My name is Mark Rutstein. 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 three 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 Trop-2 ADC, versus docetaxel in advanced non-small cell lung cancer. Next slide. As brief background, standard of care, second-line chemotherapy in non-small cell lung cancer has significant limitations, and Dato-DXd is a Trop-2-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%-60% of patients had received one line of therapy, and then about a third had received two 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 to 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 endpoint of progression-free survival. This is in the intent to treat analysis. We can see that this is a positive study. The overall 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 two 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 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 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 versus 3.9, with a hazard ratio of 1.38. 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. Median is 12.4 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 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 AE seen with the Dato-DXd, mostly low grade. You can see in the table, stomatitis had a 6% grade three 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 grade greater than or equal to 3 rate was 3% Dato-DXd versus 1% docetaxel, and then grade 5, 2% versus 0.3%. 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 grade greater than or equal to 3 ILD, including some fatal events, and this highlights the need for careful monitoring and investigator adherence to the management guidelines. Interim overall survival results, as we showed, do favor Dato-DXd, and we will continue to the final overall survival analysis. Dato-DXd is a potential, 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. 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 one actionable genomic alteration. The alterations are listed there. We will look at them on the next slide. And they would have received at least one targeted therapy as well as a cytotoxic-containing regimen. They received Dato-DXd monotherapy. The primary endpoint is overall response rate by BICR. If we could move to the next slide, please. 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 T790M 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 are the safety. On the left, treatment-emergent adverse events occurring in 15% or more of patients. You can see nausea, stomatitis, and, 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. 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 one 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, a study, it's time in breast cancer, Dato-DXd versus chemotherapy in advanced, HER2-negative, 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%-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 Trop-2 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 many have seen the structure, but what I, what I would mention is in the bottom left of the slide, we did see very promising anti-tumor activity in an early phase study in this same hormone receptor-positive, HER2-low or negative breast cancer population. Next slide, please. Here is the study design of phase III TROPION-Breast01. These are patients, again, hormone receptor-positive, HER2-low or negative. They had received one to two 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. The 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, equal split in both the arms with one-to-one randomization. I would point you to the fact on the left, in the Dato-DXd, 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. 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 one prior line. That is about two-thirds, and then approximately a third, or a little bit more than a third, received two prior lines. This means this is 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 are 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 versus 4.9 months. 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 three 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 one and two. 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. 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 were—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 one patient who experienced an adjudicated, grade 5 drug-related ILD event. 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-low or 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, 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 in 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 1/2 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've 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 one and part two expansion of Arm 7. Next slide, please. Here are the baseline characteristics, and also the disposition. 62 patients are 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 expressers with a TAP less than 10, less than 10%. Next slide, please. Here is the waterfall plot, suggesting very strong evidence of anti-tumor effect. We can see since the prior analysis, with a 74% response rate, the response rate is now 79%. There are six 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 expressers, this is very encouraging to see when Dato-DXd is 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 is 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. If we move to the next slide. 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. You can see there was an 11% grade 3 rate. There were 3 patients who had adjudicated treatment-related ILD and pneumonitis events. Two grade 2 events, one 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 anti-tumor effect in this frontline triple negative, population, triple negative breast cancer population. And, as we mentioned, biomarker unselected and responses were observed regardless of PD-L1 expression, 79% response rate, median duration of response, 15.5 months, an overall tolerable and manageable safety profile. 