CG Oncology, Inc. (CGON) Earnings Call Transcript & Summary

Good morning, everyone, and thank you for standing by. Welcome to the CG Oncology's BOND-003 Results Conference Call. [Operator Instructions] Please be advised that today's conference is being recorded. At this time, I would like to turn the conference over to Sarah Connors, Vice President, Communications and Patient Advocacy at CG Oncology. Please go ahead.

Thank you, and good morning to everyone on the call. Earlier this morning, we issued a press release summarizing the encouraging results from Cohort C of our registrational BOND-003 study of Cretostimogene in high-risk BCG-unresponsive non-muscle invasive bladder cancer. The press release and the slide deck accompanying today's webcast are available on the Investor Relations section of our website. With us on the call today are Arthur Kuan, Chairman and Chief Executive Officer; and Dr. Mark Tyson, Urologic Oncologist at Mayo Clinic Phoenix, Arizona; Ambaw Bellete, President and Chief Operating Officer; and Dr. Vijay Kasturi, Chief Medical Officer, will also be available for the Q&A session following prepared remarks. Before we begin, I would like to remind everyone that during this call, we will be making forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Such statements may involve significant risks and uncertainties, and therefore, actual results could differ materially from those expressed or implied on this call. Factors that may cause such difference include uncertainty associated with clinical development and the regulatory approval process as well as difficulty in forecasting sales, revenues and expenses. CG Oncology is not under any obligation to update statements regarding the future or to confirm these statements in relation to actual results unless required by law. With that, let me turn the call over to Arthur.

Welcome to our investor conference call. Today, we are honored to have the lead PI on BOND-003, Dr. Mark Tyson, share the late-breaking top line results of BOND-003 with you. Without further ado, I would like to hand over the mic to Dr. Tyson.

Good morning. Thank you, Arthur. My name is Mark Tyson, and I'm a urologic oncologist. Delighted to be here with you today to provide a top line result for BOND-003, a Phase III registrational trial evaluating cretostimogene grenadenorepvec monotherapy for the treatment of BCG-unresponsive nonmuscle invasive bladder cancer. Just by a way of brief review, cretostimogene is a conditionally replicating oncolytic adenovirus that enters the cell through the CAR receptor, and it employs a dual mechanism of action. First, the E2F-1 promoter restricts replication to Rb pathway deficient tumor cells, thereby causing direct tumor cell lysis and sparing normal tissue. And second, the GM-CSF transgene expression primes tumor-specific immunity after the release of viral and tumor-specific antigens. Together, this makes cretostimogene a highly immunogenic and well-tolerated oncolytic immunotherapy. Moving on to the design of BOND-003. This is a registrational Phase III study evaluating cretostimogene in the treatment of BCG-unresponsive nonmuscle invasive bladder cancer according to the strict FDA definition. The induction and maintenance treatment follows the classic BCG induction and maintenance paradigm with repeat induction permitted for patients who have persistent disease at the initial disease assessment. Complete response rate at any time point is the primary endpoint and the key secondary endpoints are listed there. Mandatory biopsies are done at 12 months with central path review. And I'm happy to report that enrollment is now complete and cretostimogene has been given fast track and breakthrough therapy designation from the Food and Drug Administration. In terms of baseline characteristics, the trial population was broadly representative, but predominantly white older men. 2/3 of the patients came from the United States. And as expected, the cohort was heavily pretreated with BCG, intravesical chemotherapy and systemic immunotherapy. The median number of BCG treatments was 12, which is pretty standard for these populations and about 38% had received intravesical chemotherapy and 7% had received systemic immunotherapy. And I'll just note somewhat parenthetically that these are very, very difficult patients to treat. Next slide. Turning now to efficacy. As of September 30, 2024, the efficacy population demonstrated a complete response rate at any time point of 74.5%, with a 95% confidence interval indicating a range of plausible CRs between 65% and 82%. At 12 months, 46% of the cohort was in complete response with 25 confirmed complete responses so far at 24 months. Progression to muscle invasive disease was very rare in this cohort as well with a 97.3% progression-free survival rate at 12 months and a 90% cystectomy-free survival rate at 12 months as well. Beyond complete response rates, cretostimogene demonstrates sustained efficacy with a median duration of response that exceeds 12 months, though it has not yet been reached. At a median follow-up of 14.5 months for responders, 63.5% and 56.6% maintained their complete response at 12 and 24 months, respectively. The swimmer plot is shown here, and I would just note several responses have been observed beyond 30 months. We also note that 50% of reinduction patients went on to complete -- to convert to a complete response with 2/3 of them durable at the time of the data cutoff. This indicates that reinduction may bolster efficacy potentially through the establishment of the immunologic memory. In terms of how this drug compares across the landscape of other approved agents and other agents in the pipeline, the median duration of response compares very favorably at 27 months. The next highest was pembrolizumab at 15 months, followed by nadofaragene at 10 months. 803's median duration of response is not in the label and it has not yet reported for TAR-200. In terms of how this drug compares across multiple patient subgroups, cretostimogene has done very, very well. You can see in this sore spot, there's very little variation in complete response rates. This indicates that cretostimogene is effective across multiple patient level demographic and clinical characteristics. I would just point your attention to a few high-risk phenotypes here, too, the CIS and T1 population there, the point estimate is nearing 80%, which is probably the highest risk cohort and demonstrating very effective complete response rates. Beyond efficacy, cretostimogene is well tolerated with mostly Grade 1 and Grade 2 AEs. There were no Grade 3 or higher treatment-related adverse events and no deaths. There were 2 Grade 2 SAEs. In one case, a patient developed noninfective cystitis. In another case, clot retention. These are 2 very common observations in any patient receiving intravesical chemotherapy. Importantly, and certainly a distinguishing feature of cretostimogene is that 97.3% completed all protocol-defined treatment with no treatment-related discontinuations. And certainly, from my experience in the clinic in talking with patients, the tolerability of this agent is one of the things that really sets us apart. Next slide. This is not meant for comparative purposes, but more for just descriptive purposes, but you can see how the complete response rate, the durability of response and the tolerability of each of these agents compare across the spectrum. The 75% complete response rate at any time point is every bit as good as anything else that's been published so far. And then the tolerability, obviously, is, again, I think, a distinguishing differentiator for cretostimogene. On behalf of all of my co-investigators, we would like to thank the patients and their families as well as the study coordinators and their nurses whose dedication made the study possible. Thank you.

