Eisai Co., Ltd. (4523) Earnings Call Transcript & Summary

[Interpreted] Thank you very much for taking your time today out of your busy schedule to attend the information meeting of Eisai. It is now time. We would like to begin information meeting for March 2025. This is conducted in a hybrid format combining in-person attendance and virtual attendance. And for those of you who are attending in person, deck of slide is circulated to you. And those of you who are attending virtually, please check our website for the slides. Let me introduce the presenters. Mr. Haruo Naito, Representative Corporate Officer and CEO; Mr. Keisuke Naito, Representative Corporate Officer, Executive Vice President, COO and Chief Growth Officer. Mr. Naito, CEO, please.

Thank you. What you see on the screen is a cartoon of Zodiac. I draw Zodiac every year, and this is the Zodiac for this year. This year is a year of wood snake. This is not merely a year of the snake, but this is the year that comes every 60 years. This is a year of Zodiac that indicates growth and financial good luck. And despite difficulty, if efforts are exerted, there will be a good fortune according to this Zodiac. And this is a Zodiac that suits very well with Eisai. Aricept and LEQEMBI are 2 of our successful products. In 1997, Aricept was launched in the United States for more than 30 years, we have developed a number of products. As you see on the body of the snake, these projects were pursued. And finally, we arrived at LEQEMBI and E2814 is a promising tau antibody, which will be described later, and this is being developed. And that is what I try to indicate with this cartoon. Today, I would like to start by presenting the status of LEQEMBI before medium- to long-term outlook is discussed by Mr. Keisuke Naito. Starting with LEQEMBI, according to recent media report, in Japan, Alzheimer's disease and other dementia are the leading cause of death in Japan. There is a comparison with 1990 on the left side, due to advancement in medical technologies, various diseases are becoming less serious. The society is aging. There is demographic change and Alzheimer's and other dementia have become the leading cause of death in Japan. That was a report in the media. Today, I would like to stress that Alzheimer's disease is a progressive and fatal disease. Due to aging, people may become forgetful but Alzheimer's disease is different from simple forgetfulness, and it is progressive. And it leads to death. It is a very serious disease. Once again, we need to realize that Alzheimer's is such a serious disease. This is a disease that should be a target of active treatment. That is a common understanding I would like to establish with you. We would like to show about 3 sets of data that will support this argument that Alzheimer's is a serious disease meeting treatment. Even after a beta plaques are removed in progressive Alzheimer's disease, -- it does not mean cure. There -- the disease continues to progress according to this data. This is from Phase II study of LEQEMBI, Study 201. Data is from that study and I do see the graph below, core study is the actual study period with the treatment and a transition to open-label extension study. But in this study, there was an average of 2 years of gap period where no treatment was given before the start of OLE in active arm and placebo arm no treatment is given during the gap period. A-beta, amyloid beta may turn negative. And after amyloid beta turns negative, what happens can be discerned from this very important data. Amyloid PET is shown on the left side looking at amyloid reaccumulation, gradually, there's reaccumulation that has started during the GAAP period. On the right side, A beta 42/40 ratio is shown. This is a biomarker showing the deposition of A beta. And at a faster pace there is a worsening, as you can see from this graph. Treatment suspension, the reaccumulation of A-beta was shown during treatment discontinuation. Early start of the treatment, may sometimes lead to improvement in cognitive function. This was almost a positive surprise indicated by the data as shown on this slide. This is from CLARITY AD study Phase III study and substudy from that, the sub study is called Tau PET substudy, Tau PET is used for assessment and evaluation. And the group of patients included here are low Tau group, no or low Tau group. These are patients who are MCI patients in relatively early stage of MCI. And left side in 76% of the patients cognitive function was maintained and of them or rather in 60% of the patients there was an improvement. Even AD patients may see improvement in cognitive function when treatment is started early. And for the first time in the world, that was shown with this data, indicating importance of early treatment. Continued treatment, continued administration may provide a continued benefit according to this data. This has been shown a number of times. This is also open-label extension up to month 36 from Phase III study. The top line is a group that was given active drug throughout the period. The middle line was given placebo during the core period, but active drug switching to active drug during OLE. The bottom red line is [indiscernible] cohort data, which has same baseline as a reference. Group that was given active drug throughout the period and the middle group which switched from placebo to active drug if you compare these 2 groups, after start of the active treatment, the slant of the slope is the same as a group given active drug throughout, but the gap never diminished. This also indicates importance of early start of the treatment. As for effect size between placebo group and active drug group, 0.45 in CDR-SB was at month 18. Upon 36, this has extended to 0.95. You see expansion of effect size or increase of effect size. LEQEMBI is removing the causative material substance of the disease, showing a disease-modifying effect. With early start in continuous treatments, LEQEMBI may lead to sustained suppression of clinical decline with continued benefit. As for the mechanism of action, in the beginning A beta cascade understanding, there was certain A beta cascade understanding, which has since evolved. Mechanism of action that is necessary for AD drug is slowing of progression in the center of LEQEMBI's mechanism of action is to act on soluble A-beta protofibrils that is shown in the diagram above. We believe that this is the toxic species that is at the center of the disease. At the same time, on the right side, after further aggregation, there are insoluble species. There is a process where the fibrils become insoluble. And the plaques shown and recently, there is an understanding that the fusible fibrils surround the core of the plaque. And LEQEMBI also has affinity to diffusible fibrils. And therefore, it also has the action of removing plaques. Protofibril shown at the center is key in suppressing the progression of A beta cascade. But as you see with 2 arrows pointing downward, it also leads to neurodegeneration and therefore, there is a blocking effect of neurodegeneration. Protofibril act on a membrane destruction -- protection. And on the right side, another important pathology Tau cascade is shown and the trigger of Tau cascade is also inhibited. Protofibrils also are known to start Tau cascade. And LEQEMBI plays an important