Status Update

Jun 8, 2021

Slides

Thank you for waiting. We are now ready to start Dice Central's conference call to present ASCO twenty twenty one highlight. Please note that today's call will be recorded. Doctor Manabe, please go ahead. Hello, colleagues. My name is Sonoma Manabe, and I am the President and CEO of Dai Sankyo. Thank you for joining the conference call focusing on key highlights of the data presented at 2021. Today, I will present our progress since ASCO twenty twenty and our new five year business plan. Following my presentation, Ken Takeshita, our Global R and D Head, will present about R and D. Today's event will be his debut in his new role, so please look forward to it. Please see Slide three. This slide shows the progress of our three ADCs since ASCO twenty twenty. With respect to NR2, 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. Regarding gastric cancer, we added 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 nine studies for breast and gastric and other broad cancer types. With respect to Datadx D, we formed strategic alliance with AstraZeneca in addition to EHA2 and I expect clinical development to be accelerated. We have initiated a pivotal study for MSCLC 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 three other LGS UC studies. With regard to R3 DxD, we initiated a pivotal study for NUSCLC third line treatment. In addition, other NUSCLC and CRC studies have been initiated. Please see Slide four. In April, we have launched our new five year business plan that covers fiscal year twenty twenty one through fiscal year twenty twenty five. Our new five year business plan is a plan designed to realize our 2025 vision and to shift toward growth stage year to achieve our 2030 vision of being an innovative growth global healthcare company, contributing to the sustainable development of society under 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 source of profit in each business unit and contributing to sustainable development of society through our business. Next is Slide five. This slide describes the strategic pillar for our new five year business plan. R and D capabilities will especially be important for the first and the third pillar. The first strategic pillar is to maximize three ADCs. We will maximize Enhertu and Double DXC through our strategic alliance with AstraZeneca and Halfway DXC will be maximized by ourselves without partner. The third strategic pillar is to identify and build pillar for further growth. Our target is to identify the new growth drivers following three ADCs as well as to select and advance promising post DXD ADC modality, driving our new five year business plan period in order to achieve sustainable growth. Please see Slide six. This slide describes our plan for cash allocation. During the new five year business plan period, we will prioritize R and D and capital investment on three ADCs for sustainable growth and will enhance shareholder returns through dividends and take account of our profit growth. Our plan is to allocate approximately 1,500,000,000,000.0 to R and D prioritizing three ADCs and to allocate approximately 500,000,000,000 to capital expenditures focusing on enhancing ADC supply capabilities. Please see Slide seven. Using this slide, I will explain our financial targets for fiscal year twenty twenty five. By steadily implementing strategies for the new five year business plan, our target is to achieve consolidated revenue of 1,600,000,000,000.0 and oncology revenue of JPY 600,000,000,000 or more in fiscal year twenty twenty five. We expect our operating profit to change depending on R and D investment, which will also change with the progress of our pipeline. Our target is to increase the operating profit ratio before R and D expense to 40% in order to secure profitability for our sustainable growth and for increasing shareholder value. Moreover, we will take equity cost 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 three ADCs during the previous five year business plan period. Through the new five 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 eight. As I explained earlier, through research activity that take advantage of our strength in cutting edge science and technology and steady global development bringing promising products, we will, we will maximize three ADCs, identify the growth drivers following three ADCs and select both the next 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 on next growth drivers is extremely important. Please see Slide nine. I selected Ken Takeshita with a strong confidence that he is the best to play such important role. I look forward to working together with Ken to lead Daishangqiu 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, Madame Sanda, 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 then and 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 of my career history. I I was educated in The United States mostly. It's the various colleges and universities on the East Coast Of The United States. And my 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 eighteen years ago, I switched to industry, where I worked on various antibodies, small molecules and cell therapies at various companies listed here, Amgen, Celgene, and Kite Pharma. And as you may know, I have been at Dai Sungkyu as the head of r and d since April 1. Next slide. So let me very briefly tell you why I came to Daiichi Sang Kyo in the first place. First, I saw a very strong internal research capability. It was very productive in the last few years to produce at least three ADCs so far and possibly more in in active pipeline. I also saw that there was a lot of courage to change. And there are, as you know, two different kinds of changes going on right now at this company. One from a cardiovascular disease focus to oncology. And second, a Japanese pharmaceutical company with a Japan focus to to transforming itself into a global pharmaceutical company with the Japan headquarters. And, of course, we are all aware of the early successes in regulatory approvals with NCHOR two so far. Next slide. So so here is my vision on our r and d group, especially, as part of Dysfunctional. 