Thank you, Dr. Tyson, for your insightful presentation. Before we open the floor for questions, I'd like to share a few closing remarks. The data that you've just seen represent a decade of hard work of being a patient-centered organization that continues to fight for patients every single day in our existence. Over the past 10 years, we've witnessed tremendous progress in the field of NMIBC, and yet there remains a significant need for new and innovative treatment options for patients. CG Oncology's singular focus on attacking bladder cancer has led us to develop what we believe is a potentially best-in-class bladder-sparing therapy. The BOND-003 monotherapy data demonstrates cretostimogene's compelling efficacy and favorable safety profile, which allows patients to stay on therapy longer and keep their bladders longer. I will highlight a couple of key points here. This is the largest data set in BCG-unresponsive high-risk NMIBC. We've shown one of the highest CR rates against approved therapies, even in patients with prior chemotherapy, which represented up to 37% of the BOND-003 trial. The landmark DOR at 12 months and 24 months, which were 64% and 57%, tell us that if you're a responder, there is a high probability of maintaining a CR even out to 2 years. As of the data cutoff on September 30, the median DOR is greater than 27 months, and it is still ongoing. We look forward to continuing the follow-up in these patients. And as you've seen in our swimmer plot, we have a number of patients who still remain in response even beyond the 24-month mark, with one patient who have already reached 139 and is still responding. We attribute these remarkable results to the fact that cretostimogene was designed and engineered as an oncolytic immunotherapy with a differentiated MoA. We believe this unique modality is a key driver for the favorable safety and adverse profile that we have seen. One of the most important things when it comes to adoption in this concentrated market is that cretostimogene integrates seamlessly in existing workflows at urology practices. Creto is delivered by a medical assistant without the need for retraining. Lastly, I'll just close with a special thank you to all of the patients who have participated in the clinical trial as well as all the investigators and their staff who made it possible. I also want to thank all of our partners, investors who have entrusted us with their capital and trust and have supported us throughout the years. There is still a lot of work to be done, but we are encouraged by these results today. They strengthen our commitment to bring this product to patients as quickly as possible. Thank you. Now I'll turn it back to the operator for questions.

