Daiichi Sankyo Company, Limited (4568) Earnings Call Transcript & Summary

My name is Mark Rutstein, and I lead Oncology Clinical Development at Daiichi Sankyo. I am very happy to be here today. In fact, I'm excited to be here to have the opportunity to present to you the data from Daiichi Sankyo's pipeline from ESMO, in fact, have an opportunity to share data across a number of our DXd-ADCs. So with that, we'll get right into the presentation. If we could go to the next slide. So the first set of data is from one of our 3 late-breaking abstracts. This is a pivotal trial result from TROPION-Lung01 that was presented at the Presidential Session at ESMO. This is a study of Dato-DXd, our TROP2 ADC versus docetaxel in advanced non-small cell lung cancer. Next slide. So as a brief background, standard of care second-line chemotherapy in non-small cell lung cancer has significant limitations. And Dato is a TROP2-directed ADC. We have seen in a Phase I study, a 26% response rate in a late-line non-small cell lung cancer population. Next slide, please. This is the study design. This is a randomized open-label Phase III study. These are patients who have received prior treatment, however, no prior docetaxel. They are randomized to Dato-DXd or docetaxel. Primary endpoints are dual PFS by BICR or overall survival. Next slide, please. Here are the demographics and baseline characteristics of the study. In this non-small cell lung cancer population, you can see in the bottom left, the majority of patients were non-squamous. You can see on the right side that 17% of patients had actionable genomic alterations, patients enrolled into this study were both AGA and non-AGA. You can also see on the right prior lines of therapy, approximately 50% to 60% of patients had received one line of therapy and then about 1/3 had received 2 lines of therapy. So this is largely a second and third-line advanced non-small cell lung cancer population. Next slide, please. This is patient disposition. I would really only point you to the top row. You can see that of the patients randomized, the Dato-DXd and docetaxel, 18% were ongoing at the time of the data cutoff for this analysis in the Dato-DXd arm, 6% in the docetaxel arm. Next slide, please. Here is the dual primary end point of progression-free survival. This is in the intent-to-treat analysis. We can see that this is a positive study. The overall -- the progression-free survival hazard ratio is 0.75, statistically significant with a p-value of 0.004. The median progression-free survival in the Dato-DXd arm was 4.4 months versus 3.7 months. On the bottom of the slide, we can see overall response rate is supportive of progression-free survival, where Dato-DXd approximately doubled response rate relative to docetaxel and also demonstrated a longer median duration of response. Next slide, please. Here are key subgroups. I would point out 2 of them to you. The first is according to histology. And you can see the progression-free survival in the non-squamous non-small cell lung cancer population was 0.63. However, in the squamous population, the patients did not appear to achieve benefit, hazard ratio of 1.38. In addition to that, if you look at the actionable genomic alteration subgroup, patients who had actionable genomic alteration had a lower hazard ratio than patients who did not. Next slide, please. Here is a further look at those subgroups according to histology. On the left, non-squamous non-small cell lung cancer, this is with and without actionable genomic alteration. You can see the medians are 5.6 months versus 3.7 months, hazard ratio is 0.63, suggesting benefit in this population and supported by the response rate and the duration of response. On the right side, you can see the squamous non-small cell lung cancer population with and without AGA. You can see the medians are 2.8 months versus 3.9 months with a hazard ratio of 1.38. And you can see the directionality favoring docetaxel is found not only according to the hazard ratio, but also response rate and duration of response. Before I leave this slide, I would like to point to the bottom left because we did also look at an additional subgroup, which is a PFS hazard ratio for the non-squamous patients without AGA. This is 0.71. This is an important exploratory subgroup because it represents that the benefit and the activity of Dato-DXd is not just related to AGA status. Next slide, please. These are the interim overall survival results. Overall survival here did not cross the threshold for statistical significance. This is at a 74% information fraction, and we will have follow-up for final overall survival. The hazard ratio here is 0.9 -- excuse me, 0.90 favoring docetaxel, medians 12.4 months versus 11.3 months. You can see subgroups beneath the Kaplan-Meier curve, non-squamous non-small cell lung cancer hazard ratio, 0.77 versus squamous 1.32. And as I stated, we will continue to follow to the final overall survival analysis. Next slide, please. Here is the overall safety. So we can see that the median treatment duration is longer for Dato-DXd than docetaxel, 4.2 months versus 2.8 months. There were importantly fewer Grade 3 or higher treatment-related AEs with Dato-DXd compared to docetaxel. That trend held true also for treatment-related AEs leading to dose reduction or discontinuation, which were higher in the docetaxel arm. Next slide, please. Now we look at the specific adverse events that occurred in greater than 10% or more of patients, stomatitis and nausea were the most frequent treatment-related AEs seen with Dato-DXd, mostly low grade. You can see in the table, stomatitis had a 6% Grade 3 rate, hematologic toxicities, including neutropenia and febrile neutropenia were not surprisingly more common with docetaxel. Overall, no new safety signals were observed with Dato-DXd. Next slide, please. This slide shows adverse events of special interest. So stomatitis and oral mucositis associated with Dato-DXd resulted in a low discontinuation rate, 0.7%. That is important because the overall rate was approximately 50%, but very low rate of discontinuation. There were ocular events, which is an adverse event of special interest for Dato-DXd, dry eye being most common, followed by increased lacrimation. There were 7 adjudicated drug-related Grade 5 ILD events. There was a higher rate in the non-squamous population compared to the squamous population 1.7% versus 4.6%. You can see on the table on the bottom right, the greater than equal to 3 rate was 3% Dato-DXd versus 1% docetaxel and then Grade 5, 2% versus 0.3%. And there also was 1 Grade 3 infusion reaction for Dato-DXd, and the majority there were low grade, of course. Next slide, please. Here are the conclusions for this pivotal trial that was presented at the Presidential Symposium at ESMO. So Dato-DXd is the first ADC to demonstrate a statistically significant improvement in PFS over docetaxel in previously treated advanced non-small cell lung cancer. As we could see, the PFS benefit was primarily driven by patients with non-squamous histology. As I showed, this was supported by overall response rate and duration of response as well. There were fewer Grade 3 related events and no new safety signals with Dato-DXd. As we showed, there was greater than equal to 3 ILD, including some fatal events, and this highlights the need for careful monitoring and investigator adherence to the management guidelines. And interim overall survival results, as we showed, they do favor Dato-DXd, and we will continue to the final overall survival analysis. So Dato-DXd is a potential new treatment option for patients with non-squamous non-small cell lung cancer. I'm now going to transition to the next slide, please. So this is a supportive study to the Phase III study we just discussed. This is TROPION-Lung05. This time a Phase II study, and these are in patients treated with Dato-DXd, non-small cell lung cancer with actionable genomic alterations. As I showed you in the previous slide, approximately 17% of patients enrolled in TROPION-Lung01 Phase III trial, or AGA. But here, we have a dedicated Phase II study to AGA to supplement TROPION-Lung01. Next slide, please. So this is a single-arm Phase II study, and you can look at the eligibility. You can see that these patients are advanced non-small cell lung cancer, but they have to have at least 1 actionable genomic alteration. The alterations are listed there. We will look at them on the next slide. And they would have received at least 1 targeted therapy as well as cytotoxic containing regimen. They received Dato-DXd monotherapy, but the primary endpoint is overall response rate by BICR. If we could move to the next slide, please. So here are the patient demographics as well as the genomic frequency. You can see that this is a heavily pretreated patient population with a median prior lines of therapy of 3. You can