All right. Good morning. Good afternoon, everyone. Thanks for joining us here at the Goldman Sachs Healthcare conference. Thrilled to be joined today by Arthur Kuan from CG Oncology. Maybe I'll just kick it off with a kind of high-level question. If you could provide an overview of the company, and let's focus on some of the key value drivers over the next 12- 24 months.
Sure. Arthur Kuan from CG Oncology. We are in this really exciting and growing market called non-muscle invasive bladder cancer, which is about 75% of all bladder cancer from an incidence perspective. Within that, we have a product that addresses both the intermediate risk and high-risk population. That is about 70% of the 75%. In numbers terms, we are talking about 50,000 patients incidence in the U.S. alone. It is exciting. We are filing our BLA in the second half of this year. It will be the company's first BLA in the BCG- unresponsive high-risk NMIBC population. That is about 15,000 patients a year. There are three products approved in that category, but they have not made any meaningful penetration yet. We can go into that.
Yeah.
This is an exciting space where these providers who are urologists have not previously experienced a kind of a boom in the buy-and-bill setup. But this is their chance to do so. We are here to really revolutionize and really evolve this whole space. This market will continue to evolve and grow over the next several years. We are very excited about that.
Awesome. Lots to talk about. Maybe we'll start with some of the data updates that you've had recently. You had a big update at AUI. Maybe you can talk us through some of the key outcomes that you shared at that particular conference. I think the 24-month update was one of the more key kind of features of the data. We'll focus on that as well.
Sure. So just to remind everyone, our modality is an oncolytic immunotherapy. And it's very important to keep that in mind because ultimately, we believe our MOA is one of the key drivers of the clinical data and outcomes I'm about to share. So in a 110-patient trial called BOND-003, in a specific cohort called Cohort C, we enrolled patients with carcinoma in situ disease that cannot be resected. So the FDA allows us to use complete response as an endpoint, as well as duration of response as a secondary endpoint to assess these patients. And in those patients, we saw a 75.5% complete response at any time that we reported at AUI this year. And importantly, these responses are highly durable. So at one year, the KM estimated duration of response is 65%. And at two years, it's 58%.
Meaning if you have a response at any time, your probability of lasting greater than two years is north of 50%. That is really exciting. When we think about the landmark analysis, regardless of kind of when the CR occurred, but let's say you started therapy on day one, at 12 months, over 46% of patients are in a CR. At two years, the data is still reading out fully. So far, we have nine more patients who are pending. Excluding those, we are already at 31%-34% CR rate at two years. KOLs would tell you if you hit a 30% CR at two years, that is game-changing. None of the competitors out there that are approved are even close to that 30% plus mark.
With nine more CRs pending assessment, and kind of given the long-tail immunotherapy that we're all accustomed to, we certainly think that that number could further increase.
You kind of alluded to this. Maybe you can contextualize for us how those response rates stack up versus other agents currently on the market or in development in non-muscle invasive bladder cancer.
Sure. Yeah. So I'll start with KEYTRUDA's response rate at two years. KEYTRUDA was the first approved agent in this space in 2020. At two years, they have a 9% complete response rate with a 13% grade 3/4 side effect profile. It's not surprising that their penetration rate in this space is probably in the low single- digits. Next to that, we have Nadofaragene, which is a gene therapy product secreting interferon alpha. They do about 19% at two years. Then there's a combination product, IL-15 plus BCG. That's probably in the 24% range. Anything north of 30%, I think psychologically is a big step up. If we can even kind of be on the high end of that kind of 30s range, it would be unheard of.
If you couple that number, which this number is also going to go inside the label, it's cystectomy-free survival rate. There are a couple of ways of doing it. I think what one of our competitors, J&J, who hasn't read out the two-year data yet, they're reporting a CFS rate of about 90% at one year in responders. In contrast, we have a 90% CFS rate in responders out to two years already. Meaning if you have a CR, there's a 90% chance that you're going to be cystectomy-free out to two years. That's also another meaningful endpoint for folks to see.
