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

Hello, colleagues. My name is Sunao Manabe, CEO of Daiichi Sankyo. Thank you for joining our briefing session focused on the key highlights of the data presented at ASCO of this year. Slide 4 show today's agenda. First, I will update our 5-year business plan for sustainable growth. And next, Ken Takeshita, our Global R&D Head, will present a summary of R&D progress and our updated R&D strategy. Finally, Mark Rutstein, our Head of Global Oncology Clinical Development, will show you the highlights of our presentation at ASCO this year. Now let's move on to Slide 5. On This slide also highlight the position of our 5-year business plan for ensuring sustainable growth. Our 5-year business plan covers fiscal year 2021 through fiscal year 2025, is a plan designed to achieve our 2025 goal of being a global pharma innovator with a competitive advantage in oncology and to shift towards growth stage to realize our 2030 division. Next, please. Slide 6 show the financial targets for fiscal year 2025 and the strategic pillars for our 5-year business plan. The financial targets for fiscal year 2025 are: consolidated revenue of JPY 1.6 trillion, of which the revenue from oncology will be more than JPY 600 billion. Core operating profit ratio before R&D expense of 40%, an ROE of 16% or more. We have adopted dividend on equity, DOE, as a KPI for shareholder returns and the target is DOE of 8% or more in fiscal year 2025. Out of our 4 strategic pillars for our 5-year business plan, there are 2 pillars, which are highly related to R&D. The first strategic pillar is to maximize 3ADCs. We will continuously maximize ENHERTU and Dato-DXd. Through our strategic alliance with AstraZeneca and HER3-DXd will be maximized by ourselves without a partner. We will efficiently keep expanding our development capabilities and supply capacity depending on changes around the product potential. The next strategic pillar is to identify and build pillars for further growth. From the projects running in already clinical stage and from the multiple modalities entering clinical phase during the 5-year business plan. We will identify the post 3ADC growth drivers and select promising post DXd-ADC modalities. Today, I am happy that Ken Takeshita will be presenting a new R&D strategy, which will ensure our successful and sustainable growth. Next slide, please. Slide 7 shows our current expectation on oncology in revenue. The oncology revenue in fiscal year 2025 is expected to reach JPY 900 billion or more mainly driven by the revenue growth of ENHERTU and Dato-DXd, exceeding the initial plan. This graph shows an image of oncology revenue growth during the 5-year business plan. And for ENHERTU, we expect strong growth in breast cancer market based on DESTINY-Breast03 and DESTINY-Breast04 study results that exceeded our original assumptions. In addition, the acceleration of the studies for indication expansion as such as DESTINY-Breast09 will contribute to increased revenue from product sales and development milestone payments. And for Dato-DXd, we expect higher sales compared to the initial plan as a target patient population at the launch is anticipated to be broader than the original assumption. NSCLC patients with actionable genomic alteration, AGA, has been added to TROPION-Lung01 study, which was originally designed for a patient without AGA. And therefore, we expect that we can deliver Dato-DXd to more patients compared to the initial plan. Furthermore, the acceleration of the studies for indication expansion such as TROPION-Lung08 will also contribute to increase revenue from product sales and development milestone payments in fiscal year 2025. Next, please. On Slide 8, shows a well-balanced investment for growth and shareholder returns. Considering the higher revenue growth, mainly driven by ENHERTU plus also the cash allocation, during the 5-year business plan is expected to increase by approximately JPY 300 billion compared to the initial plan. To realize sustainable growth, we will increase R&D expenses and capital expenditure, which is an investment for further growth. We will, of course, continue to consider the best balance between investment for growth and shareholder returns. And for R&D expenses, during the 5-year business plan period, we will increase by JPY 300 billion to approximately JPY 1.8 trillion, prioritizing the investment for the [indiscernible] 3ADCs, including the projects, which Ken Takeshita will explain later. And for capital expenditure, we will increase by JPY 100 billion to approximately JPY 600 billion, mainly to enhance ADC supply capacities. Next, please. On my last slide shows our current expectations around achieving fiscal year 2025 KPIs. We expect that our consolidated revenue will reach JPY 2 trillion, exceeding our target by JPY 400 billion, mainly driven by the increase in oncology revenue. As for core operating profit ratio before R&D expense, we will continue to aim for our target of 40% as we expect an increase in SG&A along with the revenue increase. Since we launched our 5-year business plan, we have continuously obtained positive data from DXd-ADC clinical trials, including the data, which Mark Rutstein will explain later. To realize sustainable growth, we will actively invest in R&D to maximize our product value. Last but not least, we will continue to commit to shareholder return that we promised by increasing dividends in line with profit growth and by flexibly acquiring own shares. We continue to aim for a DOE of 8% or more in fiscal year 2025. This is all from me for today. Thank you. Now I will hand over to Ken Takeshita.

Manabe, thank you very much. Next slide, please. I'm Ken Takeshita from R&D. And I'm going to go over with you in a few slides, a general overview of what we are doing in R&D and our overview of our strategy specifically. I think many of you are very, very familiar with the content of this slide. This illustrates really are the clinical trials that are part of the 5-year plan that Manabe just talked about. Many of them are the breast cancer trials from the DESTINY programs and ENHERTU programs. We also have the lung and breast cancer programs from Dato and HER3-DXd lung cancer programs. So we are right in the midst of all these clinical trial programs during this 5-year plan. And I have to say that I think we are doing quite well in accomplishing all the goals that are listed here in the 5-year time frame. Next slide. I do want to make sure to introduce you to 2 additional antibody drug conjugates that we have in our pipeline. The first one is called DS-7300. This is also based on the original DXd-ADC technology, but it target a new antigen called B7-H3. We are fairly early in stage in understanding the clinical spectrum of this ADC. However, we have already seen very good signal in small cell lung cancer. And we are well on our way to having a registration program leading to approval in this particular indication. Next slide. Another new ADC is called DS-6000. It targets an antigen called CDH6, cadherin-6. And here again, even though we are fairly early in the program, we are seeing very good activity in ovarian cancer. And so we anticipate, of course, a new registration program for this compound in ovarian cancer. So both of these 7300 and 6000 still have a long way to go before we fully understand the potential of these 2 ADCs beyond the 2 indications that I just mentioned. So we are very, very hopeful that we'll see a lot of interesting clinical signals as these programs move forward. Next slide. So here again, I want to make really a very important announcement here, which is that -- on the left-hand side, you'll see what we used to call our program, 3ADC and alpha. That's what we used to call our program. But because of the addition of these 2 new ADCs, we are calling our entire development program, 5 DXds and next wave. The 5 DXd-ADCs are listed here, the original 3 plus the 2 new ones. And the next wave refers to additional assets we have in our pipeline that are not DXd ADCs that will really contribute to the longer-term goals of this company. Next slide. So here is really an illustration of how we think about our R&D strategy and really how our pipeline fits into our strategy. And it's simplest to describe this as an expand and extend strategy. Expand means really a focus on the DXd-ADCs and really to make maximize the value of these 5 ADC assets in many indications, not just breast cancer and lung cancer, but of course, many, many other indications for which these ADCs are active. For example, the PanTumor data that you saw earlier today at ASCO with ENHERTU program. And of course, this expand strategy really refers not just to the ENHERTU but every single DXd-ADC that we have. I also want to make sure to mention that as part of our extend strategy, we have many other drugs coming up through our research pipeline into our clinical pipeline. These include next-generation ADCs, second, third and fourth generation ADCs as well as very interesting drugs that are not ADCs. And what we want to do, of course, is to develop each of these individual assets as they're on their own as an independent asset. But interestingly, some of these assets -- some of these new drugs with a very different mechanism of action compared to DXd-ADC, show very strong synergy in animal models to our existing ADCs. So that really generates a whole new set of development strategies in which we can combine these newer research stage assets with existing ADCs. And this is very important for us in order to maintain our presence in important cancers such as breast cancer and lung cancer. Next slide. So here again, a summary of what we are doing. We had the 3 ADCs -- DXd-ADCs. And now we have added 2 more to our group of ADCs, and we have 5 DXd-ADCs. And most importantly, for the long-term future, we have our next wave strategy to extend our growth to address remaining unmet medical needs in oncology. And now I'm going to ask Mark to come up and review our highlights.

