All right. Good afternoon, everyone, 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 introduce the company and talk about what you think about as key value drivers over the next 12- 24 months.
Sure. 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. 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 hopefully first approval in NMIBC setting. Really towards the back half of this year, there'll be additional data around durability of our product in the BCG unr esponsive setting, as well as when we combine it with gemcitabine, additional durability updates will be available as well.
Great. Maybe let's start at the highest level. As you look at the non-muscle invasive bladder cancer category, could you talk about how you see the unmet need and how patients are stratified within that indication?
Sure. 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. That's in the intermediate risk category as well as the high risk category. 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. As you think about the unmet need and how patients are treated today, what do you think is the goal for new therapies entering the market, and particularly cretostimogene?
Sure. We'll start with high risk. Within high risk, the standard of care for frontline patients who are BCG naive is BCG. Following BCG therapy, you fall into this BCG unresponsive category or BCG exposed category. 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. There are a couple of approved therapies now. I still think our target product profile represents really the strongest profile in that category. In terms of BCG exposed, this is an emerging category that really based on the FDA definition of unresponsive, we think is a bit stringent.
It does 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. That's a procedure where the urologists have to go in and resect a tumor in the OR. Oftentimes these tumors continue to recur to the point where the bladder has been scraped so many times, sometimes also less functional than before.
Okay, great. 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 have shared.
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. At 12 months, from a landmark analysis standpoint, we've shown a 46% complete response rate. Most notably, if you go from 12 months- 24 months landmark, cretostimogene as a monotherapy still had a 42% complete response rate. You'll notice that there's a tail from 12- 24 months, and we continue to highlight that as one of our key differentiations versus others. 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. 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 any of the other programs in development or approved?
Sure. When we think about the different ways to cut that data, if you just take this landmark analysis at two years. KEYTRUDA has a 9% complete response rate at two years. nadofaragene firadenovec, another product, is probably in the 20% range, and then Atevio is in the 20% range. We don't know yet what TAR-200 has shown at two years. 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? Could you talk about the infrastructure requirements that would be necessary for a physician's practice to administer the product?
Sure. We've made a lot of improvements over the delivery as well as storage conditions of cretost imogene. One of the things that we heard from our customers directly is that, A, not everyone has an ultra-low freezer. These are freezers that are -60 to -80. 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 two to eight degrees Celsius, which is a regular fridge. In that condition, the product can stay stable from four to six weeks. 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 retrainings as required.
One of the things we've heard is the dwell time consideration. 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.
Yeah. From a standard care BCG, for example, on label, requires a two-hour dwell time. In practice, people only dwell for maybe an hour. Really, after the first visit, typically in the second visit, they get instilled BCG, which doesn't take long, maybe less than ten minutes, and then they would just go home and void at home. 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 Creto. Creto is probably up to 45 minutes, an hour dwell time. All in, an hour and 15 minutes. After that, they could go home or they typically, right now, they're staying in the waiting room. 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 which is more in line with how BCG's done.
Right. In terms of the specific subgroups within BCG-unresponsive, maybe CIS, papillary only, any mixed patients, I guess, are there any particular populations where you think the profile of Creto is particularly differentiated?
I think that's a great question. Our BOND-003 pivotal trial, we had the highest, most heavily pretreated population.
Unlike other competitors, we have a lot of patients with prior chemo in addition to failing two courses of BCG. I'm referring to patients who failed Gem or gemcitabine. Even in that category of patients, Creto continues to show a very consistent response rate. That is data that we're certainly going to lean into as we think about the launch and profiling different accounts, both academic and large practice sites, large oncology group practice sites. That's certainly one aspect that I think is quite unique.
Okay. As physicians look at, they now have a couple of therapeutic options that they can pick from. What do you think they're going to pick which products they'll use? What portion of patients then do you think we'll see Creto at some point during their course of treatment?
Yeah, I think, ultimately, they care a lot about safety and efficacy. That's the base case. Whether it requires a lot of modifications or changes to their work considerations or the bare minimum that they think about therapies. You can look at the one-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. 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. There certainly will be a sequencing play here. Of course, I think the target product profile, the durability, will all play in a role here.
