Operator: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Ken Keller: Thank you, Okuzawa-san. Hello, this is Ken Keller. I am Head of the Global Oncology Business Unit. I will provide an update on business performance beginning with Enhertu. Next slide, please. Enhertu delivered another quarter of outstanding performance. Global product sales reached JPY 464.5 billion, an increase of 45.9% year-over-year, or JPY 146.1 billion. This performance demonstrates the strength of Enhertu today and the scale of the opportunity still ahead. Growth in the Q2 comes from three clear drivers. First, deeper penetration in existing indications. Second, expansion into new indications. And third, broader access for patients around the world. Importantly, this growth is broad-based. The US region led with 55% year-over-year growth, followed by our ASCA region at 49%, Japan at 37%, and Europe at 26%. In the US, we have launched three important new indications this year.
Ken Keller: In January, we launched the first-line HER2-positive metastatic breast cancer indication, and this is based on DESTINY-Breast09. I am happy to report the adoption has been impressive. Enhertu has already become the market share leader and the new standard of care, and we expect adoption to continue as physicians gain experience with this regimen. This indication has also recently been approved in China, Japan, and Europe. Based on the strength of the US launch, we see a substantial opportunity, and we expect to replicate that success globally. Equally important is our progress in early-stage breast cancer. Bringing Enhertu into the early-stage curative setting has always been our goal. Since our first approval in late-stage advanced setting, we felt Enhertu's greatest and biggest impact would be in the early treatment setting where cure was still possible.
Ken Keller: It is gratifying to us and the entire oncology community to now have launched Enhertu in both the neoadjuvant and the adjuvant settings based on DESTINY-Breast11 and DESTINY-Breast05 in the United States. I am pleased to share with you that Enhertu's adoption is increasing month after month in both settings. Based on the early adoption and the feedback from oncologists, we are confident that Enhertu will soon become the market share leader and establish itself as the new standard of care in both settings.
Ken Keller: As I stated, these are potentially curative settings, which makes this expansion and our progress especially meaningful, both for patients and for the long-term growth profile of Enhertu. We are also making progress in expanding access. Following extensive negotiations, I am happy to report that Enhertu has achieved public reimbursement in the United Kingdom for HER2-low metastatic breast cancer after chemotherapy.
Ken Keller: This provides access to approximately 1,000 patients who have been waiting for a new treatment option. ENHERTU has already transformed the treatment of HER2-positive metastatic breast cancer. As ENHERTU moves into earlier stages of disease and reaches patients globally, we believe its clinical impact and commercial potential will become even greater. ENHERTU's overall Q2 picture is one of accelerating growth as its addressable market continues to expand, and there is significant headroom. ENHERTU is nowhere close to the limits of its opportunity. Next slide. Now, I'll turn to an update on DATROWAY's performance. DATROWAY is rapidly emerging as our next major growth driver. Q2 global product sales reached JPY 48.3 billion, an increase of JPY 32.6 billion year over year. Growth accelerated sequentially during the quarter, and we expect continued momentum throughout the H2 of this fiscal year.
Ken Keller: In the US, market share continues to expand in the EGFR-mutated non-small cell lung cancer setting. As physicians gain experience with DATROWAY and their confidence in its clinical profile grows, we expect substantial growth in the coming years. Importantly, the experience gained from prescribing DATROWAY in this lung cancer indication will serve as a strong foundation as we ready for the top-line results of multiple lung cancer trials in fiscal 2027. Our May launch in the first-line PD-L1 inhibitor-ineligible metastatic triple-negative breast cancer setting is progressing very well. Market penetration and new patient starts are increasing every month. Physicians are highlighting three important attributes in their treatment decisions. First, it's DATROWAY's unique overall survival benefit, its doubling of overall response rate, and its convenient dosing.
Ken Keller: At last week's ESMO meeting, we also presented new data on DATROWAY's CNS activity in triple-negative breast cancer based from our TROPION-Breast02 trial. This is important because up to one-third of patients with triple-negative breast cancer eventually develop brain metastasis, an area where there is significant unmet needs and very limited treatment options. These data showcased the CNS efficacy of DATROWAY in triple-negative breast cancer patients with baseline brain metastasis. The trial demonstrated that DATROWAY significantly improved progression-free survival, response rates, and CNS disease control compared to investigators' choice of chemotherapy. The median CNS progression-free survival reached 9.5 months with DATROWAY compared to 2.6 months with chemotherapy.
