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

Thank you for waiting. We are now ready to start Daiichi Sankyo's conference call to present ASCO 2021 highlights. Please note that today's call will be recorded. Dr. Manabe, please go ahead.

Hello colleagues. My name is Sunao Manabe, and I'm the President and CEO of Daiichi Sankyo. Thank you for joining the conference call, focusing on key highlights of the data presented at ASCO 2021. Today, I present our progress since ASCO 2020 and our new 5-Year Business Plan. Following my presentation, Ken Takeshita, our Global R&D Head, will present about R&D. And today's event will be his debut in his new role so please look forward to it. Please see Slide 3. This slide shows the progress of our 3 ADCs since ASCO 2020. With respect to Enhertu through the strategic alliance with AstraZeneca, addition of launched countries and new indications as well as clinical development are all proceeding smoothly. As for breast cancer indication, we have successfully launched in Europe in addition to U.S. and Japan. And regarding gastric cancer, we had the indication for HER2-positive third-line treatment in Japan last September and second-line treatment in the U.S. this January. In terms of clinical development, we initiated 9 studies for breast and gastric and other broad cancer types. With respect to Dato-DXd, we formed strategic alliance with AstraZeneca in addition to Enhertu, and I expect clinical development to be accelerated. We have initiated a pivotal study for NSCLC this February. Furthermore, I believe that it's fresh in your memory that interim data for triple-negative breast cancer cohort in our Phase I study was presented last month at ESMO breast. In addition, we initiated 3 other NSCLC studies. With regard to HER3-DXd, we initiated a pivotal study for NSCLC third-line treatment. In addition, other NSCLC and CRC studies have been initiated. Please see Slide 4. In April of this year, we have launched our new 5-Year Business Plan that covers fiscal year 2021 through fiscal year 2025. Our new 5-Year Business Plan is a plan designed to realize our 2025 vision and to shift toward growth strategy -- growth stage geared to achieve our 2030 vision of being an innovative growth global healthcare company contributing to the sustainable development of society and ESG management. The specific company that we strive to be in 2030 is a global top 10 in terms of oncology revenue, having additional pillars as source of growth, new products being sourced of profit in each business unit and contributing to sustainable development of society through our business. Please see Slide 5. This slide describes the strategic pillar for our new 5-Year Business Plan. R&D capabilities will especially be important for the first and the third pillar. The first strategic pillar is to maximize 3 ADCs. We will maximize Enhertu and Dato-DXd through our strategic alliance with AstraZeneca, and HER3-Dxd will be maximized by ourselves without partner. The third strategic pillar is to identify and build pillars for further growth. Our target is to identify the new growth drivers following 3 ADCs as well as to select and advance promising post DXd-ADC modality regarding our new 5-Year Business Plan period in order to achieve sustainable growth. Please see Slide 6. This slide is our plan for cash allocation. During the new 5-Year Business Plan period, we will prioritize R&D and capital investment on 3 ADCs for sustainable growth and will enhance shareholder returns through dividends and take account of our profit growth. Our plan is to allocate approximately JPY 1.5 trillion to R&D, prioritizing 3 ADCs, and to allocate approximately JPY 500 billion to capital expenditures, focusing on enhancing ADC supply capabilities. Please see Slide 7. Using this slide, I will explain our financial targets for fiscal year 2025. By steadily implementing strategies for the new 5-Year Business Plan, our target is to achieve consolidated revenue of JPY 1.6 trillion and oncology revenue of JPY 600 billion or more in fiscal year 2025. We expect our operating profit to change depending on R&D investment, which will also change with the progress of our pipeline. Our target is to increase the operating profit ratio before R&D expense to 40% in order to secure profitability for our sustainable growth and for increasing shareholder value. However, we will take equity costs into account, and we will aim for ROE of 16% or more, and DOE of 8% or more through improving capital efficiency and further enhancing shareholder returns. We have been investing aggressively on 3 ADCs during the previous 5-Year Business Plan period. Through the new 5-Year Business Plan, we expect to see significant revenue and profit growth, and we will shift to a new stage for realizing our 2030 vision. Please see Slide 8. As I explained earlier, through research activity that takes advantage of our strength in cutting-edge science and technology and the steady global development, bringing promising products, we will maximize 3 ADCs, identify the growth drivers following the 3 ADCs and select post DXd-ADC modalities to aim for sustainable growth. To that end, a strong leader that can effectively lead both research and development and can assess and judge our next growth drivers is extremely important. Please see Slide 9. I selected Ken Takeshita with a strong confidence that he is the best to play such import role. I look forward to working together with Ken to lead Daiichi Sankyo towards a new phase. This is all from me for today. Thank you. Now I would like to hand over to Ken Takeshita.

