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

Welcome to the CG Oncology Conference Call to discuss updated results from the company's BOND-003 Phase III clinical trial of cretostimogene for the treatment of high-risk BCG unresponsive non-muscle invasive bladder cancer. [Operator Instructions] As a reminder, this call is being recorded today, Friday, May 3, 2024, and I would now like to turn the conference call over to Laurence Watts of New Street Investor Relations. Please go ahead.

Thank you, operator. Joining us on the call today from CG Oncology are Arthur Kuan, Chairman and Chief Executive Officer; Ambaw Bellete, President and Chief Operating Officer; Dr. Vijay Kasturi, Chief Medical Officer; and Corleen Roche, Chief Financial Officer. During this call, management will make forward-looking statements, including statements related to the efficacy and safety of our product candidates and our clinical development plans which constitute forward-looking statements for the purpose of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of risks and uncertainties associated with our business, including those discussed in our filings with the SEC and the press release we issued earlier today. CD Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events or changes in its expectations. The data we'll be discussing on this call are the subject of a press release we issued earlier today which can be found on the News section of CG Oncology's website. Today's call also will reference a slide deck that can be downloaded from the IR portion of CG Oncology's website at www.cgoncology.com. With that, I will turn the call over to Arthur Kuan, Chief Executive Officer of CG Oncology. Arthur?

Thank you, Laurence, and good afternoon, everyone. We are excited to present updated results of CG Oncology's BOND-003 single-arm, open-label Phase III registrational study, evaluating cretostimogene grenadenorepvec monotherapy for BCG unresponsive non-muscle invasive bladder cancer. The data was presented earlier today by Dr. Mark Tyson in the paradigm-shifting plenary session at the American Urological Association meeting in San Antonio, Texas. And it is the largest data set presented in BCG unresponsive disease thus far. As a reminder, we reported 75.7% CR at any time in 66 patients last December at SUO 2023 and it is encouraging that our CR rate at any time maintained at 75.2% out of 105 patients. Here are 4 main points we like everyone to take away about cretostimogene from today's call. Number one, complete response rate at any time, which is our primary end point. Number two, duration of complete response, number three, safety and tolerability. Last but not least, our novel mechanism of action, which supports the 3 points I mentioned. Before now, I would like to turn it over to Dr. Vijay Kasturi, our Chief Medical Officer.

