It is now time. We would like to begin the information meeting of Eisai Co, Ltd for 2022. The presentation is streamed live and broadcast to those who are participating via telephone lines. Those who are on the call via telephone, please download the slides and click the slides forward to move the slides. Those who are watching live stream, please continue to watch the live streaming. The presenter is Representative Director and CEO, Mr. Haruo Naito. I would like to invite Mr. Naito without further ado. Thank you. This is Naito. I hope you can see a drawing of tiger on the screen. Zodiac, Chinese zodiac for this year is tiger. This is a year that is full of luck, and the gaze of tiger is fixing its aim, and it is trying to achieve its aim. That is the intention of this drawing. Yesterday, we issued a press release regarding Aduhelm. Economic arrangements or collaboration agreements are to be changed. As for the background of the change, as indicated on this page. Regarding AD-DMT, there is very active discussions in the last year or so. Discussions include, for example, data. Whether or what is happening with regards to publication, there were some discussions concerning data. Regarding approval, there is accelerated approval discussion and full approval discussion, and there were also discussions of the requirements for approval. Value or price were also discussed. Price setting and value proposition of AD-DMT. What is the appropriate level, and is it open? Recently, regarding reimbursement, there are various discussions ongoing. Public comments were sent in large number. Antibodies are related to A-beta. There are about four on the horizon, and we are also seeing new environment in terms of competition. As for access, this is access to deliver the drug to those in need, and there is also very active discussion concerning access. To put all of these in perspective, Alzheimer's disease-modifying therapy is strongly hoped for by the society. Patients and doctors both want to use AD-DMT sooner. That is the type of new therapy. In order for such a therapy to be recognized in the society and to be accepted in the society, what needs to be satisfied in terms of conditions in the environment? I think that has become clearer through the discussion over the past year. The direction of these discussions has to be clarified so that conditions are met for AD-DMT to be accepted by the society. I think the direction is becoming clearer. As for the events anticipated going forward related to Aduhelm, on April 11, CMS NCD final policy is expected. This is going to be a major event. Regarding lecanemab for accelerated approval, filing is expected to be complete in around April-May of this year. As for lecanemab pivotal study, Clarity AD, this is also underway steadily. Top-line results may be obtained in around September this year. As for accelerated approval of lecanemab, potentially during 2022, this may be granted. With the results of Clarity AD, filing for full approval may be completed during fiscal 2022, and potentially full approval for lecanemab may be granted during 2023. These are the anticipated events. In a nutshell, major events, important events will be following one after another, and we have to be proactive and forward-looking in terms of change. As the management, I believe we have to change proactively and in a forward-looking manner. The background of the change in collaboration agreement is summarized briefly. The existing agreement was entered into in 2014. In 2017, regarding Aduhelm, Eisai exercised its option, which made Aduhelm a jointly developed and commercialized product. This time, as I explained, we took a decision to amend the collaboration agreement to define new roles and responsibilities. In a way, this is an opening of a new chapter. This is such a forward-looking decision. I hope that you will understand this change in collaboration agreement in this way. As for the changes, I would like to discuss the changes. With respect to Aduhelm, effective January 1, 2023, there will be a change from sharing of global profits and losses to a global royalty arrangement, where a certain percentage of revenue will be received as a royalty. As for the sharing of profits and losses, there was a background of the sharing of expenses in accordance with profits and losses. Regarding Aduhelm, the profit & loss sharing and expense sharing, effective January 1, there will be no obligation for Eisai and no rights for Eisai. As for lecanemab supply agreement, currently, we have five-year agreement with Biogen. This is extended to 10-year agreement to ensure long-term manufacturing and receive more long-term commitment. In regards lecanemab collaboration, basic framework remains unchanged. The current framework of agreement will be continued. Under that framework, Eisai will continue to serve as the lead of development and will have final decision-making authority. Upon approval, both companies will co-market and co-promote, and Eisai will book all sales for lecanemab. Profits and losses will be shared 50/50 between the two companies. That framework remains unchanged. I would like to discuss in more detail. The existing contract, current contract, was a profit and loss sharing agreement by region, and the ratio is determined for each region. For example, Eisai Biogen 45, 55 in the United States, where Eisai is 55. In Japan and Asia, 80 - 20. 