Thank you, Manabe-san, and thank you to all of you on the line for your time this morning. In the next few slides, I would like to first introduce myself to you, followed by an update from me on our oncology pipeline and our research and development status. And followed by a very brief summary of the news flow that you can expect for the rest of the year. Next slide, please. Just a very brief background of my career history. I was educated in the United States mostly at various colleges and universities on the East Coast of the United States. And my career started out in academic medicine in -- at Yale University and NYU mostly focused on laboratory-based research as well as clinical research and patient care. About 18 years ago, I switched to industry where I worked on various antibodies, small molecules and cell therapy at various companies listed here, Amgen, Celgene and Kite Pharma. And as you may know, I have been at Daiichi Sankyo as the Head of R&D since April 1 of this year. Next slide. So let me very briefly tell you why I came to Daiichi Sankyo in the first place. First, I saw a very strong internal research capability that was very productive in the last few years to produce at least 3 ADCs so far and possibly more in active pipeline. I also saw that there was a lot of courage to change. And there are, as you know, 2 different kinds of changes going on right now at this company: one, from a cardiovascular disease focus to oncology; second, a Japanese pharmaceutical company with a Japan focus to transforming itself into a global pharmaceutical company with a Japan headquarters. And of course, we are all aware of the early successes in regulatory approvals with Enhertu so far. Next slide. So here is my vision on our R&D group especially as part of Daiichi Sankyo. And it is really to become a true global pharmaceutical company and really to optimize organization and cultivate human resources in a global manner. That will result in competitiveness that's a global theater to build on our strengths to continually improve and enhance our sciences and technology beyond just the 3 ADCs to include, of course, the next-generation ADCs and the various other modalities that we have in our shop. We also want to establish a global R&D unit with all the research capabilities and asking the right clinical questions, whether it be in oncology or in non-oncology areas, and also enhance to transition from research to the development. And finally, we want to establish a global development capability that is able to accelerate overall development speed and also to hire and grow global talent to support our global development desires in oncology as well as emerging non-oncology areas. Next slide. And so our fundamental R&D research strategy, however, remains exactly the same as before, the emphasis on the 3 ADCs and the Alpha program. The 3 ADCs, of course, being the Enhertu, Dato-DXd and HER3-DXd. And Alpha really covering all the other pipeline agents in oncology as well as in specialty medicine. And so this really has not changed at all. And I think you are all aware that Antoine Yver has departed from Daiichi Sankyo, but we have had a very good transfer of the baton between Antoine and myself over the last 2 months. And I do not anticipate at all any major changes in our strategic thinking or the strategic direction of our pipeline. And the same goes for the alliance with our AstraZeneca partner for the 2 of our ADCs. I think you are aware that José Baselga is no longer at AstraZeneca due to his recent death, but his successor has been very good. And between the 2 of us, we do not really anticipate any major changes in the strategic direction. And we have certainly established a very close working relationship so far. Next slide. So just a few more detailed slide on our 3 ADCs. Here are the goals for Enhertu. Here, really to establish Enhertu as the new standard of care for HER2-positive breast cancer. And second is also to really change the breast cancer treatment regimen and paradigm by going into this new disease area, which we call HER2 low breast cancer. This is a new disease area that we are trying to define using Enhertu. And of course, we are very interested in non-breast cancer cancers such as gastric cancer, lung cancer, et cetera, that you will hear more about. Next slide. In terms of the Dato-DXd program, also known as the 1062 program, we want to establish Dato-DXd as the best-in-class TROP2 ADC. And also to establish Dato-DXd ADC as a choice for breast cancer. And you'll hear more about this a little bit later in our presentation. Next slide. And for HER3-DXd, as you know, we have -- we are making progress in this area. And our initial goal here is to established HER3-DXd as the first-in-class ADC for EGFR-mutated non-small cell lung cancer. And of course, we are continuing to explore additional indications for this agent. Next slide. Okay. So now for the next few slides, we will go over some data that's been presented at ASCO and recently at other conferences. And in view of the time limitations, we will not be covering every single slide from every single poster or oral presentation but we will just summarize the key data to give you a flavor of how we are thinking about the data. Next slide. The first data to discuss here is the what we call DESTINY-CRC01, colorectal cancer 01 trial. Next slide. This is an exploratory study and -- in which we studied 3 different cohorts of colorectal cancer patients. HER2-positive patients and HER2 low patients in green and yellow. And so these are very important different cohorts, somewhat similar in thinking to the breast cancer cohorts that we have previously defined, which are basically HER2-positive and HER2 low, and HER2 low is really comprised of 2 different categories, IHC 2+ patients and IHC 1+ patients. Okay. Next slide. And you'll see here that the efficacy is quite good. In the middle column labeled Cohort A. This is what we would call HER2-positive patient population. And you can see that the response rate is 45.3 %. In the other categories, the green and the yellow, you can see that the efficacy, the response rate is quite low, really 0. And so immediately, you can see some differences in outcomes based on the treatment to Enhertu. Next slide. And this observation is further strengthened by the progression-free survival data and overall survival data. And you can immediately see again that the Cohort A patients, the HER2-positive patients, have a much better outcome to this agent, Enhertu, compared to the other 2 categories. Next slide. This is a listing of the adverse events seen. And really, these are basically very quite similar in profile to what we might to see with Enhertu in other indications. Next slide. I do want to, however, mention that the AE of special interest, namely interstitial lung disease, there were, in fact, there were 3 patients with Grade 5 ILD -- really, 3 fatal cases that were adjudicated centrally as drug-related ILD. And so based on these findings and additional findings from other clinical trials, we have instituted new guidelines on how to manage the ILD pneumonitis, the steroid use. Next slide. So based on the results that you just saw from CRC01 study, this is the next study that we are currently running. This is called the CRC02 study, in which we are studying really the HER2-positive patients. And we are testing 2 doses, the 5.4-milligram dose and the 6.4-milligram dose. Let