Okay, good morning everyone, and welcome to the Morgan Stanley Global Healthcare Conference. I'm Sean Laaman , Head of U.S. SMID Cap Biotech Equity Research at the firm. Before we begin, for important disclosures, please see the Morgan Stanley Research Disclosure website at www.morganstanley.com/research-disclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have the pleasure of hosting from CG Oncology, CEO Arthur Kuan, and President and Chief Operating Officer Ambaw Bellete. Welcome, gentlemen, and thank you for your time today.
Thanks for having us.
Yeah, what we're doing with all of our companies, we've got some macro questions to begin with, and then we'll dig into the guts of CG. First one, with China's rising biotech innovation, how do you think about CG Oncology's competitive position here, and will this influence your R&D and business development strategy?
Yeah, we pay attention to the China landscape very closely. In fact, in 2019, we partnered out Cretostimogene to a Chinese pharma called Lepu Biopharma. They're the ones who actually have out licensed a lot of their global rights to U.S. companies. I think, you know, through that relationship, we continue to stay close to the developing landscape over there. I think ultimately, for U.S. companies, we really need to focus on the novel, disruptive innovation that serves a large U.S. population that's largely untapped. I think those are opportunities that we want to continue to focus on.
Wonderful offer. How are you currently leveraging AI or thinking about AI 's disruptive potential?
Sure, I can kick us off, and Ambaw will comment too. Outside of CG , all I think about is AI , robotics, and automation. I think I'll just briefly touch on some of the repetitive tasks that we see in our supply chain, whether it's testing, filling. Those are the things that we're thinking very closely about, about how to leverage AI today, but we're also thinking about what we could do in the future as well.
Yeah, I mean, I think one of the other areas that we focused on is how it can be an enabling activity for us internally, how it can increase efficiency, such as even small things like meetings, and how we create notes, follow-ups, those types of action steps, document writing, large volume document writing, and comparisons for correlation as well. We are employing those types of activities in addition to how we show up to the customer, really trying to put models into place, such as avatars, for example, in physician engagement, and how we can utilize key opinion leaders in those kinds of aspects of it. Those are some of the areas that we continue to explore and move on.
Thank you, Ambaw. I guess on the regulatory side, what's been the most impactful? Has it been FDA changes? Has it been concerns around MFN or tariffs? What's been the most impactful?
Yeah, I can start, and Arthur can definitely chime in. I would say probably FDA. You know, that's near and dear to us just because our first BLA is going to be submitted to the agency. You know, we are keeping track of all the changes that are happening within the division. We've been really very actively engaged with the agency as well, and happy to really see that our review team, as a whole, has been relatively stable compared to other teams. We're within the CIBO organization, and our review team has been relatively stable. That's an aspect of it. Obviously, the other piece was tariffs, macroeconomics. We make Cretostimogene in the U.S., from a tariff perspective. We feel very little exposure from that vantage point.
From an MFN perspective, obviously that's a future state, but we're not partnered in Europe, nor have we started activities in the European markets and other OECD type of markets right now. That's something that we will continue to look at. FDA, I would say out of the three.
Wonderful, thank you. Now to get CG specific. Starting with CReDO and high-risk BCG-unresponsive NMIBC, with CIS with or without Ta/T1 disease, which is the population that you intend to file in later this year. You presented the BOND-003 C ohort C results at AUA, and then you've had the most recent durability data update last week. Can you remind us of what we saw here, Arthur?
Sure, so just a quick recap. At AUA, we still had nine patients pending CR assessment. Essentially, we have 34 out of 101, about 33%, evaluable for the landmark at two years, right? Two years from the start of treatment. Our Kaplan-Meier projection at two years at that time was 42%. It had censorships of those who are CR, but not discontinued. Last Friday, we reported a 42% complete response rate at two years. This is actual observed. Effectively, we added nine. Nine out of nine CRs all converted. We had three additional CRs who we booked as non-responders at AUA. Basically, they were sent for review adjudication, and two were in CR who basically discontinued treatment but stayed on study. Per protocol, they still got followed up, and all three were in CR.