role in blocking that start of the Tau cascade. Another point about AD treatment is that our view is that it needs to be administered for long term. And therefore, safety over long term is needed. A beta drug safety-related to is microhemorrhage and macroedema known as ARIA. And the main cause of ARIA is shown in the schematic diagram above CAA A beta aggregates, cerebral amyloid angiopathy A beta aggregates that are observed around brain blood vessels. These are said to be positive of ARIA. And regarding CAA A beta aggregates, LEQEMBI has low affinity as it has been demonstrated. And as you see at the bottom of the page, in the U.S., Japan and China, according to real-world evidence, ARIA incidents is within the range indicated on the label at low level. Around 6,000 patients are analyzed in all case follow-up in Japan and ARIA incident. Amongst these, about 6,000 cases is 2.5%, 0.25% for symptomatic. ARIA-H is 2.8%, 0.21% for symptomatic. ARIA incidents in real world has been quite low. In a safe environment, LEQEMBI be administration is continuing. And another important characteristic is immunogenicity, which is shown at the bottom of this slide. By continuing treatment, antidrug antibodies may be generated. And many of them are neutralizing antibodies. And therefore, the effect of the drugs will be offset by neutralizing antibodies. But in case of LEQEMBI, the incidence of such neutralizing antibodies is very low, as also noted on our package insert. LEQEMBI is believed to have safety profile and physical properties essential for long-term administration. I would like to summarize at this point. Early initiation and continued treatment of early AD may slow disease progression and delay decline to the later stages of disease, we believe LEQEMBI has the potential to serve as a standard of care in early AD treatment. Next, I would like to discuss the 3 points with regard to the LEQEMBI value expansion. So first of all, I the maintenance regimen. In January, FDA has granted approval -- so after 18 months of initial treatment, which required biweekly treatment, but after 18 months of treatment, it can be shifted to monthly dosing. This new option is now added. And this -- there are 2 important implications to this. As indicated on the right-hand side, the first bullet points. Naturally, it could reduce the burden of infusion to half after 18 months. And also for the patients, the hospital visit, the burden has been reduced and also for the hospitals, the infusion procedures burden is reduced. But actually, it would also have a major effect in further promoting the initiation of the treatment. What it means is that after 18 months, the dosing vacancy is halved as a result the initial hurdle for the initiation of the treatment would be recognized by the physicians as well as the patient and family members, and that would motivate the patients to start the LEQEMBI treatment, and that is actually the effect that we are seeing in the market. The next point is the introduction of the subcutaneous formulation with auto injector. And we believe that this can be a very important game changer. So this requires the separate BLA submission from IV submission. And currently, for this maintenance regimen at 360-milligram dose, and we are currently working on the rolling submissions under fast-track pathway. And we have already completed this process, and we expect the announcement for the approvability to come on August 31. And that will be followed by the submission for the initiation dose at 500-milligram and it is to this end that we are getting prepared. So for the initiations as well as maintenance, and we expect the approval for SC-AI in the first quarter of FY '26. We believe that, as I said, this can be a game changer for the streamlining of pathway. So as indicated on the right-hand side, the treatment would be enabled for the patients at home or at site. And patients themselves or the care partners can give the administration, which would eliminate the need for the patients to actually go to the infusion centers and also for the medical institutions, they would no longer have to compress the infusion capacity problem. And along with that, nurse burden would be reduced, and this could be a very important impact. And at the bottom, you see preclinical AD, and we call this study is ahead 3, 4, 5. And the protocol for this study is based upon the protocol with the complete agreement with FDA, and this is a pivotal study. In June of last -- rather October of last year, the enrollment is completed. This is a 4-year study. And so FY '28 we are expecting the top line readout and the study is steadily progressing. There are many different factors to the protocol, especially it includes the BPM in many different stages in this protocol. What is so important about this study is that patients can start the treatment at the stage of MCI, and we have actually recognized important expansion of the effectiveness. But now we may be able to advance the initiation of the treatment in one more stage and then we can expect even greater expansion of the effectiveness on the patients. And therefore, with the approval of the preclinical indications, we expect that the initiation, the timing can be further advanced and we believe that it would lead to the significant expansion of the effectiveness. Next, I would like to talk about the pathway. In 2023 in July, we received full approval in the United States. But since then through out, we have been working on the improvement of pathway. And through various struggles and we have come today, but throughout this streamlining and optimization of the pathway, we have tried so hard to try to find a way to achieve this. And naturally, and we have been supporting the initiatives of the SCPs with overwhelming efforts. And there are 3 points I would like to discuss here. The first point is targeted DTP. P means patient. So it is more like direct-to-consumer kind of advertisement given to the patients. And so this is really for the patients who have been already diagnosed for AD, and we want to provide the information for LEQEMBI. This is information provision activities. And through this for the patient, as well as for the family members, we want to support the medical decision-making so that we can see the further increase in the number of patients starting LEQEMBI treatment. So that is something that we are starting in the United States. And also currently in U.S. There are some IDNs that are very large scale, treating more than 500 patients on LEQEMBI per center. And so all these successful IDNs are achieving the very good collaborative relationship with the PCPs in the community. And that is a very important feature. For instance, they may have the fixed referral format so that the patient -- the referral form can be sent directly to certain named doctor or they would expect the PCP testing to be already done by the PCP. And that procedure would have been already educated by IDN and the whole thing would lead to a very smooth collaboration between PCP and IDN. And in FY '25, we would like to start our efforts in further strengthening this collaboration between PCP and IDN. The last point is aria, monitoring them by MRI. And there, FDA has granted an approval for AI software to support this. This is called icobrain-aria. When it comes to aria