80 for Eisai. In accordance with that, profit and loss sharing, expenses are also shared. Overall, the share is about 46-54. As of January 1 next year, as I explained earlier, Eisai will be receiving royalties on sales of Aduhelm, and there will no longer be expenses and profit sharing related to Aduhelm. Biogen will have sole decision-making on commercialization. In calendar year, as noted in the bottom part of the slide, in calendar year 2022, from January 1, 2022 to December 31, 2022, this period will be a transition period since this is an important change. In calendar 2021, economic arrangements will remain materially unchanged, but Eisai's share of expenses is capped at $335 million. There is a cap on Eisai's share of expenses in $335 million, as shown at the very bottom of this slide, asterisk five, this cost includes development, commercialization, and manufacturing costs related to Aduhelm. All of these are included. In manufacturing cost, manufacturing-related cost, if there is inventory of Aduhelm, and if impairment must be recognized, or if manufacturing volume is reduced, and if there is idling cost of the idle manufacturing facilities, those costs will also be handled within this capped amount of $335 million. As for the ratio of royalty, as noted at the very end, up to $250 million, 2%. Between $250 million - $500 million, 3.5%. Between $500 million-$1 billion, 6%. Greater than $1 billion, 8%. Those are the ratios of royalty. We have to develop the environment and prepare the environment for upcoming events, anticipated events. Prospectively, roles and responsibilities were determined. To summarize, Eisai will increase its focus on lecanemab to maximize the value of lecanemab. While Biogen will make swift, agile decision-making regarding Aduhelm and will maximize value of Aduhelm. Large scale manufacturing of antibodies will be required. For that, a very sophisticated advanced technologies and stable production are necessary, and this will be committed to over long term by Biogen and will be carried out by Biogen. These roles and responsibilities were defined. These are forward-looking changes. From Aduhelm, what are the learnings? There are many learnings. Here I would like to point out that Aduhelm was granted accelerated approval by the FDA. This fact, this achievement is quite significant. For Eisai, in 1996, Aricept was approved in the United States. Since then, Eisai has been the pioneer of pharmacological therapy development for dementia. Aduhelm accelerated approval added a new page to the history of development of these pharmacotherapy by Eisai without doubt. Through accelerated approval of Aduhelm, clinical research, regulatory aspects, ways of value proposition, data publication, reimbursement, and access. In these respects, we were able to acquire various experience and knowledge. From Aricept to Aduhelm, we have gained experience and knowledge. We will be focusing on lecanemab and draw on that experience and knowledge while we focus on lecanemab. Now, today's main topic is Eisai's corporate philosophy, management based on corporate philosophy, hhc. We put patient first, and we put importance on their happiness and sadness. The modern-day interpretation of that is that Eisai aims to realize social good efficiently. What is social good? There are various types of social good, but for Eisai, as noted at left bottom, relieving anxiety over health and reducing health disparities. We believe that these two are the social good for Eisai. Efficiency can be interpreted in many different ways, but here we would like to interpret efficiency as bringing to bear expertise while we pursue partnership and collaboration. We believe that is the key to achieving something that is big. Gathering expertise is pointed out here. We would like to realize social good efficiently, but we are not a government agency. We are not an NPO. We are not an NGO either. We are an enterprise, a corporation. We are entrusted with a precious capital by our shareholders. With that capital, we are deploying business, and we are to provide returns to shareholders. That is the mission as an enterprise. Therefore, the entrusted capital has to be high in productivity. That is the basic premise. When we discuss efficiency, we cannot overlook capital productivity. Efficiency and the gathering of expertise as we pursue efficiency. What are the expertise or strength of Eisai? Five are listed here. First, manufacturing or production. Our strength is organic synthesis for small molecules. In particular, based on natural product chemistry. In this area, many advisors say that Eisai is world-class. We also have accumulated clinical trial data. Of course, we have spent much cost and much effort to gather clinical trial data, and this is a precious asset. Globally, we have been granted approvals. This is also a difficult thing to accomplish, but we can count this as one of Eisai's strengths. Globally, there are scientific hubs, and we have our bases in these scientific hubs in the form of R&D bases. This is not easy. In each region, in a very balanced way, we are generating profit. There is a gathering of people who achieve that in a regionally balanced fashion. That also is our advantage. I would like to go over these quickly one by one. First, organic synthetic technology based on natural product chemistry. Mr. Naito, that's old, that's classic, you might say, but that is not at all the case. This is a cutting-edge technology that may be worth many Nobel Prizes. What is undruggable is turned druggable, and the basic technology for that is small molecule science. One such example is our HALAVEN. In the beginning, as shown in the photograph in the middle, there are black marine sponge in abundance off the coast of Miura Peninsula, and they were collected, and substance was extracted. The toxin of this marine sponge was known to have antitumor effect. Everyone was paying attention to that. After isolating that, total synthesis was successfully carried out by a group led by Professor Kishi of Harvard University. We have Eisai Research Institute of Boston in Andover and this research institute was in close collaboration with Professor Kishi's lab. Halichondrin toxin synthesized by Professor Kishi, and out of that, there is a discussion to develop a drug. In the middle, there is a huge structure shown of halichondrin, and on the right side, we found that there is an active center. From this, HALAVEN was synthesized. HALAVEN or eribulin mesylate was synthesized. Circled are chiral