Ken, thank you so much. And it's my pleasure to be here. My name is Mark Rutstein, and I lead Oncology Clinical Development. And so what we're going to do now is walk you through the key data from ASCO in the recent ESMO Breast Meeting. So it wouldn't be surprising based on what Ken presented that we have a very active pipeline. And we're proud to have presented a number of posters presentations at both the ESMO Breast 2023 Congress and the ASCO 2023 Congress, and you can see multiple oral presentations as well. So if we can move to the next slide. So what we'll first do is we'll give some updates of data in HER2-positive metastatic breast cancer and HER2-low breast cancer areas where ENHERTU has transformed the standard of care. And now I'll show some data in patient subgroups, clinical subgroups, molecular subgroups and quality of life data as well as some updated safety in our HER2-low population from study DB-04. So if we move to the next slide, please. So here we look at age subgroups. This is very important to think about elderly patients who represent a relatively underserved patient population, who may have suboptimal outcomes in oncology clinical trials. So we've done a pooled analysis in DESTINY-Breast01, 02 and 03. These are the pivotal studies for HER2-positive metastatic breast cancer, looking at age less than 65 and greater than 65. You can see on the bottom of left across these 3 studies and across those 2 age cuts, there's a consistent progression-free survival. The same is true on the right side with respect to overall survival. So similar outcomes regardless of those age categorizations. If we would move please to the next slide. So continuing this age subgroup analysis in our HER2-positive metastatic breast cancer trials, we turn to overall response rate on the left, and we can see across the 3 trials, similar response rates according to those different age cutoffs of less than 65 and greater than equal to 75%. Of course, we want to characterize both benefit and risk. And on the right side of the slide is a representation of safety according to these age subgroups. And what you can see is that the safety is very similar. In some AE categories, adverse event categories, there are some modestly higher rates in the greater than equal to 65 population. However, overall, we can see consistent positive benefit risk profile regardless of these age subgroups. If we could now move to the next slide, please. So this is an important slide, which looks at patient quality of life from our DESTINY-Breast02 pivotal trial in HER2-positive metastatic breast cancer. And of course, when we conduct the trials, we look at safety and efficacy but it is certainly important that we look at the patient experience and patient reported outcomes measures. And what's shown on the slide is a time to definitive deterioration analysis in patient-reported outcome measures. You can see various scales, including physical functioning, emotional functioning, pain and symptoms, et cetera. And what you see for ENHERTU compared to chemotherapy arm, the TPC arm, you can see consistent improvement in time to definitive deterioration in these outcomes favoring the T-DXd or in HER2 arm in each case. So very important and confirmatory of a favorable benefit/risk profile to understand that patient quality of life was maintained longer with ENHERTU and it was favorable in this time to definitive deterioration analysis, which is consistent across both the DESTINY-Breast02 and the DESTINY-Breast03 trials. So if we could move now to the next slide. So now we shift to a hormone receptor subgroup analysis. And this is in our DESTINY-Breast04 HER2 low metastatic breast cancer trial. So we looked here at estrogen receptor subgroups. And in a sub-analysis of these subgroups, we can see that compared to TPC arm and chemotherapy, patients with HER2 low ER-negative that's IHC 0 for the estrogen receptor and HER2 low -- ER low, that is IHC 1% to 10% for the estrogen receptor. Across these subgroups, patients benefited in terms of the overall survival analysis that you can see in the Kaplan-Meier below. This is important that these patients who are ER low represent a poor prognostic subgroup. And therefore, it was important to demonstrate and look within this population and to confirm the benefit here. So overall, we can see that in this subgroup, consistent efficacy or the rest of the patients studied in this HER2 low study. If we move to the next slide. Now we look at the safety side. And so to complement the efficacy, we look at the safety profile in this subgroup of estrogen receptor low-expressing or 0 expressing. And we can see compared to -- from ENHERTU compared to the chemotherapy and TPC, a consistent safety profile with the entire patient population treated with ENHERTU in the DESTINY-Breast04 trial, therefore, confirming a positive benefit risk profile in this hormone-based subgroup. So now if we would move to the next slide. And here, we shift to molecular subtypes. So instead of clinical subtypes, we look at some biomarkers. And we look again here with ENHERTU low population of the pivotal trial DESTINY-Breast04. And what we see is that regardless of whether -- regardless of intrinsic subtype, on the bottom, ESR1 mutation, PIK3CA mutation or CDK4/6 inhibitor resistance markers that we see consistently an improved overall response rate over the TPC arm across the board. If we could now move to the next slide. Now we look further beyond overall response rate in these subgroups that I've mentioned, these molecular subgroups now toward the time-to-event end point. And here, we can see, regardless, again, of intrinsic subtype, PIK3CA mutation status or ESR1 mutation status, we can see longer progression-free survival in the ENHERTU arm compared to the TPC arm thereby, showing a consistent benefit across the subgroups. And if we would move to the last slide in this molecular subgroup analysis. Here, we look at patients who have been treated with prior CDK4/6 treatment on the left, on the bottom and patients that have not been treated with a prior CDK4/6 inhibitor treatment, and they're broken out by whether or not they have these CDK4/6 resistance markers. And across both of these subgroups and within the considerations of whether or not patients have these CDK4/6 resistance markers or not, the benefit of ENHERTU over the TPC arm is maintained. If we move to the next slide. So the last slide in this section now, again, providing an overview of patient subgroups, quality of life and molecular subgroups in our HER2-positive metastatic settings, pivotal trials as well as HER2 low is an update of a detailed safety analysis of our DESTINY-Breast04 HER2 low metastatic breast cancer trial. And here, what we've done is engage in exposure-adjusted incidence analysis of adverse events. This is important because the duration of therapy on ENHERTU is longer than it is on the TPC arm or chemotherapy. Therefore, exposure adjustment helps to provide a clear analysis of the safety. And here, what we can see in these exposure-adjusted analyses are the rates of anemia, neutropenia, alopecia or hair loss and fatigue are lower in the ENHERTU arm and whereas nausea, vomiting thrombocytopenia and interstitial lung disease were higher compared to the chemotherapy arm. Very importantly, on the right side of the slide, we have a look at the ILD, interstitial lung disease, and we can see the majority of cases were low grade. So this further look into the safety confirms the overall positive benefit risk profile of ENHERTU in its approved indication based on the DESTINY-Breast04 data and HER2 low advanced metastatic breast cancer. So if we move to the next slide. So this is the summary of our first section. And what we conclude is the data that we present continues to support the benefit of ENHERTU in patients with both HER2-positive and HER2 low metastatic breast cancer, again, places where ENHERTU has been approved and has transformed the standard of care for patients. In HER2-positive breast cancer, ENHERTU is an effective treatment option with a favorable benefit risk profile in elderly patients and data continue importantly to show improved quality of life in patients treated with ENHERTU. In the HER2 low setting, the benefit of ENHERTU is observed across baseline subtypes of HER2 low metastatic breast cancer. And a detailed safety analysis continues to support ENHERTU as a standard of care in this setting. So now we're going to shift from breast cancer to the PanTumor or multiple tumor type setting beyond breast cancer. So if we could move to the next slide. So I'm excited to present data that we've just presented at this ASCO as well that relates to colorectal cancer. So here, we have a CRC02 study, which is a randomized study in a global multicenter study in patients with metastatic colorectal cancer. These patients express HER2, they're HER2 positive. And importantly, we enroll patients regardless of RAS mutation status, RAS wild type or mutant. They were BRAF wild-type. And they were centrally confirmed for HER2 status. And you can see they were randomized to 2 doses initially and that is 5.4 milligram per kilogram q3 weeks versus 6.4 milligrams per kilogram q3 weeks. And you'll notice that in the 5.4 milligram per kilogram group, there was an additional stage. So additional patients were enrolled to take it up to approximately 80 at that lower dose. The primary endpoint being response rate. And if we move to the next slide, please. So here, we see the key data, the primary endpoint. And what you can see is evidence of clinical benefit in both on the left side, the 5.4 milligram per kilogram group, with a response rate of 37.8% or on the right side with the 6.4 milligram per kilogram dose, a response rate of 27.5%. So both subgroups experiencing benefit but with a greater numerical benefit in the lower dose group. If we move to the next slide, please. I had mentioned importantly that this study enrolled patients regardless of RAS mutation status. And you can see here, and it is highlighted in red that there is benefit regardless of RAS mutation status. So even patients in that poor prognostic group with RAS mutation status have an evidence of benefit. Another notable aspect of this trial relates to the HER2 status subgroups. And as you can see, the response rate in the IHC 3+ group was significantly higher than the response rate in the IHC 2+ ish plus lower HER2-expressing subgroup, 46.9% versus 5.6%. And you can see a consistent benefit across the remainder of the subgroups on the slide. So if we could move to the next slide, please. So now we've presented the efficacy data, and now we present the safety data. So what we see overall, regardless of patients in randomized to the 5.4 milligram per kilogram group or the 6.4 milligram per kilogram group is that the safety profile is consistent with what we know about ENHERTU. However, if we look at the adverse event rates, we can see some of the rates are higher in the 6.4 milligram per kilogram group compared to the lower dose group. And therefore, we would conclude along with the response rates that I showed you as well, that the benefit risk is more favorable in the 5.4 milligram group, the lower group compared to the 6.4 milligram per kilogram group. So this is a very interesting data set for us because it represents, again, extension beyond the existing indications in which ENHERTU is approved, which includes, of course, breast cancer, lung cancer and gastric cancer. But now we've continued to look beyond even colorectal cancer. And if we look to the