see that patients received a variety of treatments, including platinum, also, of course, targeted therapies and immunotherapy agents. On the right side, you can see of the actionable genomic alterations, the majority are EGFR mutation followed by ALK rearrangement. If we could move to the next slide, please. Here is the efficacy summary. In the table on the left, in the far left column in the 137 patients that were eligible for efficacy, the confirmed overall response was approximately 36% with a median duration of response of 7 months. In the middle column there, these are patients with EGFR mutations, specifically a subgroup of 78 patients. And you can see here the response rate is nearly 44% with a similar median duration of response. There was also antitumor effect in patients with ALK rearrangement, however, a lower numerical overall response of 23.5%. Below the table, there is mention of a EGFR subset. These are the 68 patients who had sensitizing or T790 mutations who would be previously treated with osimertinib. And in that subpopulation or subgroup, the ORR was 49%. You can see on the right, clear evidence of antitumor activity in both the waterfall plot above and the spider plot below. And I would just point you to the spider plot where you can see there are patients who have very durable responses. Next slide, please. Here with the safety, on the left, treatment-emergent adverse events occurring in 15% or more of patients, you can see nausea, stomatitis and alopecia were most common. There were also 29% of patients with treatment-related Grade 3 events and higher. I'm on the right side of the slide now, there were 5% of patients with serious adverse events, Grade 3 or higher. And there were 22%, 10% and 2%, respectively, of dose reductions withdrawals and deaths. In the adverse events of special interest table on the bottom right, you can see that Grade 3 stomatitis occurred in 11% of patients. The overall rate of ocular toxicity was 26%, with only 2% of patients having Grade 3. There were no Grade 3 infusion reactions, and there were 4% of patients experiencing ILD, including 1 event that was a Grade 5 event. Next slide, please. So in this AGA focused Phase II study, we see encouraging antitumor activity with Dato-DXd in patients with AGA, and Dato did have a manageable safety profile. And that is a relatively low incidence of drug-related Grade 3 or higher toxicities. The ongoing study, TROPION-Lung01, which was presented at the Presidential Symposium, of course, includes patients with actionable genomic alterations. I'd like to now transition to the next slide, please. Now we're going to talk about the second pivotal trial that was presented for Dato-DXd at the Presidential Symposium at ESMO. This is a study and this time in breast cancer, Dato-DXd versus chemotherapy and advanced HER2-negative -- or excuse me, hormone receptor positive, HER2-negative or HER2 low breast cancer. This is TROPION-Breast01. Next slide, please. In this setting, hormone receptor positive HER2-negative or low breast cancer is the most common subtype of breast cancer. It accounts for 60% to 70% of all cases. And there have been some new therapeutic options, but an unmet need remains. Chemotherapy is widely utilized but underperforms and existing TROP2 ADCs can have significant toxicities, including diarrhea, neutropenia and thrombocytopenia. Next slide, please. So I won't spend time too much time talking about Dato-DXd because I think many have seen the structure. But what I would mention is in the bottom left of the slide, we did see very promising antitumor activity in an early phase study in the same hormone receptor positive HER2 low or negative breast cancer population. Next slide, please. Here is the study design of Phase III TROPION-Breast01. So these are patients, again, hormone receptor positive, HER2 low or negative. They had received 1 to 2 prior lines of chemotherapy in the advanced setting, and they had experienced progression on endocrine therapy or endocrine therapy is no longer suitable. You can see they're randomized to Dato-DXd versus an investigator's choice of chemotherapy. The chemotherapies are listed there. We have dual primary endpoints, progression-free survival by BICR and also overall survival. Next slide, please. A little bit on the statistical methodology. The primary PFS analysis targeted 419 events, and at the time of the primary PFS analysis that is presented here, there's an interim analysis conducted. And this study importantly is considered positive given its dual primary endpoint structure if PFS and/or OS is statistically significant. Next slide, please. Here is the patient disposition. There were 732 patients randomized. You can see approximately equal split in both the arms with 1:1 randomization. And I would point you to the fact on the left, in the Dato-DXd arm, 93 patients were still ongoing treatment at the time of this data cut, on the right, in the investigator's choice arm, only 39 patients were ongoing at the time of the follow-up, and this represented a 10.8 months median study follow-up. And on the right side, I would briefly mention the majority of patients received eribulin. Next slide, please. Here are the demographics and baseline characteristics. I would point you to the prior lines of chemotherapy in the middle of the table. You can see that the majority of patients received 1 prior line. That is about 2/3 and then approximately 1/3 or a little bit more than 1/3 received 2 line -- 2 power lines. This means this is a second -- largely a second and third-line population. The majority of patients have received prior CDK4/6 inhibitor and taxane or anthracycline. Next slide, please. Here is the progression-free survival curve. Again, this is a dual primary endpoint, statistically significant with a p-value of less than 0.001, hazard ratio, 0.63 and a difference in the median of 2 months between 6.9 months versus 4.9 months, and you can see a clear separation of the curves. If we could go to the next slide, please. Here are the PFS subgroups by BICR. And you can see across these various subgroups, there is largely a consistent treatment effect and hazard ratio. If we could go to the next slide, please. Supportive data comes from overall response rate, where we see an overall response rate of approximately 36% in the Dato-DXd arm and 23% in the investigator's choice arm. On the right side, we show the interim overall survival results with a median follow-up of 7.9 months. This represents an information fraction of 39%. So this is a relatively immature analysis. There's a numerical trend favoring Dato-DXd with a hazard ratio of 0.84. And of course, the study continues to the next analysis for overall survival. Next slide, please. Here is the overall safety. And we can see the median treatment duration is 6.7 months versus 4.1 months with chemotherapy. Importantly, the rate of Grade 3 or higher treatment-related adverse events in the Dato-DXd group was less than half that in the investigator's choice group. There were also fewer events leading to reductions or interruptions with Dato-DXd. The overall safety profile suggests favorability toward Dato-DXd. Next slide, please. These are treatment-related adverse events occurring at most frequency. We can see most of them are Grade 1 and 2. In terms of adverse events of special interest, oral mucositis and stomatitis led to treatment discontinuation in one patient only in the Dato-DXd arm. In the footnotes below, you can see that there were 3 Grade 3 ocular events of dry eye, punctate keratitis and a patient also with dry eye and ulcerative keratitis. Yes, my apology. I was referring to the ocular events now. Most were dry eye, one patient here discontinued Dato-DXd as well in terms of ocular toxicity. And as I mentioned, there are some -- there was a small percentage of patients with Grade 3. So overall, in terms of these adverse events of special interest in terms of mucositis, stomatitis and ocular events, very limited discontinuation due to toxicity. Then if we look at the adjudicated drug-related ILD rates, they were also low. I point you to the table on the bottom right, all grade ILD was 3% and also low was the Grade 3 and greater ILD rate of 1%. There was 1 patient who experienced an adjudicated Grade 5 drug-related ILD event. So overall, consistent of evidence of a favorable safety profile. Next slide, please. The conclusions for this Phase III breast cancer study for Dato-DXd presented at the Presidential Symposium at ESMO demonstrated that Dato-DXd improves efficacy and safety compared to chemotherapy in this hormone receptor positive HER2 lower negative breast cancer population, dual primary endpoint, primary PFS endpoint was positive, statistically significant and clinically meaningful. This was supported by a higher overall response rate as well. Dato-DXd from a safety standpoint was -- had