me just very briefly mentioned that 6.4-milligram dose was the dose we studied in CRC01. So we are really testing that dose that was already studied and 1-level lower, the 5.4-milligram dose. And this is a study really to find the optimal dose in the patients with HER2-positive colorectal cancer, that we can then take into a pivotal registration study. Next slide. Okay. Now we're going to switch over to breast cancer, the triple-negative cancer. And this is the BEGONIA study. So this is not our Daiichi Sankyo study, but an AstraZeneca-sponsored study in which we are collaborating as part of our alliance and partnership. And this is a combination of durvalumab with various agents, including in HER2 in this case from arm 6. This is a multi-arm clinical trial and for today, I'm just reporting on arm 6. Next slide. So arm 6 really is an examination, as I mentioned, of durvalumab, a PD-L1 inhibitor plus Enhertu T-DXd. And we are enrolling here patients with triple-negative breast cancer in the frontline setting. That is to say no prior treatment for stage 4 triple-negative breast cancer. Okay. Next slide. And we are studying here a subset of triple-negative cancer patients who are HER2-positive. Okay. So -- and this, again, is a safety summary. And you can see that in the small number of the patients, the safety data looks reasonably good. There were a couple of cases of pneumonitis. These have not yet been adjudicated by the Central ILD Committee so we will have to see exactly how they assess. Next slide. What is important here is to really note that there's substantial efficacy seen with this combination of Enhertu plus durvalumab. This is the waterfall plot. And you can see that in the small numbers of patients, the response rate is calculated to be 66.7% in the small sample size. So -- but this is really encouraging. And so -- next slide, please. And so I do want to mention that this is a very important observation. And we will come back to this particular BEGONIA data set later on in the presentation when we discuss also the 1062 program. Okay. The next slide. Okay. Finally, in terms of the ILD, interstitial lung disease, itself. I would like to go over with you some recent data presented not at ASCO, but at AACR meeting. Next one, please. This is a pooled analysis of 8 clinical trials in which Enhertu was studied in various disease settings. And this is a pooling. And you can see that there are breast cancer patients, gastric cancer patients, lung cancer patients, colorectal cancer patients and additional cancers that are not listed here. But it's a total data set of 879 patients. And you'll see here that the incidences of the ILD by grade and also by tumor type. And in general, the observations are important to note here that the percentages for the incidence of ILD appears to be higher in some diseases compared to others. And so I guess a natural question would be that do we think that there's, indeed, a disease-specific difference in the incidence of ILD? And at the moment, the answer to this question is probably no, but it's a little bit too premature to tell you for sure. And you'll see that it's because the incidence numbers are changing over time due to various institutional guidelines and safety measures that we have put into our program. Next slide. Firstly, it is very important to note that the ILD takes time to develop in many patients. You can see that the median time of the onset was about 5.5 months. And you can see that even as late as 12 months from the initial dose of the drug, we can see that there are patients developing ILD. But probably around maybe 1.5 years to 2 years, there appears to be a plateau effect so that no new cases of ILD are seen. Next slide. And what this means is that it takes time for ILD to develop in these patients and therefore, become recorded into our data set. And so all their clinical trials, namely breast cancer trials, are going to have more cases of ILD just because of this time line delay. Now I also want to inform you that in late 2019, we updated our guidelines for ILD monitoring and management in clinical trials. And the details are listed in this slide and in the next slide. But you'll see that it's really -- it's a comprehensive view of how to manage the ILD, how to detect ILD and these are really specifically spelled out in these guidelines. And we also took a lot of efforts to ensure that all the investigators and clinical sites are aware of these guidelines. Next slide. And you can see that -- and I think you can click on the next slide, too. Okay. Yes, here we go. Okay. So you can see that but the safe use campaign was initiated in June 2019 and the toxicity management guideline, which I just mentioned, were implemented in December 2019. So all the patients prior to December 2019 were not part of new guidelines. And whereas the patients who are in the trial after December 2019 are beneficiaries of the new guidelines. So you can see that there should be some effects in terms of incidence of ILD before and after December 2019. And that is really our hope here. And you can also see here geographically that many of the breast cancer studies took place long before December 2019, and possibly that explains why the incidence of ILD is higher than in other cancer types. Okay. Next slide. So here are the incidence of ILD by year. And you can see that between 2016 to 2019, the percentage of ILD any grade is hovering between 20s to the high teens. But in 2020, the percentage has dropped down to 6.9%. We are very encouraged by this. And this may be a reflection of our updated toxicity management guidelines that were implemented in 2019 December. It's a little bit too premature to -- too early to say that what the actual effect was because, as I mentioned earlier, it takes time for patients to develop ILD. However, we are very encouraged by this, and that we hope to update you on the outcome of this effort in another meeting or conference in the future. Okay. Next slide. So the next few slides are really a summary of the current clinical development plan. And let me just first say that there's really no major change or new news compared to what you have already been become aware of. Just to highlight some important things, the breast cancer, Breast 02, 03 and 04 studies, they will be reporting out some data in the next 1 to 2 years. So those are very important to note. And also in a column that's labeled planning. There are several Phase III studies listed as planning. Please note that this means that we are actively planning for these trials. And once we have the details of these clinical trials in these patient populations, we will certainly notify you and let you know the details. Next slide. This again here is a similar set of data in gastric cancer and in non-small cell lung cancer. And as I mentioned, really, there's really no new data or no new information compared to what you have been -- what you have heard previously. Next slide. And finally, similar comments about the colorectal and other cancers. And we are still -- as a reminder, we are still continuing these pan-tumor trials, the 01 and 02. These are really designed to generate data to support additional indications for Enhertu. Next slide. So in terms of a summary of the key data readouts from the Enhertu program, DESTINY-Breast02. This is the HER2-positive breast cancer versus standard of care. We anticipate being able to see the data in fiscal year 