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 an amount of very interesting and exciting data. But now I'd like to transition to T-DXd or Enhertu 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 IHC 3+ or 2+ 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 and 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 anti-tumor 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 IHC 3+ population had higher response and durability than the IHC 2+ population. You can see with a 61% response rate and a 22% median duration of response. You can see that responses were robust across tumor types with relatively lower evidence, lower response in pancreatic cancer, but overall, a clear evidence of anti-tumor 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 IHC 3+ and versus the IHC 2+, the IHC 3+ being represented by the orange KM curve. The same trend holds true on the right side for overall survival. You can see the, the median overall survival in all cohorts, 13.4 months, and, represented in the orange, orange KM line is, IHC 3+ 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. I'm sorry. There were drug-related AEs with 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 IHC 3+ at 61%. The durability, also, again, very prolonged, 11.3 months and highest in the IHC 3+ population. In terms of time to event endpoints, there were clinically meaningful, progression-free survival and overall survival outcomes with higher medians, IHC 3+ compared to 2+. The safety profile is consistent with what we already know with this drug, with no new findings. 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 a folate receptor expressing patient population. A significant unmet medical 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. 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 mg per kg in this monotherapy study, all the way up to 9.6 mg per kg. After dose escalation, there was a dose expansion, testing four 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 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 four 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 m per kilog/kg, 5.6, 6.4, 8.0. There are still patients ongoing, particularly at the lower doses, below 8.0. 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 4.8-8 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 two treatment-related deaths. In the text below the table, what you can see is that both of those treatment-related deaths were due to a 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 three related adverse events. Further assessment is ongoing now, no longer at 8 milligrams per kilogram, but only at 4.8, 5.6, 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. There was also 18% grade three anemia, close to 12% grade three, 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 that confirm overall response rate of 46%, with 1 complete response, 22 partial responses. Very importantly, there are four unconfirmed responses ongoing at the time of data cutoff. This suggests that the state, 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%, the 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, 5.6, and 6.4. 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 1/2 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 and its phase 1/2 monotherapy study, there are four 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 mg/kg 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 a 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 mg/kg or higher for I-DXd was 27.3%. And these two 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. In the upper section on the left, we can see a 73-patient cohort, this time castrate-resistant prostate cancer, metastatic castrate-resistant prostate cancer. These patients had a confirmed overall response of 25.4%, median duration of response of 6.4 months. Then 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. 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. 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 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 one grade four case at 12 milligrams per kilogram, and there was one grade five 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 two pivotal phase III trials for Dato-DXd at Presidential Symposium. 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 CDH-6 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. Please. Hello, can you hear me? Yes. Thank you very much. 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 showed the clear benefit? That's the first thing. First question. Thank you. Yes, so let me take that question first, and Mark, I'm going to ask you to add any details. For TROPION-Lung01, the ITT patient population includes both squamous and non-squamous. So typically, in a regulatory situation, 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, or a subgroup, or in this case, the non-squamous. So, that's a, a discussion that we have yet to have with our regulatory agencies. 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? Yeah. No, Ken, I, I can confirm, you know, just what you said, you know, based on filing with ITT, and then, of course, subgroups will be considered. But I, 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, that question? The second part. Yeah, I have a question. The second part may be the why, it might be a different question, but why there is such a big difference between the non-squamous and squamous, which sometimes happen on the space, but, the big difference on Trop-2, I'm surprised. Is there any reason behind it? So it's a good question. Indeed, if we would look at Trop-2 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, you know, do suggest 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 a similar expression of Trop-2 across the histologies. ... Right. I remember the second question, sorry. So, are you going to do this kind of non-squamous, squamous, or maybe Trop-2 sort of selection from now on for the maybe, maybe not ongoing, but the new trial or how are you going to communicate with the, future studies? How do you see the kind of group of patients who will benefit from this trial? Thank you. Yes, so we are looking at taking learnings from TROPION-Lung01, you know, to the broader program. 