My name's Sean Lannan. I'm the Head of U.S. Mid Cap Biotech Equity Research here at Morgan Stanley, and welcome to our Global Healthcare Conference. Before we begin, to make you aware of some important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions on that, please reach out to your Morgan Stanley sales representative. With that, we have the pleasure now to welcome from CG Oncology, their CEO, Arthur Kuan. Welcome, and thank you for your time today, Arthur.
Thanks for having me.
Maybe do me a favor and answer some of my macro questions. The first one is the rise of China-originated innovation, and if at all, how does that change competitive positioning or thoughts around R&D or thoughts around business development?
Certainly based on what we've seen coming out of China, it is something to be respected, and I don't think we should take it lightly. More broadly, I think we think a lot about when it comes to U.S. innovation, what is the competitive advantage? I still think that being close to the U.S. market, being close to the providers and patients, that in of itself, I think continues to be something that could be differentiated in terms of the rate and speed of innovation, making sure that we're well set up for clinical development and clinical operations that's fit for purpose in the U.S. population is also very critical.
Sure. Now, moving on to AI. Have you or are you implementing AI adoption within your business? Have you seen it, or can you give a description of something that's changed, whether it's on the cost front, a decision, maybe a POS assumption?
Sure. I think we're, first of all, definitely embracing AI in all aspects of our operations. Moving beyond sort of the meeting minute summary and email summaries, I think we're now asking every function within the company, from finance to accounting to CMC to clinical development, to really break down their existing workflows and work streams. Because in order to give AI the right context, you first really need to figure out and dissect your current work stream. It's basically a process of being very honest and auditing your own workflow. How ideas come to be, how ideas are embedded. The more descriptive you can be, the better it is to train your AI agent or teams of AI agents. Directionally, I think the near-term gain is going to come from productivity increase and more of an efficiency gain in the first step.
Sure. Thank you. And last one before we dig into CG specific, but which policy variable? Is it FDA, Medicare negotiation, MFN, tariffs, global pricing, matters most to your economics?
Yeah. I would say in that list, the one that is still up in the air remains to be the MFN. I think we're watching that very closely and looking at what the bigger companies are doing with their negotiations there. But certainly, that has an impact on how you think about, for example, EU pricing.
Sure. Thank you. And now we'll get on to CG, but thank you, Arthur. I appreciate it. Let's start with the BLA for cretostimogene grenadenorepvec and where it stands. So you've been submitting on a rolling basis and got it to completion in the fourth quarter with the CMC module as the final piece. What's actually left? And coming out of your manufacturing-focused alignment with the FDA, how much submission risk do you think is truly behind you?
Sure. From a CMC perspective, one of the most important things that the FDA wants to see in the module before we submit is can you prove that the process is reproducible? Is it robust enough? Is it repeatable? Do you have full control over different aspects of your process? One of the things that many companies do during this phase is they figure out new improvements to their process such that they get a higher yield, for example, or they learn that, hey, the clinical opportunity is a lot bigger than what their scale could support. Certain tweaks are made. I am happy to share that our process that led to all the clinical GMP products that enabled our clinical trials is a process that we intend to launch commercially.
All the experiments that we had performed to characterize the process, to validate the process, have already been completed, and I am also very happy to share that at least just based on the data that we are seeing, it does point to the fact that cretostimogene grenadenorepvec has a very robust process, meaning you can really stress test the process to a kind of a wide ranging of conditions and still be able to generate the same product that we are using. That is the good news. Where we are in the process is simply in this data generation and compilation of those reports, and then fitting them into the Module 3 for submission. There is a lot of authoring and writing and QC that needs to happen.
A separate work stream that I also need to mention is around inspection readiness, which is a key aspect prior to getting a potential approval. That is one where upon submission, the FDA could send a team of inspectors to your facilities and to your partnered facilities to perform a pretty thorough inspection. Our approach there has been we have engaged several ex-FDA inspectors to help prepare our sites for that inspection, and that work stream has been going really well.
Sure. Have there been any learnings from what we observed with ADCETRIS and ANKTIVA that you have been able to use as learnings to somewhat de-risk the process?
Yeah. With respect to, for example, ADCETRIS, I think that's an example where there was a process change, even a scale change. There was also certain inspection-related issues that came up. With respect to ANKTIVA, I think what's public is there was a pre-approval inspection, which again, deals with more of the inspection aspect of the risks. From our vantage point, knowing that those risks have already occurred, we definitely can't ignore them. We've really doubled down, if not tripled down on resourcing to ensure we are really pressure testing our CDMO sites, as well as the site that we now control, the fill and finish facility.
Sure. Thank you, Arthur. On scale, you said clinical and commercial are the same process, locked and agreed with the FDA. Can you remind us of what your current capacity is for the first year or years with frozen storage?