carbons. These are difficult to handle substances. These possibly look in two different directions. In HALAVEN, there are 19 such chiral carbons. This means that two to the 19th power, there is a possibility of having different stereoisomers of two to the 19th power. This has to be controlled and have to obtain the same stereoisomer constantly. This is the culmination of modern organic synthetic technology, and this has to be done on a commercial scale, on a mass production scale. That is done, and the world recognizes the strength of Eisai. In synthesis, total synthesis processes, there are 62 processes, and there are 10 very difficult reactions. It takes 1.5 years to manufacture, and this is a very precise method that is listed even in the Japanese Pharmacopeia. In MORAb-202, eribulin is the payload, and with BMS for gynecological cancer, we are pursuing development with the new modality of ADC. HALAVEN development led to this, and I will not cover in detail other developments, but on the right side, this looks at drug resistance. There can be a resistance developed for immuno-oncology through Wnt/β-catenin pathway. This is also an undruggable target, as shown at right bottom. With ordinary substance, it's not possible to engage Wnt/β-catenin pathway, but with our superb molecule, this is a middle molecule, but we have been able to develop a molecule that engages this pathway, creating a new modality. Next. Clinical trial data. AD-DMT and LENVIMA dataset are shown. In AD-DMT, from seven RCTs, approximately 10,000 subjects' clinical data are collected. We have specimens from all of the subjects. For LENVIMA, in regulatory studies, including mono and combo studies, approximately from 19,000 subjects, we have samples. In contemporary drug discovery, human biology, genomic analysis of human specimen in biomarker studies are the starting point for the next stage of drug discovery. That will not be an exaggeration to say so. These are the starting materials for that. For example, in Alzheimer's disease, A beta 42 to 40 ratio, to be measured by blood biomarker, is developed by Sysmex and others. Olympus's samples are used for validation. Without such samples, it is not possible to validate the accuracy of the blood biomarkers. Accumulation of clinical trial data and associated samples are a treasure trove. Only Eisai, only we, have such accumulation of data. As for global approvals, from 1996 Aricept, 1997 to the recent Aduhelm. This is the list of products that were globally approved. For a pharmaceutical company, being granted approval is a major milestone. What approvals were obtained, that is the track record of the company. In looking at that track record, potential partners feel that they would like to work with such a company. The global approvals are very important. Scientific hubs in the world. We have EMITS in Kawashima plant. Regarding the modalities with manufacturing facilities. Too, in cancers, H3B and G2D2 for genetics and also antibody research center for Exton. They are capable of making clinical materials. In Hatfield in the U.K., this is the facility for conducting research, sharing with academia. Research facility and manufacturing facilities are present here. There are physical meetings. In these hubs, people from academia and startups are forming a strong network together with them. Collaboration and incubation needs to be made, otherwise we would not be able to create medicine anywhere, and innovation cannot be derived from it. But customers just don't drop in to do something with us. We have such research laboratories for a long period of time, and we have been a member of the local communities. In G2D2 and the current research institute, there are incubation space, and other people can join there. Utilizing our facilities, they are doing their own research work there, so they know each other very well. This long-established relationship expertise can be brought forward from each other for conducting a joint research. Next, regional balance. Japan, Americas, Asia, including China and Europe. There are four major regions of our business. There may be discussions on which ratio could be ideal. In these regions, we are able to deploy business at certain levels in each region with earning power. This is one of the biggest advantages in which potential partners may be interested in utilizing these capabilities of Eisai. Particularly, we have talents in these regions. I believe this is very critical as one of the advantages of Eisai. Next, let me turn to social good, to relieve anxiety over health. Today, I would like to put focus particularly on dementia. Here is the demographics of dementia. On the left-hand side, surprisingly, every three seconds, someone in the world develops dementia. A little less than 80 million in 2030 are expected to develop dementia. In China or India or other high and upper-end middle income countries, the number of people living with dementia are expected to increase. Out of which, three-quarters of those people are not diagnosed yet, so they have not understood their risk of developing dementia yet. On the right-hand side, here is the global dementia prevalence rates by gender, and this shows that female has higher incidence of dementia than men. At the bottom, the number of people living with dementia in Japan, it's said to be about 7 million or so now, and it is expected to exceed 10 million in 2050. This is a very critical disease. Next, big issue is about costs related to this disease. As I said earlier, A and B at the top are both visible costs. Medical costs, JPY 1,070 billion, and public care cost is JPY 4,783 billion. These are visible costs. The issue here is invisible costs at the bottom. These are the costs borne by family members. Families of the patients with dementia are needed to take care of the patients. Therefore, if their informal care by family are calculated as costs, then it is estimated to be JPY 6,771 billion. Please call it C1. Turning