One of the areas where I think you guys have gotten pushback on the profile of GRIS imaging versus some of these other agents is on the reinduction of the drug. Maybe you can explain what reinduction means and kind of give us some context for why you think it's not as big of a deal.
Sure. Yeah. Reinduction is not something that we came up with. If you go back to the standard of care for this disease, it is BCG. BCG is given in this kind of weekly times six fashion, so once a week for six weeks. You assess whether there is a response. If not responded, you typically give another course of six weekly induction. That is what we mean by reinduction. In that reinduction, you can see north of 50%, 60%, 70% response rates in the first-line setting. It is something that the urologists are very accustomed to. The patients are also very accustomed to it, given the mechanism of action. I would say reinduction only works if your MOA supports it. In contrast, with chemotherapy, you do not reinduce a patient who has progressed on chemo.
It's just not part of the modality as well as the standard practice. In our case, we adopt a similar approach given our oncolytic immunotherapy MOA. We have seen in phase II studies where there is a delayed immune response. For some reason, these patients, if you give them another course, 50% of the time they get a CR. Those CRs are actually highly durable. In the phase three III, 28 patients were reinduced. 14 of them converted to a CR. Those CRs are still highly durable. Some are even out to two years now.
For the patients you mentioned, there was 28. And then 50% of them are kind of getting into a response. For those patients that do need a reinduction, how does their overall first year of treatment compare to the overall first year of treatment for a patient who does not need to be reinduced?
Yeah. So if you don't need reinduction, your year one number of doses is about 15 doses. If you do need reinduction, then it's 18 doses, so three extra. Year two and beyond, we do six doses per year.
It doesn't matter at that point?
Yeah.
In terms of the regulatory filing, how are the reinduced patients incorporated into the overall responder analysis?
Sure. The FDA is very clear about this to us as well as to other sponsors. If a patient gets reinduced, meaning their first CR did not occur at three months, but occurred at six months because they were reinduced at three months, and we check them up every three months, meaning their first CR would have occurred at six months, the FDA wants us to follow them for at least 12 months, so month 18 from the start of therapy. That is the only way that those patients could be included into the label. We are doing exactly that. We are even trying to push boundaries a little bit more to see if there is room to incorporate not just 12 months from the first CR, but maybe something beyond that.
Of those 28 patients, do you have data that you've shared or can you share on what the landmark looks like at 18 months or the duration of response, whatever makes the most sense?
Yeah. Yeah. But yeah, I think hopefully in kind of future conferences, we can go through those.
I think you mentioned this in your initial kind of notes on the company. You are preparing for a filing in the second half of the year. Talk to us about what are the gating factors that stand between you filing before then.
Sure. Number one, I'll start with the efficacy part. The minimum duration of response that we're looking for is at least 12 months. Certainly, we're trying to push the boundaries to see in this competitive market how do we get more duration of response data into the label. Potentially 24 months, 18 months, something beyond 12 months. There's that one aspect. The other aspect is we have announced that we're trying to simplify the administration process from a previous five steps to currently a two-step process. To be clear, cretostimogene is administered via a soft catheter by a medical assistant. A urologist or MD does not have to be involved in that process. It's done the same way that BCG is given, so no change to the practice workflow. Now, what we're trying to do is optimize the turnaround time for the centers.
We used to do kind of five steps where you do a saline wash, saline wash, DDM wash, and then you do a DDM dwell. DDM is our transduction agent that allows the virus to enter the bladder tissue. Following the DDM dwell, you give Creto and dwell it for 45 minutes to an hour. What we have done now is to eliminate the washing steps because we are voiding the patient's bladder anyway. Even if you void the patient's bladder, you are still going to have urine that comes into the bladder continuously. We are just going to go straight to the DDM dwell, drain it, followed by the Creto dwell. The time savings there could be about 20 minutes or so. I would say this is one where we believe it will be nice to have in the label.
