Good morning, everyone. Thank you to those in the room and to those dialed in on the webcast as well. My name is Faisal Khurshid. I'm one of the senior biotech analysts here at Jefferies. We are here live at the Jefferies Global Healthcare Conference in New York. Really pleased to have with us today the management team of CG Oncology. Arthur Kuan, the CEO, is here with us today. We're going to have a super interesting discussion on anything and everything cretostimogene-related. Very pivotal time for the company progressing towards a BLA, as well as several important data readouts over the course of the year. With that, Arthur, could you just start by introducing the company for us?
Sure. Thanks for having us. CG Oncology is a company that's laser focused on developing cretostimogene, which is an oncolytic immunotherapy in the setting of Non-Muscle Invasive Bladder Cancer. This is a setting in the U.S. that we believe could address up to 150,000 patients. We've been solely focused on this, and we believe cretostimogene can really make a huge impact in this specific segment.
Got it. Excellent. Let's jump right into that. I just want to understand, within the high-risk NMIBC BCG unresponsive setting, starting at a high level, how do you see cretostimogene fitting in amongst the various options that are available?
Sure. In the high-risk BCG-naive setting, these patients first get diagnosed, and then they usually receive BCG. After adequate BCG, which is defined as five plus two doses of BCG, and recurrence within one year, you then fall into this category of BCG-unresponsive disease. This is a disease that is roughly about 25,000 patients a year. Currently, there are a couple FDA-approved products. The first one was KEYTRUDA, and then there were a few other competitors. J&J's BALVERSA was also approved recently. In that landscape, I think it's still in the early innings. This is a prescriber base that is still gaining confidence with buy -and-bill products. Having a few competitors ahead of us, it's really been educating these physicians and the accounts about buy and bill and building reimbursement confidence.
cretostimogene is positioned in a very unique way in that none of the approved therapies are oncolytic immunotherapies. Some are pure immunotherapies and are nonspecific. Some are chemo-based approaches or prolonged PK of chemo. Our MOA is the most uniquely differentiated one in that group. All right. Briefly, our MOA comprises both a direct oncolysis of the tumor, as well as an anti-tumor immune response that gets activated after tumor cell kill. It's sort of this one-two punch that you can deliver in the bladder. Because our therapy does not harm normal cells, our AE profile is one of the best from a landscape standpoint right now, with currently zero Grade 3 adverse events. Because ultimately, what patients care about is preventing radical cystectomy.
Patients don't want to know, "Well, what is my CR rate at three months?" What they want to know is, "Can I keep my bladders at two years, three years, and five years, and can I prevent that from progressing into muscle-invasive bladder cancer?" Which then ultimately could turn into metastatic disease, right?
Yeah, that's a good point.
We're trying to intervene right before that.
That is a good point that you raise on durability of benefit, because I think that is one of the key differentiators that you have for the product. Could you talk to us about what durability you have shown so far? I think you've guided to giving updated durability data this year as well. Can you set expectations on that, and how does that position you relative to the competition here?
Yeah. In terms of durability, first of all, the CR rate at any time is about 76% in our BCG-unresponsive CIS cohort. The median DOR has not been met, but it's at least over 25 months. When you look at just the landmark at both 12 months and 24 months, our 12-month landmark is about 46% CR. Our 24-month landmark CR rate is 42%. Just between 12 and 24 months, 90% of patients who have a CR at 12 months remain in a CR at 24 months. That's a very interesting tale that really we believe only immunotherapies can achieve. What could come after that? The study continues out to three years, we hope to report data out beyond 24 months very shortly later in the year.
Got it. Can you talk about how that differentiates from J&J's INLEXZO? We did a bladder cancer KOL dinner just the other day at ASCO, this was brought up as a very important point in differentiation for your drug.
With J&J's product TAR-200, we've not seen any data beyond 12 months at this moment. We only know their 12-month landmark, which is about 45% or so. Given their MOA being a single-agent chemotherapy, certainly, as we know, chemo resistance does develop across different tumor types. We certainly are lacking those 24-month results or even 30 months results at this point. Obviously, another key differentiation is the tolerability profile. With their approach, there certainly is a lot more toxicity, perhaps related to the device or chemo, but we're not seeing that with our cretostimogene approach.