readout, it requires the radiologists identifying the very -- the minor -- the changes on the image, but this is a software that would greatly support this process. Through this aria monitoring burden can be reduced. So this is a new change observed. And the last one, blood-based marker. And this BBM-based per screening is significantly growing. So for A-beta negative patients would no longer be referred to the further A-beta testing. So that is one efficient process. and also IVD approval for the use of BBM for the confirmatively testing may possibly come very soon. And with this, this very heavyweight medical technologies, PET and CSF would no longer be necessary. And also U.S. Alzheimer's Association is expected to come up with the BBM-related clinical guideline. Through this, we expect the wider use of BBM going forward. So this shows overall pathway from top as well as to the bottom, there are actually 10 boxes indicated on the slide. So in this modern days of the diagnosis and treatment, actually the longest and the heaviest weight kind of pathway that we see today. And we have been trying to build this kind of pathway. And at the same time, we have been trying to streamline this. And that's exactly what we have been working on in the United States over the past 1.5 years. So at the bottom, you see some actions indicated in the arrow. So as a result of the development of technologies and with the efforts made by [ SCPs ] and for the streamlining of this pathway, there have been many measures implemented. So on the left top, and the PCP has to do the cognitive testing. But now digitalization is progressing significantly. So [ eye ] based testing or through the conversation with the patients to be evaluated by AI, that kind of cognitive assessment tools have been provided especially the lengthiest pathway part, that is the PCP to neurologists the referral time. And again, here, for the very successful IDN, they have been able to significantly save time there. through the certain educational efforts they made. And so this is where we would like to work towards for instance, in terms of the education, what kind of cognitive testing should be carried out by PCP physicians. Before the patients are referred to the neurologist with the BBM, what kind of testing should be performed before the prefer kind of agreement they will put in place. And as a result of that, we can achieve the significant reduction of this referral time. And as you go to the bottom half, as you can see, that A-beta confirmatory testing would be required. This is a very expensive testing using PET and CSF, very much a heavyweight medical technology. But by introducing blood testing, then the patients would no longer have to move into the next stage, if they are negative. And actually, up to 80% of the patients are going through this BBM prescreening. Furthermore, as indicated on the right-hand side, this is the blood testing, very soon, we should be able to achieve the confirmative testing. And then PET and CSF, the very expensive heavy medical procedures can now be replaced by the blood-based testing and that would be a major game changer. And also for these patient prescriber decisions, after the confirmative diagnosis is given, we can provide information in advance so we can facilitate this process. And on the right of that, you see the humanizing message. That is to say that after the physician explained the safety of the treatment, then they would have to explain the efficacy the patients should be expecting. And just explain that would not be sufficient. And therefore, the activities of data living, what kind of improvements can we expect. Better conversation with the family members, can restart hobbies, can start driving cars, can go to the shopping and pay for themselves. Many type of humanizing message we are trying to communicate to the patients in many different ways. We have already made some publications that made Congress -- and then through all of these efforts, we are actively trying to facilitate this process of patient prescriber decisions. And then another heavyweight process is the infusion as I already mentioned, with the IV maintenance, we have been able to reduce this process to a certain extent. But we think the most important impact would come from SC-AI. As a result, it might even happen that infusion may this year from this pathway. So that would be another major game changer there. And also AI-supported MRI reading is something that I have already explained. So let me summarize the first bullet point. So BBM can definitely confirm A-beta accumulation. The need for the burdensome diagnostic tools may be significantly reduced, simplifying, standardizing the AD diagnosis process. The second bullet point, the potential ability to administer SC-AI for the entire treatment phase may greatly improve the pathway that requires infusion capacity for traditional IV infusion. For patients, this means the significant reduction in the time and effort required for hospital visits. And the third one, another very important point that is the referral timing which is taking a long time. Again, with this IDN PCPs are a good relationship. And by sharing the testing and other burden with PCPs, we should be able to significantly save the time, which is something that we'd like to start from FY '25. So that kind of collaborations and BBM and SC-AI, we expect more to have the impact by FY 2026. Now, PCP and IDN collaboration. The importance of the medical collaboration is something that I have been discussing today. But actually, in Japan, as mentioned at the bottom for this initial administration facilities and followup facilities, this kind of collaboration system is already progressing actually already in the results for the drug, and we have a more deepened database, and we are accumulating real road experience both in terms of efficacy and safety, we are gaining further confidence. And as for the treatment pathway over the past 1, 1.5 years, we have been making efforts. And finally, we are beginning to see the prospect of the further simplification and streamlining. And now we are beginning to build the path way that would smoothly introduce the patients to the patients. And one last message I would like to share with you. Since FY 2020, our ROE actually has been on the declining trend. One cause of this is AD-related resource investment, which is expanded. So in FY '20, as well as 2021, those were the days when we had to make the significant investment into aducanumab. But from FY 2020 to 2024 R&D, SG&A as well as impairment plus an approximately JPY 300 billion worth of investment that we have made at Eisai. However, Eisai is the company that is making enormous commitment to AD. And this is really the responsibility that we have towards the world. As a result of our efforts, the QOL of the patients as well as the family members have seen significant improvement. And peak of the investment for aducanumab came in FY '24. And then in FY '25, we expect aducanumab to achieve breakeven level globally. Furthermore, as we continue investment in AG, again, in terms of the shareholders' return, we have never ever slackened our efforts. By saying this, I'd like to conclude my part of the presentation. I would like to ask Mr. Keisuke Naito to give you the mid- to long-term forecast.