Ken Keller: This data underscores the potential of DATROWAY as a first-line treatment option for triple-negative breast cancer patients. Now, I attended ESMO, and the physician feedback on these data was highly encouraging. Based on that feedback, we believe these findings further strengthen DATROWAY's clinical profile and will inform and strongly influence future treatment decisions. DATROWAY's global expansion is also accelerating. It was approved in Japan on 16 September for first-line metastatic triple-negative breast cancer. It achieved public reimbursement in Germany for first-line triple-negative breast cancer, supporting European growth. It was launched in Brazil in August.
Ken Keller: DATROWAY now has multiple growth engines, increasing US adoption, expansion into additional indications, new clinical evidence, and a growing global footprint. DATROWAY is becoming an increasingly important contributor to oncology growth, with substantial potential still to be unlocked. This foundation will position DATROWAY strongly for its upcoming clinical data catalyst expected in fiscal 2027. Next slide, please. Now I'd like to talk about the recent collaboration with Summit. Our collaboration with Summit Therapeutics is a strategically important step in maximizing the potential of DATROWAY. Together with AstraZeneca, we will evaluate DATROWAY in combination with ivonescimab across multiple tumor types, including lung cancer and breast cancers.
Ken Keller: The collaboration will begin with a phase III study in first-line triple-negative breast cancer. Our ambition is to establish DATROWAY as a backbone of treatment across multiple cancers, and combinations will be an important part of achieving that ambition. DATROWAY brings a TROP2-directed DXd ADC together with ivonescimab's dual targeting of PD-1 and VEGF. This gives us an opportunity to investigate this differentiated treatment regimen across multiple tumor types. We believe the next era of oncology will be defined not only by better individual medicines, but increasingly by the right combinations for the right patients. This collaboration is an example of how we intend to move with speed, use external innovation, and strategically work with partners to maximize the value of our pipeline.
Ken Keller: Next slide. Daiichi Sankyo has built world-class science. We must now ensure that our commercialization capabilities are equally world-class. Our portfolio is entering a new phase. We will have more indications, more markets, and more launches to manage. We will have more than 20 registrational trials expected to be read out over the next several years, together with a significant number of early-stage assets advancing through our pipeline. At the same time, the pharmaceutical environment is increasingly interconnected. A pricing or access decision in one market can influence value in many others. This creates an unprecedented opportunity to bring more medicines to more patients. It also significantly increases the value at stake. To capture this opportunity, our commercial model will evolve.
Ken Keller: Effective April 2027, we will operate as one global commercialization organization, bringing our regional businesses and our global commercial functions together under one unified accountability. This change will support faster and better decisions, more efficient resource allocation. It will elevate launch readiness and allow us to build better capabilities to deliver more consistent world-class execution across markets.
Ken Keller: It will also strengthen collaboration internally between commercial, R&D, and our technology unit. In the new commercialization organization, our responsibility and commitment is to convert our expanding pipeline into sustainable global revenue and operating growth, delivering greater value for patients, Daiichi Sankyo, and our shareholders, all with a singular goal of ensuring our medicines reach the right patient at the right time, every time, across the globe. I will now turn it over to John Tsai, our Head of Research and Development.
John Tsai: Thanks, Ken. This is John Tsai, and I am going to give you the updates from R&D over the last quarter. Next slide, please. We start with the results of DESTINY-Lung04, where we released these results at the World Conference on Lung Cancer in early September. In this study, ENHERTU versus standard of care, which is platinum pemetrexed doublet plus pembro, demonstrated a statistically significant improvement in progression-free survival with a hazard ratio of 0.63. This is in first-line patients with advanced HER2-mutated non-small cell lung cancer, and the results represented a six-month improvement in median progression-free survival. In the primary analysis, ENHERTU monotherapy reduced the risk of disease progression by 37% and a median progression-free survival of 14.3 months versus 8.3 months for the platinum pemetrexed doublet with pembro.