Very pleased to share with the public that we now have 46 out of 110 patients in the CR at two years. That really represents the highest 24-month CR rate and tracks really closely with our KM estimate. I think I want to point out that competitors, you know, actual versus KM may not track that closely because some patients who are in CR may discontinue or withdraw from the study due to AEs. This points to Cretostimogene 's tolerability and also durability. In context, KEYTRUDA is 9% at two years, you know, ADSTILADRIN is probably even, you know, 19% or lower, right? That really kind of helps you frame that, hey, we're at least 2x or more better than the competitors that have already improved on the market.
Yeah, we thought the data was the best possible outcome that they could have had. Can you frame Cretostimogene' s durability, duration of response, and safety with what has been observed with approved therapies and competitors in development?
Sure, so for the three approved therapies, you see durability from the first CR in the 40%- 50% range. That's across ADSTILADRIN, you know, KEYTRUDA, and ANKTIVA. You know, our current 12-month DOR from the first CR is in the 62% range. Our 24-month DOR from the first CR is in the 60% range. That gives you an idea of, you know, how not only at 12 months, but also this long tail, once you hit a CR at 12 months, you continue to have a very durable response rate into 24 months. We're still tracking these patients. They have to come back for follow-ups every three to six months. In the near future, potentially we could provide another update even beyond that time point. Ultimately, the end goal here is patients don't want to just save their bladders for three months.
They want to be able to keep their bladders for years. We're really trying to move the goalposts here.
Awesome. You expect to initiate the BLA submission in 4Q. What are you planning to include in the submission? Are there any aspects that remain outstanding?
Yeah, I'll start out first. We've guided early on that we are very focused on improving the administration steps of CReDO at the site level. We used to do a five-step administration, which takes about 20 minutes more than a two-step administration. We discussed with the FDA our game plan. They said, run a 50-patient trial. You don't have to do a non-inferiority analysis. We'll be expecting to report those results and submitting that result to the FDA to compare the two versus five steps. We're very confident that, scientifically, we don't see any reason why there'd be any difference there. That saving 20 minutes for a high-volume center really means a lot more, right? Other aspects include importance, stability information. Recently, we purchased a fill-finish facility that fills CReDO into vials.
We are heavily investing in that facility and upgrading its infrastructure to make sure they're inspection ready.
Right, got you. Thank you. Recent news in the space containing single arm studies, how do you think about the FDA's stance here as it relates to your upcoming BLA?
Yeah, maybe I can take on that question. You know, there have been three approved products already under that guidance. It was first acclimated in 2018, followed up with another update in 2024, in August of 2024. We also have a pending approval for TAR-200 using the same guidance. We believe that really the pathway for approval is solid based on already existing precedent of other therapies that have gone through that process. We'll also see another one very soon as well that should continue to give us confidence about the pathway there. In terms of our regulatory engagement, I would say we've got breakthrough therapy designation as well as fast track designation. You know, as part of our filing strategy, we've had multiple interactions with the agency on our submission strategy. Really, based on that particular pathway, the single arm design pathway. That's why our confidence remains strong.
Thank you. I guess sort of prior to new therapies, treatment of BCG, then on to cystectomy. Now the availability of new therapies, it might be post-filing BCG, attempt two or three different strategies to preserve the bladder. How do you position CReDO in that dynamic?
Yeah, I would say we do see, especially post our BEPS and disease data, the last AUA meeting, we've had really a number of interactions with clinicians. They do see post-BCG for the patients that BCG has failed. We do see two or three additional lines of therapy in those patients. Our goal has been to make Cretostimogene 's backbone therapy within the space. If you look at our cross-section of our clinical trials, they cover really the gamut of intermediate risk disease, high risk disease, and all points in between. Really working to make it backbone therapy as monotherapy and also potentially in the combination area as well. Earlier this year, for example, we initiated a trial of Cretostimogene's plus gemcitabine Cohort CX.