2022 in the second quarter. Breast cancer 03 study, this is the head-to-head versus T-DM1. This is an event-driven interim analysis that is projected to happen in quarter 2 of fiscal year -- of this year. Breast cancer 04 study. This is the HER2 low breast cancer study versus standard of care. And we are projecting a primary analysis of data available around the fourth quarter of 2021. And finally, the DESTINY-Lung01 study in the mutated HER2 overexpressing/mutated patients, primary analysis projected to be second quarter of fiscal year 2021. Next. In terms of breast cancer 09 HER2-positive study, this is, again, a randomized study in the front line setting comparing against THP, the standard of care currently. This was, in fact, initiated just last week with the first patient enrolled a week ago. So we are on track for that. And finally, gastric cancer program, Gastric04 study. This is a second-line study in which Enhertu is compared against a combination of ramucirumab plus paclitaxel. And this is planned for initiation in the first half of fiscal 2021. Many of these are event-driven trials, especially some of the breast cancer trials that are randomized, so the precision on the timing of the events reached and therefore, data available is not super accurate, but these are the current projections as of today. Okay next slide. So now we're going to switch over to our Dato-DXd program, also known as the 1062 program. And in the next few slides, we are going to go over the data from the initial study called PanTumor01. And first, I'm going to go over with you data from non-small cell lung cancer portion of the PanTumor01 study. Next slide. So this is just one of -- one of several cohorts in this study. The other cohorts being in several other cancer indications that are currently under study. And this one is in the non-small cell lung cancer cohort, specifically. And you'll see here that we have enrolled lung cancer patients who are relapsed or refractory at 3 different doses, 4 milligrams, 6 milligrams and 8 milligrams. Really -- so the idea here is to try to establish a dose that we wish to take into pivotal registration trials. Next slide. Okay. So this is a summary of the safety data. And you'll see here that the profile looks quite good. It's mostly based on some GI toxicities, the nausea, stomatitis, vomiting as well as some alopecia. And the frequency of hematologic AEs is blocked. I do want to note that for our later discussion here. And also, I do want to mention that previously, we have mentioned that there had been some interstitial lung disease reported in this program so far, as you can see. Okay. Next slide. These are the efficacy data so far, which really shows quite good activity of Dato-DXd at all doses for 6 and 8 milligrams. And this is an update, really, from our earlier study at WCLC conference. And I think some of you have already noticed that the numbers have changed, particularly in the middle column. And for example, the progression-free survival that we are reporting at ASCO is 6.9, where it was previously 8.2 months. And this really reflects the maturity of the data set at the ASCO compared to the immature data set seen earlier this year. And fluctuations like this in some of these numbers is typical in a clinical trial, the small numbers of patients with a fairly immature data set. Okay. Next slide. We have done some pharmacometric analysis to try to understand what is the appropriate dose that we wish to take. And these are the results of the pharmacometric analysis, meaning to say that it's the 6-milligram dose that really optimizes or balances the efficacy as well as safety. So it's the one where 6-milligram appears to give us a higher response rate but also minimize certain types of toxicities such as dose reductions due to toxicities or stomatitis and mucosal inflammation. Next slide. So again, the efficacy and safety data of Dato-DXd in lung cancer is quite promising. And based on that, I do want to mention here that we have initiated the pivotal TROPION-Lung01 study based on these results. And this is a randomized study, in which Dato-DXd is compared against the standard of care, docetaxel, and it is designed to be a registrational study. Okay, next slide -- next few slides, we will go over with you some recent data that was presented, not at ASCO, but at the ESMO breast cancer meeting. And this is data on Dato-DXd in triple-negative breast cancer. Next slide. I think you're familiar with Dato already so I will very briefly go over the data to say that this is a 40-patient trial in patients with triple-negative cancers -- breast cancer was enrolled. These are patients who had multiple prior lines of therapy and the Dato-DXd was given at the dose of 6 milligrams every 3 weeks. Next slide. Here are the patients who enrolled in the study, really, to amplify the fact that these are patients who had many, many prior lines of therapy and still had active disease from 4 prior lines of therapy as a median, and they have been exposed to a wide variety of systemic agents, including taxane, platinum, et cetera. Next slide. In terms of toxicities, it appears to be fairly well tolerated from a -- in terms of what we can expect to see with other ADCs. And no patient really discontinued due to AEs. And next slide shows some of the details of toxicity. And AEs are mostly focused on non-hematologic toxicities such as stomatitis, nausea, vomiting. So this is somewhat different from Trodelvy, which there is a fair amount of hematologic toxicities we recorded with a traditional model. The next slide. It's important to note here that so far, we are seeing very good activity of 1062, Dato-DXd, in patients with relapsed or refractory triple-negative breast cancer. Right now, the calculated objective response rate is 43%. And the durability of response, as shown by the spider plot on the right-hand side, is quite encouraging so far. It's very early, but it's quite encouraging so far. So the next slide. So let me just pause here to just summarize for you our current thinking about triple-negative breast cancer, specifically taking into account the data from the Dato-DXd program, but also from the BEGONIA study that I just mentioned to you a few minutes ago earlier as part of the Enhertu program update. So you can see now that between AstraZeneca and Daiichi Sankyo as part of this alliance partnership, we have potentially 3 agents active in triple-negative breast cancer, durvalumab, Enhertu and Dato-DXd. So this creates a very important and interesting opportunities for us and certainly, very important for patients with triple-negative breast cancer. And it's really a matter for us to understand what is the best way to develop these 3 agents in this particular disease, really, for the greatest benefit of patients with triple-negative breast cancer. And as of today, I can tell you that the strategic discussions are ongoing, and we hope to update you at a later date on our triple-negative breast cancer strategy. Next slide. So just to summarize the Dato-DXd program. Again, we have several disease -- several Phase III trials in planning. Many of the clinical trials, however, are ongoing. I did mention to you the BEGONIA study. And in fact, there is a durvalumab-Dato-DXd component to the BEGONIA study. It's called arm 7. And that is starting to enroll now. In addition, the TROPION-PanTumor01 study is continuing to explore other types of breast cancer beside