Sure. The current process can generate up to 50,000 vials of cretostimogene grenadenorepvec. We have said that we can store these vials in - 60 degrees up to four years. It is actually, from that vantage point, we have the runway, I should say, to take care of the early years of launch. Certainly, our view is the longer term would require a much higher number of vials. In parallel to this work stream, we have continued to invest in a scaled-up process. That would not be the part of the initial BLA, but it will be ready in a couple of years, just in time for that additional ramp in the future.
Sure. Maybe try and put that, how many patients does that cover in the early years, and do you need any process changes before broader indications?
Yeah, so if you were to just assume, for example the BCG unresponsive indication, a patient could use up to 18 doses or 20 doses a year. You just divide that, you get around 2,500 patients.
Sure, got you. On the commercial build, can you share more detail around your launch prep?
Sure. From a launch readiness perspective, our key focus is on account profiling. Certainly, there's a lot of other work streams that take place, but one of the most important ones is account profiling. We do that in a few ways. One is just gathering field insights by sending our team members to the key accounts. We target these accounts oftentimes by how many patients they see, and you can reference that against their BCG usage data. Now that there are a couple of branded products in the market, we're also seeing where those activities are taking place. Really the main work that we're trying to do here is we're trying to ask our customers what's their experience been like.
What were the hurdles? What were something that was good that we should continue to do? What were things that we should avoid? Once we do that, there's just a target number of accounts that we're going after that do about 80% of the volume by BCG. Our goal before approval is to make sure we get that picture in place. We could really, on the day of approval, really figure out who are the key players that we're going to be calling on early on.
Sure. So cretostimogene grenadenorepvec is an office-based intravesical treatment that fits existing BCG administration. How central is that operational simplicity to your launch pitch, and how are you quantifying it for community urologists deciding between options?
Yeah. Through the last couple of months, we've learned that workflow continues to be a very important decision-maker for these practices, who are very busy. They see a lot of patients, and what they really want is something that does not disrupt their workflow and practice patterns. Not too surprising, but it's very important to also hear that from our customers directly. So the fact that cretostimogene grenadenorepvec can be administered by a medical assistant the same way that BCG is done currently, it really fits into that practice pretty seamlessly. Yeah. Now that we have this improved storage condition, so cretostimogene grenadenorepvec can be stored at a regular fridge 2 to 8 degrees Celsius for up to eight weeks. We think that's a huge advantage over what we had previously.
Okay. We've moved through the manufacturing and some launch questions, and maybe now onto the competitive positioning. So Johnson & Johnson's ADSTILADRIN's been on the market for a year now. Has that reshaped or reformed your thinking around the competitive positioning for cretostimogene grenadenorepvec or not?
Yeah, look, I think their early launch data looks really promising, especially around the data around pre and post J-code. I think the key things I look for is around increasing the reimbursement confidence, especially in the larger urology group practices, the private equity-owned accounts. That continues to be quite favorable. I think it helps us understand the market dynamics a little bit better in terms of who might be the early, mid, and late adopters. That continues to drive confidence in our view of the market.
Sure, thank you. Beyond it looks, the CIS setting now includes a few options, and we've spoken to a bunch of KOLs over the course of the last year, and they're suggesting that patients will cycle through two or three options. Where do you think cretostimogene might fit in the sequencing, and what's the single most point of differentiation that you could be leaning on?
Sure. In terms of the patient population that we enrolled in BOND-003 Cohort C, these were heavily pre-treated BCG unresponsive patients. Up to 40% of them have had prior chemo. I think that is really what we intend to go after, like newly diagnosed BCG unresponsive patients. I think we have the added benefit of showing that, "Hey, cretostimogene can work just as well even if you had prior chemo." Because a lot of the current market is dominated by generic chemotherapy. That's a segment where I think we have a unique differentiation. I think one of the most important differentiation of cretostimogene really speaks to its MOA, and it's backed up by clinical data.
What I'm referring to is the long tail that we're seeing. If you have a CR at 12 months, there's a 90% chance you have a CR at two years. That long tail is not something that's easily repeated by others. We think that durable efficacy plus the clean safety profile that we have in conjunction, plus the workflow advantage should be something that makes it easy for us to message to the market.
Sure. Makes a ton of sense. I guess on the BCG supply side, that's about to change, I believe, with Merck opening a facility that triples capacity of BCG by the end of this year. How do you think that might change the way that BCG-naive patients are treated, and do you see any read-through for the BCG unresponsive therapies that we discussed? Does more available BCG expand the funnel of patients who eventually become unresponsive and reach you, or does it strengthen BCG's hold on the frontline and raise the bar for displacing it?