to the right, C2, based on a different set of statistical data. Because of the family's informal care, they needed to reduce employment. For example, reducing the working hours from seven hours to two hours, and then loss of productivity because of that is calculated as such. We come up with this number, JPY 1.547 trillion. A+ B+ C1 and JPY 12.628 trillion. This huge amount of costs are incurred and spent for taking care of the dementia in Japan. A+ B+ C2 is JPY 7.403 trillion is spent. In this country, JPY 5.2 trillion is spent for defense-related expenses. Comparing to that, we see how huge these costs are. Giving impact on this issue. In order to reduce these costs, I believe that it is necessary for us to bring about social goods by reducing costs related to this disease. Next, this is to show the potential effect of number of people living with AD reduced and medical care costs based upon the literature in the United States. Here is the condition. If there is a treatment started for people living with AD by delaying onset by five years by a treatment. 22.5 million people are expected to be reduced in terms of the number of people with dementia in 2030, and approximately 5.7 million in 2050. Then in relation to that, total costs related to AD in the United States, JPY 9 trillion is expected to be reduced if the treatment is introduced in 2025, with the onset of AD by five years of delay, and then $367 billion in 2050. Very impactful numbers are shown, showing a very huge impact on the society in the United States. Now, AD is considered to be on a disease continuum. It is generally understood that AD needs to be understood by this continuum from normal state to pre-clinical AD without much subjective symptoms, but amyloid beta starts to be accumulated and MCI due to AD and AD stage. These are the four major stages in the continuum. The features for each stage are on the left-hand side. First, risk of onset and worsening, one of which is ApoE gene. The SNP polygenic risk score, which is based on the weighted sum of SNPs. These data have become available in order to understand these for individual patients or people. In order to understand how much risk they have themselves, it is very important to understand that. Towards the bottom, the imaging-based biomarkers, which are improving, and CSF biomarkers. At the very bottom, you see blood biomarkers. We believe that these can be game changers. Plasma amyloid beta 40 to 42 ratio. Sysmex has developed this HIS score, where it is becoming available and tau-related biomarkers can be measured soon in a simple manner. HDL cholesterol or LDL cholesterol levels can be simply measured in lifestyle-related diseases, which have contributed to the improvement in diagnostics and treatment. Hemoglobin A1C in diabetes mellitus, which is now measurable easily, and therefore it has contributed to the improvement of the diagnostics and treatment of diabetes. Same changes can be brought about by development of these blood-based biomarkers for AD. Blood biomarkers can be game changers. Next, Clarity AD core study for lecanemab, which is ongoing steadily. The number of subjects enrolled is 1,795, out of which 152 are Japanese subjects. In the U.S., African Americans account for 4.54% and Latinos account for 22.5%. Therefore, subjects enrolled are reflecting the population mix of the United States, which is important. Discontinuation rate has been lower than estimation, 13.9%. Compared to our expectation, as well as the other AD antibody drugs, discontinuation rate is quite low. The core study period has been completed. As you can see, now patients are transitioning into open-label extension, where all the subjects are receiving active drugs. Transition has been started, and 94.3% of patients who have completed the core study wish to proceed to this open label OLE study. I believe that this is one of the signs which suggests the steady progress in the clinical trial. At the bottom, additional subjects have been enrolled for submission in China in the number of 111 patients. Now, Chinese market is very important. When we started Aricept, AD market in China were not formed. Now in China, AD market in China has become a huge market. Lecanemab, once lecanemab is approved in China, we believe that it will bring us a very significant advantage in terms of sales. For example, LENVIMA of Eisai in China accounts for a little less than 20% of global revenue. Such sales is generated in China. Therefore, new markets opened by new drug is rapidly developing. That is the case as well for Alzheimer's disease. The real AD market can be increased by the effects of launching new drug. Next, regulatory status for lecanemab is explained here. As I said earlier, for FDA, we aim to complete rolling submission for accelerated approval, which will be completed soon. Therefore, accelerated approval is expected to be granted by the end of this year. We aim to submit toward a full approval during this fiscal year based on the results of Clarity AD. For full approval, we believe that the review will be conducted in prompt manner. As for PMDA, under the prior assessment consultation system, we agreed with PMDA that we will be able to utilize this system. We are expecting to shorten the review period by this system, and the submission of application data has been already initiated. We aim to submit toward approval in around the same timeframe for the Japanese regulatory authorities as well, EMA as well. Therefore, in the U.S., Japan, and Europe, we aim to submit at the same time and also potentially getting approval at the same time. What clinical trials are ongoing for lecanemab? Clarity AD and Clarity AD OLE. A phase II study, 201 OLE study is also ongoing. Please consider the disease continuum. Preclinical AD part is targeted by this study, AHEAD 3-45. Preclinical AD is targeted here. This trial is ongoing steadily. Another is DIAD, or Dominantly Inherited Alzheimer's Disease, is targeted in