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, you know, our plans would certainly, you know, maybe be focused more on the non-squamous population. And then you asked about a biomarker and selection. Of course- Mm-hmm. Yes, right. 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, you know, in the case of TROPION-Breast01, with hormone receptor-positive, HER2-low or negative metastatic breast cancer, in these cases, including in this study, Trop-2 expression is high in this disease state. What we're doing in this study, TROPION-Lung01, is to look retrospectively at Trop-2 expression by immunohistochemistry to see if there's a correlation between Trop-2 expression and response. Mm. So we're undergoing this right now. Right. In addition to that, our partner, AstraZeneca, does have the AVANZAR study in the- Right ... frontline non-small cell lung cancer population. In that study, they are seeking to validate a Trop-2 assay. Right. Right. Beyond this, you know, we have a broad translational program. So certainly, whether it's going to be Trop-2 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 the OS, interim overall survival was shown, where that the hazard ratio in ITT is 0.9. And, it takes some time for the maturity, but to my understanding, that you can't 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 maybe changing? Thank you. Yes. So, Ken, I'm happy, I'm happy to take that. So, you know, we, we're not really at liberty to discuss our filing strategy- Sure ... and what is acceptable to the regulatory agency. But, you know, all that we've announced publicly is that we are submitting. Yeah. We will be in discussions with the regulatory agency about their expectations. With current data, right? Yes. Yeah. We would be in touch with the regulatory agency on using the current data package, correct? Yeah. Yes. Yeah. Thank you very much. Next question is from Hashiguchi-san from Daiwa Securities. Please. Hashiguchi. Hello, this is Hashiguchi. Thank you very much. Regarding Dato- DXd TL-01, I have two 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, BRAF 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 that or DxD with AGA, what is the idea of further development plan going forward? Yes. I think you had three different questions here, so let me just touch on all three of them. The first one was, why do we see such a remarkable efficacy in AGA patient population? 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're 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 was about TL 04 and whether or not the RAS was considered an AGA. At the time when the TL 04 was designed, RAS was not considered yet an AGA patient population, so that's the reason why they were excluded. But that, you know, at the moment, of course, the world of lung cancer is changing, and eventually, we do want to study those patient population as well. And in terms of you know, 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. ...Thank you very much. I have a second question that's about ILD management. In TL01 study, compared to other studies, ILD incidence was higher. And how much appropriate management could actually be done? What's the room for 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, in that sense that, Yes, it's a little bit of both. That is to say, in this TL01 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 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 programs, that's one. The lung cancer investigators are also learning more about ILD management from our breast cancer investigators. So, these are the factors that really lead us to think that ILD management, and therefore, incidence, will improve over time in our Dato program. Thank you very much. That's all for me. Next question is from Muraoka-san from Morgan Stanley. Please. Hello. Muraoka from Morgan Stanley. Thank you very much. This is a question related to, the documents released by AstraZeneca. Looking at the AstraZeneca document, TROPION-Lung 07, 08, 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, 07, is focused on non-squamous cell cancer, but today, is this going to be in line with the focus on non-squamous cell cancer as has been, presented today? That's my first question. So from our side, we have not made any announcements regarding any changes to the timelines for TL07 and 08. When we are ready to make an announcement on that, we'll certainly let you know. Of course, based on the TL01 data in the squamous versus non-squamous patient population, there's a tremendous amount of interest to consider how to further develop data 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 TL08 program. Thank you. I have another question. Trop-2, I think, either in breast cancer or lung cancer, you didn't demonstrate the definite differences comparing us and the competitors. And the Dato, it's the DAR 4, not 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 this. 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, the DAR is one of those factors. Understood. Thank you very much. That's all from me. Next question is from Wakao-san from J.P. Morgan, please. Hi, J.P. Morgan, Wakao from J.P. Morgan 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, just based on that. Do you have a data set, which can be approved? I'd like to know. ITT PFS, P value is shown for statistical significance, analysis. Subgroup, there is no P value for subgroup analysis, but you haven't done the significant, difference testing yet. Or do you have a plan to do so if you haven't done that? Yes. Yes, I think you're pointing out the very important regulatory aspects of TROPION-Lung01. You know, 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 the non-squamous patient population. I don't... Mark, do you have any more comments on this question? No, I think, I would agree, Ken. And of course, the eventual, you know, potential indication, you know, will be something that need to be discussed with the regulatory agency, you know, as to, as to whether or not, you know, that focus is, you know, on, 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 want to clarify that, the only further statistical testing that we'll do, you know, is gonna be for the, you know, follow-up for overall survival for the final analysis. So, you know, no further, statistical testing, of progression-free survival. I just wanted to clarify that. Thank you. Well, I have another question regarding OS. As of today, 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 fraction 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? Well, thank you very much for that question. 