dignity as well as enhance quality of life. To that end, we've developed and plan to commercialize our first potential backbone bladder-sparing therapeutic called cretostimogene for patients with non-muscle invasive bladder cancer. Cretostimogene is an oncolytic immunotherapy with a dual mechanism of action, really designed for bladder cancer treatment specifically. At the most recent American Urological Association meeting, we reported the best in disease durability and tolerability from our pivotal trial, BOND-003 Cohort C, for the trial of cretostimogene in patients with high-risk non-muscle invasive bladder cancer who have failed the standard of care, which is BCG.
The next course of treatment would have been radical cystectomy for those patients, which is the complete removal of the patient's bladder. Really, however, many of these patients, as you can imagine, prefer to keep their bladder. Really, despite the potential risk of muscle invasive disease or metastatic disease due to the high complications of this disease, morbidity and mortality rates, as well as post-surgery quality of life, they've selected to be on this type of therapies there. We believe that the data that we presented on cretostimogene really so far has the potential to shift the current treatment algorithm in patients with non-muscle invasive bladder cancer.
That's great. And a great deal to cover when it comes to the data updates just in April, right, at AUA. It's good to set the stage in the high-risk BCG-unresponsive. Maybe walk us through how the 12-month CR, the 24-month CR rates, and that duration really fare, and put that into perspective for us. We know, as you're mentioning, the importance of bladder-sparing approaches, the importance of durability. And frankly, at AUA, I think you sort of laid all that nicely out in a narrative. That 46% 12-month CR, the 34% 24-month CR, maybe put that into context versus a standard of care and also other competitive agents.
Sure. You know, really with the caveat that cross-trial comparisons are not always the easiest, and they're often difficult to do, I would say that pretty much cretostimogene at the AUA meeting really showed up as having the best in disease durability and tolerability from that vantage point, offering really distinct advantages compared to existing therapies such as TAR-200 or the approved therapies such as Anktiva or Nadofaragene or Pembrolizumab. You know, our conversations with urologists really have been around what are the key metrics, clinical metrics that they have discussions with their patients on. One is, does it work for me? How long is it going to work for me? And what are the side effects that I should be on the watch out for with this type of therapies?
That's really where they felt KRITOS Imaging really scored highly in terms of what they feel like they can offer to their patient. The other really very important key metric was around cystectomy-free survival. We showed a 97.3% of patients really were free from progression to muscle invasive disease at month 24. That means that if you are in CR on month 12, nearly nine out of ten patients will be in CR at month 24. It's really a very key metric that a lot of physicians are now really coming to really better understand what the durability and the importance of that durability is.
I'll say again, but you've had nine ongoing CRs that hadn't reached 24 months. Certainly quoting the data that you have from 12 to 24, but how should we think about even those nine with ongoing CRs?
Yeah, I mean, I would say that the 34% or 33.7% at month 24 is the floor. It can only go up from that point because we do have nine patients that are still pending evaluation and assessment. Our goal has really been to capture that data and incorporate it into our overall submission packet to the agency.
That's great. Okay. You mentioned cretostimogene oncolytic-based IO mechanism. Maybe go a little deeper into that. Do we have a hypothesis regarding this underlying mechanism that might enable cretostimogene to outperform other agents, including those approved therapies and earlier and current candidates that you've alluded to?
Yeah. I mean, you know, cretostimogene was designed with two modes of action. One is really oncolysis, oncolysis component whereby cretostimogene selectively targets and kills cancer cells without destroying the healthy cells. I mean, that initiates a whole cascade of cytokine and tumor-associated antigen release. This is driven by the E2F promoter that we've inserted into the cassette. That really acts as a master safety switch for cretostimogene. Second is immune priming. You know, what we mean by immune priming is whereby the insertion of GM-CSF, that cytokine built into the cretostimogene, primes the immune system to induce durable immune response, specific immunity for patients. Thereby, the clean safety profile, the sustained duration of response comes really from that element.