this study, Tau NexGen. E2814. This is our anti-tau antibody drug. Anti-amyloid beta treatment is to be provided. Before that treatment, lecanemab has been selected as the anti-tau antibody. DIAN-TU, Tau NexGen study is also ongoing. What AD treatment paradigm is going to be opened by lecanemab? As I said earlier, in early stages of disease continuum for each individual, Eisai is going to support the disease-related information. Walking, sleep, PHR, including meals, and ApoE4 status, polygenic scores, and these could be captured for each individual. We would like to support that. Simply and conveniently, digital tools are available to confirm the status of cognitive function. We would like to promote that. Like in the case of Sysmex, plasma biomarker tests will be introduced, which can be provided in easy manner. Diagnosis and the treatment will be promoted. Once diagnosed as AD or early AD, lecanemab treatment shall be initiated in order the potentially realized robust reduction of brain amyloid beta and the clinical efficacy. For lecanemab, a first dose is effective dose, therefore there is no need for titration. ARIA incidences are expected to be about 10%. Subcutaneous self-injection. By 2022, we have been trying to develop this administration. Subcutaneous injection once becomes available, and then they will be able to realize the home infusion, and remote medicine will be promoted. Once the amyloid beta and tau levels are reduced, and then regarding the treatment level, a regimen can be changed to optimize frequency and dosing, which is being developed. E2814, our anti-tau antibody and lecanemab can be combined. These tau treatments can be combined once combination therapy is realized. Then the pathophysiology of AD can be improved further with further robust disease-modifying effect. In clinical, pre-clinical AD, once phase III study is completed, then we will be able to broaden the coverage of disease continuum. To expand into the preventive treatment. Lecanemab, what we need to be mindful of is that we needed to keep transparency and trust. That is applicable to data publication. There will be pricing to be fixed, and there needs to be supporting data for pricing. That should be proposed to the public in order to seek the understanding of the general public. There are various underserved populations in the society for whom what about the processes for providing access to those people? We needed to explain that with high transparency, and we have to be accountable for regulatory status and advocacy activities and so forth with high level of transparency in order to gain trust. Without this, we will not be able to facilitate the introduction of AD treatment. Now, next generation treatment. We have been focusing on in-house projects, but today, based upon the topic of expertise, I would like to talk about collaboration between Keio University Hospital and Eisai. On the right-hand side, EKID, Eisai-Keio Innovation Lab for Dementia. The School of Medicine of Keio University is located in this Shinanomachi campus, where this EKID is located. Started in FY 2017 to 2020, there has been AMED support. From 2017 to 2026, there are three milestones. For milestone one, enhanced brain clearance. Milestone two is to get information regarding the improvement of brain homeostasis. Milestone three will provide information about activation of neural network. Eisai's strengths is, of course, centering around, extensive drug discovery experience, from Aricept. Biomarker research backed by state-of-the-art omics technology. Keio University has various strengths. In this area of dementia, centenarian cohort is held by them. 105, 110 years old people, they have samples of those centenarians. Based on the modern therapies, they have high quality cohort and bio samples from those cohorts. Professor Okano of physiology are well known in the world's advanced stem cell research technology using human iPS cells. This is very busy chart. Let me briefly explain. Start point is human sample, as shown at left bottom. Centenarian sample are people who are above the age of 100, 110. We have a sample of 141 super centenarian above the age of 110, and 6,500 above the age of 105, and 79,000 people who are above the age of 100. Even with ApoE, there are people who haven't developed Alzheimer's disease. Is it because of environmental factors or is it because of allele? We have these questions. In a very sophisticated way, we are able to obtain testing results. This is the state-of-the-art human samples which can serve as the start materials. On the right side, multi-omics studies. We have state-of-the-art mass spec machines. 10,000 proteins, hundreds of metabolites, thousands of lipids can be identified and quantitated. Biomes and lipid and metabolism or various diabetes disease information, et cetera, can be gathered. A very comprehensive omics analysis is possible. Combining clinical data and omics data, and by applying artificial intelligence, as shown in the schematic diagram, virtually using something similar to digital twin, we may be able to analyze a brain. By changing variables, new hypothesis may be built and new drug discovery targets, candidates may be created. On the left, a verification. Professor Okano was the, his lab was first to develop a human iPS cell derived system, which is similar to bio system, which is a brain organoid. In ApoE4, in Aβ accumulation, something similar to actual human brain is replicated, and these models can be utilized. As for drug targets, potential drug targets, microbiomes, lipids, cytokines come from come through artery to brains. When drainage does not work, there will be degeneration. What are the genes and what are the molecules that activate the drainage system? These are more or less elucidated based on these research before drug discovery is initiated. Secondly, we are focused on astrocyte. Astrocytes are important, nerve cells regulating microenvironments and maintaining functions