In terms of there's some sites who just are really accustomed to giving chemotherapy, and if we have data that shows even after that, Creto 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.
You're now on track, I think, for 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 satisfy for a filing, both with respect to the clinical data, which we've just discussed, but also the manufacturing piece?
Yeah. On May 8th, when we put out the press release, this was in the context of having a prior FDA alignment meeting. 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. Coming out of that meeting, we felt like all the questions we had were clarified. We know what needs to be in there, from a drafting standpoint and content standpoint. That workflow continues to be ongoing. Of course, we have a separate work stream that we continue to discuss with investors that we care a lot about inspection readiness. 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.
We're putting a particular emphasis and focus on the site that we acquired last year. This is the fill and finish site. We're doing a lot of preparation work on that. 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?
Yeah. 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. That work has already been completed. In terms of the yield and scale that we currently have, from an initial launch standpoint, we believe that covers the early years of launch. There's no changes that would be necessary there. In general, I think we're very much aligned on the virus manufacturing component.
Okay, great. Maybe as you think about filing and preparing for a go-to-market in the next year, how are you thinking about pricing the market with the eye to the broader development strategy that you guys are engaged in?
Pricing is an interesting topic. We've not provided formal guidance on this. When you think about pricing, safety and efficacy plays a huge role, as well as the benchmark of approved therapies. Right? In general, I think in terms of the ranges, on the low end, it's about $260K for one year, high end $700K for one year. I think directionally, we'd probably be on the right end of that spectrum. Again, a lot of still depends on how our intermediate-risk data will read out, because it's all linked. It's one product for two different indications.
Let's say that PIVOT-006 does work. What are the important considerations in terms of pricing differential across the two markets?
First of all, I would say, we've already done the dose de-escalation. When you go from a high-risk disease, which is 30 doses over three years, with intermediate-risk disease, we cap it at one year of 14 doses. 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.
I agree. Are there good 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'd need to take on?
When we look at kind of launch analogs in the space, I think everyone sort of comes out to be around the 50-75 field force range. I would say based on our own internal analysis, we're in that range as well. 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. 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, large groups. 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. That issue have basically led to sites referring patients to sites that have flow and have access to BCG.
It kind of compounds over time. When we think about that split, we think about what is the current practice pattern that they're already doing. Is it Gem, gemcitabine? Is it any of the branded products? We're studying the pre- and post-J-code dynamics there as well.
Okay, great. In terms of other launches in NMIBC, there's a couple that have happened recently. 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?
Yeah. I would say obviously the most recent launch is Imlexxjo, 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. Now we have not only the Imlexxjo data, we also have ANKTIVA and NanoPharax's data. That's going to help better inform our kind of initial targeting strategies. 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.
The focus is to really figure out 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. 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 product profile more physician and patient-friendly. I think sometimes there had been 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 where you need to drive a better understanding of that TPP?
Yeah. I think, of course, some of the improvements that we made in the storage condition may have been, not has been broadly disseminated. 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 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 roles that those combination programs play within the context of your broader development strategy.
Sure. 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. 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. 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. We believe this category of patients is emerging and currently there is no on-label therapies for those patients. Our current strategy is both the mono and combination of Creto and Creto-gem to see if there's any added benefit of Creto-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%-92% complete response rate at 6 months. 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. In which case, some randomization would be necessary, we could get the Ta, T1 patients who are BCG exposed on label as well.
Can you talk about the different segments of the population and where you might be able to pursue a guideline strategy versus a registrational strategy?
Sure. In BCG unresponsive disease, currently you can only get a label with the CIS-containing disease, because surgery is not required. With Ta, T1 disease, these are the pure papillary disease. Currently, there isn't any FDA-approved product on label. That typically would go through an NCCN guideline compendium listing strategy.
Maybe pivoting now to PIVOT-006 data here in the next couple of months. Maybe first we could just talk about 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.
No, that's a great question. From our vantage point, the core principles and MOA of how cretostimogene works is that it responds to a protein called E2F. This is a protein that's very important during DNA replication. 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? That's our foundational understanding and our view of that disease space. We certainly don't have data directly in intermediate-risk, low-grade patients. That is we're making that assumption that as long as there's recurrence, there's E2F, Creto could be active. That's the baseline. Beyond that, I would say, we're treating patients in an adjuvant setting. The tumor burden is already pretty low.