triple-negative breast cancer, and we hope to be able to update you on those data in the near future. Okay. So in terms of important readouts in the -- let's turn on the next slide. So in terms of what important news, recent update, as I mentioned, the TROPION PanTumor study has started the hormone receptor-positive breast cancer cohort. So we hope to be able to see that data in the near future. And as I mentioned, the BEGONIA study has also started to open the combination with durvalumab as cohort #7 in the BEGONIA study. Next slide. Okay. Now finally, we want to update you on the HER3-DXd program. Next slide. So this is the clinical trial of HER3-DXd in which patients enrolled were EGFR inhibitor resistant, EGFR-mutated patients with non-small cell lung cancer. This is really basically an update of data that has already been presented, but it's much fuller data set with additional important definition. Next slide. So as many of you know, this is a highly unmet medical need patient population and the patients have relapsed on TKI. And so in this study, patients who had prior treatment with prior TKI were permitted to enroll. And interestingly and most importantly, most patients have been treated with prior osimertinib as well as with various types of platinum-based chemotherapy. So therefore, really, you can see that this is a very highly refractory patient population with a prior lines of therapy of 4. Next slide. Okay. So in this patient population, the confirmed response rate was 39%. This included the one patient who achieved a complete response and 21 patients who achieved a partial response. So this is quite good as a response rate. And we can see that the duration of response is also good, over 6 months, and progression-free survival, over 8 months. And even if we take a look at the subset of patients who had been previously treated with osimertinib, you can see that the data is not that different compared to the all-comers in the left column to the osimertinib column. So these are quite good and very encouraging in terms of activity of HER3-DXd. The next slide. This is a very colorful slide, really, yet to emphasize that this agent, HER3-DXd, is active against many different types of EGFR TKI resistance. So down at the bottom here are various different -- the data showing mechanisms of resistance to EGFR TKIs. And it comes into forms of mutations in EGFR gene as well as mutations in other types of genes or amplifications in other genes, et cetera. So it's a very -- it's a diverse set of resistance mechanisms. It's very encouraging and very important to note that our agent, HER3-DXd, is active with very different types of EGFR TKI resistance. Next slide. And in terms of the durability of response, we can see that the patients are quite -- have a fair amount of durability. And this does not seem to be affected in regards of the prior treatments or history of brain metastases. So we are very encouraged by the data so far. And next slide. And next, this particular slide illustrates the potential relationship between HER3 expression and response. And what we are seeing here is actually not a strong relationship between HER3 expression and response. So this is what we see so far, and we are considering what kind of biomarker selection would be needed or possibly not needed in our future trials. Okay. Next slide. I do want to mention here that the toxicity profile was quite good with very low numbers of patients who discontinued treatment due to toxicities. There are really no treatment -- no Grade 5 treatment toxicities. And the majority of the adverse events seen were hematologic in nature, reduction in platelet counts and reduction in the neutrophil accounts. I do want to mention that there are a couple of patients -- there are 4 patients who are adjudicated to have had treatment-related ILD. In all of these occasions, the 4 patients' ILD had the ILD resolve completely after discontinuation of the drug and the steroid treatment. The next slide. So in a summary then, we think we are very encouraged by these data. And I do want to mention that a pivotal study, the HERTHENA-Lung01 study, is ongoing based on the results of the study. And this is the patient population that's enrolling -- exactly the patients who are -- the type patients who are enrolled in the study, namely EGFR patients with mutations in EGFR gene who progressed after TKI and also platinum-based chemotherapy. Next slide. At a summary of this program. I do -- as I mentioned, the Lung01 study is already ongoing. We have initiated a combination study with osimertinib as a combination with TKI. We also have ongoing many clinical trials exploring this compound in other cancers, including colorectal cancer and breast cancer. And we hope to be able to update you on that data in the near future. Next slide. Okay. Okay. In terms of what additional news that you can expect from our program. So that is summarized on the next slide. And this also summarizes some of the programs that you did not hear today. The first on the upper left at the European Hematology Association meeting, we will be presenting data on DS-3201. This is an EZH 1 and 2 inhibitor, and we will be presenting as an oral presentation data in -- our initial set of data in adult T-cell leukemia lymphoma and peripheral T-cell lymphoma. At the WCLC conference, we will be -- in September, we will be updating the data from the Dato-DXd program, the PanTumor01, the non-small cell lung cancer cohort. At the ESMO meeting in September, I will be presenting the DESTINY-01 lung cancer study. This is the HER2/mutated cohort data from that particular study. In addition, we will be talking at ESMO about 2 additional programs that you have not heard about today, the 7300 program. This is our new ADC targeting B7-H3 as the antigen, and we will be presenting the Phase I dose escalation of that. We also have a new ADC called DS-6000 that will be presenting some nonclinical pharmacology data from that. A few other things to note in some of the regulatory decisions, we are expecting approval for our program in malignant glioma. This is DS-1647. This is an oncolytic virus is an inactivated and genetically engineered herpes simplex virus, really, based on the clinical trial conducted in Japan. And we hope to be reporting on some good news on this in the very near future for the Japanese approval. We also have, as you know, some very important clinical trials going on with the Lixiana program and Efient program in atrial fibrillation and ischemic stroke, respectively. And these are really regulatory decisions expected in fiscal year 2021. In terms of our data key readouts, as I mentioned earlier, we are expecting data from DESTINY-Breast03, Lung01 and Breast04 sometime in the current fiscal year. We are also expecting the quizartinib, the first AML trial data, in the third quarter of fiscal year 2021. In addition, we are initiating pivotal trials for Enhertu program, 2 of them, the one is breast cancer 09 trial. We actually enrolled our first patient there. And we anticipate also enrolling our first patient in our gastric cancer program in the first half of fiscal 2021. And in terms of our DS-3201 program, this is the EZH 1/2 inhibitor program. We are initiating a pivotal Phase II program in peripheral T-cell lymphoma in the first quarter of 2021. Okay. Next slide, please. Okay. So this concludes my presentation. And so we are ready to answer your questions.