[Operator Instructions] And the first question will come from Jeff Hung with Morgan Stanley.

Congratulations on the data. Can you just talk more about the 2 additional responders that were confirmed after the data cutoff? Were these after a second induction? And how long after that until they experience the CR?

Jeff, this is Vijay Kasturi, Chief Medical Officer here at CG Oncology. Thank you for your question. So as of the September 30 data cutoff, we had reported results. There were 2 confirmed responders who were confirmed to be in CR after the data cutoff date. And therefore, in view of maintaining full transparency for all results for all patients, we are reporting them all. They were not reinduced patients.

And the next question will come from Charlie Yang with Bank of America.

Congrats on the data and all the progress. Can you just talk about kind of in terms of your filing next steps and perhaps some of the commercial strategies that you're thinking just given the competitive landscape?

Good morning, Charlie. Thank you very much for your question. This is Ambaw Bellete, President and Chief Operating Officer of the company. Our outlook is that, obviously, we're encouraged by the data that we're sharing today. In addition to that, as we've stated publicly before, we plan to submit our data package to the agency in the second half of 2025. In addition, obviously, looking at this data, it really is the best-in-class data that we've seen in the class for patients with BCG-unresponsive nonmuscle invasive bladder cancer. So we're encouraged by that as we're planning our launch strategies for commercialization of cretostimogene.

And our next question will come from Sam Slutsky with LifeSci Capital.

Congrats on this update. Just wanted to dive into the kind of baseline characteristics in terms of -- if I remember correctly, about 1/3 of patients back at AUA had received prior pembrolizumab or chemo. And if I recall correctly, responses were kind of similar regardless of whether they had prior therapy or not. Can you just discuss how that data has matured? And then just given that there are many treatments in development, how that helps you in the competitive landscape?

Sam, thank you for the question. The -- what we have reported is that approximately 47% of patients in the study had any prior intravesical therapy in addition to BCG. Of these patients, about 38% had prior intravesical chemotherapy, about 7% had intravesical systemic checkpoint inhibitor, primarily pembrolizumab. Sorry, intravenous pembrolizumab, my apology. And I'm sorry, the second part of your question.

[ Ones is ] on responses between those who had other treatments prior to your drug and not?

Yes. So we have not seen any differences as we showed in our forest plot during Dr. Tyson's presentation. We have seen no differences in the complete response rate between those who received prior intervening therapy and those who did not.

And our next question comes from Corinne Johnson with Goldman Sachs.

[indiscernible] what do you use or what are most important as you consider like which treatment option you give to patients?

I think we missed most of that question. You might have been cut off. Can you repeat the question? Yes. I think I might have missed the question.

I don't know if you guys can hear me.

Yes, we can hear you now. That's better. Go ahead.

Okay. I just asked maybe for the physician, if you could point us to the efficacy and other parameters that you think are most important as you evaluate which treatment options you give to patients kind of like looking across that comparatively.

Yes. And the question is which efficacy parameters am I looking at in choosing which therapy? Is that the question? Did I hear, okay? Okay. Yes. Thank you for your question. So as a physician, I am first and foremost, concerned with durability of response. The complete response rates are very promising for cretostimogene. But in my opinion, what's more promising is the durability. So the median duration of response at 27 months and then counting is a really important patient-oriented outcome because they don't frankly care if the complete response rate at 3 months is 75%. What they care about is whether they're going to keep the bladder for another couple of years and whether they're going to survive the disease. And so that flat curve that we see on the KM, that long tail tells us that in the people that this works in, it works really well and it's durable. Half of these responders 2 years later have kept their bladder and they've been disease-free. I'll just tell you, anecdotally from my experience with cretostimogene, this is -- these are not easy patients. These are people that have come for second, third and fourth opinions with disease that has not responded to immunotherapy, or intravesical chemotherapy and so forth. So your question about which parameter I'm looking at in terms of efficacy, it would be this. But I would also say that I think tolerability is really important. And patients don't want to -- they don't want to trade good bladder function for a lifetime of urinary frequency and urgency and pain. Many of those patients would probably just rather have a cystectomy. But we don't see that with cretostimogene. We see it's pretty well tolerated. I mean there's Grade 1 and Grade 2 urinary symptoms like everybody else, but it's not burning out their bladders. It's not causing major lifestyle changes. And just in my conversations with patients, many of them -- several of them have said to me, wow, this was a lot easier than BCG. So those are the 2 things that I look at as a physician, and I hope that answers your question.

