Welcome to the Morgan Stanley Global Healthcare Conference. I'm Jeff Hung, one of the biotech analysts. For important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have CG Oncology, with CEO, Arthur Kuan. Welcome, Arthur.
Thanks, Jeff.
So for those who may not be as familiar with CG Oncology, can you provide a brief introduction?
Sure. So CG Oncology is a company that's focused on developing and commercializing bladder-sparing therapeutics for patients suffering from bladder cancer. Our lead asset, Cretostimogene, is currently in a phase III pivotal trial for BCG unresponsive non-muscle invasive bladder cancer. We also have a second pivotal trial that's ongoing, called PIVOT-006 . It's in the intermediate-risk BCG-naive NMIBC patient population. We're excited to report additional data at the end of this year in our BOND-003 study, which has already received FDA Fast Track, as well as breakthrough therapy designations.
Great. Now, the NMIBC space is pretty competitive already. Can you just talk about how you view Cretostimogene fitting into the treatment landscape?
Sure. I think it always comes down to efficacy, safety, and then ultimately, your mechanism of action. So I'll start with efficacy. At AUA this year in May, we reported 75% complete response rates, and even at 12 months, it held up, with durable CRs of 43%. So that's the highest monotherapy response rates that we have ever seen in this space in a large sample size. So with that, we believe, you know, that also needs to be taken into context of safety. So ultimately, risk-benefit ratio does matter.
So from the safety perspective, in over two hundred plus patients treated, you know, we've seen just a very consistent adverse event profile, and in the phase III trial that we just reported, there was no Grade three or above AEs, so 0%, and we had 0% treatment-related discontinuation rate as well. So that's very meaningful when you think about risk-benefit ratio. Now, all of that is achieved because of the unique MOA that we have, that no one else has in this space. So our oncolytic immunotherapy, Creto, it works in two ways, right? It has a one-two punch. So first, it has a direct oncolysis that directly kills tumor cells, sparing normal cells, so that also contributes to the great AE profile that we've seen.
Once it lyses tumor cells, it generates a very potent antitumor immune response, which again, so far, we believe that's also contributing towards the highly durable CRs that we're seeing.
Right. Now, earlier this year, there was some confusion around the Cretostimogene and TAR-200 data at AUA. You know, first, can you just talk about your expectations for monitoring requirements after administration in the real world? And would you expect monitoring to be included in the label?
Sure. As you know, with all clinical trials, you know, the first thing that the FDA cares about is to protect patient safety. And so we've taken extra precaution to make sure... in the trial setting, to make sure we're monitoring patients, to ensure that there are no, you know, unforeseen safety events, and we have not seen any so far. So, that, we believe, will not be in the label, for post-monitoring.
And what is the criteria for reinduction? Can you just talk about your decision to include reinduction in your studies and what FDA has said about your approach?
Sure. So reinduction is basically when a patient reaches the first assessment point, which is at three months after treatment. If you have persistent disease, which is basically defined as you don't have a CR or you have not progressed, right? So if you have persistent disease, it's sort of a stable disease equivalent in other indications, then you get to reinduce. And we have shown consistent 50+% reinduction conversion rate to complete responders from three to six months across two trials now. So I would say reinduction is highly MOA-driven. With immunotherapy, I think most people would expect that there typically will be a delayed immune response, right? If immunotherapy truly were working, you're gonna have an influx of immune cells, you're gonna have some inflammation, so sometimes it looks reddish, right? It's an inflamed tumor.
And then if you give it enough time, up to six months, without harming patient safety, you know, we're seeing tremendous benefit there, right? So this also allows patient to stick with the same therapy, right? 'Cause the cost of switching to another therapy, there's, like, issues with familiarity, right, right? So we're trying to lower that hurdle so that patients can stay on Cretostimogene longer.
Great. Now, the final results from BOND-003 are expected later this year. You know, what should we expect to see and anything that investors should focus on, particularly given that interim results were presented at AUA earlier this year?