John Tsai: The results were demonstrated and consistent across subgroups, including pre-specified subgroups in patients with brain metastases, smoking status, and HER2-mutated status. At the time of the analysis, the overall survival was less than 50% mature. While there was no observed overall survival benefit at this early time point, the OS also did not favor Enhertu, but we did see greater use of HER2 therapies in the control arm. Next slide, please. I'd like to give you some regulatory updates for Enhertu. First, for DESTINY-Breast09 in the first-line HER2-mutated metastatic breast cancer setting with Enhertu plus pertuzumab, which demonstrated a decreased risk of disease progression or death by 44%. This was approved in China in August, and in September, we received the approvals in Japan and the EU.
John Tsai: Next, in DESTINY-Breast05, which is in the HER2-positive early breast cancer adjuvant setting, which demonstrated a reduced risk of invasive disease or death by 53%. This was approved in China and EU in October. Lastly, for Enhertu, in the HER2 pan-tumor solid tumors, this was approved in China and also in October, and this was based on four phase II trials across a broad range of solid tumors. With that approval in China, that equates to 10 indications for Enhertu in China. Next slide, please. Now I'd like to go over the updates for Datroway. For Datroway in TROPION-Breast02, which is in the first-line metastatic or unresectable triple-negative breast cancer setting, this was approved in the US in May of 2026.
John Tsai: Following that, we received approval in the EU in July, approval in Japan in September, and in China in October of this year. For TROPION-Urothelial04, which is in high-risk muscle-invasive urothelial cancer, we started the study, and the first subject was dosed in August of this year. Moving on to I-DXd. We voluntarily withdrew the filing for the accelerated approval of I-DXd in extensive-stage small cell lung cancer in September. This was based on discussions with the FDA, where the data from our phase II IDeate-Lung01 study did not support an accelerated filing in discussions with the FDA. We continue to enroll patients in IDeate-Lung02, our phase III trial, and the enrollment of this study is nearly complete. Next slide, please. Here, I'd like to share some additional data for R-DXd, which was shown at ESMO just this past week.
John Tsai: This is an update of REJOICE-Ovarian01, the phase II/III trial, and the results shared here is from all patients treated in the phase II dose optimization study of the REJOICE-Ovarian01. This is data that has longer follow-up than what was seen before, and the results demonstrated further improvement in duration response, progression-free survival, and patient-reported outcomes. We also demonstrated efficacy in patients with CDH6 greater than 1% biomarker. Based on this, we're moving forward with the 5.6 milligrams per kilogram, and these results demonstrated an overall confirmed overall response rate of 49.7%, a median progression-free survival of 7.9%, with a balanced safety profile of 5.8% low-grade ILDs. To note, there were no grade 5 ILDs at this dose.
John Tsai: Next slide, please. We continue to advance our DXd ADC platform in the ovarian cancer space. You can see here that Enhertu continues to advance in the HER2-positive first-line maintenance study in DESTINY-Ovarian01. In addition to REJOICE-Ovarian01, we also are advancing REJOICE-Ovarian04 in the platinum-sensitive ovarian cancer second-line space. We're advancing REJOICE-Ovarian04 in the platinum-resistant ovarian cancer space in the first-line maintenance setting, and also REJOICE-Ovarian05 in the platinum-sensitive ovarian cancer second-line induction and maintenance patients who are PARP progressors. These are our advancements in just the ovarian cancer space. Go to the next slide, please. For the news flow in 2026, the majority of these data readouts remain the same.
John Tsai: There is one change which is highlighted in blue here. That is the change in AVANZAR, which will report out in calendar year H1 2027, and specifically, it will be in Q1 2027 calendar year. One last thing before I conclude my remarks. I am proud to say that we received the International Prix Galien Award for Enhertu as the best technology product, and this is an award that is given out every two years by the Galien Foundation. This is the second award granted to Enhertu following receipt of the National Prix Galien USA Award for Best Technology Product in 2024. We are very proud to receive this honor, and this was received yesterday. With those, I conclude my remarks. Go to the next slide, please.