a favorable and manageable profile, no new signals, and patients had fewer Grade 3 or greater treatment-related adverse events as well as reductions and discontinuations. Overall, in context of a favorable benefit risk profile, the results support Dato-DXd as a potential new option for these patients. Next slide, please. We're now going to continue with Dato-DXd but this time shift to triple-negative breast cancer. These are the results -- updated results from BEGONIA. This is a study of Dato-DXd plus durvalumab as frontline therapy in triple-negative advanced breast cancer. Next slide, please. Here is the study design. So this is a multi-cohort Phase I/II trial testing multiple combinations of durvalumab and other investigational drugs. In this case, Arm 7 includes durvalumab with Dato-DXd. You can see that these are patients who had no prior treatment for advanced triple-negative breast cancer. You can also see on the bottom left, this study was previously presented. And when it was presented, the overall response rate in this population receiving Dato-DXd and durvalumab was 74%, and that was at a median of 7.2 months of follow-up. We will now update the efficacy and safety results from the Part 1 and Part 2 expansion of Arm 7. Next slide, please. Here are the baseline characteristics and also the disposition, 62 patients were treated. We can see that patients only received prior therapy for early-stage disease because this is a frontline population. The most important data is probably on the bottom right, where you can see PD-L1 expression. 87% of patients were low expressors with a TAP less than 10%. Next slide, please. Here is the waterfall plot, suggesting very strong evidence of antitumor effect. We can see since the prior analysis with a 74% response rate, the response rate is now 79%. There are 6 complete responses and 43 partial responses, and very importantly, these responses occur regardless of PD-L1 expression. Since immunotherapy alone would not necessarily be expected to have significant efficacy in low PD-L1 expressors. This is very encouraging to see when Dato-DXd has added this level of activity, including in a patient population that was 87% low-expressing for PD-L1. Next slide, please. Here is the progression-free survival and duration of response, median PFS, 13.8 months. More importantly, for a single-arm trial, median duration of response, 15.5 months suggesting durability. Next slide, please. Here with the summary of safety, there were 44% of patients who experienced a Grade 3 or 4 treatment-related adverse event. 10% of patients had a treatment-related serious adverse event, 16% discontinuing any one of the treatments. Overall, an acceptable safety profile. And if we move to the next slide. So here are the most common adverse events consistent with what we might expect for this combination of drugs and what we know about Dato-DXd. The most common adverse events were gastrointestinal and generally of low grade. Stomatitis was most common. And you can see there was an 11% Grade 3 rate. There were 3 patients who had adjudicated treatment-related ILD and pneumonitis events, 2 Grade 2 events, 1 Grade 1 event. This is certainly encouraging that when we would combine an immunotherapy, which itself can cause pneumonitis with Dato-DXd, that there was a relatively low rate of ILD in this population and that there was no -- so far, no high severity grade ILD. There were limited rates of diarrhea and neutropenia. If we move to the next slide, please. So the conclusions, Dato-DXd plus durvalumab continued to demonstrate strong and durable antitumor effect in this frontline triple-negative population -- triple-negative breast cancer population. And as we mentioned, biomarker unselected and responses observed regardless of PD-L1 expression, 79% response rate, median duration of response, 15.5 months and overall tolerable and manageable safety profile. And BEGONIA continues and another arm has opened this time with Dato-DXd in a frontline triple-negative population with durvalumab in a PD-L1 high population since the majority in Arm 7 were PD-L1 low. Next slide, please. Okay. So we now have covered the Dato-DXd from ESMO. It was certainly quite amount of very interesting and exciting data. But now I'd like to transition to T-DXd or in HER2. So here is an update of DESTINY-PanTumor02. And previously, we had presented at the ASCO, an interim analysis and now we have the primary analysis of trastuzumab deruxtecan in HER2-expressing advanced solid tumors. Next slide, please. So here is the study design, which many have likely seen. Just as a reminder, patients who are second-line plus solid tumor populations not eligible for curative therapy. Patients were to have IHC3+ or IHC2+ by immunohistochemistry. Local testing was done and then confirmed centrally. Patients who did not have local test would just have straight central testing by HercepTest. 267 patients received treatment, and you can see they received monotherapy in HER2. On the right side, you can see the variety of tumor types that are represented here. And importantly, these are patients for whom there is no available HER2-targeted therapy. The primary endpoint is confirmed ORR by investigator. Next slide, please. So here we can see the updated response and duration of response. You can see that there is very strong evidence of antitumor effect. If you look at the bottom of the slide, you can see all patients 267 with a response rate of 37.1%, median duration of response, approximately 11 months. The IHC3+ population had higher response and durability than the IHC2+ population, you can see with a 61% response rate and a 22% median duration of response. And you can see that responses were robust across tumor types with relatively lower evidence -- lower response in pancreatic cancer, but overall, clear evidence of antitumor effect in a high unmet medical need series of HER2-expressing solid tumors. Next slide, please. This is the first time in this primary analysis that we see presentation of progression-free survival and overall survival in this population by HER2 status. On the left, we can look at progression-free survival. Across all cohorts, the median progression-free survival is 6.9 months. You can see there's a higher median progression-free survival in the IHC3+ and -- versus the IHC2+, the IHC3+ being represented by the orange KM curve. The same trend holds true on the right side for overall survival. You can see the median overall survival in all cohorts, 13.4 months and represented in the orange KM line is IHC3+ with 21.1 months median overall survival. So overall, you can see consistent evidence of efficacy this time looking at time-to-event endpoints, both with respect to overall -- both with respect to duration of response, response rate, progression-free survival and overall survival. Next slide, please. Now we turn to the safety. Overall, the safety is consistent with what we know about trastuzumab deruxtecan. The drug-related Grade 3 or higher rate was 41%. There were drug-related AEs leading to discontinuation. Yes, I'm sorry, there were -- yes, there were drug-related AEs leading to discontinuation in about 8.5% of patients. There were 4 drug-related treatment deaths. And if we look to the bottom right side of the slide, we can see that the ILD rates, there were 3 Grade 5 events of ILD, overall ILD rates of 10.5%, the majority of ILD was low grade. Most common adverse events in the upper right. What we know is consistent with trastuzumab deruxtecan with no new safety signals apparent. Next slide, please. In conclusion, at this primary analysis with updated data and now showing survival outcomes, response rates and survival outcomes are robust and encouraging, observed across tumor types in a heavily pretreated patient population with a high unmet medical need and no available anti-HER2-targeted therapy. The response rate in the overall population was 37%, but that was higher in the IHC3+ at 61%. And the durability also, again, very prolonged, 11.3 months and highest in the IHC3+ population. In terms of time-to-event endpoints, there were clinically meaningful progression-free survival and overall survival outcomes with higher medians IHC3+ compared to IHC2+. The safety profile is consistent with what we already know with this drug with no new findings. And the results from this study do support the potential role of T-DXd as a tumor-agnostic therapy for patients with HER2-expressing solid tumors. If we would move to the next slide. Now we'd like to transition to R-DXd, raludotatug deruxtecan. This is a Phase I study in patients with platinum-resistant ovarian cancer that was presented at the ESMO meeting. If we move to the next slide, please. Platinum resistance is a significant problem in recurrent ovarian cancer and is inevitable. There are limited treatment options in this setting. Recently, there