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 a non-squamous overall survival data. That would be my most, the best I can do for you today, not being able to predict the future. Mark, any comments from you? No, similarly, Ken, it would be very hard for me to, you know, predict as well, and if I did, it would, it would just be a guess. Yeah. Yeah. Thank you very much. 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, you have any information on this? Yeah. So, I have not seen, you know, that subgroup analysis, so I don't have the information to answer. I'm sorry. Thank you very much. That's all from me. Next question is from Sogi-s an from Sanford C. Bernstein. Please. Thank you. I have a few questions regarding TL01 and TL005. It's very interesting that, you know, there's quite a stark difference in terms of efficacy for non-squamous versus squamous, and also the with or without AGA. Can we expect that, you know, the follow-up analysis will be presented in the future? Also, you have enough tissue sample from the patients who participated in the trial to just do the, you know, robust analysis. Thirdly, what kind of biomarker will be explored? Well, in terms of further analysis, in the, the next planned analysis is the final analysis for overall survival. And so that'll happen sometime in the future. I think in terms of, and, you know, in-- do we have enough biopsy samples to do a- AGA analysis? I think that was one of your questions. I, I-- certainly, we do have enough biopsy sample analysis to understand, exactly what patient, what exactly what mutations these patients had, so that we can determine the, 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. Yeah. And I- Probably, Sorry. Probably I should have been clarified. So, you know, my understanding is that, you know, we are trying to understand why this squamous, non-squamous, or with or without AGA actually, you know, provide, you know, such a, you know, the, efficacy difference for, the data. So what is the approach, you know, would you take to understand, you know, what is, you know, the, really driving the difference, biological difference, as you were saying? Well, ultimately, it's gonna 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'll just need to apply and generate some hypotheses to apply to not just the TROPION-Lung01 trial, but any other future lung cancer trials for this compound Dato. I see. So I actually thought that, you know, the even for this translational and the analysis, basically, you have to analyze patient tissue to understand what kind of, you know, proteins are expressed and, you know, all those things. Yes, you know, there are many different kinds of approaches. One can do protein expression, proteomics. One can do RNA expression analysis, you know, gene expression analysis, or you can even do a DNA sequence analysis. So, and 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. We can expect that, you know, those analysis will be shared at some point? Well, if we have some interesting data to report, we will certainly do that. Yes, of course. Okay, great. Yeah. Thank you very much. Yeah. Next question is from Tony Ren, Macquarie. Please. Yeah, thank you for taking my questions. So first of all, a couple of small quick ones on the clinical aspect. 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 01. Is there any reason that you can think of that might contribute to this? Is it 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. 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 you know, I'm in Madrid right now. I attended the AstraZeneca briefing last night, and there were, you know, just like this session, tons of questions on TROPION-01 and the following strategy protocol. And I think, you know, why 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 six weeks, which means that the 0.7-month finding could be spurious. So if we were to go with the subgroup analysis. I suppose the question is, like, Ken, Ken, like you said, by definition, these subgroup analysis do not carry any statistical power. No trial is powered for a subgroup. So have you seen any precedent of the FDA approving a drug based on a pre-specified 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, you know, in HER2, targets HER2 versus Trop-2 for Dato. It does appear, for example, that you know, Trop-2 is expressed in the mouth mucosa or in the eyes, whereas HER2 is not. And similarly, I think we think that the myelosuppression seen in 7300 may be 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 really that we're going to file with a positive ITT patient population data or PFS. 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 the regulatory agencies. And Mark, any additional comments on this? Yeah. No, Ken, I'm not sure I got all the questions. I think you've answered two of them. But agree with you. Agree with your responses, and certainly, even though deruxtecan, you know, backbone is shared by, you know, these ADCs, that the target, the difference of the target and the target expression can absolutely convey a different, you know, side effect profile. But I wanna make sure we got all the questions, and I'm not sure we did. Yeah. I think the only outstanding one, I think, Ken partially answered, is whether you have seen within HER2 whether you have seen any ocular toxicity. Oh, okay. So in HER2, we're not seeing much in the way of ocular toxicity that we are seeing with the dato. That's correct. Okay, great. Yeah. Thank you. The next question, which is from Tsuzuki-san from Mizuho Securities, please. I am Tsuzuki, Mizuho Securities. Can you hear me? Yes. Thank you. 