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 would result in competitiveness at the global theater, to build on our strengths to continually improve and enhance our science and technology beyond just the three 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 RND unit with all the research capabilities in asking the right clinical questions, whether it be in oncology or in non oncology areas. And also enhance fluid transition from research into development. And finally, we want to establish a global developing 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 in emerging nononcology areas. Next slide. And so our fundamental R and D research strategy however remains exactly the same as before. The emphasis on the three ADCs and the alpha program. The three ADCs of course being the HER2, DactoDxD and HER3DXD 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 Eber has departed from Daishang Kyo, but, we have had a very good, transfer of the baton between, Antoine and myself over the over the last two months. And, I I I do not anticipate at all any major changes in our strategic thinking or the strategic direction of our pipeline. And the same goes along for for the alliance with our AstraZeneca partner for the two of our ADCs. I think we are aware that Jose Jose Basselga is no longer at AstraZeneca due to his recent death. But successor has been very good. And between the two 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 already. Next slide. So just a few more detailed slides on our three ADCs. Here are the goals for ANHEAR two. Here that really establish ANHEAR two as a 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 in HER2. And of course, we are very interested in non breast cancer cancers, such as gastric cancer, lung cancer, etcetera, that you will hear more about. Next slide. In terms of the data DXD program, also known as the ten sixty two program, we want to establish data DXD as the best in class TROP-two ADC. And also to establish data 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 HER three DXP, as you know, we are making progress in this area. And our initial goal here is to establish HER three DXP as the first in class EDC 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 being 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 presentation. But really to summarize the key data to give you a flavor of how we are thinking about the data. Next slide. So first data to discuss here is the, what we call DESTINY CRC one, colorectal cancer one trial. Next slide. This is an exploratory study in which we studied three different cohorts of colorectal cancer patients. HER two positive patients and HER two 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 really comprised of two different categories, IHC two plus patients and IHC one plus 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 HER two positive patient population. And you can see that the response rate is forty five point three percent. In the other categories, the green and the yellow, you can see that the efficacy, the response rate is quite low, really zero. And so immediately you can see some differences in outcomes based on the treatment to improve. 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 eight patients, that the HER two positive patients have a much better outcome to this agent and HER two compared to the other two 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 see with NHERT-eighty and other indications. Next slide. I do want to however mention that the AE of special interest, namely interstitial lung disease, there are in fact, there are three patients with grade five ILD, really three 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 the new guidelines on how to manage the ILD pneumonitis and the steroid use. Next slide. So based on the results that you just saw from CRC one study, This is the next study that we are currently running. This is called the CRC two study in which we are studying really the HER2 positive patients. And we are testing two doses, the five point four milligram dose and the six point four milligram dose. Let me just very briefly mention that six point four milligram dose was the dose we studied in CRC zero one. So we are really testing that dose that was already studied and one one level lower at a five point four milligram dose. And this is a study really to find the optimal dose in patients with HER two 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 life cycle study but a AstraZeneca sponsored study in which we are collaborating as part of our alliance and partnership. And this is a combination duvelumab of with various agents including, in HER two in this case, from arm six. This is a multi arm clinical trial. And for for today, I am just reporting on arm six. Next slide. So, arm six, really is, an examination, as I mentioned, of durvalumab, a PD L1 inhibitor plus in HER two, TDXD. And we are enrolling here patients with triple negative breast cancer in the frontline setting. That is to say no prior treatment for stage four triple negative breast cancer. Okay. Next slide. And we are studying here that a subset of triple negative cancer patients who are HER two positive. Okay. So this again is a safety summary, and you can see that in the small numbers of 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. Okay, 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 sixty six point seven percent in with a small sample size. So, but this is very 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 dataset later on in the presentation when we discuss also the ten sixty two program. Okay. Next slide. K. 