was the approval of a folate receptor alpha ADC in folate receptor-expressing patient population, a significant unmedical need does exist. Now CDH6 expression, which is the target of R-DXd is observed in a high percentage of patients with ovarian cancer. You can see on the right, R-DXd shares the deruxtecan backbone, which is similar to Dato-DXd and trastuzumab deruxtecan as well as our other late-stage DXd-ADCs. This time attached to a CDH6 IgG1 antibody. Next slide, please. So this is a first-in-human Phase I study. And here, we had a first part was Part A. This is dose escalation. You can see doses range from 1.6 milligrams per kilogram in this monotherapy study all the way up to 9.6 milligrams per kilogram. Then after dose escalation, there was a dose expansion testing 4 different doses of R-DXd, and we'll look at the data shortly. This is a patient population of ovarian cancer, not amenable to standard of care therapy, so a very high unmet medical need. We look at both safety as a -- safety and tolerability and evidence of antitumor effect in this study. Next slide, please. This is the baseline demographics and disease characteristics. You can see on the right side of the slide, the vast majority of these patients have platinum-resistant disease. They have received a median of 4 prior lines of therapy. They have received bevacizumab in a lot of cases as well as PARP inhibitor. On the left side, you can see the doses -- the dose subpopulations. You can see in each case, whether that is 4.8 milligrams per kilogram, 5.6 milligrams per kilogram, 6.4 milligrams per kilogram, 8.0 milligrams per kilogram, there are still patients ongoing, particularly at the lower doses below 8.0 milligrams per kilogram, and the median treatment duration in the study of 18 weeks. If we move to the next slide, please. So overall, the safety profile is manageable. Now doses ranging from 4.8 milligrams per kilogram to 8 milligrams per kilogram are represented here. In the table on the right, you can see 15% of patients discontinuing due to toxicity. About half of patients had a Grade 3 or higher adverse event. There were -- importantly, there were 2 treatment-related deaths. In the text below the table, what you can see is that both of those treatment-related deaths were due to Grade 5 adjudicated interstitial lung disease. Now they both occurred at 8 milligrams per kilogram. As of October 2022, the 8 milligrams per kilogram cohort was closed due to a higher incidence of a serious and Grade 3 related adverse events. Further assessment is ongoing now, no longer at 8 milligrams per kilogram, but only at 4.8 milligrams per kilogram, 5.6 milligrams per kilogram and 6.4 milligrams per kilogram. On the right side, you see the most common types of adverse events. You can see those to be nausea, fatigue and vomiting. It was also 18% Grade 3 anemia, close to 12% Grade 3 neutrophil count decreased overall and particularly considering the droppage of the 8.0 mg per kg dose, this is a favorable and acceptable safety profile. Next slide, please. Here are the efficacy results. The confirmed overall response rate of 46% with one complete response, 22 partial responses. Very importantly, there are 4 unconfirmed responses ongoing at the time of data cutoff. This suggests that this -- the data is still evolving. The disease control rate was quite high at 98%. And you can see based on the waterfall plot that the vast majority of patients experienced some reduction in their tumor measurements. Next slide, please. Here is a spider plot. Here we add median duration of response, and you can see durability was quite good at 11.2 months at the median. There's also progression-free survival here. And importantly, if you look at the spider plot, you can see that there are some patients that have been on treatment in response for quite a while. And this includes across the dose levels. Next slide, please. So in conclusion, R-DXd is the first CDH6 ADC to demonstrate promising efficacy in what is a heavily pretreated platinum-resistant ovarian cancer population. These patients were enrolled regardless of CDH6 expression, the response rate of 46%, a median duration of response of 11.2 months. As we showed you, the safety profile is manageable and toxicities are consistent with what is observed with other DXd-ADCs. Based on data to date, the 8 milligram per kilogram cohort is closed, and we continue evaluating 4.8 milligram per kilogram, 5.6 milligram per kilogram and 6.4 milligram per kilogram. And excited to say that based on this data and the signal that's observed, we believe that further study of R-DXd in late phase -- in the late-stage studies would be warranted. If we could move to the next slide, please. So the last data set that we'll show is from ifinatamab deruxtecan or I-DXd. This is our B7-H3-ADC. This is a Phase I/II study that has been updated in patients with advanced solid tumors. If we could move to the next slide, please. So in the poster presentation for I-DXd in its Phase I/II monotherapy study, there are 4 solid tumor data sets that are presented. Two of them are on this slide. You can see that I-DXd, our B7-H3 when given as monotherapy at a 4.8 milligram per kilogram or higher dose in 21 small cell lung cancer patients is a confirmed overall response rate of approximately 52%. You can see that there's also a median duration of response of 5.9 months. And then on the bottom, this is squamous esophageal cancer. This time, a 28-patient cohort and a response rate of 21.4%. The overall population that was treated with 4.8 milligram per kilogram or higher for I-DXd was 27.3%. And these 2 subsets demonstrating antitumor effect are very encouraging, and we continue to explore efficacy here and indeed are particularly encouraged by the small cell lung cancer data, which was also presented at the World Lung Cancer Congress recently, and we are interested in certainly taking I-DXd forward in small cell lung cancer. Next slide, please. Now beyond small cell lung cancer and esophageal squamous carcinoma, additional efficacy subgroups here presented at the ESMO meeting. And the upper section on the left, we can see a 73-patient cohort, this time castrate-resistant prostate cancer, metastatic castrate-resistant prostate cancer. This has -- these patients had a confirmed overall response of 25.4%, median duration of response of 6.4 months than below the squamous non-small cell lung cancer population. This was indeed the latest expansion cohort to open. The study is still ongoing, and there is relatively short duration of follow-up. Nonetheless, in the 13-patient cohort represented on the bottom in squamous non-small cell lung cancer, one can see nearly a 31% response rate. And so overall, from an efficacy standpoint, we can see this B7-H3 DXd-ADC has broad potential across different tumor types from an efficacy standpoint. If we move to the next slide, please. So in terms of safety, we can see the safety listed here across those tumor subgroups. There were no new safety signals observed and the safety profile was consistent with previous reports of this drug. The most common treatment adverse events associated with the drug discontinuation were pneumonitis and ILD. The most common Grade 3 or higher events were anemia, neutropenia, nausea and lymphocyte count decreased. In terms of interstitial lung disease, 5.7% of patients treated had confirmed ILD that was adjudicated as drug-related. Most of these cases were low grade. There was 1 Grade 4 case at 12 milligrams per kilogram and there was 1 Grade 5 ILD occurring in the highest dose tested of 16 milligrams per kilogram. So overall, when we consider both the early evidence of antitumor effect across solid tumors, coupled with the safety profile, we're encouraged by what we see and look forward to further study in these tumor types. Next slide, please. So this completes the presentation of the data. As I mentioned at the outset of my presentation, we're certainly very excited by the data. This was an opportunity at ESMO to present 2 pivotal Phase III trials for Dato-DXd at Presidential Symposium. This is an also -- this is also an opportunity at ESMO to share data from the broader DXd-ADC portfolio at Daiichi Sankyo, including data from, of course, trastuzumab deruxtecan, as well as data from our B7-H3 DXd-ADC DS-7300, our CDH6-ADC DS-6000, and although not represented here, we also did present data from our HER3-DXd in advanced EGFR mutation non-small cell lung cancer showing antitumor effect in the CNS. So overall, very excited at the progress of our pipeline and particularly excited to support really what is our singular goal to address unmet needs for patients who are in need and waiting across a variety of solid tumor types. So with that, I think I'd like to stop the presentation. I thank you for your attention. And now I believe we will transition to the Q&A. Thank you.