Got it. Then you mentioned the 25,000 patients that are BCG unresponsive high-risk NMIBC. Can you clarify if that's an incident figure, and then based on your guys' understanding, what proportion of that population is treated today with the available options of INLEXZO and KEYTRUDA?
Yeah. We think of this population as a blend of incidence and prevalence, because if you think about it, a patient needs to have received five plus two doses of BCG and recurred within 12 months, right? It's hard for someone to get that exact sequence all within a year.
You're definitely going to have patients from prior years coming over. This assumption of 25,000 is just based on a reasonable kind of blend of prevalence of what we think through that funnel of post-BCG, which would then end up in that BCG unresponsive category fitting the FDA definition.
Got it. Would you recommend that the street and investors actually model this as a prevalent pool of patients?
We believe that's the right approach. These patients have a pretty decent overall survival rate.
Yeah
The progression rate as well as the recurrence rate is very high.
Got it.
Right.
Do you feel like investors misunderstand that? I feel like one pushback that I hear from folks is, "Well, the incidence is only a few thousand." How big can this market really be?" Do you feel like this is a point that is misunderstood?
Yeah. I think this is an interesting case where the prevalence pool of those living in the U.S. with bladder cancer is about 700,000 patients a year. Certainly, we're not suggesting you look at that, but from that pool of 700,000 patients, it's important to think about who has active disease, and we think about the recurrence rate. And you can look at recurrence rates over a 10-year period, over a five-year period, or in the case of high-risk disease, even in a three-year period, you can get a high number of recurrence rates. Right? For example, most therapies that are FDA approved, take ADCETRIS for example, more than 80% of patients on ADCETRIS would recur by year one.
Yeah. Can you talk to us about where you are on the BLA progress?
Absolutely. We started the rolling BLA submission last year in Q4, and we've already guided as of May 8th that we've completed the clinical as well as non-clinical BLA module submissions. What remains is the manufacturing module that we're guiding to completion by the end of this year.
Got it. Can you talk to us a little bit more about that? This has been kind of a hot topic for investors given some of the precedent in the space. Can you talk to us about what goes into that? Frankly, among investors as well, I think there's a little bit of an educational gap on the time needed and why this is something that you guys are kind of guiding to broadly as within the year.
When we think about manufacturing and de-risking manufacturing, there's always a question on supply. Do you have enough supply that you can supply the market, which touches on scale. What we've been telling people is the current GMP scale that we have used in our clinical trials as well as the pivotal trials, that process is not changing. That process is sufficient for commercial launch, and that process on an annualized basis can currently yield up to 50,000 vials of cretostimogene. We're not changing the process. It's locked. All of our analytics and testing methods have also been locked , and there has been agreement with the FDA on what those are, so all the assays. What we focus a lot on is around inspection readiness.
This has been a hot topic with different companies, Catalent, for example. It usually is in the last step of the manufacturing process, which is what we call fill and finish. That step is simply filling the product into a vial. It sounds simple. That is the last step before the product gets shipped to the site and delivered to patients. We're spending a lot of time on this site that we acquired last year in July. Our goal is to upgrade them so that they're CBER inspection-ready. The site has previously been inspected by CDRH, a medical device division of the FDA, with no 483 cited. The standards, however, for CBER inspection are a bit different. Certainly, it's a kind of higher standards. The good news is we do have full visibility and line of sight into that, given our investment.
Got it. Is this unique amongst companies in the field to be acquiring and building your own fill-finish capabilities?
Yeah. I think different companies take a different approach. Some would just build manufacturing capabilities early on. Some gene therapies certainly do that. Cell therapy companies do that. Some would just entirely outsource. We're sort of taking more of an opportunistic blended option or a hybrid option where our production of credo is still outsourced, and then we have an in-house fill and finish set up right now.
Got it. Then in terms of the outsourced manufacturing of drug products, can you describe what process goes into that, just given the MOA of the drug?
In general, this product is made in a bioreactor. It's off the shelf, so it's not patient by patient or batch by batch. It's a very scalable process, because just by describing the MOA, this is a replication-competent vector, so the yield is actually really good, because every cell that it infects, it's making a lot more copies of itself, right? Just from the MOA itself, you can already derive that the yield is going to be pretty good. This is one where we believe the cost of goods is going to be very competitive, similar to a typical biological product.