Thank you, Arthur. Please turn to Slide 3. So what is cretostimogene? Cretostimogene is an investigational oncolytic immunotherapy certified 5 adenovirus which has dual mechanisms of action, and it has been designed to replicate in and kill cancer cells. The E2F-1 promoter drives the expression of essential viral genes, which restricts replication to Rb E2F pathway deficient bladder tumor cells. It also includes the complementary DNA for GM-CSF, which has been shown to be a potent cytokine inducer of antitumor immunity. The primary receptor for cretostimogene is the Coxsackie Adenovirus Receptor, which is expressed in all stages of bladder cancer. Please turn to Slide 4. One cretostimogene binds the CAR receptor, it enters the malignant cells where viral replication leads to tumor cell lysis and release of viral and tumor-specific antigens. These antigens are picked up by the dendritic cells and presented to T cells, which initiates a local antitumor response. Activated T cells then travel to the tumor tissue where T cell attracting chemokines recruit more immune cells, thereby potentiating this immunotherapeutic effect. Please turn to Slide 5. This leads us to BOND-003 Cohort C, the single-arm Phase III registrational study evaluating cretostimogene in the treatment of BCG unresponsive CIS, according to the strict criteria laid out by the FDA in their 2018 guidance. Concomitant papillary or high-grade TAT1 disease was allowed, but this had to be completely [ reflected ] prior to study enrollment. Importantly, patients underwent a mandatory biopsy at 12 months, which included 5 regions of the bladder as well as the prostatic urethra. Patients underwent 6 weekly sequential installations of cretostimogene, followed by a repeat induction for nonresponders and maintenance for responders. The primary endpoint was complete response at any time. Key secondary endpoints include duration of response, recurrence-fee, progression-free and cystectomy-free survival. Please turn to Slide 6. In total, 112 patients enrolled in BOND-003 and the data presented here are for the first 105 evaluable patients up to a cutoff date of April 1, 2024. This is the largest data set presented in BCG unresponsive NMIBC. In terms of baseline characteristics, most patients were white, male and of medicare age. About 20% did have concomitant factory VIII disease. And as expected, the cohort was heavily pretreated with a median number of prior BCG installations of 12 including several patients who had also received prior intravesical chemotherapy or systemic immunotherapy with pembrolizumab. Please turn to Slide 7. In terms of the efficacy analysis, the complete response at any time point for the 105 evaluable patients based upon central review was 75.2%, with a confidence interval indicating a range of possible CRs between 65% and 83%. Please turn to Slide 8. Here, the swimmer plot shows the distribution of the CRs over the entire cohort. And a key observation worth noting here is that 54% of patients who did not respond to the initial induction course of cretostimogene, responded to a second induction course of cretostimogene, including several patients whose response exceeded 12 months. This speaks to an oncolytic immunotherapy mechanism of action that the immune system switches from an innate to an adaptive immune response, as also seen with the second induction course of BCG. We also observed that 29 of 35 patients or 83% maintained their complete response for greater than 12 months, with 22 complete responders still pending evaluation. Lastly, 92% of patients did not undergo a radical cystectomy at 1 year. Please turn to Slide 9. In terms of tolerability, we observed no Grade 3 or greater adverse events and no deaths. There were 2 Grade 2 serious adverse events, which we previously reported at SUO and no new serious adverse events have been observed since then. One patient discontinued treatment, but this was due to an unrelated AE. Notably, 94.5% of patients completed all protocol mandated treatments. Please turn to Slide 10. In terms of the installation process, the cretostimogene administration is a familiar and convenient workflow. It is instilled by a nurse or a medical system and the favorable tolerability profile lends itself to enhancing patient compliance. This is supported by the observation that 100% of patients that completed their protocol mandated treatments in the BOND-003 trial, were able to tolerate the installation and the dwell of cretostimogene. Efficiency and patient experience continue to be a priority for us with even more streamlined workflows being carried forward into future studies and cohorts. Please turn to Slide 11. Recognizing the comparison across studies is difficult due to differences in the underlying population, among other factors. Cretostimogene would at least appear to compare favorably to the current nonsurgical approved therapy. The 75% complete response rate at any time point of cretostimogene in monotherapy, compared favorably to the 62% observed for combination therapy with N-803 and BCG and to the 51% observed nadofarageneas as well as the 41% of pembrolizumab. Similarly, the interim duration of complete response for cretostimogene monotherapy compares favorably with 29 of 35 patients or 83%, maintaining a durable CR for 12 months or more. Also, toxicity compares favorably as well with no Grade 3 or greater treatment-related adverse events and no treatment-related discontinuations observed in BOND-003. Please turn to Slide 12. As a reminder, the FDA has granted CG Oncology Fast Track Designation and Breakthrough Therapy Designation for the development of cretostimogene in the treatment of BCG unresponsive non-muscle invasive bladder cancer. Please turn to Slide 13. Now I'd like to draw your attention to two important amendments that we have made to our trial. We have now implemented a treatment extension phase for complete responders in years 2 and 3. And in addition, there is now a high-grade papillary-only cohort called Cohort B, where papillary-only or high-grade TAT1 BCG unresponsive patients received cretostimogene at a similar dosing schedule as Cohort C. Cohort C is currently enrolling. Please turn to Slide 14. Today, we are pleased to announce our expanded access program for cretostimogene. The program has simplified exclusion and inclusion criteria for BCG-unresponsive CIS with or without TAT1 patients and is specifically designed to enhance the geographic and ethnic diversity, collecting real-world data for safety, efficacy and patient-related outcomes. Please turn to Slide 15. We would also like to take this opportunity to highlight two important collaborations between CG Oncology and The Society for Urologic Oncology Clinical Trials Committee. PIVOT-006 is a randomized Phase III study led by Dr. Rob Svatek, comparing cretostimogene versus surveillance after TURBT in patients with intermediate risk non-muscle invasive bladder cancer. I'm pleased to report that the first few patients have been dosed in this study, and we are currently enrolling patients with more than 90 sites in North America. We are also progressing CORE-008 which is a Phase II multi-arm multi-cohort study, evaluating cretostimogene for high-risk patients who are BCG naive as well as BCG exposed. Please turn to Slide 16. We would like to take this opportunity to thank the patients and their families, the study coordinators and nurses as well as the key collaborators listed here who were instrumental in the success of this trial. I would now like to turn it back to Arthur for any additional remarks.