next slide. So earlier this morning, we saw the presentation of DESTINY-PanTumor02, and this is an interim analysis. And this is a very exciting result for us to present. So this is an open-label study in HER2-expressing advanced solid tumors. So importantly, we've enrolled many patient tumor types into this study, which really don't -- which don't have available anti-HER2-targeted therapy. And these patients aren't even typically tested for HER2. So this is an opportunity to potentially extend the clinical benefit of ENHERTU into additional tumor types and continue to potentially transform and change the standard of care. So this is a second line plus population. These patients were tested either locally or centrally and they had to be IHC 3+ or 2+ and prior HER2-targeted therapy was allowed. You can see all the patients received 5.4 milligrams per kilogram q3 weeks. And then approximately 40 patients per cohort, each of cervical cancer, endometrial cancer, ovarian cancer, biliary tract cancer, pancreatic cancer, bladder cancer and other tumors. Overall response rate per investigator was the primary endpoint. So if we could please move to the next slide. So here, we have the key efficacy overall response rate data. And I must say that there's evidence of very clinically meaningful responses as well as durability of response and both aspects are important as a manifestation of benefit. So across the entire population, the overall response rate was 37.1%. In the patients that were IHC 3+, the response rate was 61.3%. And you can see the overall response rates on the far right side of the slide, where even we show the IHC 2+ with a 27.2% response rate. On the bottom of the slide, we see the durability for all of these 3 groups. So in all patients with a response, the median duration of response was 11.8 months. In the IHC 3+ cohort, the median duration of response was 22.1 months, which is quite prolonged. In the IHC 2+, median duration of response of 9.8 months. And though I will not walk through all the individual response rates for all the individual tumors, you can see some of those response rates are quite high. And considering the fact that these patients have failed standard of care or don't have a standard care available and don't have certainly a targeted anti-HER2 therapy available and represent an unmet need, we're very pleased to see the level of -- the height of response in some of these very hard-to-treat tumors. So if we move to the next slide, please. So here's just another look at the durability. And we've already cited the median durations of response. And what I'd like to point out on this slide is the DASH, vertical line in the middle of the slide. And what it shows is that for those who responded in this trial, approximately half of them will remain in response for 12 months. Again, a manifestation of durability across the patient population that's been enrolled and responded. If we could then move to the next slide. So here now, we look at the safety and so that we can frame the benefit/risk profile. And very fortunately, the safety profile was consistent with what we know about ENHERTU. And you can see on the left, there was adverse events leading to discontinuation in only 8% of patients. And there was serious related adverse events in 12% of patients. Overall, the statistics that we have here and the metrics are largely consistent with a favorable benefit risk profile that we know of ENHERTU. And when considering the response rates is certainly, again, favors benefit over risk. Here, you can see on the right side, the most common adverse events, which reflect what we already know about ENHERTU. So overall, evidence that ENHERTU can provide to benefit to patients beyond that where ENHERTU has been approved, and we're very excited to have presented that data and to be able to provide evidence that additional tumor types and high unmet needs can be addressed. So if we could move to the next slide. So this next study is an investigator-initiated study out of Japan called HERALD/EPOC1806. And instead of selecting patients for enrollment and treatment with ENHERTU according to immunohistochemistry, here we have HER2 amplification using the Guardant360 assay to select patients according to circulating cell-free DNA, excuse me, a representation of HER2 amplification. Importantly, this testing is part of the nationwide cancer genome screening project in Japan, the so-called GOZILA study. And you can see, again, a range of tumors that represent high unmet needs, patients that aren't normally tested for HER2 and patients that aren't typically treated with anti-HER2 agents. And what you see here is that patients with esophagus, pancreas, urothelial, cervix, endometrium, ovarian, salivary, head and neck and others, very similar actually to the DESTINY-PanTumor02 data set in terms of the patient populations enrolled that I showed previously. But here again, selecting patients with a different method, still getting 5.4 milligrams per kilogram with an overall response rate by investigator primary endpoint. And so now if we can turn to the next slide, please. So this is the efficacy data. And here again, you can see across these tumor types of very high unmet medical need, clear evidence of antitumor effect and efficacy. So promising response rates as well on the left, you can see an overall response rate in the whole population of 56.5%. You can see the waterfall plot in each of those tumors -- for each of those tumors, very favorable with downward trajectory in the measurements representing tumor shrinkage. On the right side, you can see the durability -- And so here again, just using a different selection method, a biomarker selection method, cell-free DNA ENHERTU amplification, we can see that we can select patients and show benefit. If we could move to the next slide, please. So here's the safety as well. And overall, the safety is, again, consistent with what we know about ENHERTU. I can see that -- there was an ILD rate of 25% in the study. Grade 3 was very low. And importantly here, this was per investigator, whereas typically we would perform adjudication centrally in our studies, but it's an investigator-initiated study for which we assessed ILD per investigator. And overall, consistent profile with what we have seen in other studies. And then I'd like to move to the next slide, please. So what can we say about additional tumor types? And so the potential issue is really starting to be fulfilled at this point to look beyond breast cancer, gastric cancer, lung cancer and additional tumors, which show promising efficacy and manageable safety and HER2-positive colorectal cancer. We see potential to be a new treatment option based on DESTINY-PanTumor02 in multiple HER2-expressing tumors. And we see using HER2 mutation or HER2 amplification excuse me, to select patients using a cell-free DNA assay, demonstration of promising efficacy and manageable safety profile. So exciting time for us as we continue to look and expand the use of ENHERTU. So I'd like to move to the next slide, please, and this would be the next section. So we know that Dato-DXd program, TROP2 ADC program is very advanced in both breast and lung cancer. And here and based on the data presented at ASCO, we're going to focus on the non-small cell lung cancer updates. So if we could please move to the next slide. So at this ASCO, we've presented an update to TROPION-Lung02. This is a Phase Ib study where we combine Dato-DXd plus pembrolizumab with or without platinum chemotherapy in advanced small cell lung cancer. This is a patient population that does not have known actionable genomic alterations. You can see the key eligibility. It included both patients that are frontline, but it also did include some up to 2 prior lines. So there's a mix of patients here, and I think we'll focus in some of our analyses on the frontline population. You can see the cohorts there. They pair Dato-DXd with pembrolizumab with or without platinum. And there are 2 doses of Dato-DXd that were tested in each case, the 4 milligrams per kilogram and the 6 milligrams per kilogram. And we'll focus here with the data in these cohorts. The primary endpoint was safety and the secondary endpoints included looking at efficacy. So if we could move to the next slide, please. So what we see here are the waterfall plots and the response rates for all patients on the left and then the subgroup of patients that are enrolled in the trial that were frontline patients, so frontline non-small cell lung cancer patients. What you can see on the left in all patients is the overall response rate in the doublet regimen of 38%. The overall response rate in the triplet which again represents Dato-DXd plus pembro, plus platinum chemotherapy is 49%. And then in that -- in the frontline population on the right, we can see overall response rate of 50% with the doublet and 57% with a triplet. So overall, looking at this data, it's preliminary, but it is certainly encouraging. And of course, we're very happy to see how the data is evolving in support of our ongoing frontline pivotal trial program with both TROPION-Lung07 and TROPION-Lung08. And if we could move to the next slide, please. So here's the safety data. And no new safety signals were observed. The most frequent adverse events that you can see on the right were stomatitis, nausea, anemia and fatigue. And what you'll notice in terms of the difference in the adverse event profile in the triplet versus the doublet relates mostly to hematologic AEs, which isn't to surprise with the addition of platinum in the triplet regimen. So overall, manageable safety profile and suggesting the evolution when we consider the response rates and the efficacy of a favorable benefit risk profile as we proceed with this study. And if we would move to the next slide, please. So now we look at some of the adverse events of special interest in this TROPION-Lung02 study. So we can see oral mucositis and stomatitis most common adverse event of special interest, predominantly Grade 1, 2. Importantly, there were no Grade 5 adverse events of special interest of any type. And there were no grade 4 or 5 adjudicated ILD or pneumonitis events. So now I would like to move to the next slide. So I'd like to level set us to the lung cancer program for Dato-DXd in terms of the pivotal trial program. So as we have mentioned, TROPION-Lung01, the Phase III second line trial with Dato-DXD versus docetaxel in the second and third line setting, we expect readout in this Q1 fiscal year 2023 and with the potential first-to-market indication and with the potential first TROP2 targeting agents in non-small cell lung cancer. Now I presented to you the TROPION-Lung02 evolving data set, which again is encouraging, although preliminary, and it does indeed support the ongoing trials in the frontline setting that we have, which include TROPION-Lung07 as a frontline trial in the PD-L1 less than 50% population, and that's with Dato-DXd and pembro with or without platinum chemotherapy. And then TROPION-Lung08, this is in the PD-L1 greater than equal to 50% population, and that's with Dato-DXd and pembrolizumab. And we're very pleased that the TL-02 results continue to support our frontline pivotal trial program. So if we could now move to the next slide. So here, we're going to talk about HER3-DXd. And really, what we're talking about across the ESMO Breast 2023 and ASCO Breast 2023 data here is really focused on our most mature and late-stage ADCs that are in pivotal trials. And that includes HER3-DXd. And indeed, we're going to