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 timelines. You've had the trial of enrolling. The enrollment timelines have changed, et cetera. Maybe just start there on the background of the trial.
Yeah. We started enrolling in this trial around mid-2024, and then we completed the enrollment of 364 patients in September of 2025. That is, we ahead of schedule. I think, again, this is the first time that anyone has done this in the U.S., there are more conservative enrollment projections initially at the outset. Yeah, this is a one-to-one randomized controlled trial, looking at TURBT with or without cretostimogene. We do stratify for two key factors. One is perioperative chemo, which is a single dose of gemcitabine or not. And then whether the patient have high-grade or low-grade disease or not. Those are the two key stratification factors to make sure the two arms are well-balanced.
Obviously, the enrollment came in a lot faster than expected, I think there were 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?
Yeah. 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 safety analysis. I can show that the interim futility analysis has been met. The trial obviously continued. There really wasn't any advantage of having that interim efficacy analysis, because the trial would've been almost fully enrolled anyway at that point. Yeah. There's that change in sample size based on that.
Okay. How do you interpret the faster-than-expected enrollment that you guys saw?
We internally view it as just this enthusiasm that a lot of physicians have with a novel therapy for intermediate-risk disease. Right? There was a lot of skepticism initially going into it. Really, I think the enrollment rate, on some months we saw 30- 50 patients coming onto the trial. That was certainly surprising to us. We think it certainly speaks to the totality of the evidence of Creto in other settings that have sort of bled through into this setting, where a lot of physicians want to try it out as well.
You've kind of mentioned 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 come up with the key assumptions underpinning the trial size and powering, et cetera?
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. The control arm is basically a TURBT plus surveillance control. 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. 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 UroGen ATLAS trial data that came after we started the trial, we continued to rethink in a more modern trial, what could a control arm do? Right? When we looked at the total events that's been accruing, 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 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 both clinically and then commercially successful here?
Sure. 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. Even before the start of PIVOT-006, we gathered that feedback from many KOLs. From their vantage point, they just want an approved product, right? 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 arms do. I believe we're leading the charge in understanding of intermediate-risk disease. Being that first-mover advantage, it puts us in a position where we get to prime and educate the market about this disease.
Once you have an approved product, typically there are other ways where you can further enhance that. Right? In another setting such as CIS, we've shown that Creto and Gem could, at least in the early time points, add additional efficacy on top. 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 of clinical practices is that? Could you just speak about the use of surveillance versus alternatives in this intermediate patient population?
Yeah. Again, that was certainly one of the questions we had as well. Certainly, with the enrollment rate of PIVOT-006, clearly people are 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. 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 your ability to turn around with that data and file it, I guess, what should we anticipate in terms of timelines to filing on the back of PIVOT data?
Yeah. We've been guiding that in 2027 is when we could file the BLA. Currently not narrowing that. You can imagine a lot of it is just the clinical module. 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's available. Then we'll formulate that strategy. In 2027 is the current guidance.
How do you think 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, these are all BCG naive patients, at least the one we've enrolled in PIVOT-006. Right? It's interesting because, of course, the obvious answer is go after sites with high volume of BCG because that helps us with the initial unresponsive launch. There could also be a lot of sites that don't have access to BCG. Right? That's another interesting avenue that we can open up as well. In the end, the good thing is, the same physician treats both unresponsive and intermediate-risk disease. I think there's a lot of overlap in synergy where if we can bring to the customer, the HCP that, "Hey, we've got two indications now versus just one." I think that really would 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?
Yeah. 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.
I agree. 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. Currently, on May 8th, we reported we have over $1 billion on the balance sheet with no debt, and that gives us a runway through 2029. We're currently covered for all those activities that we described.
Okay. 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?
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. 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? That's really the core near-term focus for us.
Okay, great. I think that brings us basically to time. With that, thank you so much, Arthur, for joining us. Thanks everyone who joined us here and on the webcast.
Thank you.