That trial is looking at patients that are both BCG exposed as well as BCG-unresponsive patients in that trial, thereby adding on to the preponderance of clinical evidence for the management of those patients.
Thank you, Ambaw. I guess we saw J & J's TAR-200 granted priority review by the FDA, I think in July. Markets assume that it'll get to market first. How do you think, given different routes of administration and data that you've seen so far, how would you paint the picture of physician and ultimately patient preference if indeed it does get to market first?
Yeah, I mean, I would say the following things. In the patient-physician discussion with their caregiver as well as the patient, the dialogue they have is around probably three major things. Does it work for me? Is it going to work? How efficacious is it? Is it safe? Is there some changes in my lifestyle that I need to experience by taking on this product? The last and really very important question is how long? How long is it going to work for me, the durability? Now, Arthur spoke about that durability earlier as well, showing that, for example, if you're in CR at month 12, nine out of 10 patients will be in CR at month 24. It's really a compelling patient dialogue and discussion that clinicians can have about it. You know, really, patients ultimately do not want to lose their bladder.
The bladder you're born with is the best bladder that you can live with. We believe that Cretostimogene will help to expand that. In terms of TAR-200 coming onto the market, their success is actually good. We do believe that their success is a good barometer of what the opportunity is for Cretostimogene . With the best safety profile and the long duration of response with Cretostimogene , we have a unique opportunity to put it in its right place as being backbone therapy within the landscape.
Thank you, Ambaw.
I'll just add a few points to that. I think with the potential J & J approval in the near term, it'll tell investors two important messages. One is that the single arm trial using CR as an endpoint and DOR as a secondary endpoint could potentially gain full approval, even in this environment. Number two, the pricing information will be very valuable to all investors, including us. I would say from a competitive perspective, it's actually great to have a pharma kind of priming the market for us to drive up reimbursement confidence. That's a key topic that many sites continue to discuss because this is a market that's new to buy and bill, but it doesn't mean that it won't happen. It's just, it's early innings. The last one I'll say is CReDO is the only asset that's been tested in BCG-unresponsive, heavily pretreated with chemo.
Up to 40% of our trial in the BOM3 had prior chemotherapy, including gemcitabine. We can't say the same for the TAR-200 trial. We're certainly going to be leaning hard into that because, as you know, many urologists still give a lot of chemotherapy, gemcitabine monotherapy or gemcitabine doublet. That is a unique advantage that we're going to have in our data set that they won't.
Yeah, and maybe one thing I could also add, you asked about kind of how is this product used. You know, TAR-200, for example, is administered into the patient directly using a cystoscope. It's actually manipulating the patient's bladder. You're instrumenting the patient's bladder, putting a scope in to deliver the TAR-200 device into the patient's bladder up to eight times the first six months and two additional times for the rest of that year. First year, 10 times manipulation of the bladder, placement and pull-out of the bladder. Patients are already anxious about what potentially you could see. Also, the manipulation of that patient's bladder really is done by a urologist, the most part. Versus, you know, Cretostimogene , which could be administered by a nurse or a medical assistant, the same really method as BCG.
What they have undergone for BCG, the six weekly instillations, same similar process for Cretostimogene grenadenorepvec's administration. From a workflow perspective, it's something they're used to, something that can be easily adapted into their clinical practice, especially with our streamlined two-step administration process now. Therefore, the efficiency on therapy is also increased. Got you. Thank you. We touched a little bit on manufacturing early, but what manufacturing and supply considerations should investors have? How do you think about the launch? Like, how will the roll-up happen? What volume do you think you can serve out of the gate?
Sure, I'll touch on those. I think for investors looking into this space, which is an exciting space, there's been a couple kind of CRLs that occurred in our space, right? Three out of four BLA submissions have had CRLs. If you look at them carefully, they all fall into a few categories, right? Within the CMC risk category, some players have changed the process of making the product from phase III to commercial. Some have changed the sites of manufacturing from phase III to commercial. Some have changed the scale because they have yield issues. The fourth category would be a pre-approval inspection failure that largely has to do with quality management systems, SOPs. Quality related, right? Those are the kind of general buckets I would consider from a CMC perspective as it relates to risk.