That's a great question. BCG, again, works reasonably well in the frontline BCG-naive setting. The bar has always been very high to tap into that space. Should there be a tripling of BCG supply, then what could happen is more patients who are currently not receiving the full course of BCG could then receive that. You're right. I think the dynamics and split between exposed and unresponsive could potentially shift. Our current view is that the unresponsive market is 25,000 patients, and in an exposed population, it's about 50,000 patients.
T here could be potentially a shift there. Should there be a tripling of supply. I think when it comes to the intermediate-risk opportunity, it is still pretty wide open. 10 years ago, those patients would have received BCG. However, practice patterns have changed, guidelines have changed. So being potentially first in that adjuvant setting there, I think would really, even if BCG were to come back, having an improved product in that setting, I think we will still be in a very good position.
Fantastic. Thank you, Arthur. Moving on to BOND-003 and the high-risk data package. T he BOND-003 cohort data showed 75.5% complete response at any time and a median duration of response at around 28 months. You have highlighted that 90% of 12-month responders remain in response at 24 months. A mouthful. As you talk to investors and physicians, which of those numbers do you think best capture the differentiation, and how do you frame durability against the competing profiles?
Yeah. If you just look at what's I think the 12-month CR rate is usually something that people care about because it's something very intuitive that, hey, I start treatment today, am I going to have my bladder in 12 months? There's that number. I think what's often surprising is that durable tail that I talked about from 12 - 24 months. That 90% durable response during that period, I think it's quite surprising. I think it's also differentiating.
Sure. Thank you. On the label you're filing for the CIS population with or without papillary disease, help us bridge to the papillary only and the BCG-naive datasets. With Cohort P showing high-grade event-free survival in the low 80% at nine months and CORE-008 Cohort CX at 88% complete response in BCG naive, how do those cohorts factor into your lifecycle and label expansion strategy? What's the timing and how does the BCG supply outlook shape how you'd position cretostimogene in the naive setting as a BCG alternative, a combination or a therapy for patients who can still access BCG?
Great. Yeah. I'll start with the BCG unresponsive papillary patients. This has been a population that typically would not be for BLA approval. Most competitors have gone onto the NCCN and Compendium listing. And they are being reimbursed based on that. There is a competitor who has a PDUFA date for that population in January.
We will be watching that pretty closely. But we will have the 12-month results end of the year for that cohort, and we intend to publish it at a peer-reviewed journal to just get the necessary steps ready. You talked about the BCG-naive data set, the 88% complete response. I will perhaps remind you and the audience here that we actually have a very exciting cretostimogene plus gemcitabine combination data that we also shared earlier this year. That was done in a setting of BCG-exposed and BCG unresponsive patients.
Of 50 patients, we had about 50/50 each in unresponsive and exposed. The data was very similar, but we had achieved about a 90% event-free survival at six months. Very promising. With that data set, we had an alignment meeting with the FDA around a phase III concept, which is we want to enable a phase III trial in the BCG exposed setting using cretostimogene plus gem versus gem. We got the confirmation, and pending the 12-month results that we are going to have later this year. We're going to figure out the proper sizing for that study and pursue that potentially early next year. That would then help us unlock that additional 50,000 patient I spoke about earlier. I think that's a space that is a very low-hanging fruit that may not have received as much attention recently.
Sure. That's awesome. Moving on to PIVOT-006 in intermediate risk, which is the big near-term catalyst to us. The first randomized registrational trial in intermediate-risk NMIBC is pulled forward roughly a year, top line expected imminently against a surveillance control. How do you define a clinically meaningful result, and how much do you want the market focused on the hazard ratio versus the absolute recurrence-free survival split?
Great question. Given the randomized nature of the study, the primary endpoint is recurrence-free survival, and that's going to be expressed in a hazard ratio format, which again, it really means are you reducing the rate of recurrence? We've been saying, and this is based on our feedback, talking with KOLs and physicians, that a 30% relative risk reduction would be clinically meaningful. We think that given that there is no approved product in that category right now, there's a competitor product in the ablative setting.
Our position and based on our trial design, we are going after patients who have completed a full TURBT. I think this is an area where you asked about the hazard ratio versus the 12-month. From a urologist's perspective, they potentially will not compute the hazard ratio as the same way a regulator would look at it. They may also want to look at the 12-month landmark numbers.
Sure. How are you thinking about the control arm performance? Does a stronger than expected control arm worry you if it compresses the absolute benefit even with a good HR?
That is a great question. I think the control arm here, the truth is, I think PIVOT-006 will be the answer to how does the control arm perform. Obviously, ahead of that, we think the best, closest proxy would be the ATLAS trial, of which the control arm had a TURBT treatment option. That kind of trends in that 50% 12 - 15 months RFS range in that specific setting. I think when we talk about hazard ratio, it is always done in a relative risk reduction concept. As long as we can continue to achieve that, we still think we will be in a very good shape to demonstrate that we can reduce the number of TURBTs for these patients.