We definitely want to push for it because saving 20 minutes at a very high-volume center would actually be pretty meaningful. We are collecting that data for the 008 trial right now.
Talk to me about the data generation that's required to enable that. Has the agency specified what they're looking to see? And when can you complete those studies?
Yeah. In our pre-BLA meeting, we were very clear. We asked the agency, hey, how do we get this two-step process in there? Besides BOND-3 Cohort C, which used the five-step, all our other trials have gone to the two-step process. They said, hey, show us 50 patient data from CORE- 008, which looked at both the two-step and five-step. They are not asking for a kind of randomized controlled study. They just want to look at, in general, from a confidence interval perspective, safety, efficacy, is it within the same ballpark?
Are they looking at both safety and efficacy? And is there a set time point they're looking at it for?
Basically CR any time. Yeah. We believe we should have that data by the end of this year.
Once you have that data in hand, you're going to be able to submit the filing. Is there anything else on the manufacturing side that needs to be done?
Yeah. One of the things that we're trying to enhance is the experience at the site level. Our product is stored at - 60, which has a tremendous shelf life of up to five years. We recognize that maybe there are some sites that may not have access to a freezer. For those sites and for all these sites, we ship just in time. The just in time delivery is something we need to validate, which is ongoing, meaning we ship at - 60 in a carton. A product can remain stable inside that carton for up to five days. It gives them some wiggle room there.
Beyond that, we've also executed a study that allows us to take the product from - 60, move it into a fridge, which every single center would have at 2- 8 degrees Celsius for up to a month. We already have that data. Now it's just about, we talked to the FDA about how do we get this into the label. They said it's just a matter of executing kind of more lots to show them that, hey, there's this statistical variance and sampling that makes sense. That's ongoing. We believe that part is, to us, it's a low-risk execution. We just want to make sure we get that done correctly.
With all of these things, activities that are ongoing, I guess what is your level of confidence you'll be able to submit the filing by year end?
We think the guidance on initiation will remain on track. We've not requested for a rolling yet. If we do, obviously we definitely want to leverage everything that's available to us to optimize the filing efficiency.
Would you anticipate a priority or a standard review?
We do have BTD. In the past, agents that have BTD in our space specifically have received priority review. Obviously, it's something we need to ask.
Maybe as we think about the commercial opportunity, let's start high level. Can you describe the addressable market as you see it?
Yeah. In the U.S., and I'll mainly focus on incidence. The incidence in the U.S. is there are 85,000 new patients with bladder cancer diagnosed each year. 75% of those are non-muscle invasive. 70% of those are what we believe we can address in the intermediate risk and high-risk population. Our initial on-label claim for the first product would be in the BCG- unresponsive category. There are about 15,000 eligible patients each year that we can address. There are certainly a lot of kind of patients in between the BCG- naive and BCG- unresponsive category called BCG- exposed. That's a growing number of patients. That's a number probably well north of 30,000-40,000-50,000 patients that are in the BCG- exposed category. We have a couple of trials addressing that.
We have a trial addressing BCG- naive high risk that we'll be reading out later this year, CORE- 008, Cohort A. Lastly, on the left-hand side, in intermediate risk, we're going really the most upstream kind of patients. These are either de novo or recurrent intermediate risk patients who have typically not seen BCG before. When we talk about BCG- naive, I like to think about are we talking about high risk or intermediate risk? In the intermediate risk bucket, that's 18,000 new patients coming to the market each year. These patients live for a very long time. Their progression rate is really low. The issue that we're solving for is actually recurrence. They continue to recur every three months. It's become a real burden for these patients.