Thank you, Vijay. Now I would like to return to the key takeaways that I mentioned at the beginning of this call. Going to point number one, the primary endpoint of CR at any time. Cretostimogene achieved a 75% CR at any time in 79 out of 105 patients. This is the largest data set reported in this indication. 79 complete responders is the highest number of CRs reported and the CR rate also maintained from the last data cut at SUO 2023 in just 66 patients. This level of efficacy positions cretostimogene as a leading potential backbone therapy for patients with NMIBC. Number two, duration of response. Cretostimogene has shown durable responses over time with 29 of 35 patients maintaining a complete response for 12 months or more. This level of durability is potentially differentiating for cretostimogene. The next point, safety and tolerability. No grade 3 or higher AEs related to cretostimogene were observed. 94.5% of patients completed all protocol mandated treatments. This is the first time we report a cystectomy-free survival, a key secondary endpoint. As you've seen, 92% CFS was observed at 12 months and notably, 0 patients with CR underwent a radical cystectomy. This level of potential class-leading safety and tolerability could be a differentiator for cretostimogene. Finally, our mechanism of action as an oncolytic immunotherapy. This is a unique mechanism of action that serves as a basis for the above 3 points that I just mentioned. Based on these results, we look forward to presenting top line results from BOND-003 at the end of this year. Today's results also give us the confidence in our recently launched PIVOT-006 Phase III pivotal trial in intermediate risk NMIBC and CORE-008 in BCG exposed and BCG-naive, high-risk NMIBC. With that, I will now open the call up for questions. Operator?

[Operator Instructions] And our first question comes from the line of Jeff Hung with Morgan Stanley.

Congratulations on the data, I know the data is still very fresh, but what kind of feedback have you heard from clinicians on the durability of response? And how do physicians think about the importance of CR rate at any time compared to durability and safety and then I have a follow-up.

Thank you, Jeff. I'll turn it to Vijay to answer that question.

Yes. Jeff, the results have been received extremely well. We have had a high degree of urologists reaching out to us since the presentation this morning, meeting us at the booth here at AUA and asking to be enrolled into our trials, our ongoing trials, the Cohort B in BCG-unresponsive disease, the expanded access program asking us about CORE-008. They also want to join PIVOT-006. I think the degree of enthusiasm that we have seen for the results has been incredible for us. Frankly, some of the feedback that we have heard is that simplified installation process, something that they're really used to in the clinic, matters a lot to them in this process of a new agent, a new therapeutic option for their patients. And the second part of your question, I'm sorry, could you repeat the second part of your question, Jeff?

Yes. I was just curious on how physicians think about the importance of the CR rate at any time compared to durability and safety?

Yes, the feedback at least that we have gotten so far is they are receiving a CR rate anytime extremely well. They are very pleased about the durability as well. And they're especially concerned about the safety being so good. I shouldn't say concerned, but I would say they're happy that the safety looks so good. Remember, this population of patients is an older population. The median age is 73. These are Medicare patients. And tolerability is a major factor for these patients because they have multiple comorbid medical conditions. So it is very important for urologists that the patients be able to tolerate therapy, and durability is only enhanced the longer you're able to stay on therapy.

Great. If I can ask a follow-up question. Is there sufficient data yet on the patients who underwent repeat induction and converted to a CR, how their durability looks versus the other patients? And is there any difference in the patient characteristics of those who did versus did not subsequently convert to CR?

So we are still evaluating the data on the reinduction patients at the present time. What I can say is that we have seen, as we reported earlier today that several of the patients who underwent reinduction have maintained complete responses in excess of 12 months.

Our next question comes from the line of Karin Johnson with Goldman Sachs.

Two from us, one -- and I'm sorry if this is a bit pedantic, but can you just walk us through that 83% duration of response at 12 months with a particular focus on how you get to the denominator of 35 patients, and how the way you measured it compares kind of relative to how other people are measuring duration of response in the industry. I just think that was a point of confusion today. And then I would also have a question on just like how you think about reinduction as part of the profile for cretostimogene given a reasonable portion of patients had to be reinduced and then obviously went on to respond. But as like a physician, how would you think about the need for reinduction in some portion of patients?