We're focused on, you know, number one, we did not change the sites of where we made Cretostimogene grenadenorepvec (CReDO). It's going to be the same site in the U.S. that will supply it for the commercial launch. Number two, we did not change the process. We did not change the scale. If you think about CReDO's synergy, it's a replication competent adenovector. It makes more copy of itself, so yield is never an issue for us, right? From that vantage point, we're very focused on the last part, which is the inspections. This has to do with upgrading the facility's quality management systems, making sure they're following and having the right SOPs in place. If they deviate from those, did they correct them, right? These are some of the details that we're really working hard through. We hired ex-FDA inspectors to help us with that, right?
From a capacity and scale perspective, as evidenced by how fast we've enrolled our recent second phase III in intermediate risk frontline adjuvant setting, that trial was 10 months ahead of schedule. I think investors can tell that we do have drug supply. Otherwise, that trial, even if the patients were there, we wouldn't be able to supply them. At this moment, what we're saying is with the current scale we have, we can do up to 40,000- 50,000 vials a year. The beauty about CReDO is that we can store this at - 60 to - 80 degrees Fahrenheit, and it could be stable for up to five years and more, right? We can actually build inventory as we anticipate future demand. With PIVOT-006, our IR trial pulling forward 10 months, we're already thinking about possible strategies to get that onto NCCN sooner.
That will be ahead of our competitors by a couple of years.
How do you think about, you know, the access to physicians during the rollout?
Yeah, I mean, I think that's one of the areas where we've made a lot of investments in. I can just give you kind of a look into some of those examples. All of our clinical trials that are currently being deployed out are really in the top centers throughout the country. They're in the top 10 death trials, nine, seven, and eight. That'll be our future really most important customer base. One unique piece about this area and this disease state is that there's such a huge concentration of clinicians that manage these patients. Really, the top 300 centers generating well north of 50% of the opportunity that exists out of 7,000 +, for example, centers throughout the country. That has allowed us to really penetrate and really look into those.
We have a team already of Medical Science Liaisons that are already interfacing with those customers, having engaged discussions, scientific exchange discussions already today. We've been really driving on those pre-launch activities, both on the field perspective as well as payer perspective as well, learning insights about the patient journey, what's happening to patients vis-à-vis our clinical trials, as well as what's happening to other patients on other therapies as well. We've developed the team that is in place, for example, our leadership team, our commercial leadership team, as well north of over 60 years of experience in bladder cancer specifically. They know the customers. We know the customers. We're actively engaged with them on an ongoing basis, talking about Cretostimogene grenadenorepvec's imaging, talking about the landscape and what's happening within that landscape.
In fact, I do believe that's one of our value drivers, our customer intimacy and engagement, the ability to know where the customers need and what the patient needs. We're also spending quite a bit of time in understanding and working with advocacy as well as patient groups, patient ambassadors as well, to really help and inform our launch strategies.
Thank you. Just maybe to push a little bit on price. You mentioned that, you know, TAR-200, if they do come to market first, one of the value propositions is that you'll get some insight on price. Could you frame that a little bit more and maybe some expectations on price or think about the goalposts?
Yeah, I can start and tackle that question. You know, currently today, if you look at the landscape, the pricing is somewhere between $200,000 in the case of KEYTRUDA per year to over $600,000 in the case of ADSTILADRIN. That's really the price band. ADSTILADRIN is somewhere, you know, around the mid-$200,000s, so to speak, per year. You know, when we look at this landscape, really, these are the following metrics from a pricing perspective. Number one, what's kind of your target product profile? Okay, what's the expected length of treatment that a patient will be on? Those are some of the inputs in there. The third element of it is really what's the current existing landscape pricing that helps to inform what your pricing could look like and should be.