Sure. So at AUA, we showed 105 patients CR rate any time. We showed 90 patients with a 43% CR at 12 months. We cut off our survival plot at 12 months. You know, what you can expect later on this year is we'll continue to extend that survival plot beyond 12 months, with at least 12 months of follow-up on all evaluable patients. What's important is 12 months is always important. That's what patients can comprehend, right? "Can I keep my bladder for a year? Can I keep my bladder beyond a year?" So we want to continue to develop that, you know, narrative, as well as hopefully our data can continue to support that. So ultimately, you know, patients want to know if they can keep their bladders for 2 years, right?
So those are all very important questions. And again, you always have to frame it in the context of safety and tolerability, right? 'Cause if you have a very toxic product, you know, your therapeutic window is that much lower. So definitely pay attention to our safety profile in basically all evaluable patients. And you know, ultimately, I think the risk-benefit ratio continues to be a very important focus.
Now, there's also been some confusion among investors on which measures are most important in the end.
Right.
Can you just talk about your views on the relative importance of CR at any time, CR at twelve months, and then duration of response, and, you know, which matter most to the FDA?
Yeah, so I think it's a composite situation where all of them are important, right? So I'll just give you a counter example where you have a product that has a very high CR, but has a very poor DOR, right? A very poor duration. The product of that is a landmark result that ends up in a very tiny percentage. That's not helpful. You can have a product with very low CR, but a 100% DOR, then only a very small fragment of patients will benefit. So really, you need all three to look at the data, and, you know, ultimately, the FDA cares about two things, as well, three. They care about CR at any time, which goes into the label. They care about duration of those CR, that also go into the label, and of course, safety as well as other measurements.
So the landmark analysis, I would say it's a convenient way for investors and patients, as well as physicians, to contextualize this simple question: Am I gonna have my bladder in a year or in two years, right? So I would say all of them are important.
Now, the CR at any time with Cretostimogene is around 75%, while CR at any time with TAR-200 is around 83%. I guess with the caveat that that data is still fairly early, but what do you see as the bar for CR at any time? And, you know, does that CR at any time need to go up at all with the data later this year?
Yeah, I would say that statistically, you know, short of running a head-to-head trial, like, that's already within the ballpark. I think, you know, our agent is already 20 points higher than, you know, the 3 FDA-approved agents out there. When you look at central pathology results, that's very important. That's all of our data are centrally reviewed with central path results. So, you know, that's sort of the standard out there, and the FDA has not stated what exactly the bar is, but we think where we have at AUA is really highly differentiated.
And what do you see as the bar for duration of response?
Yeah, again, I think the three agents that are approved out there, Pembro, Nivo, Anktiva, BCG, they're sort of in the 46%-58% range for DOR. You know, I think, you know, anything within that ballpark, I think would be very meaningful.
Great. Now, you said that you'll provide the Kaplan-Meier estimates for the monotherapy results with the final data. You know, you've included the Kaplan-Meier estimate from the combination study in your corporate slides. Can you just talk about your decision to do that, and you know, doesn't that provide validation to approach that many in the scientific and physician communities believes, you know, may not be appropriate?
That's a great question. I would say that, you know, the reason that we're showing both is it does provide more context. I think there was another, you know, competitor in this space that have started reporting KM results in a small subset of, you know, immature patient data. I would say that by showing our combination Kaplan-Meier versus actual observed data, you can see that at 12 months, our combination had a 57% complete response rate in 35 patients by non-KM estimates, and then the Kaplan-Meier estimates boosted that by 20 points. So we have a 77% complete response rate by Kaplan-Meier estimates. So I think that just paints the picture that they are measuring different things. It's not illegal or incorrect. I think it's y ou know.