[Interpreted] Thank you. Hello, everyone. Thank you very much for attending Eisai Information Meeting today. I am Chief Operating Officer and Chief Growth Officer. My name is Keisuke Naito. Looking at fiscal '27 as the midterm target up to fiscal '32, how we plan to achieve medium- to long-term growth, that is what I would like to share with you today. And we have a simulation as of now and structural reform efforts drug discovery efforts underway. I would also like to discuss these. This is the executive summary. First of all, In March 2024, we set the revenue aspiration for fiscal 2032. To realize that, we consider fiscal 2027 as a significant milestone, including risk factors, we are disclosing information in every 3 years plan will be reviewed in a rolling fashion so that for stakeholders, information will be disclosed in a persuasive fashion. Through structural reform, global operation will be optimized. Inclusive of that, excluding onetime income, we aim to achieve a 10% plus operating margin in fiscal 2027. In 3 years from fiscal 2025, between in-house R&D and shareholder returns, we aim to balance investments in both. And through partnership investment, we would like to improve efficiency, success probability of drug discovery and enriched pipeline drug discovery partnership and also, we will also be making active investment in nondrug area. And I would like to achieve social good and the performance through drug and nondrug areas. This is the consolidated revenue simulation. In March 2024, we published simulation and this was reviewed more closely. And in the near term, up to fiscal '27, there has been an update. And as noted in the slide, on the left side, dark blue is LEQEMBI. And the pale blue part that is a larger includes LENVIMA, DAYVIGO. On the right side, these are the assumptions and business milestones. And I will start from the top for LEQEMBI revenue, it is expected to be JPY 250 billion to JPY 280 billion in fiscal 2027. The delayed uptake in the U.S. market and learnings from launches in each region are reflected. And a competitive situation and health policies are also taken into account and several scenarios have been analyzed. And as a result, we believe that this range indicated here is realistic at this point in time. Within the bar graph in the left, others include LENVIMA. And LENVIMA continues to be a very important drug for Eisai. In various countries, there are policies to reduce medical expenditure but LENVIMA has obtained -- potentially we'll be obtaining additional indication and LOE extension may be possible, and we believe that we are able to maintain JPY 250 billion level. LEQEMBI and LENVIMA are the major factors, but there are also various events expected in the pipeline. There are also various expected pipeline status and events. These are important items leading up to fiscal 2027. And please note these as important status in events. And we would like to maintain revenue at a certain level and up to fiscal 2027 and aim to achieve aspiration target in fiscal 2032. Of course, there are risks as well in the rolling fashion every 3 years, plan will be reviewed while we continue to make efforts to achieve these objectives. On the other hand, in business, there are various risks. As we turn on the offensive, As I mentioned earlier, on the other hand, profitability is also important in supporting our efforts. As CEO mentioned earlier, we are entering into a new phase for global business. And based on this development, we will optimize operation globally and this will not be a mere reduction of expenses. We will be -- fundamentally we'll be viewing organization and process to continuously evolve overall profitability structure of the company. There are 2 boxes, and we believe that there is a potential in these 2 areas. First, resource investment in globally, we believe there is a room for optimization. There will be a Chief Business Officer, who oversees strategy, planning, finance and investor relations functions and receive reports from global commercial regions. And around Chief Business Officer function globally, there will be also improved efficiency of various functions and resource allocation will be optimized in the operations. On the right side, standardization of systems and processes, IT systems and infrastructure were developed in various regions. But for each region, we saw that operation will be optimal while maintaining that in -- globally, there will be standardization of IT system and infrastructure to reduce duplicate investments. By so doing, we will maintain growth investment and that is how we see the impact of structural reforms. And we believe that there is especially a room for improvement in SG&A expenses. Structural reforms aim is that in fiscal '20, excluding onetime income, operating profit margin of 10% plus. Through achieving this, we would like to become profitable without a reliance on onetime income. Structure reforms and business milestones, by achieving these we should have funding available. And this slide shows how we plan to use those -- that funding. Resource allocation funds, JPY 1 trillion level. That is what we expect to have. First, evolve a profit structure through structural reform, efficiency increased profitability, and this should allow us to have increased the investment capital of JPY 700 billion plus cash on hand, JPY 300 billion comes to JPY 1 trillion level resource allocation fund. We would like to achieve both the growth investment and shareholder returns and in-house R&D investment, partnership investment we will continue to make active investment in major products and areas, meaning mainly in neurology and oncology, that is about the investment. At the same time, we will be strengthening in-house R&D, R&D. This is a core activities for a pharmaceutical company. in-house R&D is core. At the same time, partnership is also a part of a very important strategy for us, especially in oncology, there are opportunities for partnership and collaboration. We would like to explore such opportunities widely. In neurology as well, we have various in-house items, and I believe there is also potential for exploring partnership. But partnership potential in oncology can be important. And dementia ecosystem development investment will continue as well. As for in-house manufacturing of major products, as an R&D-oriented pharmaceutical company, we believe that it is important to have such capabilities. So we will also consider capital investment in production capabilities. And that is how we plan to spend JPY 1 trillion of funds allocating that amount appropriately between investment for growth and shareholder returns. Next, about partnership model that I've mentioned on the previous slide, we have focused areas of neurology and oncology and in the initial stage, we have in-house products, and we are applying partnership model. Aricept and HALAVEN in the earlier years [ used to have a ] partnership. And these led to LEQEMBI and LENVIMA, the major products that we have today. And through partnership, the effect that we can expect is -- of course, it includes onetime income. But in principle, collaboration with academia and collaboration with other companies should accelerate innovation in cost and risk sharing through joint development and maximization of product value through our joint distribution. And innovation may become possible, where it is not possible single-handedly through partnerships, such innovation may become possible. And these are areas that we have focused on so we will continue to explore potential partnership in neurology and oncology. In neurology, we have in-house products and we would like to enhance values mainly focusing on in-house products. And I would like to add value to that through partnership potentially. As for oncology, through a partnership, we may be able to enrich pipeline, I think that will be 1 of the main focuses in oncology. In these 2 important areas, we will be exploring important partnership opportunities as important strategy. There are 3 pillars shown here. And you might wonder where the 3 pillars are since there are many boxes, but there are boxes with numbers. the bottom structural reforms. This is what I have discussed just now. operation excellence will be pursued. And the core for Eisai, which is our drug discovery and also development in nondrug area. These are growth strategies, and they will be supported by structural reforms. And so I have so far mainly described structural reforms. And above that, there is a drug discovery, R&D, progress of R&D drug discovery and creation of new area R&D. I would now like to elaborate on these. Regarding drug discovery R&D, we will continue to focus on neurology and oncology. But it is not that we will be pursuing neurology, oncology separately these 2 will not be separately be developed as separate specialty areas. What brings the 2 together is human biology. As for human biology, this is a term that is used quite often in many areas, but I would like to convey that our human biology concept is slightly different. Understand disease pathophysiology to start development. That is the concept of human biology, and that will be applied to neurology and oncology. And