focus here on the updates in breast cancer. So if we could move to the next slide, please. So this is an ongoing Phase II study, BRE-354 in collaboration with Sarah Cannon, which is a partner academic research organization. This is a study of our HER3-DXd in patients with metastatic breast cancer. It has multiple components. And what we'll look at here is specifically the Part A, which is in the HER2-negative metastatic population presented at ASCO 2023. And I want to point your attention to the bottom right of the slide. Because even though I don't have the data to show you right now, that's a part of the study called Part Z. And that's where we're actually looking at sequencing HER3-DXd at its 5.6 milligram per kilogram dose after patients have been treated with ENHERTU that are HER2-positive. And so we'll be able to answer multiple questions in this study and we await the results of Part Z, that we'll show you today the results of Part A. So if we could move to the next slide, please. So certainly, this data continue to support the potential of the HER3-DXd asset in the metastatic breast cancer setting. And we can see in Part A in this HER2-negative population, which is heavily pretreated, we can see the response rate of 35%. Importantly, what the data on the left shows is that these responses occur across a range of HER3 expression. So when we develop these targeted agents, we certainly look to see whether or not the target expression of the ADC could potentially predict response. Here, in this small set, what we can see in a preliminary fashion is that this drug appears to be active across the range of HER3 expression. And then there's the safety profile on the right side. Overall, quite manageable, consistent with what we've previously presented for HER3-DXd. And overall, an evolving favorable benefit/risk profile here. If we could move to the next slide, please. So this is another study with an academic partner. This time with the institute, Gustave Roussy, in Paris. This is an ongoing Phase II trial called ICARUS-Breast01, and these are interim results, And this is in hormone receptor positive HER2-negative metastatic breast cancer. Again, these patients have been pretreated. And the overall response rate here at 3 months preliminary here, data, early data is 28.6%. Importantly, a low rate of adjudicated ILD with only 1.8% being Grade 1. So an evolving manageable safety profile. And what I want to mention about this trial and that we can present at further meetings is the richness of the biomarker data in this trial. If you look at the schema what you'll notice is, there's the potential for sequential biopsy in this trial. This is an exploratory biomarker analysis that may allow us to answer key translational mechanisms about the HER3 DXd and the HER3 biology. And so we look forward to future presentations to the data. Already what's been presented in terms of biomarkers is circulating tumor cell analysis. And we can see in the study so far, preliminarily, we see reductions in total in HER3 circulating tumor cells after the first cycle of the drug. So more to come from a biomarker standpoint on this one. And if we could move to the next slide, please. So this is the last slide I'll show for the HER3-DXd. And now we shift to the early stage setting. So the previous 2 studies I mentioned focused in the metastatic setting. And here, we focus on the primary disease setting. This is the SOLTI TOT-HER3 trial that's being done in collaboration with a group there in Spain. And this is -- these are patients who are basically candidates for surgery. So giving a HER3-DXd or HER3-DXd plus [ Letrozol ] the anti-hormonal agent or a standard chemotherapy in a randomized fashion and the patients are having surgery. And what we see here from the preliminary analysis is that after a single dose of HER3-DXd, there's a 30% response measured by ultrasound. So this isn't pathologic response, but this is a first assessment of overall response. And so this is encouraging after a single dose of HER3-DXd. There's also some biomarker work that's interesting being done in this study. It's called the CelTIL score. And that's looking at the influence on cellularity and immune infiltrate after the administration of HER3-DXd. And indeed, the CelTIL score did go up, again, representing immune infiltrate and cellularity going up after one dose. The toxicity profile was more favorable in the lower dose tested, they tested both 6.4 and 5.6. And there's more correlate work ongoing here. So again, a rich biomarker study. What I want to mention on the bottom of the slide is that there's another ongoing trial called SOLTI-2103 VALENTINE. That is also in the neo-adjuvant and primary disease setting. And again, hormone receptor positive HER2-negative population. And what we'll be able to see from that trial is pathologic assessment. So when we start to think about efficacy in neoadjuvant setting, it will be in the VALENTINE trial that's ongoing for which we'll be able to determine HER3-DXd's ability to improve pathological outcomes and to look at like pathologic complete response. So if we could move to the last slide for HER3-DXd. So we continue to look at HER3-DXd in breast cancer. We can see that there's a clear efficacy signal in the advanced metastatic setting. We're also exploring opportunities, as I've explained in the post ENHERTU setting and that's in that Sarah Cannon trial. And then in the early breast cancer setting in combination -- excuse me, in collaboration with the SOLTI Group in Spain. So new data continue to support the potential of this asset in metastatic breast cancer, and we'll wait for the data in Part Z of that Sarah Cannon study to show us the sequence of HER3-DXd after ENHERTU. And we'll wait for the VALENTINE trial to get a further understanding of efficacy of HER3-DXd in early breast cancer setting. Okay. So now I'd like to move to our last section of the presentation. And this is on combinations. And I think as we think about combinations, I want you to recall that Ken had presented a framework in which we both expand in our R&D strategy that is, we take our DXd-ADCs, and we expand -- we look for new indications or earlier lines of therapies and also extension, which is we take our DXd-ADCs and we combine them with new assets in our pipeline that may have a longer LOE and may have promise in terms of rational combinations. So if we could move to the next slide, please. So this is an overview of the combinations where we're looking to expand our DXd-ADC's opportunities. I won't list -- I won't explain all of these individual trials. In fact, I think we've presented them in one way or another in prior presentations. But the key is to say that we're doing various studies in breast cancer and lung cancer on the top half of the slide with checkpoint inhibitors. That includes combinations with pembrolizumab, both in the Phase II and also the Phase III setting that includes combinations with durvalumab also in the Phase II and the Phase III setting. That's the PD-L1 inhibitor, pembrolizumab, of course, being the PD-1 inhibitor. And then at a poster, a trials in progress poster at this ASCO, we show TROPION-Lung04, which is in a non-small cell lung cancer advanced population where we combine AZD-2936 or 5752 with Dato-DXd. And these are our partner AstraZeneca's bispecific antibodies that are PD-1 TIGIT or PD-1-CTLA-4. So certainly, a number of opportunities, including for expansion into earlier lines of therapy, again, that expansion theme with combinations with immunotherapy. But then there are targeted therapies. And we do have studies ongoing with pertuzumab, of course, our flagship frontline HER2 metastatic positive breast cancer trial, DB-09, with pertuzumab in combination or with an HER2 monotherapy. We also have tucatinib, another anti-HER2 agent. We have combination with capivasertib. This is an AKT inhibitor from our partner, AstraZeneca, that's being tested in DESTINY-Breast08. And we have combinations with osimertinib. Osimertinib, which was also profiled and some key data presented at this congress, and here, we have combinations with either Dato-DXd in combination with osimertinib, ORCHARD trial or HER3-DXd in combination with osimertinib, and that's the U-103 trial. Now beyond these combinations at the top of the trial, it's important for us to point out that we are doing combinations with our own pipeline agents, right? So that's important that when we think of this extension as part of our R&D strategy that we have 2 ongoing combinations within HER2, the first is with our EZH1/2 inhibitor small molecule in HER2 low metastatic breast cancer. That's an ongoing trial in collaboration with Memorial Sloan Kettering -- excuse me, with MD Anderson Cancer Center, MDACC. And then we have ENHERTU in combination with the SIRP-alpha antibody. And that's also going to be planned for disease states, including breast cancer. And that's the first subject dosed in this fiscal year first half of 2023. And importantly, we have additional agents. Our scientists are hard at work in our preclinical pipeline. And so you'll see in the coming presentations, in the coming times that we gather, we'll see more combinations that leverage our pipeline with our extension strategy. So we would move to the next slide. So here's an example of those combinations and one that I mentioned, this is a DS-1103. This is an anti-SIRP-alpha antibody. And as I've mentioned, we've engaged in a combination trial within HER2 and we plan to test on the bottom right, an expansion trial in HER2 low advanced breast cancer. So the SIRP-alpha pathway is an important pathway. It's so called the don't eat me signal. And fundamentally, what we have here is DS-1103 would block the SIRP-alpha CD4 axis. And that is on the presence in macrophages in dendritic cells. And by blocking this pathway, releases macrophages in phagocytic cells to attack the tumors. So basically overcoming don't eat me signal. We have very promising preclinical data, when we combine DS-1103 SIRP-alpha antibody with ENHERTU. And this is the basis by which we have then moved into the clinic to look at what we think is a very exciting combination, which, again, is just one example of what we hope to show you in the time to come. So I'd like to move to the next slide, please. So in conclusion, we do have plans -- we have ongoing plans, extensive plans for combinations with our DXd-ADCs, both assets that are external to our organization as well as with our internal assets. We do have the combination with ENHERTU and our EZH1/2 inhibitor, as [indiscernible]. We have a combination with ENHERTU with a SIRP-alpha antibody and further combinations are in planning and are on the way. And now I'd like to close the session. And if we could move to the next slide. And I appreciate your attention for a lengthy presentation. So certainly, I hope you would agree with me based on seeing the data and what we know about our DXd platform, the approval of ENHERTU in multiple indications, the extension of ENHERTU into now different tumor types and meeting additional unmet needs. The evidence that we have a deep pipeline for which we're now able to combine our late-stage DXd-ADCs like ENHERTU with our own internal pipeline agents. And indeed, what we seek to do is serve patients. That is the very reason we get up in the day, and that is very much what we serve to do and what I hope I communicated to you today as evidence of what we do. Thank you so much, and I appreciate your time. And what we'd like to do now is to answer any of your questions. Thank you.