The guidelines recommend kind of one dose perioperative chemo and then kind of observe for recurrence. If BCG were to be available, you can give BCG. We have this unique window where there are no BCG currently available in the U.S. to give to the IR patients. That is why we're able to run our PIVOT-006 trial, which is a randomized phase III controlled trial against TURBT. It is an adjuvant trial where one arm gets TURBT plus Creto , the other arm just gets TURBT. We're looking for RFS as an endpoint. That trial, we just guided this past quarter that we're six to nine months ahead of our enrollment schedule. That is really encouraging. We've never seen enrollment rates this fast in any trials in this space. It is actually one of the market segments that we believe we have a unique advantage in.
I'll explain why. Number one, I mentioned there's this BCG shortage enabling us to enroll in this space. Number two, because of the shortage, all the pharmas with a PD-1 can't really enter this space because the PD-1 agents need to be an add-on to another agent, such as BCG. It's really a kind of a blue ocean segment for us. The two other players that are in this space, one is obviously UroGen, which they have to leave the lesion behind and allow their chemo gel to ablate the lesion. There's going to be some segment of the market that may prefer that. We think the majority would prefer resecting the tumor that they can see and giving drug afterwards. The other part is J & J has an erdafitinib product in a pretzel called TAR-210. They have to do two cuts.
First cut is FGFR3 positivity, either by tissue or urine. Another cut, they have to exclude high-grade Ta lesions, which again, those are patients that we include. We think it's about 30% of the market that are in the high-grade Ta category. FGFR3 is probably per J&J 70% of the pie. When you do those two cuts, their target population then shrinks by 50% relative to ours. If we were to get our label, this is going to be the broadest label, no testing required, and the safety profile we anticipate to translate over from the unresponsive setting. That's really our view of getting to the most upstream of all these patients. In the back end, we have the unresponsive label. We'll slowly come in between to capture the high-risk naive and high-risk exposed patients.
Let's go back to the unresponsive group because it's going to be the first you get approved in. In that population, you mentioned a 15,000 patient incidence. Talk to us about the carcinoma in situ versus papillary pieces of the population. What's the breakdown? What's the path to market for each of those groups?
Sure. The initial on-label claim will be in the carcinoma in situ group. Those patients take up about 40% of the unresponsive market. The remaining 60% are TaT1 or papillary lesions that do not have CIS present. That is 1% of the market. For CIS, we are going to go for the full approval on label. For TaT1, the FDA has said that to get on the label, you need to run an RCT, which currently is not feasible because there is no control arm in that setting that would be appropriate. The strategy there is to go for an NCCN compendia listing. What you need to do is show in 50 patients with a 12-month follow-up of RFS a number that is probably north of 40% at 12 months. We believe that is the path to get on NCCN for level 2b evidence.
The CIS population will get like a level 2a. Once you're on there, based on our market feedback, the sites are getting reimbursed by payers.
Talk to us a little bit about the competitive landscape in BCG- unresponsive. There are a couple of drugs that are already approved. J&J is expecting to get approval later this year, I think. Talk to us how you expect the market kind of to segment with the available therapies. Also, how are you thinking about sequencing?
Sure. This market is really interesting because it's partially driven by this compounding BCG shortage issue. Over the years, these sites continue to concentrate. If you're not seeing patients, you're not getting more BCG. You're starting to refer patients out to centers that have BCG and have volume. It kind of just snowballed over time. We're really focused on the top accounts in the country, call it 300 accounts. We're putting them on our trials. We're calling on them right now ahead of launch. Those are the customers that we're focused on. Of those, you're probably thinking about half of them are academic and half are large urology group practices that are typically owned by private equity. Our focus is really on both. We can say that because we've enrolled both kind of provider types on our studies.