Okay. Okay. Maybe just cover some of the reception. Obviously, the data, the clinical data, which is really what physicians are always swayed and intrigued by. Even when it comes to understanding and acknowledging that MOA, I mean, certainly a novel one, how do we think about this driving receptivity as well as adoption when it comes to the clinical data, pairing that with the unique MOA that you've been characterizing?
Yeah. I mean, the physician community, along with the patient community, has been very, very responsive to our data. In fact, that's one of the reasons, for example, our PIVOT-6 trial is really now going to be able to finish up a whole six months in advance of our projected timelines of it. The increased interest by clinicians as well as the patient community has been very tremendous. We've really tried to deploy our clinical trial programs. We have six ongoing programs throughout those large community centers where many of these patients are seen. There's been a great interest in actually the deployment of Cretostimogene as part of their armamentarium of treatment for their patients, even in the clinical trial setting.
Great. Great. Of course, the other stakeholder where we want positive reception is with regulatory agencies. Certainly investor focus does preside over what you're going to do with this ongoing data set on the BLA filing preparations. For those of us who don't know, just walk us through what your committed timing is and the depths.
Sure. I think we've indicated that, you know, we will initiate filing the second half of 2025. Really, we're very engaged with the agency to finalize our approach from our filing strategy perspective. Our goal has always been to have a very optimized package insert for commercial success. Really, that is critical, especially when you're coming into a market where there's already three approved agents, potentially a fourth one that could be coming to market. What do we mean by that? I'll give you some additional picture as to what we mean by that. That's like, for example, the two-step versus five-step process that gives us for higher throughput when it comes to its implementation in clinical practice. 24-month data on all patients. We have nine patients that are still pending.
Getting that data on those patients is essential and a very important key metric for us. Those are some of the things that we're doing to optimize really for success of CG Oncology. That optimized label really will help us in the commercialization of CG Oncology into the marketplace.
That's helpful. So we've covered some of those gating factors, the nine patients. Everyone is interested in when it's going to start, which is starting the submission. What is reasonable to expect as far as completing the full submission? We think about the full life cycle of the submission, the various modules that you're lining up. Do we have a sense of that timing?
Yeah. I mean, I think it's hard for us to really give a certain guidance today of what that timing would look like. I think once we initiate, we'll be in a better position to really give further guidance around that. We're meeting with the agency with a high degree of frequency around our submission strategy. That will inform us in terms of once we initiate that filing, what that timing will look like.
That's helpful. In terms of administration of the treatment, many of these instillations, many of these new therapies entail unique administration. I want to talk a little bit about how you navigate that, the complexity, I'll call it, of cretostimogene administration. There's saline, detergent washes. Maybe others in the landscape have different protocols. Maybe with cretostimogene, there could be some degree of nice integration with current workflow. Maybe walk us through the key features of cretostimogene administration and how you think that compares and fits in.
Yeah. I mean, this is very similar to what patients will undergo for BCG treatment. The big difference would be the DDM wash. Again, this is a product that is intravesically delivered into the patient's bladder via a catheter. The first part of that instillation process is DDM. DDM is given to remove the GAG layer to increase infectivity of cretostimogene. So that is about 15 minutes of DDM use, followed by cretostimogene for about 45 minutes. All in, you're looking at about a one hour procedure. BCG procedure is about an hour and a half. If you look at a gemcitabine procedure, which is another product that's used in this particular space, it's about two plus hours just because of the two different medications that are there. That's probably the range I would give in terms of that time.
That's great. Maybe just remind us, as part of the care team in the clinic, who is doing what? Who is administering and performing this? Which support team is also required as we talk about the labor involved?