[Interpreted] First, Mr. Muraoka from Morgan Stanley, please.

[Interpreted] Hello, Muraoka from Morgan Stanley speaking. May I?

[Interpreted] Yes, please.

[Interpreted] May I ask questions in Japanese?

[Interpreted] Yes, that's fine. But Takeshita may respond in English.

[Interpreted] I have 3 brief questions. First, regarding Dato-DXd in triple-negative breast cancer, the data is great. Looking at the spider chart on Page 56, a few cases deteriorated. What was their profile? And also, how do you see this compared to Trodelvy? That's my first question. Is it better to ask all questions now?

[Interpreted] Could you ask one by one, please?

[Interpreted] Okay, understood.

[Interpreted] Takeshita is going to respond.

[Interpreted] You're talking about the spider plot on Page 56, correct?

[Interpreted] Yes.

[Interpreted] For about 3 patients?

[Interpreted] Yes.

[Interpreted] Understood. We don't have the details at hand today, such as how these patients are different from others. We will report to you later, if you like.

[Interpreted] How do you see this compared to Trodelvy?

[Interpreted] May I respond in English? From a numerical sense, the response rate, 43%, as you know, is higher than what is reported in the Trodelvy pivotal study? So from an efficacy standpoint -- but if you look at just the response rate number, perhaps it does put a little bit better. However, I have to say that these are very different clinical trials on the different time points in breast cancer by different companies, different regions, different patients. It's very difficult to compare side by side. I think what we can say is that the safety profile looks a little bit different between this compound and Trodelvy. As I mentioned, Trodelvy does have more hematologic toxicities than the Dato-DXd. And ultimately -- but perhaps some of the other toxicities are a little bit different. And ILD also has a very different profile for Trodelvy versus the Dato-DXd. So I think those are kind of very important differences to note. But ultimately, whether it is better or not for the same ultimately come out in clinical trials that we conduct as well as those conducted by Gilead oncology people. And I am sure that, ultimately, it's going to be of major benefit to patients and the physician to have a choice in selecting which one to use based on the clinical data that we generate.

[Interpreted] By the way, should I assume that the timing of the next update on Dato-DXd in triple-negative breast cancer will be San Antonio Breast Cancer Symposium at the end of this year?

[Interpreted] I think that may be a reasonable guess, but the timing has not been decided yet. So we will check.

[Interpreted] Okay. Understood. Next, DS-7300, B7-H3 ADC was not mentioned much in today's presentation. As for competitive product by MacroGenics, I was not sure about its tolerability. How do you see your ADC in comparison?

It's a little bit premature. We are very early in 7300 program and so it's really difficult to say anything. I have to say that we're going to have to ask you to wait until our data presentation at ESMO before we can have an actual discussion.

[Interpreted] Okay. Can we expect good safety tolerability from DS-7300?

Well, I hope that you will wait for our presentation at ESMO.

[Interpreted] One last question. It was mentioned that there is going to be no big change. But Takeshita-san, since you joined Daiichi Sankyo, looking at various projects, is there anything you find very interesting and want to give a higher priority? Please let me know, if any.

[Interpreted] Such decisions are data driven to a certain extent. For DS-7300, for example, there are other competitive ADCs. When data becomes available, depending on that data, priority could be higher.

[Interpreted] Next, Mr. Wakao from JPMorgan Securities.

[Interpreted] Wakao from JPMorgan speaking. Can you hear me?

[Interpreted] Yes, please.

First, I'd like to ask you questions about HER3-DXd. I think the results were very good. Based on these results, is there any change in your assessment of its potential in the second line and the first-line settings and beyond EGFR resistance? According to your explanation by now, I have got the impression that your expectations for HER3-DXd have been a little bit lower compared to other products. How has its positioning changed internally in response to these results you presented today? How do you see its potential in the second-line settings and beyond EGFR TKI resistance? This is my first question.

[Interpreted] Takeshita is going to respond.

Okay. So for the HER3-DXd program, our current focus on EGFR-mutated non-small cell lung cancer, that's really a data-driven decision that we see a very good positive signal here, and we are just following the clinical signal into a registration approval path. We are still waiting on additional data in other types of cancers, including other types of non-small cell lung cancer. And once we have a little bit more data accumulated, we will be in a position to make some decisions in the future of this compound.

[Interpreted] Understood. Your press release yesterday or the day before yesterday mentioned that you're going to accelerate your clinical development based on these results. I think there is no particular change on Page 69 in your presentation material today. As was explained, are you going to look at data more and present to us if there is going to be any change? If you have a plan for acceleration as of now, could you please explain?

No, look, actually accelerated really means that we do want to ensure that the Lung01 study is going to enroll well. And, in fact, right now, it's going to be a matter of how fast this clinical trial enrolls. So we are going to be focusing on the operational aspects of the lung cancer 01 study. And so -- and then also in terms of the rest of the program, we are considering additional possibilities for this compound in the same indication but earlier lines of therapy. And so the osimertinib combination, which is a new trial that would allow us to get into much earlier lines of therapy by combining with osimertinib. So these are kinds of things that we are emphasizing as part of our acceleration program focusing on this particular type of cancer.

[Interpreted] Understood. Lastly, you have great data with all projects in triple-negative breast cancer. You mentioned in your presentation that you're going to consider priorities and strategies based on the results to be obtained in the future. Around when can we expect concrete plans, including the priorities to be determined for each compound and the specific contents of the future studies? Now there are ongoing studies, so is it going to be after they're completed? Or in the near future, can we expect more concrete development plans for these 3 products in triple-negative breast cancer? This is my last question.