Got it. I know more investors are familiar with when it comes to viral vectors, AAV, for example. How would you compare this to AAV? Is that even a valid thought to have?
Yeah, I think in terms of AAV, the main differences are typically that the AAVs are not replication-competent. They do not lyse—
Yeah
...the host cell. Right? I would say the yield for us is even higher than AAV approaches.
Yeah.
Got it. Okay. Then with regards to the CMC challenges that the field has had, can you refresh us on what those challenges have been, what risks you feel do apply to you, and what risks you feel do not apply to you?
Yeah. If you think about just within the bladder cancer landscape, there was a CRL applied to a company called Sesen Bio that currently is not here anymore. They had, I believe, a process change that also had some clinical-related CRL topics as well. Ferring, for example, I can't talk too much about the details, based on public information, it seems to be also related to a process change. They had scale-up issues related to the cost of goods. Again, ADSTILADRIN is a product that, even though it's an adenovirus, actually does not replicate, and it creates a payload called interferon alfa that also technically is pretty toxic that could kill the host cell. Right? That manufacturing approach, given its MOA, is very different from ours.
I'm saying that the risk category is a bit different because we're not needing to change our process for commercialization. Another company, ImmunityBio, they had a pre-approval inspection failure that led to a CRL, and that's the category of risk that we believe could be preventable if you focus on what is important around quality systems. These are things that we are laser focused on by getting the ex-FDA inspectors into our facilities to really make sure we can prep them well for an actual inspection.
Got it. You've had ex-FDA inspectors on a contract basis come over and take a look at everything going on?
Yes.
Interesting. Okay, cool. Shifting over to commercial readiness, this is a field where it's dominated by these large community practices. Can you talk to us a bit about the commercial dynamics and your commercial preparations?
It really starts with our relationships, and we've been doing clinical research and clinical trials with a lot of these sites, starting with our BOND-003 trial with different cohorts, CORE-008 with different cohorts, and PIVOT-006. We had up to 90 sites in the U.S., and a huge proportion of them were community sites. The market we tend to look at who are the highest users of BCG, who perform the most number of TURBT, et cetera. There are a few metrics that we look at. Who are the ones that are using branded products? We take all that information, and we think about how we start to profile these accounts, how we segment the market, and how we position cretostimogene based on their site's specific practice patterns. We have all that information, and we're already building out our commercial infrastructure.
We'll talk about that more later. We have a team of MSLs already in the field engaging with customers who are very interested and curious about our data, and as well as publications. All that is really ongoing, and it's been ongoing since last year.
Got it. Talk to us about the product handling and administration side of it. For these large urology group practices, what does that look like? Is that different from other drugs that they use? I remember when KEYTRUDA launched, they had the challenge of these LUGPAs not having infusion chair capabilities, so that was a little bit of a point of friction. How does your administration handling differ from what these sites are currently capable of?
We typically tell the site that if you can give BCG, you can give cretostimogene. That's really resonated really well because most of these LUGPA accounts that see a high volume of patients, they understand the BCG workflow, and they understand how cretostimogene can seamlessly fit into that workflow without changing any existing practices. From a shipment standpoint, the product is shipped frozen. It's actually an advantage of ours because we get to build inventory. It's very stable when it's frozen. At the site, once it arrives, they just take it out of the box and put it into a fridge at two to eight celsius. Every single site would have a fridge, and it's stable at, we previously said, between four to six weeks or potentially even more.
That resolves a lot of the logistics concerns that were previously circulating. We also have an adapter called the Closed System Transfer Device . We didn't invent this, but it's off the shelf, and it simply just sits between the vial as well as a syringe, and it gets straight into the saline bag, which then gets instilled into the patient's bladder. Once you have that system set up, if you have a hood, great, you could use a hood. If you don't have it, you could do your proper benchtop prep using the Closed System Transfer Device . We rolled this out during COVID, and it was really well received by a lot of physicians.
Got it. No hood. Is there any need for a cleanroom or cleaning down the room after that, anything like that?
Just proper bleaching. You could put a bleach tablet in the toilet bowl as necessary. Again, based on the Closed System Transfer Device , the product is not exposed to the open air.