Sure. Maybe I can even give you an example of how a patient would be treated. Maybe that's actually a good way to give it as a reference. I'll give you kind of the supply chain element of it as well. Let's say the patient is scheduled for today to come in today on a Wednesday to get cretostimogene administered. The office will receive the product either on Monday or Tuesday for administration on a just-in-time basis. They can leave the product in the box for up to five days because it's shipped at negative 60 degrees Celsius, or they can take out the product and put it in their normal refrigerator. The patient comes in on Wednesday for their scheduled time. Let's say it was 11:30 A.M., for example, which is when we're talking now. I would say that the patient will then be checked for any active infection.
They'll do a UA. Some offices don't do a UA. They will prep the product. That prep takes about 10 to 15 minutes to take it out, to thaw, and prep the product for administration onto the patient. The patient will walk into any clinic room or any infusion type of facility, and medical assistant or nurse can administer the product via a cath. All in, in the office, you're talking about an hour and 15, an hour and 30 minutes, and an hour. That kind of describes to you what that process looks like.
Great. Great. You touched a little on manufacturing. Maybe just share a bit as to where we are, where you are with manufacturing. Certainly in this environment, of course, over this first quarter, a great deal of interest from investors, but also from the larger population, just about supply chain production, U.S. versus ex-U.S.. What can you tell us about cretostimogene going in manufacturing?
Yeah. From a manufacturing process, we make cretostimogene in the U.S.. Cretostimogene is manufactured completely in the U.S.. I'll repeat again, with a top five global CMO manufacturer with a significant presence both in the U.S. and ex-U.S.. Our process is very high yielding. We use really single-use bioreactors to allow for optimized manufacturing campaigns. Therefore, we believe our current scale that we're making is able to address our first indication in BCG-unresponsive disease. We plan to scale up for our future indications, such as in the intermediate-risk area. That is really the focus of our approach in terms of our CDMO strategy or manufacturing strategy.
That's great. Okay. So we covered in the U.S., for those that missed when my mic fell off, covered the workflow, the scalability as well, and also your going in on capacity. Maybe as you think about some of the lessons you and the team have learned when it comes to other product launches that have targeted BCG-unresponsive high-risk non-muscle invasive bladder, maybe some of those have been limited, some of the adoption. How will your strategy differ? Maybe account for that? What are you learning from those experiences, those launches?
Yeah. I mean, I think you really do not usually get an opportunity to see how other launches have happened in your category. This is a unique marketplace where there are three available products. We can learn a lot from what they are doing in the field, how customers are adopting it into their clinical practice, what are the challenges that they are facing in terms of the procedure itself, whether it is the buying process, where they are keeping it. All of those aspects are all the key learnings that we are taking. We already have a team of medical science liaisons already calling on customers today. They have been calling on customers since last year. We are taking real-time feedback as to how those launches are going in terms of what is happening in the field. I would say a few things.
First of all, I think each of those products, whether it's Anktiva or Nadofaragene or Adstiladrin, have their own sets of kind of variables in terms of launch success. They're also, we're launching into a marketplace where there's significant demand from clinical trials zapping a lot of those patients. I think it's an important factor in terms of adoption as to what has happened. When you've got multiple trials that are currently being conducted in that same indication, a lot of those patients are going into clinical trials versus being on a particular product and so on. There's also been what I call executional type of related items that we've observed in terms of how they've executed in terms of their launch strategy, whether they used an outside sales force versus an inside sales force of their organization or not.
Those CSO utilization has also impacted some of that, I would say.
That's great. Very helpful. Maybe we'll move on to BOND-003 and Cohort P, how you think about commercialization. Also, in this papillary-only cohort, you shared some early data recently. Just remind us of the three- and nine-month, I believe it was 91% in 2024 patients. How does that fare? What are your next steps and when will we see some additional updates?
Yeah. I mean, we shared at the American Urological Association meeting this past April our early data on 24 patients, both at three months and nine months for cretostimogene at 90.5%, high-grade recurrence-free survival data is what we shared at the meeting. We will have the full data set later on this year in that sub-cohort of patients, Cohort P, which are BCG-unresponsive patients that have only TaT1 disease only. So we'll be sharing that data. Pembro has shown their three-month data at 87.7%. Nado reported 72.9% at three months. N-803 did not report or Anktiva did not report their three-month data, but they did report their 12-month RFS data, which was about 55%. We really are encouraged by the data that we've seen, the 90.5% that we've seen for cretostimogene.