of nerve cells in brains. ApoE4 protein is produced in astrocytes. By focusing on astrocytes, we may be able to obtain hints for drug discovery that leads to improvement of brain homeostasis. The third is activation of neural networks. From neural stem cell, there is differentiation. A normal network of nerves that will be developed. But with neurodegeneration, this is damaged, and this can be regenerated or reactivated. That is the ultimate objective. EKID research is underway towards that end. The focus is on maintaining and enhancing the brain's robustness and protective mechanisms, innate mechanism against genetic backgrounds, aging, and environmental changes. Eisai has been the top runner in AD, and the starting point is that we take pride in the fact that we understand the anxieties of people living with dementia. Globally, over 20 years, annually, our people have spent time together with people living with AD through more than 300 hhc projects, doing something together or having meal together. Through these, we are able to understand the anxieties of people living with dementia. These anxieties are: When will the symptoms appear? Is there any way to prevent the onset? And is there any way to prevent causing trouble to the family members? We have a strong belief that we have to address and relieve these anxieties, and that strong belief is held by all of our 10,000 employees. We are opening new chapters continuously in treatment, starting from Aricept in 1996. In 2014, DLB approval was given for Aricept after LOE. This was after LOE, and Aduhelm approval was granted. We hope that approval may be granted for lecanemab this year. New page of treatment has always been opened by Eisai, and therefore we take pride in that we are the top runner in AD. Next, future wealth is potentially brought from businesses for people, including prevention. Our people's business is hhc eco. We are bringing together expertise through collaboration in this ecosystem. The collaborative partners are shown on the outside frame of this diagram. From different industries, for example, from telecommunications industry, FCNT has introduced an easy-to-use smartphone, which has NouKNOW pre-installed as an app. We would like to have various content that we developed installed on their smartphone. Through collaboration with telecommunications provider, using a delivery method of easy-to-use smartphone, we are able to deliver solutions to the people. That is the approach. Similar approach is possible with food industry, with ITO EN through the sales of tea products. With insurance industry, there is a dementia insurance product. In designing dementia insurance product, those people who buy the insurance, what the probability of onset of dementia is a very important information. Capturing such information, if a insurance product can be designed, then it will enhance the service level of insurance industry substantially, and it will assist in correctly designing the insurance product. We are collaborating with insurance industry players. In automotive industry, a drive recorder included MCI risk projection alerting. These are the areas we are collaborating. Collaboration with other industries is business for the people in hhc eco, where expertise can be brought together. In the middle, we have Eisai Universal Platform, and the basis of this is R&D. What is important is data and R&D. As we have seen in the example of EKID, this is a repeat of deep learning processes. Collaboration, incubation of academia, startup, and industry are actively pursued, and we have clinical trial data, medical data, and cohort data. Data from daily life, including diet, sleep, and walking. PHR data is obtained. Based on that data, various content can be created by Eisai. That can be offered, delivered to people in different segmentations. People who are interested in maintaining health, preventative package can be delivered. For example, prediction of onset of dementia or ApoE measurement or PREPAsize. This is a brain performance maintenance exercise or consultation, a navigation system for dementia worries. These package can be delivered in various ways. One such way is easy-to-use smartphone. Raku-Raku Smartphone. We would like to deliver such package in collaboration with other industries. This is a business for people with a focus on preventative aspects. One example of content is shown here. This is personalized algorithm for prognosis called AD Continuum Curve. This is a content for our service. What this is is that as you can see in the chart in the middle, there are three lines. This is personalized. Red line is in case lecanemab treatment is given, change of cognitive function over time for that person A. Blue line is if this person does not receive lecanemab treatment, what the change in cognitive function over time may be. Green line, this is irrespective of lecanemab. This is average transition in cognitive function in people with dementia. All of these require data, lecanemab treatment effect and without using lecanemab. This is actual drug data and placebo data. Green line requires cohort data. For example, ADNI data, U.S. ADNI, J-ADNI data can be powerful data. Based on such data, we are developing this. More precise, sophisticated data is what we are trying to collect. How effective can this be or in what way can this be effective? Well, people might be wondering about receiving lecanemab treatment. Is it going to be truly effective for that person? If there is a worry on decisiveness, then the physician can show the data. This is the predicted prognosis, and this kind of therapeutic effect is expected. Such information can be shown to a patient, or patients may be wondering if they should continue with lecanemab. By continuing with the treatment effect, treatment effect can be greater rather than stopping in comparison to when they stop. Such information can be shown to motivate patients. This is an advantageous information, and only we are able to provide such information from the great efforts that we have spent in developing and gathering such information. We are now engaged in GREEK cohort project, Greek national project. 