Mm-hmm. Got it. Interesting. With respect to the buy and bill dynamics of this, to what extent are the LUGPA practices well equipped to do that and comfortable with doing that, especially given the price tag associated with some of these or the approved product at least?
Yeah. Really, I think with the TAR-200 launch, I think that's really one of the best things that could happen for us anyway as a fast follower, where they're out there driving reimbursement confidence at many of the accounts that we're also highly interested in serving as well. All right. I think certainly it's still the early innings for buy and bill in this market segment, but it's certainly going to continue to grow.
Understood. Then can you talk to us about when you launch the product, how we should think about the time from launch to commercial reimbursement and revenues in the door with respect to things like J-code and some of the logistics associated with that?
This product category, in the first six months, you get a misc. J-code, a miscellaneous J-code, and then after six months, you get a permanent J-code. Again, we're looking at in real time how that dynamic is playing out, right? There's a chemo gel product, right? The ADSTILADRIN product. We're seeing that dynamic pre- and post -J-code. Certainly, there's also the time it takes to get to NCCN as well. A segment of the population, the T1 patients, would go on NCCN guidelines once you have a publication. Right. Those dynamics are very important to track early on.
Got it. Great. Is there a possibility to do an EAP or have you guys contemplated that at all to get some of that earlier usage and familiarity?
Yeah. Given that the product has breakthrough therapy designation as well as the safety and efficacy profile that we have, we have launched an EAP program in the U.S. We're not guiding any specifics of it, but there's definitely a lot of enthusiasm around the EAP.
Great. You guys have the PIVOT-006 data for intermediate-risk NMIBC. You guys have pulled up the timing guidance on that. Can you introduce us to the study design and remind us when you intend to have that data?
Sure. PIVOT-006 is a trial that is entirely in North America. It's 364 patients, one-to-one randomized. We're looking at patients with the broadest spectrum of intermediate-risk Non-Muscle Invasive Bladder Cancer Disease. This is based on the AUA/SUO definition of intermediate-risk disease. What's differentiated versus others in the intermediate-risk space is we include a subset of patients with high-grade Ta disease that are less than or equal to three centimeters with a solitary lesion, and these are usually, or all of them are, newly diagnosed patients. This trial is looking at it in an adjuvant setting, looking at recurrence-free survival. The treatment arm has TURBT followed by cretostimogene, and then the control arm is just TURBT with surveillance. We do offer a crossover on the surveillance arm if they recur and want to access cretostimogene.
Both arms allow for perioperative chemo, which is a single dose of chemo that you give after TURBT. The practice in the U.S., maybe up to 30%-40% of centers might be giving single-dose perioperative chemo. We're stratifying for that to make sure it's balanced across two arms. In terms of the high grade versus low grade, we are also stratifying for that to ensure that both arms are balanced. The primary readout is recurrence-free survival. It's going to come in the form of a hazard ratio. What we've been telling investors who are very interested in knowing what the control arm might do, well, the truth is no one has done such a study like PIVOT-006 before us, right? That primarily enrolls in the U.S., that looks across the entire IR NMIBC population. We'll be the first to show.
In terms of proxies and analogs that people can look at, we've been telling people that the ATLAS trial could be one that could serve as a potential proxy. It's not the perfect proxy. There are certainly study design differences in ATLAS, but roughly speaking, between 12 and 15 months , the control arm on ATLAS, which just had TURBT, did about 50% RFS or so. We think that's a reasonable benchmark to look at for PIVOT-006.
Got it. What hazard ratio would you need to see to feel like you have a compelling profile in this setting?
Given that there is no FDA-approved adjuvant therapy in this space, we believe based on our discussions with KOLs before starting the trial, they want to see a 30% relative risk reduction.
Got it. Given the timing of the rolling BLA where you've submitted your clinical module, you're working on some of the manufacturing and inspection side of it, but you're going to get this very important data in the near term. Is there a possibility that you can fold that data into your ongoing BLA filing?
What we've been saying regarding that is they'll likely be two separate applications. We still believe that the BCG-unresponsive filing would be completed first, and then we'll follow on with a separate filing for the intermediate-risk population.