Kaplan-Meier obviously censors patients who are in a CR that have been lost to follow-up, so you take them out of the denominator numerator. So it does tell you a different, you know, answer, right? These are patients who are elderly, the Medicare population. Some could be very happy with a CR at nine months and choose not to come back at 12 months, right? So what do you do with those? You could strictly say, "Hey, they're probably a non-responder at 12 months." That's the strictest way of cutting the data, and that's what we have been doing. I think some investors prefer that, "Hey, what if you censor those patients, right?" We're happy to provide that data cut as well. I think what's the most important is to show both, so that investors can, you know, make their own assessment. Yeah.
In the end, I'll say, FDA cares about non-KM results for Landmark.
Okay.
Yeah.
Thanks. Any more question on the combination, y ou know, you presented final results from the combination with Pembro at ASCO. You know, what types of patients do you think will be the ideal candidates for the combination, and, and what are the next steps for the program? and, and maybe you can just talk a little bit about what you've seen in the data.
So obviously, we're very excited about the combo, but I think again, it has to be framed in the context of risk-benefit ratio. Our monotherapy data continues to mature in a very positive direction. In the first 12 months of mono, really statistically overlaps with combo, right? Combo did show very promising results. When you hit 12 months CR at with the combo, we only lost one patient between 12 and 24 months. So our CR rate went from 57% - 54%, losing only one patient. And there is 0% of patients who have progressed, right? In terms of progressing into muscle-invasive disease. So that's encouraging. We need to see how our monotherapy results will mature beyond 12 months, right? So then, we do have some clues as to what Pembro's monotherapy result is at 24 months.
It was 9% CR. So it'll be important to see what is Creto's monotherapy potential. Right, and we continue to want to focus on Creto as a backbone therapy, on its own, and then leverage combination results as a proof of concept so that we could potentially expand into adjacent Creto plus X strategy.
Some of your competitors have touted, at least for them, that, you know, the benefits of their product candidates in terms of handling. You know, can you just talk about your just-in-time approach and any considerations that are needed for freezing and thawing?
Sure, yeah. So I'm pleased to share that we now have data for moving our product from minus eighty storage, whether in a freezer or a just-in-time delivery, into a 2 - 8 degree fridge. So this completely eliminates all cold chain storage considerations or concerns, because it can stay in the fridge for up to three weeks, and potentially longer. So we think that's a huge enhancement for our product and our ultimate mission of getting wide adoption. And these are the type of adjustments and improvements that we'll continue to focus on as a company.
Could you just walk us through the latest on manufacturing? You know, any CMC challenges or things that still need to be addressed before launch?
Yeah, you know, thankfully, I think this process is highly robust, reliable, scalable, and consistent, so that even for our initial indication, we do not need to change the scale of what we use in the phase III trials for commercial launch, right? So at launch, we expect to cover the initial indication without an issue. We have guided that for the intermediate-risk indication, which is much larger. There are 18,000 new patients per year on that, not including prevalence. We do intend to scale up, and because of, you know, we use single-use consumables, and it's a process that's easily scalable, you know, we expect that activity to be done, you know, starting now.
Great, and could you just talk about your commercial strategy? You know, what kinds of sales footprint do you need to cover, you know, the high-risk NMIBC patient population?
Yeah. So the setup in this disease space is that the standard of care is BCG, and it's been shortage for the past ten years and ongoing. So, in a setting like that, you're starting to see this concentration or hyper-concentration of the key accounts, right? So the supplier of BCG, there's only one in the U.S., typically would supply BCG to sites that utilize the most BCG. So you compound that over ten years, you start to see a concentration of accounts to both academic centers and also large urology group practices, right? So that's what we're going after. And so, you know, we're really just following the data, right? If you have BCG, whether you're academic or a LUGPA, we'll go to you and really service your patients who are unresponsive to BCG.
Can you just talk a little bit more about that, though? You know, I know that some of your competitors may be focused more on, say, like, community docs, but, you know, what are your expectations for patients being treated with Cretostimogene at academic centers versus community docs? Do you see any differences in, you know, potential, like, the rate of adoption in one versus the other?