Thank you, Mark. We'll now take questions. The first question is from Yamaguchi-san from Citigroup.

Can you hear me?

Yes.

So good evening from Tokyo and maybe good afternoon for the European time. I have a quick question on TROPION-Lung01, which is the most kind of focused asset. The first one is that this non-squamous versus squamous data difference is quite large. So it is naturally people think that you have to select non-squamous patients from now on for all the trial or filing from here. But is it the right way to understand or you may be filing with all the data at the same time or you will file with the non-squamous data set which show the clear benefit? That's the first thing -- first question.

Yes. So let me take that question first. And Mark, I'm going to ask you to add any details. For TL-01, the ITT patient population includes both squamous and non-squamous. So typically in a regulatory section, we will be filing for the ITT patient population as a data set. And of course, we will be discussing with the regulatory agencies, whether or not there is an interest to focus on the ITT patient population or a subgroup or in this case, a non-squamous. So that's a discussion that we have yet to have with our regulatory agencies. But you can -- but I think it's very important to note here that we achieved a positive statistical significance data on the PFS in the ITT patient population.

Right, right, right.

Mark, any additional comments from you?

Yes. No, Ken, I can confirm just what you said, based on filing with ITT and then, of course, subgroups will be considered. But I think there was a second part of the question was there not related to other studies. Was that correct? Could you please repeat that question, the second part?

Yes, I have one question, but second part may be that why -- it might be a different question, but why there is such a big difference between the non-squamous and the squamous, which sometimes happen in the space, but then the big difference on TROP2, I'm a bit surprised. Is there any reason behind it?

So it's a good question. Indeed, if we would look at TROP2 expression in squamous and non-squamous histology, it is relatively high and directionally similar in both histologies. So the reason for the observed difference in the efficacy subgroups in TROPION-Lung01 is not clear. But of course, these are subgroups, but they certainly do suggest, of course, differential benefit. We will continue to investigate the etiology for this difference from a translational standpoint and in other studies. But for now, do not have a clear mechanistic explanation, especially considering similar expression of TROP2 across the histologies.

Right. I remember the second question, sorry. So are you going to do this kind of a non-squamous, squamous or maybe TROP2 sort of selection from now on for the -- maybe not ongoing, but a new trial or are you going to communicate with the future studies? How do you see the kind of group of patients who are benefiting from this trial?

Yes. So we are looking at -- we are looking at taking learnings from TROPION-Lung01 to the broader program. I don't have anything in that regard specifically to announce. However, based on the data we do see today, certainly in non-small cell lung cancer, our plans would certainly maybe be focused more on the non-squamous population. And then you asked about -- you asked about a biomarker and selection, of course, it is a strong priority for us to find a biomarker that would predict response. When we look at non-small cell lung cancer or even in the case of TB-01 with hormone receptor positive HER2 low or negative metastatic breast cancer, in these cases, including in this study, TROP2 expression is high in this disease state. What we're doing in this study, TROPION-Lung01 is to look retrospectively at TROP2 expression by immunohistochemistry to see if there's a correlation between TROP2 expression and response. We're undergoing this right now. In addition to that, our partner, AstraZeneca, does have the AVANZAR study in the frontline non-small cell lung cancer population. And in that study, they are seeking to validate a TROP2 assay. And so beyond this, we have a broad translational program. So certainly, whether it's going to be TROP2 by immunohistochemistry or some other modality or another marker, we are diligently investigating. At this point, we do not have a selection marker for this drug.

Okay. Finally, quickly, on OS, interim overall survival was shown where that hazard ratio in ITT is 0.9. It takes some time for the majority. But to my understanding, you can file with PFS ITT and you do not need OS data for the filing. That's what I heard in the past. But is it still the right thing, but -- or it maybe changing?

Yes. So Ken, I'm happy to take that. So we are not really at liberty to discuss our filing strategy and what is acceptable to the regulatory agency. But all that we've announced publicly is that we are submitting, and we will be in discussions with the regulatory agency about their expectations.

With kind of data, right?

Yes, we would be in touch with the regulatory agency on the -- using the current data package, correct? Yes.

Next question is from Hashiguchi-san from Daiwa Securities.