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 eight clinical trials in which HER2 was studied in various disease settings. And this is a pooling and you can see that there were breast cancer patients, gastric cancer patients, lung cancer patients, colorectal cancer patients, and additional cancers that are not listed here. But the total dataset of eight seventy nine 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 the natural question would be that do we think that there's indeed a disease specific difference in 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 then 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. First, it is very important to note that the ILD takes time to develop in many patients. You can see that the median time to the onset was about five point five months. And we can see that even as late as twelve months from the initial dose of the drug, we can see that there are patients developing ILD. But probably around maybe one point five years to two years, there appears to be a plateau effect so that no new cases of ILD are seen. Next slide. And and what this means is that it takes time for ILD to develop in these patients and therefore become recorded into our dataset. And so older clinical trials, mainly breast cancer trials, going to have more cases of ILD just because of this timeline delay. Now, I also want to inform you that in late twenty nineteen, 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 a really 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 effort 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 on the next slide too. Yes. Oh, here we go. Okay. So you can see that that the safe use campaign was initiated in June 2019, and the toxicity management guidelines, which I just mentioned, were implemented in December 2019. So all the patients prior to December 2019 were not part of new guidelines. And where the patients who are in a trial after December 2019 are beneficiaries of the new guidelines. So you can see that, there should be some effects in terms of an incidence of ILD before and after December 2019. And that is really our hope here. And you can also see here graphically 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 twenty sixteen to 2019, the percentage of ILD edit grade is hovering between twenties to the high teens. But in 2020, the percentage have dropped down to six point nine percent. And we are very encouraged by this. And this may be a reflection of our updated toxicity management guidelines that were implemented in twenty nineteen December. It's a little bit too premature, 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 zero two, zero three, and zero four studies, they will be reporting out some data in the next one to two years. So those are very important to note. And also in a in a column that's labeled planning, there are several phase three 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 comment about the colorectal and other cancers. And we are still as a reminder, we are still continuing the these pan tumor trials, the zero one and zero two. These are really designed to generate data to support additional indication for M HER two. Next slide. So in terms of a summary of the key data readouts from the Enhertube program, Destiny's breast two. This is the HER two positive breast cancer versus standard of care. We anticipate being able to see the data in fiscal year twenty twenty two second quarter. Breast cancer three study, this is the head to head versus PDM one. This is an event driven interim analysis that is projected to happen in quarter two of fiscal year of this year. Breast cancer zero four study. This is the HER two low breast cancer study versus standard of care. And we are projecting a primary analysis of data available around the 2021. And finally, the DESTINY long one study over in the mutated HER2 overexpressing the mutated patients primary analysis projected to be 2021. Next. In terms of breast cancer nine HER2 positive study, this is again a randomized study in the frontline 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, gastric four studies. This is a second line study in which INHER2 is compared against a combination of ramucirumab plus paclitaxel. And this is planned for initiation in the 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 the our data DXD program, also known as the ten sixty two program. And in the next few slides, we are going to go over the data from the initial study called pan tumor one. And first, I'm going to go over with you data from non small cell lung cancer portion of the pan tumor zero lung study. Next slide. So this is just several cohorts in this study. The other cohorts being 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 non small cell lung cancer patients who are relapsed or refractory at three different doses, four milligrams, six milligrams and eight 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 profile looks quite good. It's mostly based on some GI