different from what we have understood before, we can look at these areas as a different grouping based on this concept of human biology. So this means it will be cross process -- cross field effort to apply knowledge in drug discovery, that is the characteristic of Eisai. And there are various descriptions on this page. Integrated med chem part in drug exploration and discovery, this is the cross-functional across area function. Med chem clinical data platform are cross disciplinary functions, translational research will be connecting discovery and clinical processes. Translational research will be connecting various processes. So cross process, cross-disciplinary knowledge is important in translational research, and therefore, is going to be very characteristic for Eisai. Molecular profiling technology is one of our core technologies. Through these efforts, we aim to reduce development duration and increased precision in our developments with the technologies indicated on the box -- in the box applied. With that capacity sooner and in more certain fashion, we will discover drugs. Now I would like to describe in more depth -- more in-depth each field, oncology and neurology, human biology is applied, and there is also a pipeline that we have and how the concept is brought to bear will be described as I will discuss the pipelines. As for cancer continuum, this means that cancer is a process of early-stage onset to recurrence of metastasis resistance, et cetera. And each process is involving a different molecular process. But by looking at this as one lump sum cancer can be understood as a continuum. And across cancer types, development will become possible by understanding cancer as a continuum. There's descriptions, the first bullet point, in-house products combination clinical trials to explore potential standard of care and importance of proteins for resistance will be also researched and we will be approaching them with a small and medium molecules. This is our oncology pipeline that we have. LENVIMA has been discussed excessively before in the past. So I will focus on some other aspects. Next slide. We have in-house developed pipeline in combination with LENVIMA. LENVIMA resistance can be overcome by modulating wind pathway, and that is the concept of E7386. So this utilizes our organic molecule synthesis technology. This is an approach that is not possible for a company that has only antibodies. We have a middle-sized module technology as well. And E7386 is a medium-sized molecule that modulate wind pathway to overcome resistance. LENVIMA is one of our flagship products. And by developing combination therapy of LENVIMA in-house, we can expect to expand LENVIMA further. Endometrial cancer Phase I/II study is underway where we are already obtaining suggestive indications of overcoming resistance. And I believe development is underway smoothly. Cancer's Big 4. what is known as cancer's Bif 4. This was mentioned in earlier earnings call, beta-catenine is one such cancer's Big 4 and that is addressed by this, this can become an important platform, and this is a technology to target what has been difficult to target. We have such technologies. And first-in-class, best-in-class in a reproducible fashion will be pursued with the technological platform that we have -- has shown here. Undruggable target to be transformed. Cancer's Big 4 are the so-called undruggable targets. Eisai's strength is small and medium molecule and these can be applied to oncology targets. There are various difficult technological backgrounds. We have various modalities, and this is one of the in-house approaches that we can apply. Splicing platform genetic information is translated by protein, and that will be approached by splicing modulator. IO-sensitive cancer cells will be made cancer cells with high sensitivity to IO by inducing neoantigen and targeting refractory solid tumor with low immunogenicity and poor responsiveness to the cancer immunology will become possible, which was not possible with the existing technologies before. And proximity guided compound platform is similar by promoting degradation of undruggable target by bringing the protein closer to proteolytic enzymes or bringing proteolytic enzymes closer to such proteins. This is needless to say, but undruggable targets are targets that are difficult for drugs to be discovered. But by attempting drug discovery, targeting such undruggable targets, we aim to become first-in-class, and we believe that, that is possible in this area. IO/ADC modifying therapies first-in-class therapy will be pursued in oncology. So in oncology, we have drug discovery platform we will be utilizing biomarker data obtained from LENVIMA, HALAVEN, interpreting based on human biology concept. And we will be creating a backbone therapy, applying that concept and middle and small molecules can be used to transform an undruggable target to a druggable target in oncology drug discovery platform. As for small- and medium-sized molecules that can act on undruggable target in the cells that cannot be acted on by the antibodies. Well, I mentioned in passing before, we believe that these are cross disciplinary approach in oncology, that is only possible for Eisai, and we would like to utilize our own technology and expertise, and we'll also be exploring partnership opportunities to create -- to continue to create innovation in this area. Now from here on, I would like to discuss neurology, and CEO has already covered part of this. So it is about neurodegeneration continuum. A-beta tau neurodegeneration is a disease -- what it means that the provision of AD is regarded as the continuum followed by the biomarker. And beyond ATN is also something that we are trying to explore A-beta tau, and I would like to explain this. So this is our neurology pipeline. And these are the kind of compounds that I'd like to discuss today. So once again, I would like to go over the ATN story. So when we look at the pathological change in AD and there is the aggregation of amyloid as well as this tau aggregation. And so we do see the changes, neurodegenerative changes as well as this the biomarkers, accumulations or the degeneration that we would like to focus on and would like to put them in this continuum to look at this on the basis of the ATN story. So on the left-hand side, you see the natural course of AD continuum. So this is the time and biomarker aggregations without any treatment, this is called JAK curve. And with the advent of lecanemab does modify A-beta. And therefore, the AD continuum with the AD treatment. This AD is natural, the course of the continuum would undergo changes. So with lecanemab, after modifying A-beta, what kind of integration can be achieved. So biomarkers itself will be modified and then it may act on other biomarkers. And therefore, we need to be following up on all of these biomarkers. That is going to be very important. So A-beta modified continuum is really the basis of our thinking and coming up is the combination therapy. As indicated in the bottom at the very bottom here, you see this process showing the aggregation of A-beta, synapse the changes and then that will be reflected in tau leading to the influence on the neural function and also how we are trying to approach them? What kind of mechanism we are trying to bring in that is described on the slide. And so we have been trying to approach them and with -- by combining all the teams, we can come up with combining therapy after removing A-beta with lecanemab and then with [indiscernible] type, we can further slow down this cognitive decline and also with synapse regeneration, we try to attack from both sides with the enhancement of resilience as well as the neuro function recovery. And also, we have the data source and data size in order to combine them and new kinds of mechanism of actions or the most optimal. The combination is something that we can propose. And that is really the part of the concept of new degeneration continuum. So E2814 anti-tau, and this slide is really trying to explain this mechanism on the left-hand side, with new biomarkers, AD stages are now being redefined. That is to say that, first of all, there is this clinical symptoms based understanding. And also the pathological understanding about the [ CNL ], the plaque as well as tau aggregate would be measured. But when it comes to the detailed understanding of this -- what kind of biomarkers would be interacting to result in these conditions, and that is what we are trying to learn. So the combination of the biomarkers to understand the activities in the brain. That's what we are really trying to do. And so the new liquid biomarker, MTBR tau 243 that we have been able to discover centered on that by combining different the biomarkers, what kind of degeneration is related to biomarkers with different combination of biomarkers, we have been able to come up with the biomarker panel, and that is greatly supported this MTBR tau 243 and by defining this AD with these biomarkers, and we try to come up with this new drug discovery. And so based upon that knowledge, and we are now able to come closer to this precision medicine in the field of AD. So in this way, we do have the brain health