They do behave a little bit differently. The leukocytes are very much kind of P&L driven, very much focused on a bottom line. The academic centers, they may have their preferences. Maybe a quarter of them, they really prefer chemo, such as Gem/Doce combo. For those patients, our approach is to simply lean into our data set. We're the only company that has generated data post chemotherapy. Forty percent of our patients on bond three have had prior chemo. Of those, maybe 50% of them have had prior Gem/Doce. We're showing that response rates are very consistent in these different subgroups. We're going to lean into that and just, hey, hey, what would you use after Gem/Doce? Is it more chemo or is it immunotherapy? We're going to address that segment, want to build trust with them and let them experience Creto.
For the others, we've had working relationships with them for a long time. They've been part of our trials. They've been innovating with us with new trial designs. We feel very confident with that. Some of the kind of community-related questions, do you have a hood? Do you have a freezer? The academic centers will not have those issues at all. That segment we feel very comfortable in. Even in the community setting, thanks to COVID, many of these centers actually have freezers on site. If they do not, we're covering a lot of the high-volume centers by BCG volume by enrolling them into our trials. If they do not have freezers, we would have addressed that issue during the trial period. Actually, to our surprise, very few centers that are high volume actually would not have a freezer.
That actually is a good setup for us to keep our sales force very focused on these key accounts.
You kind of started to allude to this, but there have always been questions around the infrastructure that a physician or a group practice would need to implement to be ready to offer Creto. Can you talk to that? What does a doctor's office need to do in order to start prescribing cretostimogene?
Yeah. So really, the first question we ask is like, hey, do you give BCG right now? That's sort of the first kind of line of questionnaire. If they do give BCG, that means they know how to prep a BSL level 2 product safely, protecting their staff. They have a specific workflow, which does not take up a procedure room with the full kind of camera setup where you need to perform a cystoscopy in. Given that existing workflow, we do not need to change that process at all. Typically, a medical assistant would be assigned to this task and administer Creto with a soft catheter. We then focus really on kind of the throughput and how they're going to get reimbursed and all that kind of step-by-step walkthrough with them.
You mentioned the ability to shave off 20 minutes. What is that relative to in terms of if I walk in as a patient, how long am I going to be at the doctor's office? When can I leave?
Yeah. So currently, it would be about an hour and 30. I think with this new process, it could be potentially down to an hour. In the future, post-launch, there are centers that give BCG and the patient goes home and dwells at home. That would just be administration and leave. That is sort of the long game that we envision. Obviously, studies would need to be conducted to get to that point. We currently have the hypothesis that there really is no reason that you need to dwell in the clinic. Once you get Creto , you can go home. That is kind of the end state. For now, it would be an hour and 30, shortening to potentially an hour. In the future, shorter than that.
In terms of provider economics, I guess I think you mentioned earlier buy-and-bill and that being kind of new for this market. How should we think about the provider economics and how that will shape their decision-making?
Yeah. So it really comes down to the drug, which is ASP + 6%. There are administration fees associated with administering Creto, which is an intravesical instillation delivery fee. And that's called $80-$100. Really, what they're going to make money off of is going to be from the creto ASP + 6%. Obviously, reimbursement confidence is very important here. I think with the three approved agents, as well as maybe a fourth, those are all going to continue to drive reimbursement confidence with these providers. It's very important because they've not had to experience kind of a high-priced tag buy-and-bill model before. Having them being fully primed and ready by the time we launch is very important.
Cohort P, which is the papillary population that we talked about earlier, that study is expected later this year. Maybe you can talk about the key endpoints for that group of patients and what the benchmarks are to kind of get to the NCCN compendia listing.
Sure. So we showed a preliminary cut of the data at AUA this year. In 24 patients, we have a recurrence-free survival rate of about 90% in nine months. This is just in 24 patients, so it's still small. The full set, which would be in about, call it 50-55 patients, that's expected to come out probably mid of next year. Later this year, we should have additional data out to 12 months in those earlier patient populations. I would say the benchmark is for the two agents that made it into the NCCN guidelines, they're about 40% at 12 months in terms of RFS. I would say being well north of that would be very important. Yeah. We got to publish the paper, and then it could then be considered.