Yes. We do not need to wait for completion of clinical trials to make decisions. We already have substantial amount of data in triple-negative breast cancer from these 2 programs. And so we can start to do the analysis for sure, and we do not necessarily need to wait for completion of clinical trials to make decisions.

[Interpreted] Next, Mr. Yamaguchi from Citigroup Securities.

[Interpreted] Yamaguchi from Citigroup speaking. Can you hear me.

Yes, please.

[Interpreted] First, I have a question to Dr. Manabe. While you're maintaining your relationship with AstraZeneca, Heads of Oncology changed hands at both companies. Now under a new organizational structure, I'm sure AstraZeneca is also busy on its end with vaccines and others. How do you see the recent 2x2 relationship between the 2 companies?

[Interpreted] From our side, Ken Takeshita and Ken Keller are participating. As for relations with AstraZeneca, we believe the good relationship is continuing. I also contact its CEO, Pascal Soriot, on a regular basis. We are keeping the good relationship continuously trying to maximize the 2 products.

[Interpreted] Secondly, I have 2 brief questions about Dato-DXd. Various questions were already asked about TNBC today. Trodelvy was approved for TNBC based on ORR results. Is there any possibility of accelerated approval based on biomarkers or rather early data such as ORR in terms of your strategy?

[Interpreted] Takeshita will respond.

As it is a possibility in some countries, but...

In the U.S.

Yes. And possibly other countries such as Japan. But we are still also considering other options that use different endpoints. For example, the time endpoints such as progression-free survival or over survival that would require randomized. But it's a matter of choosing what kind of data set will provide strong support for the content. And as you may know, single-arm trials with a response rate endpoint doesn't really give you a full assessment of value of the compound. So we're assessing many different options currently.

[Interpreted] Secondly, about the positioning of Dato-DXd. Looking at AstraZeneca slides, Dato-DXd is also included in low HER2 as well as Enhertu. Do you have a strategy to develop Dato-DXd also in low HER2 in the future?

There is a sufficient possibility, there is a possibility. But depending on the data, I think there is a sufficient possibility.

Thirdly, regarding BEGONIA study for IO combination, ORR is very high. But on the other hand, I have the impression that IO is not so effective in TNBC. Is there any possibility of using BEGONIA study results for accelerated approval? In other words, is there any possibility to obtain approval based on ORR results?

[Interpreted] I don't think we can, based on a clinical trial like BEGONIA study. Atezolizumab was already approved for triple-negative breast cancer based on randomized controlled studies with Abraxane in a control arm. I think such clinical study design will be necessary.

[Interpreted] I see. Lastly, about HER3-DXd, there is a great potential as it can work on various types of resistance. On the other hand, other companies are taking a precision medicine-like approach to say that their compound works on a particular resistance, this one or that one. Which do you think is going to be better for the future concerning EGFR resistance?

[Interpreted] Regarding HER3-DXd, right?

[Interpreted] Yes.

[Interpreted] Similarly, we need to decide by each indication. This will also depend on data. So we'd like to wait for the data to become available and the timing, the direction. You think you can get approval for various types of resistance all at once as an indication, correct? That is going to be the most ideal. For example, HER3-positive any tumor as a way of thinking. But it is very difficult in reality. So I think initially, it's going to be something like HER3-positive by indication.

[Interpreted] I'd like to move on to the next question. Mr. Sakai from Crédit Suisse Securities.

[Interpreted] Sorry about what happened before. Can you hear me?

[Interpreted] Yes, hello.

[Interpreted] I have 2 questions. My first question is about the ILD mentioned in Dr. Takeshita's presentation, It's true that after step 3 or the monitoring guidelines was updated, the frequency and the severity of ILD have been decreasing. I understand that very well. On the other hand, I thought you indicated in your comment that this may be a disease-specific incident for ILD. I don't know if it was your personal opinion, but can you elaborate a little more on this? What direction did you mean to take in your statement? If this is disease-specific, are you considering a method or measures using some kind of biomarker. Please tell me your thoughts on this point. This question is about Enhertu.

[Interpreted] Well, I think we don't know if it's disease-specific or not just yet. That's my opinion. That's because if you look at the figures alone, breast cancer seems to have a high frequency. However, many breast cancer patients were enrolled a long time ago, around 2017 or 2018. The ILD management was not well developed at that time. With that in mind -- and it's not like a study -- I think you can't really compare it. Therefore, I think a final and additional analysis is necessary for that.

[Interpreted] Understood. So you're not sure about the time frame yet, correct?

[Interpreted] Correct. I believe it requires further follow-up or analysis.

[Interpreted] Understood. I have another question regarding Dato-DXd. I guess either Mr. Takasaki or Mr. Koga commented last time that by dropping 8 milligrams per kilogram, it was decided to go with 6 milligrams per kilogram. And Phase III of Lung01 has been running already, but how about an impact of dropping 8 milligrams per kilogram on the value of this drug? The fact that Phase III started in December last year is listed in clinicaltrial.gov. So what has changed or has not changed, including the patient enrollment? I believe this will be, of course, a collaboration with AstraZeneca. Can you explain what impact the exclusion of 8 milligrams per kilogram would have?

[Interpreted] The fact that the 6 milligrams per kilogram dose was selected over the 8 milligrams per kilogram dose didn't impact the value issue that much as the program tells you. In other words, this is a normal process of determining the dose for the pivotal trial by dose escalation and dose assessment. It's a usual method in oncology.

[Interpreted] I see. So I take it as no specific impact.

Right. I believe there was no impact.