Got it. Can you just clarify what the reasoning for that is? I think some of the KOLs are super excited about this and wondering or hoping if This is something that I heard from a KOL actually, not even an investigator.
Yeah,
Because I'm not even an investor. I mean.
Yeah. I think one of the things that we've said is, since we completed the last patient who enrolled in PIVOT-006 around Q4 of last year, we've stated that we believe we need at least 12 months of follow-up in all patients before we can pursue a filing there. Certainly, the timing could be relatively close to each other, but there still would be a sequential approach in this case.
Understood. Then when should we expect that data?
What's that?
When should we expect that data?
We've said in May that it could be available in the coming months.
Got it. Okay. I was almost hoping it would be today so we could talk about it live, but we'll wait a few more weeks.
It's an event-driven trial again, you never know exactly when those final events are going to occur.
Yeah. Makes sense. In terms of commercial readiness, tell us about your level of commercial preparedness, how many reps do you think you'll need, how many sites do you need to be able to get into, et cetera?
The focus this year is really just on account profiling and really understanding our accounts at a very deep level. Who are the key decision-makers? What were their experiences with prior branded products? Why did they choose? Are they on gem/doce? What would they give after gem/doce? These are the insights that we continue to gather to just have a very in-depth picture of all the key accounts that we plan to go after in the early phases of the launch. In terms of field force, if you look across the space, given the concentration of accounts, everyone is sort of landing in the 50-75 field force number. We believe we likely will be in that similar range as well.
Got it. Okay. At risk of asking this question with four minutes left, there is a very active competitive landscape. I know we talked about the other approved options, or a couple of them, in BCG-unresponsive high-risk NMIBC. In terms of the development stage landscape, can you just tell us what you are focused on, what you see as credible competitive threats, and how you believe cretostimogene Immunogen is positioned?
Yeah. Look, I think there was a non-viral competitor. I think we still believe that MOA is very important. I think certainly we're keeping an eye on novel chemo approaches that could potentially increase its PK. Ultimately, I think what puts us in a very strong position is how fast we're developing our follow-on indications or moving the space into intermediate risk, which are all BCG-naive patients, as well as BCG exposed. I think the future is going to mainly lie in BCG exposed. Unresponsive gets us the first approval, but BCG exposed are all these patients that fall outside of the unresponsive type definition that was set by the FDA.
We think there are at least 50,000 patients there. We're in a position relative to the competition to make investments in that area first, and that's with our CORE-008 Cohort CX data, which was one of the cohorts in CORE-008. We looked at the cretostimogene plus gemcitabine combination. In that study, we already showed, at least in the evaluable patient population, a 92% complete response rate. We also enrolled some unresponsive patients in that trial. We found that there were no real differences between unresponsive and exposed, at least in that study. If you think about it, the benchmark for the CR rate mono versus combo with gemcitabine, if you just look at BOND-003, the CR rate at any time was 76%. Now with the combo, we brought it to 92%.
To us, that's very exciting if that continues to hold up at, for example, 12 months, which we're going to have data for later in the year.
Got it, that'll be an update from the data that you had at AUA?
Correct.
Got it. Okay, cool. I like to wrap up with a question like this. You're going to have a bunch of investor meetings today. As you think about it, what is the one investor question that you wish you didn't have to answer anymore? That people ask and you're like, "Man, I don't want to answer this anymore." What is the one investor question that you sit there thinking like, "Dang, I wish someone would ask about XYZ"?
Sure. Look, I think every meeting is about what's the benchmark for PIVOT-006, what's the timeline for BLA? I truly believe manufacturing is going to be CG Oncology's core competency, and again, only time will tell, and we have to prove it to everybody, but to me, we will turn that into a strength in due course. I would definitely hope more people ask me about BCG exposure because I certainly really believe in that market.
Got it. Maybe just one last one. You've had some leadership changes. Can you just characterize how you feel the company is positioned going forward?
Sure. We're definitely in a very strong position. The board and I determined that it's important to have a Chief Commercial Officer fully and solely dedicated to thinking through the launch strategies and launch preparedness into, we believe, a very competitive launch. It is a very large TAM, and we certainly want someone just focused on that completely.
Got it. Makes sense. Well, thank you so much, Arth, for joining us. Really appreciate it.
Thank you.
Thank you.