So we'll now take questions.

So this is Tony Ren from Macquarie Capital. I want to ask you about your top 2 asset. It is -- some people describe it as fancy chemo, right, because it doesn't have a biomarker. That being said, in the press release this morning, AstraZeneca and you guys said that you guys are doing a study called, I believe it's called Venza study, right, where you are going to use a TROP2 assay to identify patients who can benefit from that. So just want to get some sense from you on that assay selection. Is it going to be at the current thinking? Is it an IHC? Is it a next-generation sequencing? Is it tissue? Is it liquid? I just want to get some understanding about how to target that? It is -- I believe it's nearly ubiquitously expressed surface antigen, right? So that's my first question. The second question, which I posed at the AstraZeneca event just earlier as well is that the TROPION-Lung02 study, the -- there is literally a 20% interstitial lung disease, right? So it is pretty high. I mean I think we're hoping to see it below 10%. But most of the time, it's below -- it's around 10% to 15%. So 20% is a bit higher than what I had expected. So I just want to get a sense, is it -- did you guys apply your mitigation for this study? So that's on the ILD in TROPION-Lung02. And also in terms of activity, I know it's a small sample. But I noticed that over time from WCLC in 2022 to the ASCO abstract and to the data today, I noticed sort of a mean reversion or trending down of the doublet activity, but the increases in the triplet activity. I just want to get some understanding why that is taking place? I actually do have a few other questions, but I think I'll probably just stop here and get back into the queue.