The next piece is really from an access perspective, both at the patient level as well as the account level, how would they access that particular price? I think we look forward to seeing where they will land. Based on what has been, you know, publicly available in terms of what's been communicated at least publicly, really of what their targets are for the next coming years in front of us, you know, you have two drivers. Either you penetrate or you have price or you have a combination. We do believe that those would be the important aspects of how we will evaluate it. We're just kicking off our pricing studies now to really look at the landscape. That's the formula we're going to be using.
Wonderful, wonderful. I've now got some questions on upcoming data. I believe the pivotal BOM3 cohort P data is set for Q4. Can you remind us of the early data that you presented at AUA? What do you hope to present in Q4?
Sure. Cohort P is for the papillary cohort or the TaT1 BCG-unresponsive cohort. This will not be on our label, but we intend to publish this data quickly and get on NCCN. There are already two precedents ahead of us. KEYTRUDA as well as ADSTILADRIN have both made it into NCCN. Their data around 12 months is about 50% or so RFS, right? These are patients who have completely resected their tumor and the drug is given adjuvantly, right? From our data sets, we showed about 14 patients' worth of data at AUA this year, and the current RFS rate is about 90% at nine months. There is obviously more to come later this year. We hope to report a more mature data set later on, and hopefully beating the benchmark of what's already out there in the guidance right now.
Thank you. The data in AICAP BCG-unresponsive patients with TaT1 without CIS, otherwise known as papillary disease, can you remind us how that population differs in terms of both patient market size opportunity from the CIS population with or without papillary tumors?
That market is about, in our view, about 60% of the pie, right, the TaT1. The CIS with TaT1 is about 40%. That's certainly a very important segment for us to go after.
We've also got the phase two core double OA data in BCG-naive patients. What is the patient size and the commercial opportunity there?
Yeah, so, you know, BCG naive is, you know, probably about 25,000 patients in the U.S. incidence-wise. We don't view it from a prevalence perspective because pretty much all of those patients will get some form or dose of BCG, and they all turn into BCG exposed right away. Right? If you have received five plus two doses with recurrence within 12 months, you then become BCG unresponsive. In our view of the market, BCG exposed is going to be the largest share of the market in the future. Right? Core 008, we've got a few cohorts there. Cohort A is where we're going to read out data this year. This is in the BCG naive high-risk NMIBC cohort. We never intended this to be one where we believe it's going to beat BCG, but it's very important for us to show monotherapy data there.
Most importantly, we're generating the two versus five step information for FDA. From there, we do have cohort B and CX. B is in BCG exposed, monotherapy. We do want to establish CReDO as a monotherapy there in about 150 patients, and that is that market in BCG exposed. People have asked us how to think about that market. The way we think about it is if the naive market is 25,000 patients a year and they all turn into exposed that same year, right, we think it's at least twice of that from an eligibility perspective. Right? From a BCG unresponsive market, our current view is it's about 25,000 patients that we can address. Right? Cohort B, again, monotherapy and exposed. Cohort CX is, as Ambaw mentioned, CReDO plus gemcitabine in both BCG exposed and BCG unresponsive.
The motivation there really is we have demonstrated CReDO plus KEYTRUDA as an add-on could boost our response rate and durability. However, we recognize the issue of KEYTRUDA being sold to MedOnc and CReDO is staying within the urology practice. We want something that the urologists can administer at the same time or together. Right? Gem is something that the urologists routinely give. We have preclinical studies that's not published where we have demonstrated the synergies between gem and CReDO in the right doses and right combination. We're very excited about that trial.
Cool. Thank you. I'm listening to recent data in the space from the PD-1 inhibitor, cisalimab. Can you contextualize that for us?