[Operator Instructions] The next question comes from Josh Schimmer with Cantor Fitzgerald.

Two for me. One, what is the status of the patients who progressed to MIBC? And then second, maybe you can give us an update on manufacturing scale-up and how that's going ahead of expected launch.

Josh, it's Vijay Kasturi. So as you know, 97.3% of patients are progression-free to -- from MIBC. So the small minority of patients who progress to MIBC have either gone to cystectomy or received systemic treatment. Arthur or Ambaw, for the second question.

Yes. So in terms of CMC, we're very encouraged that the stability of cretostimogene at 2 to 8 Celsius continues to be very stable. So we now have up to 4 weeks of stability at that condition. So we believe this is a significant improvement and will greatly help with adoption. And in terms of the overall preparation for CMC, the beauty of cretostimogene is that it is manufactured in a very simple and robust process. So we've not had to change any processes between our Phase II and Phase III trials as well as the commercial launch products. So we're very encouraged by the simple process and our ability to be fully ready at launch.

Our next question will come from David Dai with UBS.

I just have 2 from my end. One is just looking at the number of patients who enrolled, you're looking at 112 patients. But then when you presented here for the CR, there's 110 patients. So just wondering what happened to those 2 patients that were not included in the CR analysis? And the second question is just around maybe for the physician, Help us understand the CR at 12 months, the actual CR rate of 46% versus the Kaplan-Meier estimate of 50%. How would you -- if you were to look at those 2 numbers, what exactly is the right number to evaluate for you looking at durability?

Thank you for that question. So 2 patients -- so of the 112 patients, 2 patients did not complete the protocol-specified 3-month efficacy assessment, and thus were removed from the efficacy analysis set, which is why there's 110 patients in the efficacy analysis set. As far -- I will turn it over to Dr. Tyson to talk about the CR [indiscernible].

Yes. Thank you for your question. The number I look at here is the 46% CR rate. This simple mathematic way to tell you how many people in the cohort 1 year later is disease free. The KM estimate at 12 months here is accounting for those 2 patients that Vijay just mentioned. It's an estimate of what their counterfactual outcome would have been. But I think given the maturity of this cohort, you don't really need to look at the KM estimate for 12 months. You should look at the complete response rate at 12 months. But the KM estimate is very helpful for the 24-month time point because we don't have a mature follow-up for the cohort for many of the cohort at 24 months. So that's where the Kaplan-Meier estimate is really helpful to tell you projecting after censoring and dropout and all of that, what is the response rate going to look like in all likelihood at 24 months.

And the next question will come from Gregory Renza with RBC Capital Markets.

Congrats on the data. Arthur, maybe just 2 for me. Just given creto is an oncolytic virus, maybe you can just discuss a bit what you had talked about with respect to the ease of use and the seamlessness within a practice and the installation. What setup might be required for treatment centers to administer such a therapy? And any additional sort of post-install safety measures and protocols that are worth mentioning? And then secondly, now that we have this data and what you've seen in CORE-001, what's your level of interest in exploring the combo and the prioritizing creto and KEYTRUDA to potentially increase this therapeutic efficacy? Congrats again.

Thanks, Greg. So the beauty of creto is that it really just fits right into the existing workflow. And these urology practices are so familiar with giving standard of care BCG, which is also a BSL Level 2 agent. So really, there is no meaningful changes that's required or retraining that's necessary. So we're very confident that this oncolytic immunotherapy will actually be seen as a great positive because it is more selective and specific relative to BCG, and there are major differences in side effect profiles as well as noted by some patients and physicians. In terms of your second question, the combination data definitely was very impressive. And however, as you've seen today, the monotherapy results have a median DOR greater than 27 months, and it is still ongoing. This is -- this compares very favorably relative to pembro's model, which was only 16 months of median DOR. So we're very encouraged by the model, and we believe this on its own will be the backbone therapy of which that will build our business upon.

[Operator Instructions] I show no further questions at this time. Thank you so much for participating. This does conclude today's call. You may now disconnect.