If you look at TAR-200, which also reported their six-month and nine-month RFS numbers of 85% at six months, 81% at nine months, really we do show that we continue to be best in disease in terms of response rates with respect to TaT1 disease.
Okay. And what is the commercial potential for cretostimogene in papillary?
Yeah. I mean, I think we look at the totality of BCG-unresponsive disease, which is made up of patients that have CIS disease or carcinoma in situ disease with or without TaT1 disease, and patients also that have TaT1 disease alone. The split is about 60-40. There are about 15,000 patients that are diagnosed on a yearly basis from an incidence perspective with BCG-unresponsive disease. The split, as I shared, is 60-40.
Great. Great. Maybe in the last moments we have, as we think about the translatability, the benefit risk for cretostimogene, how it fares going to the intermediate-risk patient populations, of course, with PIVOT- 006 and this naive and exposed patient population in 008. Just walk us through your confidence level of that shifting over.
Yeah. I mean, I think when we look at the data in Cohort P, that type of data gives us a lot of encouragement as to what we will probably observe in the PIVOT 6 trial. That is an event-driven trial, 364 patients with AUA/SUO guideline-based intermediate-risk NMIBC, which includes patients that are high-grade Ta patients less than 3 cm. It's an important distinction and differentiation versus the TAR-200 trial, the Moonrise trial, which doesn't include patients that have Ta disease less than 3 cm, or the Atlas trial, which is also in a low-grade patient population as by AUA/SUO definition as well. That really gives us that confidence that we've seen with respect to the data that it could really be a look into what the potential could be in the intermediate-risk category.
Okay. Great. Great. Just with the thesis for cretostimogene's use in BCG-naive and BCG-exposed, there's certainly that acceptance of the BCG shortage out there. I just want to get your views on the anticipation of the shortage to continue, how cretostimogene and others can play into a long-term solution while maybe some of the supply is being worked out. Maybe we've seen some movement to manufacture recombinant BCG by the competition. How is this all shaking out, and how can this affect the broader market opportunity?
Yeah. I mean, look, in the BCG-naive area and BCG-exposed category, we're conducting our CORE-008, Cohort A and Cohort B, which is really in that subset of patients as a signal-finding trial that we're conducting. We're also conducting a trial in the combination of cretostimogene plus gemcitabine also in the BCG-exposed and the BCG-unresponsive patient population. We believe that really the difficulties in BCG really allow a window of opportunity for products such as cretostimogene to be looked at in those patient populations. What we've observed really, based on what Merck has indicated about the availability of BCG in the landscape in the marketplace, the latest that we've heard is sometime in 2026 with FDA approvals and so on. The availability of BCG may potentially increase in time. We don't necessarily see that happening very fast.
Number two, I think the recombinant BCG that ImmunityBio has tried to introduce on an emergency basis, the FDA statute for a new strain has been very, very firm. You need to conduct a trial, a head-to-head trial in order to actually achieve that. I think that still exists. That has not changed.
That's helpful. Just before we break, I want to see if there are any questions from the audience here in New York. Okay. All right. Maybe I'll close in, Ambaw, just on resource allocation and your cash position. Maybe just a word on how you're balancing this, driving cretostimogene towards the filing, the commercialization, but also investing in some of the clinical development that you've referenced.
Yeah. I mean, we did a raise last December. That raise, just based on our recent 10Q, will give us a runway into the first half of 2028. That is really the full execution of our clinical trial program, the launch of our first indication. Therefore, we're really well-resourced and financed to be able to actually address what's the road ahead for us.
Great. We'll leave it there. Thanks for joining us. Great to see you. All the best. Look forward to tracking the progress.
Thank you again.
Thanks, everyone.
Thanks again.
All right. Let's see.