[Interpreted] This is Hashiguchi. Regarding Dato-DXd, TL-01, I have 2 questions. First question is that with AGA, the efficacy was higher. Why is the reason? And what is the view at the moment, how you estimate the reason? Why with AGA, efficacy is higher? And in TL-05 study, RAS mutation, the patients were not included, why? I'd like to know the reason. Is it because you couldn't expect the efficacy? And if that's the case, why is that the reason? And Dato-DXd with AGA, what is the idea of further development plan going forward?

Yes. So I think you had 3 different questions here. So let me just touch on all 3 of them. The first one was why do we see such a remarkable efficacy in AGA patient population. And I think as with the earlier answer about why non-squamous versus squamous, we do not yet have a clear biological understanding of what we are seeing here in the AGA patient population. I think we have to do further translational research analysis to understand what we're seeing. I think the next question about -- was about TL-04 and whether or not the RAS was considered in AGA. At the time when TL-04 was designed, RAS was not considered yet on AGA patient population. So that's the reason why they were excluded. But at the moment, of course, the world of lung cancer changing. And eventually, we do want to study those patient population as well. And in terms of further focus, I believe on the AGA patient population specifically, I think, of course, we are very interested in all different subtypes of non-small cell lung cancer, but we have not made any announcements about any particular focus with respect to the AGA patient population for the Dato program.

[Interpreted] I have a second question. That's about ILD management. In TL-01 study compared to other studies, ILD incidence was higher. And how much appropriate management could be actually done? What's the room of further improvement of management in the [ ENHERTU ] development plan? I think in the early days, ILD incidence was high, however, management has been sophisticated. And as a result, I think ILD happened less. And in Dato-DXd, can we expect that this incidence of ILD will decrease or based upon ENHERTU, you did very good management. However, still, you see this rate of ILD in that sense that...

Yes, it's a little bit of both. That is to say, this TL-01 study was one of the first studies that was initiated in the Dato program. And as you mentioned, as time has passed, we have learned much more about ILD management from the ENHERTU program that was transferred over to the Dato program. I think that's an important concept. I think I also want to very much mention also that there's a very important difference in the ILD manifestations and incidence between lung cancer patients and breast cancer patients. You can obviously see that in many lung cancer patients, there is an existing chronic damage to the lung parenchyma likely due to long-term smoking. And so the -- how ILD manifests itself in a clinical trial like this is going to be quite different in -- compared to breast cancer patients. And finally, we may be starting to see some difference even within the subgroup of non-small cell lung cancer patients. These are very small numbers, but the incidence appears to be possibly different between squamous and non-squamous lung cancer patients. So I think there's a lot to learn about the ILD management in lung cancer patients. I think that specifically, ultimately, I think what you're asking is whether or not the incidence of ILD will decrease as our clinical trial progresses. And of course, I think our optimistic view is that yes, the lung cancer program in Dato is learning from our ENHERTU program. That's one. The lung cancer investigators are also learning more about ILD management from our breast cancer investigators. And so these are the factors that really lead us to think that the ILD management and therefore, incidence will improve over time in our Dato program.

Next question is from Muraoka-san from Morgan Stanley.

[Interpreted] Muraoka from Morgan Stanley. This is a question related to the documents released by AstraZeneca. Looking at the AstraZeneca document, TROPION-Lung07, TROPION-Lung08, regarding those studies, the results could become available very early. It says it's going to be available in 2024. Beyond in 2024, 2025, the results are going to be published and becoming available. These studies TROPION-Lung07 is focused on non-squamous cell cancer. But today, is this going to be in line with the focus on non-squamous cell cancer that has been presented today? That's my first question.

So from our side, we have not made announcements regarding any changes to the time lines for TL-07 and TL-08. When we are ready to make an announcement on that, we will certainly let you know. And of course, based on TL-01 data and the squamous versus non-squamous patient population, there's a tremendous amount of interest to consider how to further develop Dato in the -- in this non-squamous versus squamous patient population. But again, I don't think we have made any specific announcements regarding the direction that we're going here. So please wait for announcements on what we're doing with the TL-08 program.

[Interpreted] I have another question. TROP2, I think either in breast cancer or lung cancer, you didn't demonstrate the definite differences comparing [ U.S. ] and competitors. And Dato, it's the [ DAR 4, not DAR 8 ]. Is that the reason? And the next-generation ADCs that you are currently developing, do you have any idea to set the DAR higher?

That's a very difficult question to answer. How does the DAR relate to whatever differences we may see in the safety or efficacy. I don't think we have ever done a very definitive clinical trial to understand. So I guess the answer to your question is we do not know the answer to your question. I think you had a separate question about the next-generation ADCs. So by next-generation, I assume you're referring to payloads other than DXd. And of course, when we talk about the next-generation, we do try to optimize the DAR as well as many other factors that are involved in creating an ADC. And of course, DAR is one of those factors.

Next question is from Wakao-san from JPMorgan.

[Interpreted] Wakao from JPMorgan speaking. First of all, TROPION-Lung01 study filing and whether it's going to be approved or not based on your filing, based on the discussions by now, you would file based on ITT population, but non-squamous cell with a benefit could be submitted and there can be a possibility of approval just with non-squamous cell cancer, looking at the data just based on that, do we have a data set which can be approved? I'd like to know. ITT PFS p-value is shown for statistical significant analysis subgroup, there is no p-value for subgroup analysis, but you haven't done the significant difference testing yet. Would you have a plan to do so if you haven't done that?

Yes. So yes, I think you're pointing at a very important regulatory aspects of TL-01. Yes, we are going to be submitting the ITT patient population, but we do see a very interesting pattern in the non-squamous patient population. Do we think it's important? Of course, we certainly think it's important clinically and also statistically in a sub -- in a non-squamous patient population. I don't know Mark, do you have any more comments on this question?

No. I think I would agree, Ken. And of course, the eventual potential indication will be something that needed to be discussed with the regulatory agency as to whether or not that focuses on a certain subgroup or not or ITT. But there was a question, I think related if we would do more statistical testing, I think. And so just wanted to clarify that. The only further statistical testing that we'll do is going to be for the -- a follow-up for overall survival for the final analysis. So no further statistical testing of progression-free survival. I just wanted to clarify that.

[Interpreted] I have another question regarding OS. As of today, the hazard ratio is 0.9 on ITT. And whether or not in the end, it will demonstrate the statistical significance, how confident are you to achieve that? And the hazard ratio is 0.77 and the upper limit is 0.1, and even the information fragment is -- the 74%. Therefore, for non-squamous, I can expect that there will be probably a good result. However, ITT, what about your confidence level?

Thank you very much for that question. And of course, what we're looking at here is the interim analysis data, very difficult to predict the future. We have to wait for the final analysis to see what the ITT overall survival looks like as well as non-squamous overall survival data, right? That will be my most -- the best I can do for you today, not being able to predict the future. But Mark, any comments from you?

No, similarly, Ken, it would be very hard for me to predict as well. And if I did, it would just be a guess, yes.

Yes.