Operator: [Foreign language]
[Analyst 1]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 1]: [Foreign language]
Ken Keller: Thank you very much for the question. In the United States, when we look at Datroway and the triple-negative breast cancer indication, the real drivers of choice today are overall survival, overall response rate, ease of use, and then another factor that comes in there is comfort with the drug and habit. In the United States, our competitor was launched before we were. Today, physicians are gaining experience with Datroway in our new indication. I can say the feedback is very positive. Specifically, your question about is the broader indication or the lack of it making an impact? Not very much at all. It is more about the comfort of physicians who have been using that competitive product. Now they are trying Datroway, and I think as they try it, you will see adoption accelerating even further from here. Thank you.
[Analyst 1]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 1]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Operator: [Foreign language]
[Analyst 2]: [Foreign language] Question for John. About AVANZAR and the data. Do the existing data suggest immunotherapy like in long-term PFS tail? I mean, because we are wondering like AVANZAR delayed readout reflect the slower event accrual beyond the medium with the medium PFS largely unchanged. Would the Weibull model with a declining hazard over time be a reasonable assumption here? Thank you.
John Tsai: Thanks for your question. It is very helpful. We are eagerly awaiting the results of AVANZAR just like everyone else. Given that the study continues to be blinded, we do not have the insights specifically around AVANZAR and the curves. I think once the results are available, we will have much better insights. I am sorry that I do not have the details, but because the study is currently blinded, we do not have any insights on what those curves look like. As soon as we have those, we will be glad to share them. Thank you.
Operator: [Foreign language]
[Analyst 3]: [Foreign language]
John Tsai: Yes, happy to give you some insights about AVANZAR. As you know, AVANZAR is designed to evaluate both the non-squamous intention to treat unselected population and the biomarker positive population. This is designed to have co-primary endpoints for both PFS and OS. Because OS is an important endpoint for first-line non-small cell lung cancer patients for approval for regulatory agencies around the world, we included OS as one of the co-primary endpoints. The primary endpoint analysis for PFS is timed so that we should have sufficient maturity to characterize the overall OS trends. We have not conducted any PFS interims in this trial.
John Tsai: This is an exception to the rule of disclosure of interims. We usually do not discuss interim results, but in this specific situation, we are sharing that we did not conduct any interims in this study. These are some of the insights that I can share regarding the way that we have looked at and evaluate AVANZAR from a study standpoint. Thank you.
[Analyst 3]: [Foreign language]
John Tsai: That is correct. We have not made any event assumption changes. We continue to advance the study as we originally intended.
[Analyst 3]: [Foreign language]
John Tsai: Sure. Thank you for your question. I will reinforce that the primary endpoint analysis for AVANZAR is for progression-free survival, PFS. That should allow us to have sufficient maturity to characterize the overall OS trends. In that respect, that is how we have powered AVANZAR. For TL07, we continue to progress as we have always intended, and there has been no changes in the design. Overall, we continue to have those timelines with a slight delay in AVANZAR. Thank you.
Operator: [Foreign language]
[Analyst 4]: [Foreign language]
[Analyst 4]: [Foreign language]
[Company Representative]: [Foreign language]
[Unknown Analyst]: [Foreign language]
[Company Representative]: [Foreign language]
[Analyst 4]: [Foreign language]
John Tsai: Sure. Thank you for your question. As you correctly stated, the results for AVANZAR will be in the Q1 calendar year of 2027, and AVANZAR will be around the same time. It will be in the H1 calendar year of 2027. So they are timed very closely together. We have not looked at the specific timing for submissions to various congresses, but we will be very prompt in sharing these results at a major congress. We have not decided which congress to share this with, but as soon as the data is available, we will be sharing it at an upcoming congress. So we will not delay. Thank you.
[Analyst 4]: [Foreign language]
Operator: Next question is Tony Ren-san, Macquarie, please.
Tony Ren: Okay, can you hear me?
Operator: Yes.
Tony Ren: Okay, perfect. Yeah, great. Thank you. A couple of questions to John. The first one is about the CNS activity of your DXd platform. I was at ESMO as well, and it appears to me that one of your competitors, a leading competitor, they refuse to recruit any patients with CNS disease into their studies. I think that's your big differentiator. John, could you explain to me how do you think about what makes one topoisomerase I ADC to have CNS activity, whereas another one doesn't? That's my first question.