toxicities, nausea, dermatitis, vomiting, as well as some alopecia. And the frequency of hematologic AEs is low. And I I do want to note that for for our later discussion here. And also, do want to mention that and previously, we have mentioned that there have been some interspecial lung disease reported in this program so far as you can see. Okay. Next slide. These are the efficacy data so far. And it really shows quite good activity of DATO and DXP at all doses for six and eight milligrams. And and this is an update really from our earlier study at WCLC conference. And I think some of you have already noted that the numbers have changed, particularly in the middle column. And for example, the progression free survival that we are reporting at ASCO is six point nine where it was previously eight point two months. And this really reflects maturity of the dataset at ASCO compared to the immature dataset seen earlier this year. And fluctuations like this in some of these numbers is typical in a clinical trial, There's small numbers of patients with a fairly immature data set. Okay. Next slide. We have done some pharmacometric analyses to to try to understand what is the appropriate dose that we wish to take. And these are the results of the pharmacometric analysis really to say that it's a six milligram dose that really optimizes or balances the efficacy as well as safety. So it's the one where six milligram appears to give us a higher response rate, but also minimize certain types of toxicity such as dose reductions due to toxicities or stevatitis and mucosal inflammation. Next slide. So again, the efficacy and safety data of data DXT in lung cancer is quite promising. And based on that, I do want to mention here that we have initiated a pivotal troponin lung zero one study based on these results. And this is a randomized study in which Vetod XD is compared against the standard trocaridocetaxel, and it is designed to be a registration study. Next slide. Okay. Next slide. The 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 Theta DXD in triple negative breast cancer. Next slide. I think you're familiar with data already, I will very briefly go over that data to say that this is a 40 patient trial in which patients with triple negative cancers, breast cancer was enrolled. These are patients who had multiple prior lines of therapy, And the data DXD was given at the dose of six milligrams every three weeks. Next slide. Here are the patients who enrolled in the study really to emphasize the fact that these are patients who had many, many prior lines of therapy and still had active disease from four prior lines of therapy as a median. And they have been exposed to a wide variety of systemic agents including taxanes, platinum, etcetera. Next slide. In terms of toxicities, it appears to be fairly well tolerated in terms of what we can expect to see with other ADCs. And the other patients really discontinued due to AEs. Next and next slide shows some of the details of the toxicity. And AE, they're mostly focused on the non hematologic toxicity such as dermatitis, nausea, vomiting, etcetera. So this is somewhat different from Trodelvy in which there is a fair amount of a hematologic toxicities reported with Trodelvy. Okay, next slide. Important note here that so far we are seeing a very good activity of ten sixty two data DXP in patients with relapsed refractory triple negative risk. Right now, the calculated objective response rate is forty three percent. And the durability of response as shown by the spider plot on the right hand side is quite encouraging so far. Very early but it's quite encouraging so far. So next slide. So let me just pause here to just summarize for you our current thinking about triple negative breast cancer, taking into account the data from the data DXT program, but also from the Begonia study that I just mentioned to you a few minutes ago earlier as part of the NHERTU program update. So you can see now that between AstraZeneca and DaiPSankyo as part of this alliance partnership, we have potentially three agents active in triple negative breast cancer. Durvalumab, and HER2 and data DX2. So this creates a very important and interesting opportunity for us and certainly very important for patients with triple negative breast cancer. And it's really really a matter for us to to understand what is the best way to develop these three agents in this particular disease, really for the for the 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 data DXD program. Again, we have several disease, several phase three 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 data DXD component to Begonia study. It's called arm seven, and that is starting to enroll now. In addition, the tropon pan tumor zero one study is continuing to explore other types of breast cancer besides 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, let's turn on the next slide. So in terms of important news, recent updates, as I mentioned, the Atropion pantomotor 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 I I mentioned, the Begonia study has also started to open the the combination with durvalumab as cohort number seven in the Begonia study. Next slide. Okay. Now finally, we want to update you on the HER three DXD program. Next slide. So this is a clinical trial of HER3 DXP 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 dataset with additional important information. Next slide. So as as many of you know, this is a highly highly unmet medical need patient population once the the patients have relapsed on TK. And so in this study, patients