panel and this is the AD-related biomarker panel database and also this panel leveraging data science, we try to analyze this. And through this, we do have enough resource to achieve the precision medicine. So Brain Health panel, which is the biomarker panel and for the creation of this drug discovery hypotheses. And for the proof of that this can be applied through this, we should be able to shorten the development time period as well as the improvement of the probability of success can be achieved. I will be discussing both later on, and that is also based upon this kind of concept. And so this can be applied for such drug development. And also in terms of the new kinds of biomarker, we can stratify the patients. And for each patient population, we can also propose the most appropriate option. That is another thinking behind this. And so disease subtypes or the AD continuum. Again, as we learn more about AD, and we can expect further changes. And there, we believe that we would be able to really drive that kind of changes. So this is another platform that we have over 20 years. So we have been focusing on the orexin as neuropeptide. This is a very important neuropeptide to maintain the wakefulness. So leverage general orexin platform concept we came up with the Dayvigo, the orexin receptor agonist, and this is approved for the insomnia treatment that is achieving the top market share in Japan. We do have the technology to be able to develop both agonists as well as antagonist of orexin. And this is really unparalleled technology in the world. So as the next step, we are coming with E2086. This is the orexin agonist. And so for the narcolepsy type 1 patients with the excessive sleepiness during the data, and we are carrying out the study. And Phase I proof of mechanism, the study top line is expected to come by the end of 2025. So we would also like to keep you updated on this. Now this one, this is the in-house brain delivery by specific antibody -- and this is quite often called as a brain shuttle or brain transporter. And we call this Evolpath, why Evolpath as a name for this? So in the process of screening, so we have applied the molecular evolution method technology. This is also called the phage display method. And this kind of technology we have applied. And then human biology or lecanemab, drive concept for the ideal antibody that we have to deliver it on them. And from the more than 52 billion antibody repertoire, we have been able to come up with the most appropriate antibody and as a result, we call this Evolpath. And so simply put, the objective of the brain delivery by special antibody is to achieve the higher efficacy at a lower dose, and that is the basic requirement. When it comes to Evolpath of ours, on top of that, in terms of the safety, it is really emphasizing the safety profile of this technologies. And so Evolpath, as we move into this ATN drugs for various antibodies, and we believe that this technology can be applied. So this brain delivering bispecific antibody is also progressing very well. So I would like to also have the future opportunities to keep you updated. So the Brain Health Panel platform and of the analysis of the Brain Health Panel has been reflected into lecanemab, as well as the new degeneration continuum. And that has always been the very important resource. By leveraging them going forward, we would like to further drive this ATN continuum and how to combine them all. And we think that we will be in a position to be able to propose the good options. And also orexin platform is very important in order to maintain the continuations of the innovations. And also Evolpath is the technology that can be applied into the antibody and others. And therefore, through this, the Eisai is working to generate reversible innovation in neurologies going forward. Now from here, I would like to discuss ecosystem. So it's Alzheimer's disease is a social issue. So there are a lot of life-threatening diseases, but when it comes to the cost of this, this is something that we have to really focus on that is to say that in terms of the cause of this, and it is very high in terms of the cost of test in the world and even getting higher for the high income countries and also it is also true in Japan. And as for the social costs, when you look at the global social cost, it is reported to be $1.3 trillion. And also in Japan, the JPY 17.4 trillion is the social cost in Japan and actually out of which JPY 7.4 trillion is really covered by uncompensated care by the family members that is called informal care cost. And therefore, when you think about the fatal disease. Of course, it is the challenge for the patient themselves. But when it comes to the carriers as well as for the entire societies, we have to recognize this to be a very important social challenge. And another important characteristic here is that this is a disease that can be completed just within the framework of Medicare. We do have Aricept, we launched Aricept and we still have Aricept. And what we have always said is that Aricept is never the panacea. That is to say that this is not something that you can resolve everything just with medications. And therefore, at the medical institutions and we have really tried to activate the role of medical institutions where all kinds of related issues can be manifested. And so for the healthy state for high risk on certain treatment, the follow-up and prognosis in different stages, different challenges to exist. And we try to address all of these challenges. And as we are working on the Alzheimer's disease, both with drug development and nondrug approaches, and we are really trying to transform this environment. So we have been building up on the capabilities to support the dementia ecosystem. For Eisai Company Limited nondrug approaches, even from the days of Aricept, we have been working on very hard. And as an extension had that we have been collaborating with the local government. And on top of that, for instance, for the healthy people, the health management service is offered by [ Alteryx ] or as the dementia portal site management and also the data to be really collected in this data platform which is being offered and also another important core solution in dementia field, we believe. That is the nursing care area. And with the noncontact centers, and they're really trying to monitor the sleeping activities of facility residents in real time, and this is the EcoNaviSta program that is offered by EcoNaviSta. Therefore, building off this capability is progressing very smoothly. And through this, we would like to continue pursuing the further partnership in this area. So I mentioned healthy, high-risk uncertain treatment, the follow-up and prognose in different stages. What kind of challenges are there. And also for the respective -- the challenge is, what kind of solutions are we ready to offer -- and so they have different -- the concerns in different stages. We need to offer the solutions for each and every 1 of them. And also second one and also at the bottom. And we need to connect them all with a single platform. And we are trying to deploy them all at the same time. So again, at Eisai, when we are engaged in the drug discovery. And it is a very important core of activities. But again, it's pretty much focused on onset and treatment. But around that, for the healthy state, Arteryex is offering. And also, we have other collaborations database support side would be encompassed in the Trios technology support of site. So from healthy to high risk to onset and treatment leading to the follow-up and prognosis, we need to really link them all and we didn't have the core solutions to link them all. And that's where the Envista would come in. So with EcoNaviSta we believe that we now are able to really cover all of these stages and yet, there are some challenges. For instance, some gaps that we do see in -- for instance, in the healthy states. So we need to do that. So with the drug solutions as well nondrug solutions, they are in the sort of the complementary positions. And therefore, we'd like to continue working on them. So this is why -- conclusion, there can be business is transitioning from its initial investment phase to a critical stage of driven by BBM and formulations. We aim to maximize our capabilities in drug discovery and product development through cash generated from structural reforms aimed at pursuing efficiency by accelerating the development of in-house pipeline and focused on neurology and oncology and continuous growth investment. So do have this -- the strength in the drug discovery. And also, we would like to demonstrate capability in nondrug discovery. So in the field of dementia, I mentioned there are 4 different stages, and we are trying to cover -- and we believe that is our obligations. And therefore, we would like to continue with protein both drug discovery as well as no drug discovery. And so that we would like to achieve the social good as well as the business performance through this, and we aim to support the people's lives from a healthy state to the final moments, and we believe that, that will be really the most best business model for us. Thank you very much.