John Tsai: Yeah, thank you for your question. As you correctly stated, we released results at ESMO of both the CNS activity for Enhertu as well as for Datroway. We've seen very good activity for our DXd ADCs for CNS activity, particularly those patients who had brain metastases. Specific to your biologic question of understanding exactly why this works and what happens with the competitors, certainly we don't comment about why competitors have excluded patients from their trial. We are very happy with the results that we've seen in the CNS activity.
John Tsai: We don't know if this is a bystander effect or what we've seen is that the DXd ADCs have very strong effects in terms of the results that we've seen when you are approaching the monoclonal antibody, whether these are around TROP2 patients for DATROWAY or HER2 patients, because we do know that there's HER2 receptors and TROP2 receptors in various organs throughout the body. As we've seen these results, we do see this activity, and it is a differentiated activity for our DXd ADCs. Thank you.
Tony Ren: No, thank you, John. The second question is about ovarian cancer. You obviously are going with a cadherin-6 approach, right? We also see some news announcements at ESMO, without data, just top-line news about folate receptor alpha. How do you think about these two somewhat overlapping sub-patient populations in ovarian cancer?
John Tsai: Yeah. The ovarian cancer space, as you noted, has seen really good results, and this is great for patients, both with folate receptor alpha targeted agents as well as for CDH6 ADCs. We've seen very good results with CDH6. They are differentiated in terms of the results. I think we will find out more as patients begin to see the responses from these two different classes of agents. I'll also note that there are differences in the AE profiles, and I believe this is going to be also another point of differentiation. But I do think that there will be further classification and understanding of ovarian cancer across these different groups and different classes of agents. Thank you.
Tony Ren: Do you think one class will be positioned ahead of another?
John Tsai: I think that's to be determined. But as I said, perhaps there may be differences in the AE profile and familiarity of the oncologist of which agents they would choose in terms of treatment. Thank you.
Operator: [Foreign language]
[Analyst 5]: [Foreign language]
John Tsai: Sure. Thank you for your question. Thank you for your question. For I-DXd, as you asked around the withdrawal of the accelerated approval approach, you also noted that the competition has advanced very quickly. In light of the benefit-risk in the discussions that we have had with the FDA, the FDA wanted us to continue with our phase III program, which is almost completed for enrollment. Based on those discussions, we decided to withdraw the I-DXd approach for accelerated approval, and we are advancing with the full phase III program. That is why we have decided to actually continue, given that we are almost fully recruited for the I-DXd phase III program. In terms of the differentiation, I think it really comes down to efficacy and also looking at differentiation versus the safety profile.
John Tsai: The current advances that were demonstrated at ESMO, not everyone can tolerate the bispecific that is currently out in the market. As we move forward, we have a number of programs for I-DXd, and we continue to advance them with excitement on moving forward. You did ask a question on differentiation for TROP2. I did not know if you were referring to the non-small cell lung cancer space versus small cell lung cancer space. For the small cell lung cancer space, we are obviously continuing to advance with I-DXd. We also have next steps of combination of gocatamig, which is our DLL3, plus I-DXd for the B7-H3 approach in the first line small cell lung cancer space. That is how we are differentiating. So, referring to TROP2 for non-small cell lung cancer, and you asked about differentiation.
John Tsai: The way that we are differentiated there is, we have a number of global non-small cell lung cancer first line studies that we will be reading out. I did refer to those earlier. The AVANZAR trial that will be coming out in the Q1 of next year, TROPION-Lung07, which is in the PD-L1 less than 50%, in the TROPION-Lung08 greater than 50%. We also have PD-L1 across the board for EGFR mutated population, which is TROPION-Lung14, and in the second line, EGFR mutated patient, which is TROPION-Lung15. That is five global trials in the non-small cell lung cancer space in the TROP2 biomarker, and that is the most extensive first line non-small cell lung cancer program that has been conducted by any company. So that is how we are differentiating between both small cell lung cancer and non-small cell lung cancer. Thank you.