who had prior treatment with a prior TK were permitted to enroll. And interestingly and most importantly, most patients have been treated with a prior postemergency as well as with various types of platinum based chemotherapy. So therefore really can see that this is a very highly, highly refractory patient population with a prior lines of therapy of four. Next slide. Okay, so in this patient population, the confirmed response rate was thirty nine percent. This included the one patient who achieved a complete response and twenty one 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 six months and progression free survival over eight 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 birth rate UHD. So next slide. This is a very colorful slide really yet to emphasize that this agent, HER3DXT, is active against many different types of EGFR T resistance. So down at the bottom here are various different data showing mechanisms of resistance to EGFR TKIs. And it comes in forms of mutations in EGFR gene as well as mutations in other types of genes or amplifications in other genes, etcetera. So it's a very diverse set of resistance mechanisms. And it's very encouraging and very important to note that our agent, R3DXD, is active with very different types of EGFR TKN resistance. Next slide. And in terms of the durability of response, can see that the patients are quite, a fair amount of durability. And this does not seem to be affected regards of prior treatments or history of brain metastases. So we are very encouraged by the data so far. And next slide. And next slide, 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 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 five treatment toxicities. And the majority of the adverse events seen were hematologic in nature. Reduction in platelet counts and reduction in neutrophil counts. I do want to mention that there are couple of patients, there are four patients who are adjudicated to have had treatment related IOD. In all of these cases, the four patients of IOD had the IOD resolved 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 HERFEMA lung zero one studies is ongoing based on the results of the study. And this is the patient population that's enrolling exactly the patients who are enrolled, the type of patients who are enrolled in the study, namely EGFR patients with mutations and EGFR gene, who progressed after TKI and also platinum based chemotherapy. Okay. Next slide. As a summary of this program, as I mentioned, the Lung one study is already ongoing. We have initiated a combination study with Osimertinib combination as with TKI. We also have ongoing many clinical trials exploring this compound in other cancers, 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 did not hear today. The first on the upper left at the European Hematology Association meeting, we will be presenting data on DS-three thousand two hundred and one. This is an EZH1N2 inhibitor, and we will be presenting as an oral presentation data in our initial set of data in adult T cell leukemia lymphoma and the peripheral T cell lymphoma. At the WCLC conference, we will be in September. We will be updating the data from the data DXT program, the pan tumor zero one via the non small cell lung cancer cohort. At the ESMO meeting in September, I will be presenting the DESTINY one lung cancer study. This is the HER two mutated cohort data from that particular study. In addition, we will be talking at ESMO about two additional programs that you have not heard about today. The 7,300 program, this is our new ADC targeting b seven h three as the antigen and we will be presenting the phase one dose escalation data. We also have a new ADC called DS 6,000 that will be presenting some nonclinical pharmacology data from there. Few other things to note, from the regulatory decisions. We are expecting approval for our program in malignant glioma. This is a DS sixteen forty seven. This is an oncolytic virus with 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 the Japanese approval. We also have, as you know, some very important clinical trials going on with the Lixiana program and Effient program in atrial fibrillation and ischemic stroke respectively. And these are really regulatory decisions expected in fiscal year twenty twenty one. In terms of our data key readouts, as I mentioned earlier, we are expecting data from DESTINY breast three, lung one, and breast four sometime in the current fiscal year. We are also expecting the crizotinib, the frontline AML trial data in the 2021. In addition, we are initiating pivotal trials for the imperative program. Two of them, the one is breast cancer zero nine 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 the fiscal twenty twenty one. And in terms of our DS 3,201 program, this is the EZH one two inhibitor program. We are initiating a pivotal phase two program in peripheral T cell lymphoma in 2021. Okay. Next slide, please. Okay. So this this concludes my presentation. And so we are ready to answer your questions. Now we'd like to take questions from the audience. First, Mr. Morocco from Morgan Stanley, please. Hello. Muruka from Morgan Stanley speaking. May I? Yes, please. May I ask questions in Japanese? Yes, that's fine. But Takeshita may respond in English. Okay, understood. Thank you. I have three 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? Could you ask one by one, please? Okay, understood. Takeshi is going to respond. You're talking about the spider plot on Page 56. Correct? Yes. For about three patients. Yes. 