Yes. I'm glad to start with your 3 questions. So in terms of the AVANZAR study and the endpoint structure where AstraZeneca will look at TROP2 expressing patients, that's actually a study that they're independently conducting. So in terms of questions about that study, we would need to relate those questions to our partner. We, of course, are interested in TROP2, and we have not disclosed an assay strategy. But certainly, in our trials, we'll look in an exploratory fashion and are considering translationally different approaches. But of course, we have not in our trials to date and certainly not in our pivotal trials. We have not selected patients nor based on these assays. And at this point, TROP2 is exploratory for us. And as you said, TROP2 is expressed at a very high rate in non-small cell lung cancer. Indeed, that approximately -- approximates 90%. So when we enroll that patient population, the majority of patients should express the target. You commented on the ILD in the triplet. Indeed, we see a 22% response rate of ILD. I think very importantly, there was a lower rate of Grade 3 ILD. ILD is important to us. Fortunate that there's been just Grade 3 and no Grade 4 and Grade 5. I think it's early here. We have a dose modification guidance in the protocols. We're watching this very carefully as we go. And we do think this is a manageable toxicity for us. Of course, ILD has been observed in pivotal trials that we've run. And the key is that we need to weigh both benefit and risk. And so overall, with what we see here preliminarily, we believe the data is encouraging. We believe the data is headed in the right direction. And with the majority of the ILD being low grade, we think the evolving benefit/risk profile is favorable. You also asked about the response rates. So certainly, it's preliminary data. I don't think we can make conclusions regarding the comparison of the response rates in either the doublet or the triplet cohorts at this time. It's a bit early. And also the study is not designed to compare efficacy between these 2 arms. What we see in the 57% versus the 50% is directionally encouraging. And we believe this is supportive of our ongoing frontline pivotal trial program, TL-07 and TL-08. But indeed, as you suggest, the response rates may evolve over time. And indeed, the data can be considered preliminary at this point, and we're not able to draw a conclusion based on the efficacy data to date only that it's directionally supportive and encouraging to us.