We would now like to open the floor for questions. We will be taking questions from those attendees in this room, attending in person before taking questions from online attendees. Due to time constraint, we would like to ask you to limit the number of questions to 1 per person so that we can take questions from as many people as possible. If you have a question, please raise your hand, and please also give us your name and affiliate for your question. Attendee seated in the fourth row, please.

I'm Yamaguchi from Citigroup. Since I can ask only 1 question. I have a question regarding Evolpath. There are various existing technologies for brain delivery, how do you differentiate? And Ono pharmaceutical, I think there were before [indiscernible] product. Do you still have some right or does Ono still have right? Amyloid beta and tau bispecific antibody, that may be the idea. And when will clinical development begin?

That question will be addressed by Mr. Ido.

Thank you for your question. I'm a DHPL discovery strategy councilor, my name is Ido. Regarding the first question of how Evolpath is differentiated from others. Efficacy, high brand deliverability and safety are our focus. Our technology is such that as shown here, it is a very high-quality diverse -- it is based on high-quality diverse library. And we are also combining that with a proprietary brain screening to identify high brain deliverable antibodies. We also have continued drug discovery in AD. And what safety issues we should pay attention to? We have very good understanding of that, and that is reflected in the design of the antibodies. And that is why we have obtained high-quality candidates.

The second question, if I may, right, before [indiscernible]. When will clinical development begin?

At the moment, we target 2027 but we will make efforts to accelerate that to earlier timing.

Next person, the person on the second column.

JPMorgan, Wakao. So FY '27, LEQEMBI and LENVIMA, THE basic assumption is something I would like to know more about for it can be. In FY 2027, you didn't give us the number, but I think you're aiming at JPY 500 billion. So I think you have made a downward adjustment for us. Based upon the market consensus, it seems to be high. And so why did you give this downward revision and also how feasible would that be? And as for the LENVIMA, so you're expecting JPY 300 billion at the end of this fiscal year. And the reason for reducing that to JPY 250 billion, is it just the ROA? Is that a reason for this downward adjustment for this number.

Iike is going to respond to your question.

Thank you very much for your questions. So I would like to respond to your questions. About LEQEMBI, so compared to the previous version, -- it's not as if we have reduced our focus. It's more like we have renewed and have come up with a separate forecast. That's how you should be looking at. So you are really the pro of the forecasting. So I'm sure that you know how it is, for instance, early AD. So there are 14 million patients in the United States and we have to allow some yield. And currently, it is about 10,000 and therefore, it's only about 0.2%. And when we are trying to decide whether to launch or not, we were not able to identify this kind of number. It's not as if we have tried to come up with any stretch goal but now that we have been in the market for a year and 1.5 year, and we now see all these factors, and we have reformulated a model. That's an honest reason. But in 2 years' time, to what extent the BBM would be utilized and how much of SCAI to be embraced in the market? So there is always the range. And therefore, we try to come up with the range forecast. So as Mr. Keisuke Naito mentioned, I would like to update this on the rolling question. The second question about LENVIMA. It's not just about IRS you have pointed out. And so for these thyroid cancers and RCC, new kinds of indications are coming up. So considering all of these impacts, and we certainly would like to overachieve this forecast. That's the number that I have.

Follow-up question. Regarding the LEQEMBI, the range, the top range of bottom range, do you have any scenarios? And what is the impact of IRA?

It is indicated in this slide. BBM penetration, it depends on how widely it will be penetrated in SC-AI acceptance. And most pronounced way in the U.S. As for the impact of IRA, I would like to refrain from discussing it in terms of percentage. But looking at recent days and weeks, months, not so much but next year and year after that, there certainly are risks. So we are taking a conservative view.

Next question, please.

Hashiguchi, Daiwa Securities. Page 16, pipeline, major neurology pipeline and partnership is also mentioned, for what product, what development stage in terms of timing, that form of partnership, will you be exploring? Well, it depends on who the partners are, so it may not turn out as you expect at the moment. But could you elaborate on your idea currently?

Specifically, anti-tau antibody and narcolepsy for these 2 themes, LENVIMA and LEQEMBI, we had full pledge of partnership for LENVIMA and CEMBI, and we also would like to pursue such partners -- partnership for these 2 themes. But in forming partnerships, of course, there are necessary data that we have to acquire. So when the timing is going to be, I cannot immediately answer. But we hope to have such data within 1 to 2 years so that we can establish a solid collaborative relationship.

So next one, the person seated at the front.

UBS Securities, Sakai. And this is my questions to CEO. So dementia ecosystem is a wonderful idea. So your social contribution is really demonstrated here. But whereas in this concept, A meaning uncurable disease, when you think about that, it seems as though this is really the negative cost being deferred to the future. So this occurrence of this negative cost, how do you think about this in this system? And would you be able to express in one way or the other in the future? I don't really mean to ask you about the exact number, but if you can share with me this idea, I would appreciate.

So this concept, [ HCC ] so that's what we have been trying to achieve is a drug discovery effort. And when it comes to drug discovery effort, it takes as long as 20 years. It is very important. It's a fundamental solution. This remains unchanged. Whereas once we can achieve that as a tunnel, it's sort of the impact expected in all of these directions, but this burden that is currently felt, it does not have the direct impact. And when we think about the situations, and there are different burdens, and there are solutions in different ways. For instance, the care burden for the cars and we may be able to achieve some positive impact for dementia. But at the same time, we are really trying to offer the solutions to achieve the improvement in all of these areas. And someday, this discovery efforts, we believe that will lead to this fundamental solutions to this dementia, but it would take time. And we cannot simply be engaged in drug discovery. So we are really trying to really come with the current difficulties. And there are other things we need to do. For instance, the brain panel health -- brain health panel, and this is something we have to create in order to achieve precision medicine. And so a high accuracy data we are gathering from here. And then a digital biomarker that is really linked to such quantitative measure we should be able to come up with. So I did mention that they are really in the comment or relationships. So what cannot be achieved with the drug discovery alone, we would continue to pursue as well. And then that would lead to the other findings in different stages as well as the building of the pathway that we can achieve. I'm sorry to be so quick in my response. Let me try to add. Now think about the quality of life. So the quality of life for the patients. And in case of the dementia, we also have to think about the quality of life of the caregivers. And so we have to add the mall and then have to try to find a way to try to improve on the overall quality of life. Currently, from the patient's quality of life. Now we are really trying to subtract the quality of life of the caregivers and regarding that is a negative quality. However, according to [ the Kona ] business, the tool introduction, we know that the quality of life family members would significantly be improved. Like if it is introduced in patients home, and this would significantly save the burden of care giving. And so we have to look at this as additive factor rather than deducting this, and that is something that we are looking at in terms of this care services. I may not be responding to a question properly. If you have any kind of data that you can share with us, if you could come up with the kind of data, we would appreciate if you can share that with us.

Next question.

I'm Muraoka from Morgan Stanley. Earlier, partnering partnership in neurology candidates the 2 candidates for given to antibody and anticantibody and narcolepsy drug regarding tau. You already have established a distribution platform. More or less, you have completed investment. And will you still pursuit partnering, I think I understand that cost can be high, but it may be somewhat wasteful. And do you plan to see partnership for both or only 1 of the 2?

Muraoka-san, thank you very much for your very valuable input. It is not easy to discuss in further detail. So I will take note of your opinion. Thank you.

So the next person on the second row.