[Interpreted] Lastly, regarding the subgroup analysis on Page 10, second-line or third-line, you didn't look at it from that perspective. In second-line and third-line settings, the efficacy was higher in the second-line settings. Have you obtained such data? Regarding that trend, do you have any comment on this point, if any?

Mark, do you have any information on this?

Yes. So I have not seen that subgroup analysis, so I don't have the information to answer. I'm sorry.

Next question is from Sogi-san from Sanford Bernstein.

I have a few questions regarding TL-01 and TL-05. So it's very interesting that there's quite the stark difference in terms of efficacy for non-squamous versus squamous and also the with or without AGA. And so can we expect that the follow-up analysis will be presented in the future? And also that you have enough tissue sample from the patients who participated in the trial to just do the robust analysis? And thirdly, what kind of biomarker will be explored?

Well, in terms of further analysis in the next planned analysis is the final analysis for overall survival. And so that will happen sometime in the future. I think in terms of -- and do we have enough biopsy samples to do AGA analysis. I think that was one of your questions. Certainly, we do have biopsy sample analysis to understand exactly what patient -- exactly what mutations these patients had so that we can determine the AGA patient population. Non-squamous versus squamous, that's a fairly typical pathology analysis really done in a routine pathology lab. So we do not expect any difficulty in getting that information.

Yes. Sorry, progress should have been clarified. So my understanding is that we are trying to understand why this squamous, non-squamous or with or without AGA actually provide such an efficacy difference for the Dato. So what is the approach would you take to understand what is really driving the difference, biological difference as you were saying?

Well, ultimately, it's going to be an approach that combines clinical data with translational research data to try to understand what predicts efficacy benefit, what predicts lack of efficacy or benefit. I think these are very complicated analysis, and that eventually, we just need to apply -- generate some hypothesis to apply to not just the TL-01 trial, but any other future lung cancer trials for this compound data.

I see. So I actually thought that the -- even for this translational analysis, basically, you have to analyze patient tissue to understand what kind of proteins are expressed and all those things.

Yes. There are many different kinds of approaches. One can do protein expression, proteomics, one can do RNA expression analysis, gene expression analysis or you can even do a DNA sequence analysis. So I mean, there are many, many different approaches to doing this translational research analysis. And of course, we're very interested in looking at this issue from many different biological points, RNA, protein-DNA.

And we can expect that those analysis will be shared at some point?

Well, if we have some interesting data to report, we will certainly do that. Yes.

Next question is from Tony Ren-san, Macquarie.

Yes. So first of all, a couple of small quick ones on the clinical aspects. So between TROPION-Lung05 and the TROPION-Lung01, it appears that there are quite a bit more stomatitis and ocular toxicity in TROPION-Lung05 versus TROPION-Lung01. Is there any reason that you can think of that might contribute to this? Is there anything related to the biomarkers or is it just because of the small sample size? Another one is that I noticed the ocular toxicity doesn't appear to be an issue with ENHERTU, but it does appear to be with the other DXd-ADCs. Could you confirm this? The next one is that the ifinatamab deruxtecan appears to have some myelosuppression. And that is, again, not very commonly seen with other deruxtecan payload structures. Any thinking about why that might be the case? So these are the couple of questions on the clinical data. And I'm in Madrid right now, I attended the AstraZeneca briefing last night, and there were, just like this session, tons of questions on TROPION-Lung01 and the following strategy protocol. And I think what people continue to ask is because the answers were not considered satisfactory. So you mentioned the ITT population, PFS advantage of 0.7 months of prolongation is statistically significant. That being said, I believe that's below the scanning frequency of 6 weeks, which means that the 0.7-month finding could be spurious. So if we were to go with the prespecified subgroup analysis, I suppose the question is like, Ken, like we said, by definition, the subgroup analysis do not carry any statistical power. No trial is powered for a subgroup. So have you seen any precedents of the FDA approving a drug based on a prespecified subgroup analysis?

Okay. So a lot of questions here. So let me try to tackle some of these questions, and maybe, Mark, you can take on some of the other ones. So in terms of things like stomatitis and ocular toxicities and then the myelosuppression and differences in the pattern of these toxicities among the different DXd-ADCs. So we don't yet fully understand the nature of these differences from a biology standpoint. But it appears that some of the -- some or maybe most of the differences can be explained by the difference in expression pattern of the targets with these ADCs. So for example, ENHERTU targets HER2 versus TROP2 for Dato. And it does appear, for example, that TROP2 is expressed in the mouth mucosal or in the eyes whereas HER2 is not. And similarly, I think we think that the myelosuppression seen in DS-7300 maybe due to some low level of expression of B7-H3 in some of the hematopoietic progenitor cells. So that is where we stand in terms of understanding the differences. Okay. And then I think you had a very complicated regulatory question, which really is that I think the answer is we're going to file with a positive ITT patient population data for PFS. And whether or not the FDA thinks the subgroup analysis is important from a clinical standpoint, I think that's really going to be our, I believe, one focus of our discussion with regulatory agencies. And Mark, any additional comments on this?

Yes, no, Ken, I'm not sure I got all the questions. I think you've answered 2 of them, but I agree with you -- agree with your responses. And certainly, even though deruxtecan backbone is shared by these ADCs that the target -- the difference of the target and the target expression can absolutely convey a different side effect profile. But I want to make sure we got all the questions, and I'm not sure we did. Yes.

I think the only outstanding one, I think Ken partially answered is the -- whether you have seen -- with ENHERTU, whether you have seen any ocular toxicity.

Okay. So, ENHERTU, we're not seeing much new way of ocular toxicity that we are seeing with the Dato. That's correct.

The next question, which is from Tsuzuki-san from Mizuho Securities.

[Interpreted] I'm Tsuzuki, Mizuho Securities. Can you hear me?

Yes.

[Interpreted] Regarding the TL-01, I have a question. First, in this TL-01 study, I think you are waiting for the final analysis. And if OS is not achieved, then can you still make a filing? Of course, you will discuss with the regulatory agency, but when we'll be able to know, I mean the timing of this event, a particular event of the regulatory procedure, I'd like to know?

Yes. So what we announced already is that we are not waiting for the final analysis to file. We're going to file with the current data set that you just saw at this moment. In terms of when we will see the number of events required for the final analysis of OS, we haven't really made that announcement yet. So we will let you know once we get there.

[Interpreted] Understood. One more question. DS-7300, this time, Phase I/II study data was presented. There, SCLC is moving on to Phase II. From your perspective, SCLC, what's next after SCLC out of the 3 tumor types in particular?

Okay. Yes. So with DS-7300 data set that you saw, of course, you can really see that there's a lot of interesting efficacy data that's emerging in prostate cancer, esophageal cancer, in squamous type non-small cell lung cancer. This is all very interesting. And let me just be very clear to make sure I understand that we have taken note of the data so far. And as soon as we are ready to announce whatever new programs, registration trials we are initiating, we will be announcing that to you.