This is Yamaguchi from Citi. I have two questions. The first question regarding your ENHERTU. You disclosed the CRCO2 data and also PanTumor data, both of which is pretty good. What's going to happen on the filing process of those things, especially that the PanTumor. I think [ Dr. Stara ] who was talking about the potential tumor-agnostic approval -- I mean, upon approval ENHERTU. So can you give me the strategy for those things, first of all? That's the first question. Second question regarding more general questions. I see so many ADCs showing results at this ASCO. I don't know. They're saying 140 ADCs in the clinical trial, and you are ahead of a competitor, I understand that. But can you give me some comments how you're going to keep this lead and also a global company sometimes a very quick development. So are you going to change your strategy to speed up, especially the 7300 and 6000, which you don't have a tie up at this moment?

Yes. So thank you for your two questions. So you've asked about the regulatory strategy based on DESTINY-PanTumor02. At this point, we're not disclosing the regulatory strategy. We're certainly very encouraged by the data and its potential. And we will and are planning to engage the regulatory agencies and that could potentially lead for us to come back and share a strategy with you. But at this point, we're just encouraged by what we see. We're excited by the capability to discuss with the agencies, but do not have a submission plan to discuss now nor to discuss a particular regulatory strategy. But we'll come back to you as soon as possible with this. Then you asked your second question, I'm sorry, can you remind me?

The ADCs.

Yes, the ADCs. So certainly, at this ASCO, a prominent theme was the fact that we saw many ADCs being developed. And of course, our DXd platform has been a leading platform and has led to changes -- substantial changes in the standard of care, not just increments, but true changes in the evolution of the standard of care. And so we believe we continue to have a leading technology. We are aware that this competition -- we are aware that the competition continues to grow. As a result of that, we will certainly maintain our vigilance. So we will certainly continue to enhance our pivotal trial execution capacities. When we also design pivotal trials, we will do so in an efficient manner with the design that can produce results as soon as possible in considerations of the various designs we can consider. So both with respect to trial design, efficiency and also operational efficiency, we are focusing on both these aspects, understanding that we are not alone in this race to help patients.

Okay. I may add some comment to your second question. Through the partnering with AstraZeneca [indiscernible] budget have been reduced. The remained budget and other capabilities can be allocated to the following ADCs other than ENHERTU and Dato-DXd. At this moment, we believe we can maximize following ADC alone. But in the future, if we may consider it is very difficult for us to maximize along, we may look for partnering opportunity, maybe or might be.

Wakao from JPMorgan Securities. [Operator Instructions]

This is Wakao from JPMorgan. Can you hear me?

Yes.

I have two questions. Firstly about cancer data. As for HER3-DXd, it has been effective regardless HER3-DXd expression level. Do you think this is due to high activity of HER3-DXd? Or is it due to scientific feature or what HER3 receptor? And what do you think the future positioning of HER3-DXd in negative breast cancer? This is the first question. Second question is about TROP2 antibody competitive landscape. Frontline data was very encouraging. And I'd like to know your thought on the competitive landscape for TROP2 antibodies? I think data on SKB264 TROP2 antibody was presented at this conference. How did you view this SKB264 data? And do you think it's -- it causes SIRP2, I think you are clearly ahead of SKB264 in terms of data accumulation and speed of development. And I'd like to know your thought on this priority in light of this SKB264 data?

Yes. Okay. So to the first question, thank you, regarding HER3-DXd and your observation that there was expression across the range of -- there was efficacy across the range of HER3 expression. So we're still trying to find -- to try to understand the biology of HER3. And indeed, the cohort that you saw is relatively small. So we probably can't draw a conclusion that HER3-DXd is effective regardless of HER3 expression status. We may need to have a larger data set to draw that conclusion, even if this early preliminary analysis in a limited set of patients may suggest that the HER3 expression does not predict efficacy. We cannot claim based on that data set. We cannot draw that conclusion. We would need a larger data set and probably to have a randomized trial in a control arm. Now I think you've asked a good question about HER3 biology and how that could influence HER3 expression as a biomarker. And this is something that we seek to understand. We don't, at this moment, have the answers. But as you saw with those trials, both the one at the Institute Gustave Roussy and with the Sarah Cannon which produced the analysis that you're asking about, there is additional biomarker work to be done, including sequential biopsy that may help us, and that's in the Gustave Roussy collaboration study that may help us very much further answer the question that you asked. Second question that you asked, I believe, and please clarify I'm wrong, is what is our impression of the data from the Kelun and Merck TROP2 ADC that was presented at the ASCO and what do we think about this data, if I understood correctly.

Yes. That's right.

Yes. So the data -- so what we can see, the TROP2 ADC is active. But it's very early, it's very early. And the overall responses that we see certainly demonstrate activity, but it's too early to draw any conclusions regarding that asset versus our Dato-DXd. That's primarily because we have a lot more data with our Dato-DXd. And this data is very early and emerging. So at this point, I don't think we can draw any conclusion regarding any type of differentiation because of the size of the data set that we have there. And that includes also the subgroup analyses that they show in both EGFR wild-type and EGFR mutation-positive patients. It's hard to conclude across these subgroups and draw any conclusions. What I would say is what I believe that you alluded to is that we're certainly now at a more advanced stage than this asset. We do understand there's the intent for those parties to move the asset forward very quickly. But of course, we already have an ongoing pivotal trial program in the frontline. We are about to read out soon, as you know, the randomized pivotal trial in the second and third line with Dato-DXD. So there is definitely a time difference in these 2 -- for these 2 programs. And what I can tell you is, based on the presentation of that data today, we will certainly be -- continue to be vigilant. We will certainly continue to execute with efficiency in our ongoing and what is a very large pivotal trial program for Dato-DXd.

Next question is from [indiscernible] Sanford C. Bernstein.

I have one question regarding the observed efficacy of in CDK4/6 treatment of the recent market negative and positive populations. And so I was wondering the additional observed efficacy, what is the implication for the first line, the potential of anchors in HR-positive and HER2-low population.

Yes. So I think that's a good question. I mean the analysis was done to understand if ENHERTU is going to be active certainly in patient populations that either have received prior CDK4/6 or have resistance markers. So we have not disclosed any further study of ENHERTU. In HER2 low metastatic breast cancer, of course, what we have stated is we have an ongoing study, DESTINY-Breast06, which is in HER2-low population that is chemotherapy naive. However, as we continue to explore ENHERTU and look at those subgroup populations that you cite, we can certainly think of how such data could inform additional potential study. But we're not able to disclose at this point what studies we may do further that relate to additional lines of therapy or in relation to any CDK4/6 inhibitors.