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 will you be able to know, I mean, the timing of this event, particular event of the regulatory procedure, I'd like to know. Yeah. So what we announced already is that we're not waiting for the final analysis to file. We're going to file with the current dataset that you just saw at the ESMO. In terms of when we will see the number 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. Understood. Thank you very much. One more question. DS-7300. This time, phase 1/2 study data was presented. In SCLC, it's moving on to phase II. From your perspective, SCLC, what's next after SCLC out of the three tumor types in particular? Okay. Yes. So, with the 7300 dataset 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 the squamous type, non-small cell lung cancer. These are all very interesting, and let me just be very clear to make sure you 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. Additionally, there are three other tumor types. Are you going to accelerate to start all the three indications all at the same time? So that's, of course, that's certainly a possibility. Yes. Ah, I see. Thank you very much. Next question is from Sakai-san, UBS, please. Sorry, still 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 four 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 event 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 event, especially, on the top of the, this table? Nausea, anemia, these are probably mostly common, but, as far as the number of incidents concerned, seems to be, well, probably well tolerated. However, in a real setting, what do you think these, adverse event could impact the physician and patient, tolerability? That's my first question. Okay. So I think that you had two questions. One was about the, are we interested in any, any indications in addition to the four that, that we just mentioned before? And so in terms of the 7,300 program, I think you're aware that this antigen, the B7-H3, is widely expressed in many different cancers. And, we have not yet fully explored the activity of 7,300 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 DXd ADCs that we have. I think you pointed out that anemia is a fairly common one here for the 7300 program. Of course, now, 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? You know what? I speculated earlier that in the bone marrow, where the red blood cells are produced, that 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 oncologist in terms of how to manage these toxicities, including nausea, anemia. You know, I think these are fairly common toxicities that are seen with many other drugs in cancer patients. All right. Thank you. So as you're saying, as these anemia and nausea are 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 were 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 and poised 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 you know, we are still dose optimizing, and in fact, you know, at the World Lung Cancer Congress, where we presented focus on the small cell lung cancer cohort, right? There was also mention of the fact that, you know, we have a phase II study in small cell lung cancer. And as an example, you know, looking at two different doses. Just to mention that, what you see here in terms of rates, right, you know, cuts across the different dose groups. So I think that's important because, you know, when you're doing like a phase 1/2 study, you see that you see the rates, you have the opportunity to adjust your dose modification guidance, and you also can, you know, optimize the dose, right? Prior to entering phase III. So I hope that also helps to understand and put this data into context. Thank you. Okay, thank you very much. Just, so sorry, I'm just being sticky, but why not NSCLC, you know, non-small cell lung cancer, why, 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 cancer? Ah! Okay. We are now 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 was all planned, it just happened that way. Oh, it happened that way. Okay. That's, that's, that's understandable. Yes. Thank you very much. The last question is from Mamegano-san from BofA. Please. Hello, can you hear me? Yes, we can. I'm sorry, but my microphone didn't work well. Well, that or Dato-DXd, TROPION-Lung01 and 05, regarding those data, in the patients with AGA, I think the efficacy is very high. So what's your development plan in the population with AGA? Not just that or Dato-DXd, but maybe HER3 could be also a good candidate. And, it seems to me that these two may be overlapping, and, you are having a, a partner with the different, partners. Therefore, I'd like to, to ask you, although it might be difficult for you to explain, but what's your plan? So, so we haven't made any announcements about how we are going to specifically target the AGA patient population from in terms of these two 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 having patients having multiple options and multiple choices is not necessarily a bad thing, and it's actually a good thing that patients have multiple options. So, so it's certainly possible that, we will further develop both the HER3 and the Dato programs in the AGA patient population, or not, you know, really depending, I think a lot of it is depending on how we interpret the data. A lot of it really is going to be a data-driven decision. If it looks like that from our standpoint, both are worthy, then we may consider to develop further both of these drugs in the AGA. But that's yet to be determined. Thank you very much. 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, we are 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 TLO1 ITT population was AGA as a result of an amendment sort of later in the study. You know, this is also why we, you know, we had the TLO five 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, and it is a subgroup, but the AGA patients appear, you know, to benefit. So it is possible that the later enrollment of the AGA patients, you know, could have an influence on the overall survival results when we do the final overall survival analysis. However, it is hard to predict. The reason it's hard to predict is that, of course, they only, you know, 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. Thank you. Thank you very much. Thank you. We will now conclude Daiichi Sankyo's ESMO highlights. Thank you for joining today.