[Analyst 5]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 5]: [Foreign language]
Operator: [Foreign language]
[Analyst 6]: Thank you. I have a couple of questions to John. So, John, you briefly mentioned that the OS is a co-primary endpoint for AVANZAR, and I actually thought that it was a dual endpoint rather than a co-primary. I thought that if the AVANZAR hit positive for QCS positive PFS, that should actually secure the technical success of the trial. So, it would be great if you can elaborate on that. I also have a similar question about TL07. TL07 has more arms, experimental arm, a triplet, doublet, and also, of course, it is looking at ITT and QCS positive population for PFS and OS. It seems that it is quite a lot of the primary endpoints. I am wondering how the design manages the alpha allocation. Thank you.
John Tsai: Yeah, thanks. Specifically on your question around the dual primary endpoint versus the co-primary endpoint, if in either situation where we reach the PFS or the OS, that would be considered statistically significant and positive for us. So, whether you want to call that the co-primary endpoint or dual primary endpoints, in either case, whether that would be PFS or OS, those would be considered positive. On the TROPION-Lung07, in terms of the powering, we do not comment on the alpha and powering for these studies, unfortunately. So, for us, while we have conducted the three arms as you outlined, we continue to move forward with these studies, and we do think that we have robust patients recruited and sufficient powering for our endpoints. Thank you.
[Analyst 6]: Great, thank you. So, one more question. This is regarding your collaboration with Summit for a combination with ivonescimab. So, you have already included the lung cancer is one area for a potential combination for DATROWAY. First of all, is it reasonable to assume that you are waiting for AVANZAR and/or the TL07 data to come out to make a decision? Also, how do you think about ivonescimab's seeming preferred efficacy in squamous rather than non-squamous, in which the DATROWAY has been developed for non-small cell lung cancer?
John Tsai: Yeah, thanks for your question. As you know, we have seen a lot of positive data in the PD-1, PD-L1 bispecifics, and those have demonstrated really good results. Many of those results are in the Chinese population versus the Western population. We are having really good discussions on advancing these programs, both in breast cancer, also in lung cancer, and other tumor types. Whether we will wait for these results before moving forward, these studies are in the design phase. As we move forward, obviously, the results that we get from our studies will help guide us on how to further improve the approach that we take for all of these studies. So, currently, we are advancing in these discussions and collaborations in the design. As the results become available, we will certainly leverage the insights to improve the overall strategy for us in the combinations with ivonescimab. Thank you.
[Analyst 6]: Thank you.
Operator: [Foreign language]
[Analyst 7]: [Foreign language]
John Tsai: Thank you for your question. What we have seen so far is really good results from PD-1 as the starting point. If we look back for the last 5 to 7 years, the approach many people took was combinations of immunotherapy with immunotherapy, and we have not seen very much progress in combinations of immunotherapy, PD-L1 or PD-1 specifically, with other IO agents. However, I think complementary mechanisms of approach for tumor types, such as non-small cell lung cancer, is one that has demonstrated really good effects. What we have seen so far is, in specific populations, the PD-1 plus VEGF, where you are starving the tumor of their vasculature, actually with immuno-oncology, is a unique mechanism that demonstrated advancements.
John Tsai: Also, what we are testing, and we should be able to find out in the very near future, is the TROP2 ADC with a specific cytotoxic payload differentiated from previous ADCs may have an effect through DATROWAY. In this way, complementary mechanisms of immuno-oncology with a VEGF, potentially with an ADC such as a TROP2 ADC, may have the best effect. That may be approach looking at approaching tumor types such as non-small cell lung cancer that would allow us to get the best effect, and that is what we are really driving for, and that is what we are hoping to get results from in combination with ivonescimab and potentially other PD-1 VEGFs in that class of drugs.
John Tsai: Obviously, some of the approaches that we are going to have to take is to find the right balance of what is the right dosing for these drugs, and that is some of the steps that we will be taking based on the results that we see. Thank you.
[Analyst 7]: [Foreign language]
Operator: Next question is Michael Nedelcovych-san. TD Cowen, please.
Michael Nedelcovych: Thank you so much for the questions. I have two for John. John, first, just a follow-up on your comment around AVANZAR interim PFS analysis not having been conducted yet. Can you confirm whether that also means futility analyses have not been conducted?
John Tsai: Yeah, thanks for your question. We did not conduct an interim PFS, and the futility we passed, so there's no concerns about futility in this specific patient population.