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. Thank you. How do you see this compared to Trodelvy? May I respond in English? From a numerical standpoint, the response rate 43%, as you know, is higher than what is that reported in the Trudelvy pivotal study. So from an efficacy standpoint, if you look at just that response rate number, perhaps it does look a little bit better. However, I have to say that these are very different clinical trials run at 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 the Trodelvy. As I mentioned, Trodelvy does have more hematologic toxicities than than the they told DXD. And ultimately and but perhaps some of the other toxicities are a little bit different than the you know, the and ILD also is a very different profile for Trodelvy versus, the TxD. So I think those are some very important differences to note. But, ultimately, you know, whether we it is better or not for the same, it will ultimately come out in clinical trials that we conduct as well as those conducted by Gilead Oncology people. And, you know, I am sure that it's ultimately going to be of major benefit to patients and the physicians who have a choice in selecting, which one to use based on the clinical data that we generate. Thank you. By the way, should I assume that the timing of the next update on Datto DXD in triple negative breast cancer will be San Antonio Breast Cancer Symposium at the end of this year? REPRESENTATIVE:] I think that may be a reasonable guess, but the timing has not been decided yet. So we will check. Okay, understood. Next, DS7300B783ADC 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 very 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 to deal for before we can have an actual discussion. Can we expect good safety and tolerability from DS7300? Well, I hope that you will wait for our presentation at this. Thank you. 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. Such decisions are data driven to a certain extent. For DS7300, for example, there are other competitive ADCs. When data becomes available, depending on that data, priority could be higher. Next, Mr. Wakao from JPMorgan Securities. Mako from JPMorgan speaking. Can you hear me? Yes, please. Thank you for your presentation. 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 HER3D XD 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. Takisha is going to respond. Okay. So for the HER3DXD 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 that clinical signal into a registration approval path. We are still waiting on additional data in other types of cancers, 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 on the future of this compound. 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? But actually, I don't know, but accelerating really means that we do want to make sure that the Lung one study is going to enroll well. And in fact, right now it is 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 one Study two. So, and then also in terms of the rest of the program, you know, we are considering additional possibilities for this compound in the same indication but early lines of therapy. And so the Osimertinib combination. This 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. 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 three 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 we already have substantial amounts of data in triple negative breast cancer from these two programs. And so we can start to do the analysis for sure. And, and, we do not necessarily need to wait for completion of clinical trials to make decisions. Next, Mr. Yamaguchi from Citigroup Securities, please. Hello, Yamaguchi from Citigroup speaking. Can you hear me? Yes, please. Thank you. First, I have a question to Doctor. 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 two companies? From our side, Kenta Keisha and Ken Keller are participating. As for relations with AstraZeneca, we believe the good relationship is continuing. I also contact its CEO, Pascal Sorio, on a regular basis. We are keeping the good relationship continuously trying to maximize the two products. Thank you. Secondly, I have two 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 other early data such as ORR in terms of your strategy? Is going to respond. It is a possibility in some countries, but we are also considering In The US? Yes. And possibly other countries such as Japan. But we are still also considering other options that use different endpoints. For example, time endpoints such as progression free survival or over survival that would require randomized. It's a matter of choosing what kind of dataset will provide strong support for the compound. And as you may know, single arm trials with a response rate endpoint doesn't really give you a full assessment of value of that of the content. So we're assessing many different options currently. Thank you. Secondly, about the positioning of DATO DXD. Looking at AstraZeneca slides, DATO DXD is also included in Lohr2 as well as NHertz. Do you have a strategy to develop DATO DXD also in Lohr2 in the future? REPRESENTATIVE:] There is a sufficient possibility. There is a possibility, understood. Yes, but depending on that data, I think there is a sufficient possibility. Understood. 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? 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 control studies with Abraxane in a control arm. I think such clinical study design will be necessary. 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? Regarding HER3 DXT, right? Yes. 