[Interpreted] Additionally, there are 3 other tumor types. Are you going to accelerate to start all the 3 indications all at the same time?

So that's -- of course, that's certainly a possibility, yes.

Next question is from Sakai-san, UBS.

I'm sorry. So I'm not getting used to this system. This is Sakai from UBS. I just have a follow-up question on DS-7300. Yes, there are very interesting diversified data, this Phase I, Phase II trials. The question is, are you really focusing on these 4 tumors or are you still thinking about any other optionality going forward? And the safety profile, well, presentation said there is no new safety signals. And most of the adverse events are common. But having said that, there are still high number of nausea, anemia on -- and also, there are some other things here in this presentation 63. Now are you not concerned about these adverse events, especially on the top of the -- this table? Now the anemia, these are probably mostly common. But as far as the number of incidents concerned seems to be probably well tolerated. However, in a real setting, what do you think these adverse events could impact the physician and patient tolerability? That's my first question.

Okay. So I think that you had 2 questions. One was about the -- are we interested in any indications in addition to the 4 that we just mentioned before. And so in terms of the DS-7300 program, I think you're aware that this antigen that B7-H3 is widely expressed in many different cancers. And we have not yet fully explored the activity of DS-7300 in all the different kinds of tumors where B7-H3 is known to be expressed. So this is yet an ongoing clinical trial program. And as we enroll more patients with different and diverse cancer types, we hope to see more positive clinical signal and therefore, proceed to further develop this drug in many different cancers. In terms of your question about safety, I think there are many adverse event profile that are -- that look similar or analogous to other AD -- DXd-ADCs that we have. And I think you pointed out anemia is a fairly common one here in -- for the DS-7300 program. And of course, I'm not doing a side-by-side comparison, but to my eye, anemia is a little bit more common than other DXd-ADCs. Why is that? I speculated earlier that in the bone marrow where the red blood cells are produced, there's a low level of expression of B7-H3 in the cells that are composed of the erythroid progenitor cells. So perhaps that's the reason. But overall, if we look at the safety profile, I think majority of these adverse events are well known to the practicing oncologists in terms of how to manage these toxicities, including nausea, anemia, I think these are fairly common toxicities that are seen with many other drugs in cancer patients.

All right. Thank you. So as you are saying, as these are anemia and nausea as common as the -- any other, well, treatment, you're not really concerned, overly concerned at this moment?

Well, I didn't say that they are as common as other treatments. What I do want to say is that the frequency of these toxicities is different between DXd-ADCs versus other treatments, for example, cytotoxic chemotherapy. But that in the case of -- even in the case of ADCs, DXd-ADCs, when these toxicities do appear, the practicing oncologist is well-armed employees to be able to manage them.

Ken, I would just add, if it's okay that it's a good question. It's important to realize that this is across multiple doses. So we are still dose optimizing. And in fact, at the World Lung Cancer Congress, where we presented a focus on the small cell lung cancer cohort, right, there was also a mention of the fact that we have a Phase II study in small cell lung cancer and as an example, looking at 2 different doses. So just to mention that what you see here in terms of rates, right, cuts across the different dose groups. So I think that's important because when you're doing like a Phase I/II study, you see the rates, you have the opportunity to adjust your dose modification guidance, and you also can optimize the dose, right, prior to entering Phase III. So I hope that also helps to understand and put this data into context.

Okay. Thank you very much. Sorry, I'm just being sticky. But why not NSCL -- non-small cell lung cancer, why it is SCLC, are there any reasons for this?

I think your question is why are we seeing so much activity in small cell lung cancer? Is that your question?

No, why you are prioritizing SCLC first not non-small cell lung cancer?

Okay. We are not specifically targeting small cell lung cancer as the priority. What really happened was that when we did the trial for whatever reason, the small cell lung cancer patients enrolled quite rapidly, and that was the first disease where we saw a clinical signal. So it's not like this is all planned. It just happened that way.

It happened that way. Okay. That's understandable. Yes.

The last question is from Mamegano-san from BoA.

[Interpreted] Can you hear me?

Yes, we can.

[Interpreted] I'm sorry. My microphone didn't work well. So back to DXd, TROPION-Lung01 and TROPION-Lung05, regarding those data, in the patients with AGA, I think effective efficacy is very high. So what's your development plan in the population with AGA, not just Dato-DXd, but maybe HER3 could be also a good candidate, and it seems to me that these 2 may be overlapping. And you are having a partner with different partners. Therefore, I'd like to ask you, although it might be difficult for you to explain, but what's your plan?

So we haven't made any announcements about how we are going to specifically target the AGA patient population from -- in terms of these 2 drugs. So -- but as a general principle, what I want to be very clear on is that we are very interested in drugs that can help patients and that have -- patients having multiple options and multiple choices. It's not necessarily a bad thing, and it's actually a good thing that patients have multiple options. So it's certainly possible that we will further develop both the HER3 and Dato programs in the AGA patient population or not really depending -- I think a lot of it is a bit depending on how we interpret the data. A lot of it really is going to be a data-driven decision. And if it looks like that from our standpoint, both are worthy, then we may consider to develop further the -- both of the drugs in AGA, but that's yet to be determined.

[Interpreted] One more question. Regarding TROPION-Lung01 study, protocol amendment was done once or even a few times. There, actionable genomic mutations alterations patients were enrolled later. According to my understanding, patients who were enrolled later had a better prognosis. So regarding the current OS data, there is a population who didn't respond. I think are we looking at that data right now? So you're going to follow up on this, then the results can be better compared to the current data. Is my understanding correct?

Yes. That is an outstanding question. And Mark, perhaps you'd like to answer that question?

Yes. So it's true that, as you say, the protocol was amended. And then as a result, we only had about 17% of the TL-01 ITT population was AGA as a result of an amendment sort of later in the study. This is also why we have the TL-05 study to supplement, right, with another 137 AGA patients. So I think you're asking the potential influence on the later enrollment of the AGA subpopulation into the study and how that might impact the overall survival results. Well, of course, yes, we can see from the progression-free survival analyses and the other efficacy endpoints outside overall survival that the AGA patients appear, albeit that it is a subgroup, but the AGA patients appear to benefit. So it is possible that the later enrollment of the AGA patients could have an influence on the overall survival results when we do the primary final overall survival analysis. However, it is hard to predict. And the reason it's hard to predict is that, of course, they only -- they represent 17% of the population enrolled. So I think your thought is a good one, but difficult to quantify that potential impact, but do acknowledge what you say that there are patients' AGA whose impact on the overall survival analysis may not have been fully represented in the interim results.

And we will now conclude Daiichi Sankyo's ESMO highlights. Thank you for joining today. [Portions of this transcript that are marked [Interpreted] were spoken by an interpreter present on the live call.]