I have just a quick additional question. What the percentage of population in the HR positive and HER2 low with positive CDK4/6 resistant marker?

Yes. I don't know that I have that information now, and we may need to get that back to you. So you're asking within that subgroup analysis, you're asking the HER2 -- you're asking the HER2 status across the different CDK4/6 subgroups. Is that correct?

Exactly, that's right.

Yes. I will check now, but I don't think we have that data with us here.

Next question is from Muraoka from Morgan Stanley. [Operator Instructions]

It's Shinichiro Muraoka. Can you hear me?

Yes.

Great. The first question is about the [indiscernible] strategy. Of course, I understand it's a bit preliminary right now. But is it possible you to just in terms of filing or reviewing just focusing on IHC 3+ or excluding some noneffective tumor-type like pancreatic? So also please guide me that your outlook going forward? And the second question is the Page 64, maybe almost the last page of the -- your presentation. In 2024 -- it would be a question to maybe Manabe Sunao. In 2024, you have many more robust data readout events like ENHERTU for Breast09 [indiscernible] HERTHENA-Lung02 studies as well. So is it possible that you are expecting -- more exciting days in 2024? It's the last question, but if you can share your views, it would be pretty helpul.

Okay. Well, let me into those 2 questions. And so the first question I think was concerning with the filing strategy for the PanTumor 02 data, particularly with respect to the IHC staining pattern.

Right, right.

And so at the moment, we haven't been able -- we have not disclosed our regulatory filing strategy. But I do want to remind you of the data, which says that yes, the activity is certainly very good in the 3-plus IHC, but also certainly named IHC 2+. But also in certain other types of tumors that are listed on that slide. The drug is quite actively in the 1-plus category as well. So it's a very interesting set of data for which we require further regulatory discussion.

And I think the second question was about all the data coming out that's listed in Slide 64. Is that correct? And how we view these data?

Right.

Yes. And yes -- so as with -- last year, when we had very large amounts of Phase III data coming out as well as new Phase I and Phase II data, I think that pattern of a data-rich oncology development program that we have will continue for this year. I think the most interesting one that's coming up very soon is the data on lung cancer, TL-01. But really followed that quite soon by breast cancer data from a data program and many other data that you see here. So -- but I do think that the data TL-01 is a very important one for us.

Yes, and I guess I would just add that, in addition to that, we're also talking about in 2023, the DESTINY-Breast06 trial, right, which is -- I had alluded to that earlier, the HER2 low Phase III advanced breast cancer study, where patients are naive to chemotherapy. So these are the 3 key readouts that we look at for 2023 and very look forward to sharing that information with you.

We will take one last question from the floor. Please wait for the microphone.

So yes, I just want to ask you about your assays for HER2 low. We know that Dr. Modi who presented your DB-04 study at the last ASCO, she talks about a quantity of assays quite a bit. And also, I know that Dr. Bardia talks about the spatial arrangement of the HER2 receptors on the surface of the tumor cell. So just -- so I just want to understand how is that coming along? I suspect that would have some impact to your future programs targeting HER2 low and HER2. And also, if I could just add one more. Just going back to what Mark said earlier about the lead you guys have in TROPION studies, your TROP2 ADC against Kelun and Merck's ADC. My estimate is that you guys are about 3 or 4 years ahead. I just want to see if that's your understanding as well.

Yes. So in terms of assays, I mean, we remain very diligent in our translational medicine organization. So we do understand that -- of course, HER2 low metastatic breast cancer, the assay is established, right? So -- but I think as we look to additional ADCs in their development, certainly, -- and I won't get into any specific ADC, I think we haven't disclosed the translational strategies for some of our -- the ADCs that are in the earlier stages. But certainly, we look with any targeted agent, including our ADCs, to determine whether or not we can find analytes using different modalities, different assays that can predict potentially response. Certainly, immunohistochemistry is a prominent assay, and we can see that in ENHERTU program. But we are indeed, and as you alluded to, interested in looking at beyond immunohistochemistry and additional modalities, whether that be pathological or genetic, whether it be quantitative. And so I would say, in a general sense, we have a very comprehensive translational medicine program to optimize the use of our ADCs and benefit/risk profiles, but nothing specific that I could share at this point regarding any specific ADC and how we're going beyond immunohistochemistry. And of course, you're aware that ENHERTU is also approved in mutation-positive non-small cell lung cancer. So that's another example of another type of a genetic-based assay. Yes. And for your -- remind me your second question, I'm sorry. Oh, the lead time, right? So you asked if it's 3 to 4 years lead time? Well, I really -- it would really be difficult for me to indicate. And that's simply because -- whereas I know where we stand at Daiichi Sankyo with our programs, of course. It's difficult to say where a competitor may stand. Whereas a competitor may present data, but they may present data and then we still can't tell how far they're along, right? So it's difficult to come up with a -- I would say, a precise estimate of the lead that we may have. I would say that we have -- all that we can confidently say is that we have a lead -- we have a significant lead. We have a program that's in already moved into pivotal trials -- well into pivotal trials versus a program that as far as we know is in the dose finding in the early stages. And that's about what we could add. I'm not sure if Ken, you'd want to add anything else.

Yes, we would only be speculating about the time lines and the time difference between us and other companies. So just -- I think we can only probably conclude that we are ahead. But by how much, it's hard to tell.

So your TROPION-Lung01 study, right? [indiscernible].

Yes. So your TROPION-Lung01 study, right? So if I look at clinicaltrial.gov registry, right, so from start to a preliminary data readout to the final readout, it's about 3 to 4 years, right? So do you think a competitor would have speed this up a little bit? Because in the second-line lung cancer, you would be looking at a progression-free survival of about, let's call it, 10 to 12 months, right? You need time to recruit. And the FDA will not approve something without an overall survival benefit. So I would imagine a competitor already speed it up, right?

Yes. I mean, I think it's -- as you mentioned, the landscape may very well evolve. So we hope with TL-01, we hope for a positive trial, of course, we don't know. But that could change the standard of care potentially for patients. And if that happens, then maybe the way that a competitor may approach the second line space may change. It may become more challenging as an example. But again, difficult for us to know what their development plan is. So -- and including like which line of therapy they could start with, they could initiate trials. And so the extent to which we would be ahead would depend on where they may even -- which line of therapy they may entertain starting a trial.

We now come to our ending time. So we'll now conclude Daiichi Sankyo's ASCO 2023 highlights. Thank you very much for joining today.