Yeah, no. So historically, like, we've focused a lot on academic centers when we're, you know, really starting off. You know, it's important to have the key opinion leaders buy in on a novel therapy such as Credo. And going forward, I think, you know, when we think about the community market, it's really about large urology group practices, the LUGPA, right? These are private equity-owned. Obviously, they very much care about P&L and the bottom line, so that's the type of conversation that would occur, really about efficacy, safety, tolerability, time on therapy, and throughput, right? Like, really, how many Credo can you give in a year at your practice? You know, so I think the long-term data and time on therapy will be very important for that population.
Great. Now, as you mentioned before, you know, you've dosed the first patients in PIVOT-006 in intermediate-risk patients. You know, how are the intermediate-risk patients different from high-risk patients?
Right. So intermediate-risk patients, really, they need to get BCG as a first-line therapy. However, because of the shortage, these patients are not getting BCG right now, and that is a new unmet need that has been developing. And so literally, guidelines have changed to suggest that BCG should only be used for high-risk patients in a time of shortage, right? So there may be centers that have BCG, but most of them don't. So that's the new unmet need that we have identified. And so these patients are, first of all, non-CIS. All CIS patients are, by definition, high-grade, high-risk. These are mostly Ta lesions, right? Single, multifocal, but the hallmark of it is they recur multiple times in a year, right? And then every time you recur, you have to get a TURBT procedure done.
And so some patients would have, like, 10 or 10+ TURBTs done, and that really has a negative impact on their quality of life, you know, as well as more, a really poor morbidity.
Great. Can you just talk a little bit more about PIVOT-006 and, you know, what the bar is for success and when we might see initial results from the study?
Yeah. So PIVOT-006 is designed as a randomized controlled study. We're going against, really, basically, you know, watchful waiting, placebo, and we do allow patients to cross over to the treatment arm upon the first recurrence, which is counted as an event, and we're looking at RFS as an endpoint. So typically, with intermediate-risk patients, you have a recurrence rate of about 20% - 40%. We'll have to see what it looks like in the trial setting. So that's sort of the benchmark. And again, we're running a trial and looking at what is the post-standard of care adjuvant therapy, right? So the standard of care is TURBT. So we definitely don't want to replace that, 'cause you're actually, you know, curing and removing the tumor visibly. We just want to be an adjuvant add-on to that.
Where BCG could have played a role, but currently the supply continues to be a challenge. So we're guiding first half 2026 for full enrollment of the trial, of up to three hundred and sixty patients. And then, you know, as we get closer to that, I think we'll provide more guidance on potential timing.
Okay.
Yeah.
Maybe one last question just to wrap things up. You know, after the AUA data, you know, there was some confusion among investors. I guess, what do you think that, if anything, that the street most misunderstands about CG Oncology?
Yeah, that's a great question. I think that, you know, I think when perhaps the KM results, right? I think it's not apples to apples when you're comparing Kaplan-Meier results to non-Kaplan-Meier results. I think that's one piece where we hadn't thought of before. You know, I think going forward, starting ASCO, we've started to provide Kaplan-Meier results, and I hope that investors and, you know, physicians will start to look at KM versus KM, non-KM versus non-KM. I think it'll be a more helpful comparison.
Okay.
Yeah.
Great. So we'll have data later this year. Any other, milestones or catalysts that you'd like to highlight?
Yeah, no, focus on the year-end data. I think, you know, it's important. We'll be looking at it with, you know, patients with at least twelve months of follow-up and beyond. I think the narrative will continue to develop, you know, for what patients ultimately want, which is long-term durable CRs, and they don't really have to switch therapies. They can stay on something that's safe and tolerable, and easy to use, right? So now that we have new data on our transition temperature, I think that really solves a lot of the cold chain concerns.
Great. Let's leave it there. Thanks so much for your time.
Thank you, Jeff.