What should we look for in terms of other data updates later this year?
Yeah. So we're very excited about CORE- 008. That study has three cohorts, A, B, and CX. Cohort A enrolled patients who are BCG- naive, high- risk, and NMIBC. And that population has been fully enrolled as of April. We expect to have data on that later this year. In terms of benchmark, again, at AUA, we saw that Pfizer ran a trial with sasanlimab plus BCG versus BCG. When you look at the BCG control arm there, it's probably the most current control arm data in BCG- naive using BCG mono. We saw that they had an 85% CR rate at any time, so three and six months unique CRs. At 12 months, they saw about 76% CR at a year. I would say that's probably the benchmark to look at in this population. It is a high bar.
I think we've been very consistent in our view on the market that we actually believe BCG- exposed is the opportunity. Because even in a shortage, these 25,000 BCG- naive patients are getting some BCG. The minute they get some BCG, they turn into exposed. We think the exposed market is sort of the lower hanging fruit. Those two cohorts, B and CX, B is monotherapy creto, CX is creto plus gemcitabine. Those are actively being enrolled right now. We should expect data probably also next year. The bar for exposed is harder to tell. Again, these patients already have BCG. When you give them more BCG, the response rate shouldn't be as robust as the first-line BCG- naive patients. The bar is certainly lower.
The two data sets there, both mono and combo with GEM, will help inform us of kind of where we land.
As you think about commercial launch preparation, maybe talk to us about what you're doing to prepare for a potential approval as soon as next year.
Absolutely. Our commercial leadership team is already in place, like the senior leaders. We already have a team of MSLs covering all the key regions in the country by BCG sales volume. They're calling on customers every day, new relationships, existing relationships. We're really profiling these accounts down to the very kind of detailed level to figure out who is responsible for the pre-auths, the patient experience, and all of that. There's a lot of prep work and relationship building. On the other hand, if you think about our clinical portfolio, we're addressing really all aspects of IR and HR. We've actually geared our kind of trial enrollment towards sites that we believe are going to be key customers for us.
A lot of them are actually private equity-owned leukocytes, which really helps us open a door because ultimately, they may be doing kind of more of a coordinated purchasing.
I think you mentioned there's like 300 high-volume sites that are maybe the top decile or whatever. I don't know exactly how you defined it. What portion of those are private equity-owned?
I think more than half, I would say, are private equity-owned. I think maybe 10 years ago it was maybe like 30%. The roll-up continues to happen amongst the very few players.
How many reps would you anticipate needing to kind of service this market?
Yeah. I mean, we looked at benchmarks. And we did our own analysis on kind of accounts, reach, and frequency. So based on comps, kind of the 50-60 range is what we'd expect. So small footprint.
Maybe you can talk about the cash position. What is your current runway guidance? What are the activities embedded within that?
Sure. As of Q1, we have about $688 million in cash. We have guided the street that it's good through the first half of 2028, which would cover all the existing programs I mentioned, including getting to the PIVOT-00 6, which is one of our most important trials readout, as well as our initial launch in BCG- unresponsive.
Does that include all the commercial preparation and activities that you need to do?
Yeah.
How do you think about additional sources of capital then?
Obviously, as a small biotech, we can always use more money. But we've been very disciplined in the past 10 years of our company's history. I would say there's always room to continue to invest in manufacturing capacity, which we have done. I think we actually invested in one of our drug product providers in the first quarter. So there's that aspect, including working on next-gen formulation. What I'm excited about is Adeno Vector is actually very stable with the right formulation, even at room temperature. Those are work that I see that we can continue to invest in to make that experience even better.
Is there anything that we haven't talked about today that you think is important to understand?
It's very comprehensive. Yeah. Happy to take questions if that's.
No one ever wants to ask questions.
That's true.
It was great to speak with you today, Arthur. I really appreciate all of the time. Thanks to everyone who joined us here and online.
Awesome.