So Corinne, thank you for that question. Out of the 35 evaluable patients who have reached a duration of response of at least 12 months, there are 29 confirmed complete responders who have had a DOR greater than 12 months. And they were 6 that did not maintain their DOR for greater than 12 months. There are still 22 responders that are pending assessment and evaluation at subsequent time points. So if you look at all approved therapies in this indication, were approved by FDA based on CR at any point and duration of complete response. From a regulatory perspective, these 2 endpoints are the major efficacy outcomes that are critical for an approval. From a patient perspective, they care about whether the bladders can be preserved 1 year or 2 years from now. And second part of your question, sorry, my apologies, but could you repeat the second part of the question?

I want to clarify on that last question. I guess we understand there's 22 patients pending, but there was [ 29 ] initial responders. So people are trying to understand what happens to the other 22 patients and why they wouldn't be included in duration of response. I'd just like for you to walk through why that's not included in this analysis and how it compares across the industry in terms of practice. My second question was like how do doctors and patients think about the potential need for reinfection in order to achieve response?

The 22 responders just haven't reached a 12-month time point at the present time. And then so once they reached that time point, we'll analyze those results. And we hope to present all the entire data set of patients, all the data at SUO 2024. In terms of patients with reinduction, reinduction is a common phenomenon with BCG. This has been done for 30 years because BCG is an immune therapy just and cretostimogene is an oncolytic immunotherapy. So agents such as cretostimogene with our dual mechanism of action, the reinduction is a testament to the mechanism of action for cretostimogene. So we don't foresee any issues. In fact, for the 26 nonresponders who underwent reinduction, we're very pleased to see that 54% converted to CR. That rate is actually higher than what it seems with BCG reinduction.

In addition, Corinne, this is Ambaw. My apologies. In addition, as we've seen most recently, there was a recent approval that actually also cited reinduction that was part of their package insert and communication that was out also from the agency. So reinduction really is an accepted approach in terms of how this type of therapies especially things like oncolytic immunotherapy such as cretostimogene.

Our next question comes from the line of Joshua Schimmer with Cantor.

So obviously, getting a lot of questions on the comparison of cretostimogene to J&J's TAR-200, especially as we think that the landmark 12-month CR rate. Maybe if you have any comments or cautions you might have about kind of comparing these trials at this point in drawing comparisons between the 2, that would be great.

Yes, Josh, there are different methodologies for numbers in this particular regard. But I think if you pay particular attention to the FDA guidance, what matters for the approval of agents is the CR anytime and the durability of complete response. We have seen that, as Ambaw mentioned, in the recent label for the most recently approved agent as well. There's no landmark that are considered in that approval. So we feel that our reported CR anytime today of 75.2% and the durability of complete response with 83% of the responders that be going beyond 12 months thus far is favorable compared to at least the approved therapies in this space.

Got it. So I'm also getting questions from investors on manufacturing scale-up and any issues that might be for supplying the market as well on logistical challenges of cold storage handling for cretostimogene. So if you can address those as well, it would be very helpful.

Thank you, Josh. I'll take the first part of the question. So from a CMC perspective, I think the number one point that I want everyone to take away with is, we are not changing our process because of how robust it is, we're taking the same process that went into the Phase III trial to the BLA and commercial launch. This significantly really improves the risk profile of our CMC program. Number two, we have assembled one of the world-leading CMC advisory board or ex-FDA ex-large pharma into our advisory board, leading and guiding our team forward. Number three, our CTO, Swapnil Bhargava, came from Seattle Genetics as well as other CDMO himself has handled very complex manufacturing products such as antibody drug conjugates, arguably more complex than what oncolytic immunotherapy is. And for the second part of your question, I'll turn it over to Ambaw to address the shipping and cold storage question.

Thank you, Arthur. Thanks, Josh, for your question. And just to clarify on that point, we plan to ship cretostimogene in a just-in-time manner to our customers. So that will be delivered really upon the day or the day before the procedure is going to be for instilling cretostimogene into patients. This will be in a multi day shipper box that will allow for it to be stored in that box for a period of days, while it's also at the account. We plan to ship at a negative 50-degree temperature as well. Thaw time which is an important aspect of how these products are utilized, and I would tell you the thaw time for cretostimogene for getting it ready to be intravesically delivered is 10 minutes.

Our next question comes from the line of Samuel Slutsky with LifeSci Capital.