3,500 people are targeted in this project, targeting AD patients as well as healthy adults over the age of 50 to classify subjects based on AD and biomarkers. We are participating in this project. With this, we will be able to have more precise curve based on cohort data for prognosis, or we may be able to obtain better AD and biomarkers. We are hoping to obtain such advantageous results, and we are making efforts in cohort data area as well. Now, we believe that future wealth is potentially brought from the East. What is East? Well, there are many interpretations. Here, China, India, Africa, the great economic region is what I have in mind with the word East. China, India, and looking at Africa, there are EAC, SADC, and ECOWAS, the economic communities. There are these economic communities in Africa. EAC is East African Community centering around Kenya, and SADC is Southern African Development Community. These communities are already in place in Africa. We would like to bring wealth from these regions. In China, a 100%-held Eisai subsidiary was established. In 25 years we were able to grow business to a JPY 100 billion business. We are bringing wealth from China. JPY 100 billion is as a result of achievement from many new drugs. Lecanemab, I'm sure, will immediately be making commercial contribution in China. There's a matter of being included in national reimbursement list. If it is on the list, it can have an effect, and we believe that we can expect contribution to revenue immediately. Investments towards potential wealth from the East are shown here. The current Suzhou plant photograph is shown. This has the largest capacity in Eisai plant, and there are 2,000 employees in China with more than JPY 100 billion of revenue. The middle photograph is Vizag plant. This is a huge plant with the capability of synthesis. DEC Tablets are 100% produced here for tropical disease, and various other products are produced. We have 630 employees in India, and the revenue is somewhat smaller at JPY 1.9 billion. This year, we plan to initiate efforts in Africa. In South Africa, in Johannesburg, a subsidiary is established, and in Nairobi, a branch is to be established. These are the plans. Now, in China. We believe that a digital and telecommunication giant is in China called Jingdong Group, and which has Jingdong Health. Together with them, we have formed a joint venture bringing about each other's expertise. In Fantan, centering on the internet hospital to provide a one-stop online health platform. This has been already opened. What about internet hospital? Please look at the chart below. The picture on the left hand is conducted offline. You need to receive initial medical examination first offline, but after that, everything can be done online. Second medical examination onward, and there are 1,000 specialty physicians registered now. Patients are free to choose own doctor, and if necessary, the examination can be done at the nearby facility, and the result can be communicated online. Once prescription is issued, the drugs will be of course delivered by logistics system. We aim to contribute to relieving anxiety of people living with dementia and reducing health disabilities by delivering high-quality drugs and medical services throughout China, regardless of time and location. In India as well, we are collaborating with e-pharmacy company for areas of AD and sleep disorder. Africa, we needed to establish Dementia Center of Excellence centering on South Africa, and Eisai India will be utilized as the base for growth in Africa. In Kenya, to contribute to global health and achieve SDGs, to resolve the issue of tropical diseases and utilizing the remote system like in India and China, in order to develop the business in African market. We have joined a technology with Allm Inc. In remote telemedicine, very services are available. The definitive diagnosis in remote diagnosis and decision and measurement, these can be brought about in these wide areas of markets. Toward potential health from the East, we aim to realize remote medicine in China, India and Africa that does not depend on medical infrastructure. We would like to relieve anxiety of the people over health in societies with underdeveloped medical infrastructures. I am approaching the end of my presentation. Please bear with me. I would like to talk about the tropical diseases regarding the reduction of health disparities. Eisai has been one of the most aggressive companies in dealing with the NTD issue. In 2012, there was a London Declaration where I participated. There were 13 pharmaceutical companies, but I was the only one from Japan at the time. WHO, the U.K., the U.S. and Gates Foundation and Bill Gates was well represented. By 2022, the NTD needed to be eliminated and the global health was largest public partnership. A lot of treatment have been provided and most of the NTDs have been eliminated. However, not completely yet. Far away from completion. In filariasis, Eisai, we have provided over 2 billion DEC Tablets at price zero business. From this year onward, this will be changed into a new PPP called the Kigali Declaration. This is to enhance an ownership in NTD endemic countries. There are new tropical diseases where we would like to utilize our expertise. We have such a rich pipeline for tropical disease treatment. I believe we are one of the pharmaceuticals with richest pipeline. We do not have any single project that we have developed on our own. The University of Kentucky, Liverpool School of Tropical Medicine, or Broad Institute in Boston, affiliated with Harvard and MIT. These have cutting-edge technologies, and we have been working with them. We received their derived project, and we collaborated with them. In the middle at the bottom, GHIT