Michael Nedelcovych: Wonderful. Very clear. Thanks so much. My other question is actually a follow-up on the commentary around I-DXd filing withdrawal. Can you provide any more details on that decision? Given that the application received priority review and Daiichi and Merck had just experienced a similar issue with HER3-DXd, this came as quite a surprise. You noted that the FDA emphasized the phase III trial, but it had already been initiated, so I'm a bit confused as to why the company and the FDA were not already aligned on the potential for accelerated approval. I guess one explanation could be that the phase III trial recruited faster than anticipated, but it looks like the primary completion date on clinicaltrials.gov was actually delayed in August, not advanced. Just any additional detail on how that proceeded would be very helpful. Thank you.
John Tsai: Sure. Happy to give you some additional comments and background on I-DXd. In terms of the I-DXd and the extensive stage small cell lung cancer landscape, as you probably know, the competitive set around the treatment for patients with small cell lung cancer is advancing very quickly. We had good discussions with the regulatory agency. We are almost completed for our phase III program for I-DXd, and in terms of timelines, overall, we are advancing with speed. Given the timelines and some of the discussions that we had with the FDA, we agreed with the FDA that the best approach would be to advance with our phase III results that would become available. So, that's the background that I could share with you.
Michael Nedelcovych: Very helpful. Thanks so much.
Operator: [Foreign language]
[Analyst 8]: [Foreign language] I have one additional question for John. Do you think it is reasonable to expect the KEYNOTE-189 regimen to achieve a longer PFS rate than the roughly 8 months seen in the original 189 study? If so, what factor could explain that improvement? Thank you.
John Tsai: Yeah. I cannot speculate on the results from KEYNOTE-189, but I will say that as we have seen in the general community, physicians have gotten a better understanding of use of immuno-oncology agents such as PD-1 since start of some of these trials. With that, as with any trial that gets into the marketplace, as you get more familiarity, you also understand how to manage the adverse event profiles of these drugs. While the data is blinded for our AVANZAR, TL07, and 08, what I can say is that I do believe that physicians have a better understanding of how to use PD-1 therapies, but that does not explain everything in our studies. Our studies are blinded, and I will not comment on the powering or the advancement of our programs, but I can tell you about clinical practice.
[Analyst 8]: Okay. Thank you.
Operator: [Foreign language]
[Analyst 6]: Thank you very much. I have another question to John. It looks like the bladder cancer is quite exciting, the opportunity for DATROWAY. I see that you are already conducting the phase III in second line, as well as you have been initiated the adjuvant setting. For the first line, I have a question for first line. Is this something you are not pursuing because of the strong data coming from the Padcev, KEYTRUDA, or you are waiting for some additional data that could allow you to make decision on the first line?
John Tsai: Yeah. For urothelial advancement for overall TROPION-Urothelial03 and -04, those are advancing. We do have a phase I/II study, and the information will better inform how we will advance in the first-line treatment regimen.
[Analyst 6]: One more quickly, if I may. Also, we understand that you guys are conducting phase II pan-tumor trials for three ADCs, I-DXd, R-DXd, and HER3-DXd. When are we going to see the data?
John Tsai: Yeah. As with any of our programs, we do the pan-tumor trials to understand where each of these DXds have the most effect across various tumor types. Because these are early signal-seeking studies, we actually roll out these studies over time as we fully recruit in each one of these tumor types. Over the next, whether it would be year or 2 years, as these patients are fully recruited in each of these specific settings, we will be releasing those results.
[Analyst 6]: Can I expect something starting to come up in next year, 2027?
John Tsai: I won't specifically highlight the timing because we've not disclosed those, but I think we will be sharing those information in the very near future. Thank you.
[Analyst 6]: Looking forward to it. Thank you.
John Tsai: Thank you.
Hiroyuki Okuzawa: Next question is Tony Ren, from Macquarie, please.
Tony Ren: Yeah, sure. Just another quick follow-up question, again to John. Are you guys planning to put more ADCs based on your modified PBD technology into clinical development? I know there was an earlier announcement in a year. I just wanted to see what's your thinking on that construct right now.