One more question. I'd like to ask you about the status of cancer patient enrollment, especially in the U.S. A certain manufacturer commented that due to the COVID-19 impact, there are increasing number of patients, especially breast cancer patients who visit their doctors only after their cancer progress to late stages. Can you tell me if this has been affecting your patient enrollment? Or is it just a temporary phenomenon and not affecting your entire clinical trials? I appreciate it if you can elaborate on this.

[Interpreted] I think this question is about the U.S. As for the U.S., the impact of COVID-19 has been gradually diminished and the number of patients enrolled in clinical trials is not as low as it used to be. My impression is that it has increased to the same level as around 2 or 3 years ago. So I'm not worried so far that only late-stage patients are participating in the clinical trial.

[Interpreted] I'd like to move to the next question. Mr. Arai from BofA Securities.

[Interpreted] Hello. Can you hear me?

[Interpreted] Yes, I can hear you.

[Interpreted] This is Arai from BofA Securities. I have one question regarding the future news flow. I believe you will present Dato-DXd at WCLC and Enhertu's lung cancer data at ESMO. So what kind of specific data can we expect to see in those presentations? With respect to these 2 conferences, there has been many data presentations in the past, and I believe a certain level of explanation has been brought about in the stock market. Now I would like to ask you what kind of surprise or new data can we expect to see in those very much anticipated presentations this time?

About the question on WCLC, it's an update or you may consider this as a longer-term follow-up data.

How about Enhertu's lung cancer at ESMO?

You may also consider this as a longer-term follow-up.

Understood. Now I have an additional question regarding Dato. If I remember correctly, Dato-DXd has many different development strategies, such as screening responsive patients with biomarkers -- such specific biomarkers. Or can we expect to see so-called sub-analysis data such as what kind of efficacy will be obtained when screening those responsive patients?

[Interpreted] As for Dato's biomarkers, they are currently under consideration. We haven't made any decision on the biomarkers, such as if it is TROP2-positive or if there are any other biomarkers.

[Interpreted] Understood. I also have a question about the competition in the area of Enhertu's HER2-positive breast cancer. This time at ASCO, your competition such as ARX788 and TUKYSA in combination with Herceptin demonstrated positive data giving an impression that this HER2-positive breast cancer market is getting crowded. If you have any view on the current competitive environment of HER2-positive breast cancer, can you explain that to us. That's all from me.

[Interpreted] Well, I would like to answer this question in English. I think from a HER2 ADC standpoint, there are a number of HER2-directed ADCs out there, but from an Enhertu ADC standpoint, we do believe that Enhertu has probably superior efficacy compared to other ADCs as we know it. It's really a matter of doing proof clinical trial to demonstrate that impression. And so from a competitive standpoint, I think we do have a very good chance in the competitive landscape. Yes. There are other modalities directed against HER2 for sure. Small molecule, for example, is one, naked antibodies will be another one. And there are many other types of HER2-directed therapies that are currently under investigation. And I don't know that we need necessarily to be superior to other modalities, although we may be. There's also the consideration that the patients with breast cancer might be best served by combining many of these HER2-directed ADCs using different modalities. For example, a combination of ADC for the small molecule would be a reasonable combination to study, and perhaps that will give us even better efficacy for patients with breast cancer. So I think these are kind of -- these are really ideas that still need validation, this clinical trial data. And in our program, you can see that we have some of those combinations already in progress or in planning stages.

[Interpreted] I'd like to move to the next question. Mr. Miura from Jefferies Securities.

[Interpreted] This is Miura from Jefferies Securities. I just had one question. It's about ILD related to Enhertu described on Slides 37 and 38. As you explained, I believe the incidents and the severity of ILD have been reduced dramatically since this toxicity management campaign started. Since the announcement of this result, has the sense of security about actually using Enhertu in the real-world clinical practice accelerated? Also with this data, I'd like to know the current situation and current initiatives of how your company is leveraging to accelerate the sales promotion of this Enhertu?

[Interpreted] Should I take this question? We communicated how we want this to be managed, including the safety campaign, and this was a result of their rigorous management. They should keep up with their good job. By the same token, thanks to their continued management that we requested, the figures have been reduced to this extent. So I believe there will be no change in doing it by following the current guidelines. After these data have been presented...

[Interpreted] Oh sorry, go ahead.

[Interpreted] As a result, they can use it with a sense of security. I believe they feel safe to use it. This management itself will continue. We also provide them with information, and they're currently working on it in a stringent manner. Has there been any change in the spread of that sense of security before and after the release of the data? I don't have any specific data yet. I'd like to hear other opinions, including the MRs.

[Interpreted] I'd like to move to the next question. Mr. Hashiguchi from Daiwa Securities.

[Interpreted] I'm Hashiguchi from Daiwa Securities. Hello. Slide 100 or Page 100 of the Appendix introduces a subgroup analysis of the DESTINY-Breast01 trial. Can you tell me your thoughts on the commercial impact this result would create? If there are more than a few doctors who use TUKYSA for patients with CNS metastases and HER2 for patients without metastases, I felt that the data showing good results regardless of metastases could lead to the preferential use of Enhertu in both patients. What are your thoughts on this?

[Interpreted] I will respond to this question. And if there is anything to add, Dr. Takeshita will do so. As you pointed out, I believe the data are favorable to Enhertu rather than to Daiichi Sankyo. The rest is currently under consideration as to how to convey to the physicians. We will convey the data accurately so that they can make their decisions. Please give us a little more time.

[Interpreted] An update on the package insert is required for the promotion, and you are currently discussing how to proceed with that. Do I understand it correctly?

[Interpreted] Yes, that's correct.

Since there are no further questions, this concludes today's Q&A session. Thank you for your participation. Thank you very much. [Portions of this transcript that are marked [Interpreted] were spoken by an interpreter present on the live call.]