Sure. That trial, the CREST trial, was done in a BCG-naive high-risk population globally. It was cisalimab plus BCG versus BCG. BCG in the control setting showed about an 85% CR rate in the CIS population. The combo showed about an 89% CR. The kind of EFS curve probably only separated at year three. It did hit its endpoint. However, we do question whether the 4% upfront CR spread is meaningful enough, plus all the grade III side effects, from the 10%- 30% range that you don't get with BCG. There's also a small chance of myocarditis that led to death in one of the arms of that combo. The risk-reward is not entirely clear to us. As I've mentioned, you're selling this product to different call points. Right? Can you convince urologists to give checkpoints? That's to be determined.
Wonderful. Thank you. I guess sort of moving on a little bit for intermediate risk NMIBC enrollment, it recently completed in the phase three Pivot 006 study. Can you remind us of the current treatment landscape for these patients?
Yeah, I mean, the current treatment landscape for this patient is an intermediate risk by guidelines. TRBT is really first-line therapy, you know, in this patient, followed by, you know, chemo, you know, one dose, single dose chemo from a neoadjuvant perspective as well by PIER to the operation. Now we've got, if you look at intermediate risk NMIBC, there's been a recent approval, for example, in low-grade intermediate risk in lieu of TRBT. That requires really a change from a clinician how they manage these types of patients. Again, if you look at it from really a patient population perspective, the largest and broadest patient population is really what's addressed by PIVOT-006 , which is based on AUA FCO guidelines, both low-grade intermediate risk and high-grade intermediate risk, less than three centimeters, PA disease. That's part and parcel of our PIVOT-006 trial.
Compare, for example, to the MoonRISe trial, which requires, you know, FGFR, you know, alterations whether the patient has that or not. That's that kind of a subset of population that probably cuts that patient population by 25% or so, if not higher. Really, our trial, which really rapidly, you know, enrolled over 200 plus patients just this year, were enrolled into that trial, you know, 10 months ahead of what we had projected in advance of it, really shows the robustness of the data. As we were releasing more and more data on CReDO's imaging in terms of our pivotal BOM3 data that we've been releasing, physician interests, PI interests, patient interests continue to grow. That's really what facilitated that trial's enrollment so rapidly and so quickly within that landscape.
You know, as Arthur indicated, we intend to really quickly move forward and potentially file for that indication right behind our BCG-unresponsive first indication in advance of that after we publish the data. You know, once you have an FDA approval on your first indication and have a publication, get on the NCCN guidelines. Once you have a follow-on product in advance of an FDA approval, once you have a publication in your review journal, you can seek the addition of that into the NCCN guidelines. That's the path that we're going to follow for PIVOT-006. We think from an opportunity perspective, when you look at that intermediate risk patient population, we think it's probably around 2x of the BCG-unresponsive marketplace, the 25,000 or so patients that we mentioned earlier. We think that opportunity is even that much higher, you know, for this patient population to access CReDO.
Thank you. What about muscle-invasive phases of bladder cancer and how are you thinking about, you know, Cretostimogene grenadenorepvec's potential in that opportunity?
Sure. In that setting, we've run a trial called CORE-002. This is an IIT trial where we combine Cretostimogene grenadenorepvec (CReDO) with nivolumab, given neoadjuvantly prior to radical cystectomy. About six doses of CReDO and then two doses of nivo, and then at week 10, you resect the bladder. We were looking for pathological CR, right? Nivo alone in this setting is about 7% pCR. The combo showed about north of 40% pCR. We're obviously looking at the space very carefully because the elephant in the room is EV plus KEYTRUDA. I think until that kind of works itself out, we're not in a rush to make any moves in that setting right now. It's good to know we already have some efficacy and safety demonstrated in that setting.
Okay, great. Thank you. I have one final formal question that, you know, just your cash on hand, where does that give you runway to, the funding requirements for the launch? When do you hope to get to cash flow positive?
We currently have about $660 million cash on hand, and we've guided this would be into the first half of 2028 in terms of runway, covering many kind of milestones that we talked about this morning.
Is there any question that I didn't ask or something that I should have asked today?
I think you answered, yeah.
Yeah, you covered a lot of ground. Thank you for the opportunity.
Wonderful. Thank you, gentlemen, for attending.
Thanks for your time.
Take care.
Thank you.