John Tsai: Thanks. We do have advancements in the next generation of ADCs in our research team. I am very proud of the work that they have been doing. We do have subsequent advances in looking at whether that is the linker, payload, relationship, and different cytotoxic payloads. So, you will be hearing about them. We are not specifically disclosing any of our payloads, obviously, for obvious reasons. So, as soon as that is available, we will share in generality what those are, but we will not be sharing specific details about them. But I will say that many of them are moving forward and very close to the clinic. Thank you.
Tony Ren: Yeah. Thank you.
Operator: [Foreign language]
Operator: [Foreign language]
Operator: [Foreign language]
[Analyst 9]: [Foreign language]
Ken Keller: Thank you for the question. This is Ken Keller. The benefits of creating one unified commercialization unit is that rather than making decisions that optimize a specific region, we are going to be able to make decisions that really optimize the value of our medicines across the globe. For specific things, we will make decisions in terms of resourcing where our greatest growth opportunities are, where the most patients are that we can help, and we will put our resources behind those growth opportunities. When we look at how the world has changed with international price referencing, it is absolutely critical that we make decisions as a whole for the company. Of course, we will be able to do that as well.
Ken Keller: I also believe that in oncology especially, when John's team creates new data and we share it at a meeting like ESMO or San Antonio Breast, that data instantly becomes global. By bringing a group together, we will be able to ensure that we respond the appropriate way, our medical affairs support the trials the right way. There is just so much synergy that will really help us take these great medicines and get them to as many patients as we possibly can, because that is what we are trying to do. Thank you.
Operator: [Foreign language]
[Analyst 10]: [Foreign language]
Ken Keller: Thank you for the question. This is Ken Keller again. Next week, the US government has a midterm election where basically Congress and Senate is up for vote in many different places. People are projecting what will happen. I think we are watching what will happen. I think for pharmaceutical companies, ours included, there is one thing that both parties in the US agree upon, and that is a heightened focus on drug pricing. We are monitoring this. We are very close with both physician groups, pharma groups, and whatever happens, we will be in a position to make adjustments and continue on our goal to bring this drug to as many patients as we possibly can. But it does go back to the first question, which is we will have to make decisions globally no matter what happens in the US, and we will be prepared for that.
Ken Keller: Thank you very much.
Operator: [Foreign language]
[Analyst 11]: [Foreign language]
Operator: [Foreign language]
[Analyst 11]: [Foreign language]
Operator: [Foreign language]
[Analyst 11]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Operator: [Foreign language]
[Analyst 11]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 11]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 11]: [Foreign language]
Operator: [Foreign language]
[Analyst 12]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 12]: [Foreign language]
Ken Keller: This is Ken. Thank you for the question. The main reason for establishing the new commercialization unit is to really ensure that the world-class science, our new products, are effectively delivered to all the patients across the globe. It is more of an overarching, I would say, goal of ensuring that this great science gets to all the patients. Underneath that, the international pricing and how it is now tied in the US to other countries, the global commercialization unit will make those decisions for us much simpler, much easier, and more robust decision making. That is absolutely a benefit. The real goal is to enhance our commercialization so that as these 20 top-line results for these registrational trials read out in the next three years, that we are ready to bring these to patients all over the world. That is the number one primary goal. Thank you.
[Analyst 12]: [Foreign language]
Operator: [Foreign language]
[Analyst 13]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 13]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
[Analyst 13]: [Foreign language]
Operator: [Foreign language]
[Analyst 14]: [Foreign language]
Ken Keller: Thank you for the question. This is Ken Keller. In terms of most favored nations, our intent is to ensure that these innovative drugs are able to get to patients all over the globe. The key to that is to develop medicines that are truly innovative, that add benefits to the standard of care. When we develop those drugs, it is important that we get the reflected value from it. That is how we will be able to continue to support our investments in R&D. Our goal is to work within whatever healthcare systems exist or whatever they change and get these drugs to as many patients as possible. It is important that we do, that the value is recognized when a great medicine comes to market. That is how you can invest in future products. Thank you very much.
[Analyst 14]: [Foreign language]
Hiroyuki Okuzawa: [Foreign language]
Operator: [Foreign language]
Operator: Goodbye.