Sure. The study has enrolled a broad range of intermediate-risk patients. How should we think about the pooled RFS number across that heterogeneous population, and could subgroup performance end up mattering as much as the headline?
Yeah. The study is not powered by each subgroup. We definitely have capped certain subgroups, for example, like the high-grade Ta, to a certain amount to make sure it's well-balanced, right? But across the board, these are all defined as intermediate-risk patients. We think ideally, both the newly diagnosed, recurrent, low-grade, high-grade could all be part of it, and that would give us the broadest label versus the competition.
Sure. Thank you. How are you thinking about the intermediate risk opportunity versus BCG unresponsive in terms of both addressable patients and market size?
Sure. This one, intermediate risk is one where you have to go and create the market. I think BCG unresponsive has a very well-defined market at this point. It's still growing. I think when it comes to intermediate risk, cretostimogene could potentially be the first to market, especially in the adjuvant setting. So it's one where we have the responsibility to go and shape that market. In absolute number of patients, it is twice the size of the unresponsive patients. Just in terms of sheer number of patients that are addressable, it is a much larger opportunity.
Sure. Assuming that you do have a positive readout, what is the path and timing to a second filing, and could it quickly become a commercial contributor along with the high risk?
Yeah. So that is one where what we have been saying is, once we have the data, we are going to have to engage the FDA.
Certainly, there are different filing considerations here. I think we will have a very open dialogue with the FDA because they share a lot of the same parts. They share the same non-clinical and CMC modules. The only part that is different is the clinical module.
Right. Thank you. Moving on to some questions around combination and earlier lines and CORE-008 and Cohort CX. What did the combination teach you, and how does it change how you think about positioning monotherapy versus combo as you move into earlier lines?
Yeah. This is a great example where early on in our development plans, we had tested cretostimogene plus a systemic checkpoint agent, for example, and the results were additive. We learned quickly that the urologists would really prefer to keep the patient in their practice, meaning that a pure intravesical combination versus one intravesical, one systemic might be preferable. Here's a case where cretostimogene plus gemcitabine, these are two orthogonal MOAs coming together, and based on the sequential treatment regimen, which is creto/gem , it seemed to generate really good results versus the concurrent creto/gem .
We're more likely going to take forward the creto/gem sequential therapy. It's going to be less burdensome for the patient because each visit, there's only one agent that's being administered. Gem, when it's given on its own, it doesn't have a lot of long-term side effects either. Given the early data, it seems to be additive, and so we await to see the 12-month results. If it holds up, it's definitely very promising.
Sure. Thank you. On the BCG exposed population, that in-between group that's neither naive nor unresponsive, why do you believe in that market? How large is it? How do you think about the path to addressing it?
Yeah. Conceptually, every year in the U.S., 25,000 new high-risk BCG-naive patients come to the market. They all get some form of BCG, even during the shortage. Because, in fact, BCG should be preserved for these patients. From there, you then have two pools of patients, one who are BCG exposed, one who are BCG unresponsive. In our own experience, we have to turn away a lot of patients who don't fit the FDA definition of BCG unresponsive. Which is five plus two doses of BCG, recurrence within 12 months. Anything outside of that, this is a really wide net that currently is all off-label.
Based on the BCG claims data, we know there are a large number of patients actively on BCG, and we understand that the narrow FDA definition was really meant for a regulatory purpose. Really having this potential label really helps us capture everyone downstream of receiving BCG.
Sure. Thank you. Moving on to financials and strategy. You have roughly $1 billion in cash runway through 2029, and you have recently added $500 million through the ATM. With quarterly burn around $80 million and launch spend ramping, how are you thinking about whether the current position fully funds you to and through launch, and what would prompt you to tap the ATM further?
Yeah. Currently, all the programs that I just described, including the BCG exposed phase III, they all cover part of our current cash runway guidance. I think in general, our view on this is any kind of SG&A spend would have to be fit for purpose on where the needs are with respect to commercial as well as R&D. I think you kind of titrate up and down depending on where you are with those activities. When it comes to R&D, I think we still think there is a number of opportunities that we can potentially tap just with cretostimogene and just within bladder cancer. We have already done some of the building blocks with, for example, muscle-invasive bladder cancer, but more work will be done on that. So we remain pretty disciplined with how we are spending capital.
Right. Sure. I guess the number one inbound I get is when are we getting the PIVOT-006 data? What is your latest answer to that, Arthur?
Yeah. As recent as August and even at this conference, we're saying that it's in the near term.
Okay. Fair enough. Now, I've run out of my questions. Apart from this final one, is there anything that I didn't ask that I should have or any message you'd like to leave investors with?
No, we just appreciate everyone's support. We have a lot of exciting catalysts coming up, and so I think you've covered all of them.
Okay, great. Appreciate your time, Arthur, and thanks everyone for listening.
Thank you.