Sanford C. Bernstein. My name is Sogi. So this time, FY '27 simulation that you have given us in terms of the sales revenue forecast for LEQEMBI, when you think about this FY '25 to 26, there will be 2 years in between. And we would like to know the evolution to achieve this number mentioned for FY '27. SC-AI, BBM, all of these events may naturally be driving this, which is to say that FY '25, '26, so when you think about the year-over-year growth rate, are you expecting this to be rather low growth? But then are you expecting a much higher growth expected for FY '27? We would appreciate your input on this. And so far, so the process for the patients to reselect LEQEMBI treatment and you have been focusing how challenging that has always been, however you have LEQEMBI?And also Lilly, they have [ Kisenda ]. And then as a fundamental challenge, when it comes to the value of such treatment. But the majority of the doctors and majority of the patients they may not necessarily embracing the value of this treatment based upon the data that are presented. However, the pull of the patient is very significant, though the majority of people may not accept this, this much of sales,we sort of expect that you will be able to achieve? And having said that, it's been like 1.5 years since you started selling this product and then especially in the U.S., sort of the doctor's acceptance of the redial meaningfulness of this treatment, have you witnessed any kind of changes?

So with regard to the first part of your question is, the FY '25, '26, evolution of the sales, Mr. Iike is going to respond.

So as I listen to your questions, I'm almost forgetting first part of your question. So up until FY '27, we are not anticipating any major changes to come. So this is FY '24. And as we try to explain on a yen basis. Our focus is JPY 42.5 billion global sales, and we are quite certain to achieve this. Now how about the number for FY '24. And we are expecting higher than double the kind of level that we'd like to aim at. And in that context, we will go through FY '26 and then reach FY '27, especially the blood biomarker in the United States. And the -- this use of it as a confirmable biomarker, to what extent this will be accepted? So that is certainly reflected into our forecast for FY '27. So that certainly would be an important factor. And the second part of the questions. So the U.S. doctors' acceptance of the clinical meaningfulness.

Thank you very much. I am [indiscernible] responsible for LEQEMBI in the U.S. market. I would like to respond to your questions. Currently, LEQEMBI is continuing on the double-digit growth and maintaining close to 90% of the market share. And therefore, confidence in LEQEMBI remains unchanged and very solid, as Mr. Ike mentioned, in FY '25 in the United States as well. And we are anticipating doublefold growth. So as you have mentioned in your questions about the clinical meaningfulness, at the end of January, maintenance regimen was approved. And especially the fact that the patients can move into the maintenance regimen after 18 months of treatment, that is very -- that is making it very easy for the patients and family members to accept this treatment. As CEO mentioned, AD is the fatal disease and chronic disease, and therefore, has and many of the patients want to continue the long-term treatment, especially having maintenance in starting the treatment and it is making much easier to convince the patients. And for the patients who are under treatment, they see the MSC scores bidding improved and also this the activities of daily living is improving like they can now enjoy what they could not do before. And ADT or NS congresses are expected next week. And there, they can be a real word data, especially ADL based real-world data, we try to present there. And the more specific data what we presented in next phase of congress. But again, from the patients, we are getting the impact that they're really enjoying the clinical value of this treatment. And that data we can publish next week. And industry, we are making a very significant advancement. And I would also like to explain, as you have mentioned, now LEQEMBI, how the patients would respond to this. And CSPs an improvement of 0.45. If the doctors give that kind of response, it would never be a message for the patients accepted acceptance, but it's more about the improvement of the family relationship, the patients would not become so upset or they can go to the shopping and can really pay out of the pocket and also their hobbies, they can enjoy playing violin, they can take care of their pets. So their hobbies they can now enjoy and also driving cars. They can continue driving costs as a result. So. In their average daily life, they do witness the improvement. I mentioned humanizing message, and that's something that we are really trying to gather. And then we would like to publish this in medical congresses or try to communicate this in the peer-to-peer channel in a compliant way, we are really trying to share this kind of message to the patients. And I think that is having a major impact, if I may add. As our CEO just mentioned, again, for the SAPs, the meaningfulness of this treatment, they accept this very positively. But for the SEP to convince the patients of this meaningfulness, and that is really the important point. And therefore, so as a method, we are really trying to send out humanizing message. That's where we are.

I understand that you're really trying together that kind of data and trying to reflect that into our messages that was very encouraging. But another point, the doctors understanding is perhaps not about the clinical meaning for, but it's all about the data. So data would know of the clinical data, but would that be truly clinically meaningful for that going forward, you need to collect all the examples. And also what kind of lives the patient can now enjoy. And therefore, in that sense, I'm very much looking forward to that. So in terms of the clinical meaningfulness, the regulatory authorities, we never grant approval unless there is the clinical meaningfulness. So FDA or the PMDA or CED in China. So -- now that they have recognized the clinical minutes, they have granted approval. So there is no room for doubt. So this is the drug with clinical meaningfulness. Otherwise, we would never have received the regulatory approval. Maybe I have said this too strongly. So I certainly heard your message. I know that you can never compromise on that.

Are there any other questions? If not, are there any questions from those who are participating online? There is one person who is waiting to ask a question. So this will be the final question. Mr. [ Tony Ren ] from Macquarie Capital Limited, please. Can you hear me?

Yes. Yes. Can you hear me?

Yes.

Okay. Perfect. Yes. Great. So just 2 quick ones from me. So on Slide #8, in like you guys in Japan are detecting 5% of the patients with RE or EH. I just wanted to see how are these patients detected. Most of them appears to be asymptomatic. And then I just want to get a sense about if you have any update about the European CHMP recommendation update? And when do you think you can launch in Europe?

Lynn Kramer will address that question.

Yes. Thank you for the question. I'm Lynn Kramer, the Chief Clinical Officer. That question has 2 parts. And the first question was about the area rates in real-world evidence. As you have correctly commented, the rates are very low in Japan and the rates in other regions like the U.S. are similar to those that are described in their labels. In terms of the CHMP we were very pleased to hear in February that the CHMP has agreed by consensus that no changes were needed to the November 14 positive opinion from LEQEMBI. That was the outcome we had expected. Lakembi has now been referred to the European Commission for a decision on the marketing authorization. The EC have clear procedures that they must follow for final steps. These procedures are underway, and we look forward to sharing with you a positive outcome from the European Commission soon.

I think those Japanese ratio area is based on official report, and we have a mandatory reporting in Japan for all cases. So those are quite precise reports by either neuro [indiscernible], the specialist report. So it's a very, very precise and accurate one.

Are they -- yes, just on that one -- yes, thank you, Naito-san. Are they detect other cases of ARIA detected using scans using clinical assessment? Just want to see how are they detected?

It's based on MRI.

Since time has come, we would like to conclude information meeting. And thank you once again for your attendance. [Statements in English on this transcript were spoken by an interpreter present on the live call.]