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 determine 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. Okay, understood. That's all for me. Thank you very much. I'd like to move on to the next question. Mr. Sakai from Credit Suisse Securities, please go ahead. Sorry about what happened before. Can you hear me? Yes. Hello. Thank you. I have two questions. My first question is about the ILD mentioned in Doctor. Takeshita's presentation. It's true that after Step three 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 a biomarker? Please tell me your thoughts on this point. This question is about Enhertu. 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 long time ago around 2017 or 2018. The ILD management was not well developed at the 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. Understood. So you're not sure about the time frame yet, correct? Correct. I believe it requires further follow-up or analysis. Understood. I have another question regarding Datto DXT. I guess either Mr. Takasaki or Mr. Koga commented last time that by dropping eight milligrams per kilogram, it was decided to go with six milligrams per kilogram and Phase III of Lung one has been running already. But how about an impact of dropping eight milligrams per kilogram on the value of this drug? The fact that Phase III started in December 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 eight milligrams per kilogram would have? The fact that the six milligrams per kilogram dose was selected over the eight 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. 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 US. A certain manufacturer commented that due to the COVID-nineteen 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. I think this question is about The U. S. As for The U. S, the impact of COVID-nineteen 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 two or three years ago. So I'm not worried so far that only late stage patients are participating in the clinical trial. Okay, understood. Thank you very much. I'd like to move to the next question. Mr. Arai from BofA Securities, please go ahead. Hello. Can you hear me? Yes, I can hear you. Thank you for your explanation. This is Arai from BofA Securities. I have one question regarding the future news flow. I believe you will present Datto DXT 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 two 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 in HER2's lung cancer at ESMO? You may also consider this as a longer term follow-up. Understood. Now I have an additional question regarding Datto. If I remember correctly, Datto 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? As for Dado's biomarkers, they are currently under consideration. We haven't made any decision on the biomarkers such as if it is TRP-two positive or if there are any other biomarkers? Understood. Thank you. I also have a question about the competition in the area of Enhertu's HER2 positive breast cancer. This time at ASCO, your competitions such as ARX-seven eighty eight and TUKAYCE 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. Well, I would like to answer this question in English. From a HER two ADC standpoint, you know, there are a number of HER two directed ADCs out there. But from the HER two ADC standpoint, we do believe that in HER two, it has probably superior efficacy compared to other ADCs other than public. You know, it's really a matter of doing appropriate clinical trials to demonstrate that impression. And so from a competitive standpoint, I think we do have a very good chance in competitive landscape. There are other modalities directed against HER two for sure. Small molecule, for example, is one. Make it antibody to be another one. And there are many other types of HER two directed therapies that are currently under investigation. And I don't know that we necessarily could be superior to other modalities, although we may be. There's also the consideration that the that the patients with breast cancer might be best served by combining many of these HER two directed ABCs using different modalities. For example, a combination of ABC 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 based on clinical trial data. And in our program, you can see that we have some of those combinations already in progress for implant procedures. Thank you very much. I'd like to move to the next question. Mr. From Jefferies Securities. Please go ahead. Hello. This is Miura from Jefferies Securities. I just had one question. It's about ILD related to Enhertu described on Slides thirty seven and thirty eight. As you explained, I believe the incidence 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 nHer2 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? 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 oh, sorry, go ahead. 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 others' opinions including the MRs. Thank you very much. That's all for my questions. I'd like to move to the next question. Mr. Hashiguchi from Daiwa Securities, please go ahead. I'm Hashiguchi from Daiwa Securities. Hello. Slide 100 or Page 100 of the appendix introduces a subgroup analysis of the DESTINY Breast one 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 NHER2 in both patients. What are your thoughts on this? UNIDENTIFIED I will respond to this question. And if there is anything to add, Doctor. 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. 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? Yes, that's correct. Okay. Thank you. That's all for my questions. Thank you very much. Since there are no further questions, this concludes today's Q and A session.