Fund. Japan established this fund in 2013. Japanese government, private companies, including pharmaceuticals, Gates Foundation and other drug-related industries participated later. JPY 26.7 billion has been provided as funding, and most of the projects have been funded from this fund. On the right-hand side, a Geneva-based NPO called the DNDi. Many of the physicians are from Doctors Without Borders, and they provided a network on the ground, and they are collaborating with us as well. Therefore, this is the typical example of the efficient collaboration network in modern days. Lastly, I would like to talk about the capital productivity in terms of efficiency. ROAC and ROA and ROIC and ROE, return on assets, return on invested capital, and return on equity. We believe that it is very important to keep the right balance between these. We always have tried to realize the stable dividends and improvement of profitability and shortening cash conversion cycle, or CCC, and a divestiture of assets. We would like to continue to improve the efficiency of the capital. In the middle, of course, in the medium to longer term, we would like to aim at expanding PBR to enhance the capital productivity. To pursue efficiency, we believe that it is important and indispensable measure. Lastly, to cap, I have focused on the dementia today. The future wealth is potentially brought from business for the people, including prevention, and future wealth is potentially brought from Eisai to reduce health disparities, tropical diseases mainly in Africa. Capital productivity is also a very important metrics. We would like to improve and realize this with good efficiency. I would like to seek your continued support and understanding. Thank you very much for your kind attention. Next, we would like to begin Q&A session. Today, we will be entertaining questions from those who are participating over the phone. Please press asterisk and one if you would like to pose question. Please press star and one if you would like to ask question. You will be queued to ask question. First, we have Yamaguchi-san from Citigroup. Mr. Yamaguchi from Citigroup, can you hear me? Yes. Please go ahead. Thank you for taking my question. I have two questions. This year, focusing on lecanemab, there will be many anticipated events. I agree. April 11, final decision on NCD is still not known. As of now, NCD on Aduhelm, if we presuppose that it will not change much, then when lecanemab becomes available with accelerated approval, situation will not change. When data becomes available in September, then NCD circumstances might change as a result of the data. Seen from outside, it seems NCD is very stringent, and in what way you can break through is difficult to understand. These are based on assumptions and hypothesis, but could you share your views on this? Thank you for your question. The benefit of accelerated approval is that ahead of others in the world, approval was granted. For a pharmaceutical company, this is something that we can be proud about. First, we are the top runner in the AD field. If there is a possibility of becoming the first to receive approval, then naturally we will pursue that as a business behavior. As for the accelerated approval, there is also effective advantage. That is, the review will be moving ahead. Clarity AD results are required for clinical module, but for pre-clinical module and CMC package, accelerated approval review will be carried out. Review is done during a accelerated approval phase ahead of full approval. Only the remaining part for full approval review is Clarity AD data. Up to the full approval, review period, we expect, will be substantially shortened. That is the added advantage we are expecting. In accelerated approval, during that time, what is the size of the commercial opportunity? There is also a question mark on this point. In the meantime, there is much that we need to do. For example, it so happens that accelerated approval and Clarity AD data becoming available if they fall in the same time frame, then major medical institutions will be considering adoption of the drug. At time of the accelerated approval, we are able to engage in activities. We cannot expect the right size of actual sales yet. Products given accelerated approval and without accelerated approval, there is much difference in terms of what we can do before we obtain full approval. Thank you. There is a follow-up question. NCD decision on the basis of Aduhelm is expected to be difficult. Even if for full approval, if data is good, I think our data will be used. NCD decision. If lecanemab data is good, do you think that there will be a different NCD decision? Thank you for that question. Well, actually, in what way final decision will be given in relation to NCD, this is very difficult to foresee. Approved drug, there is only Aduhelm. Other antibodies are not yet approved. What will happen to that classification? There is a lack of visibility here. When NCD final decision is given, then to overturn that, full approval data may be necessary. That is what we are assuming, but this is not certain. However, in case of lecanemab, the time between accelerated approval to full approval can be very short. We are hoping. In terms of insurance reimbursement, we currently do not foresee any major hindrance for lecanemab in terms of insurance reimbursement. Thank you. Very briefly, Alzheimer's-related drugs. There are antibodies and other therapies that are developed. Aricept was an oral drug, which was advantageous. You discussed organic synthesis of small molecules. BACE inhibitor you did not mention. Eventually, I believe you want to develop oral formulations. Including ASO, small molecule potential is fully pursued. In exploratory stage, we have multiple potential candidates. There are candidate compounds. We are not completely giving up small molecule potential. With the BACE inhibitor, there was one failure, but that experience can be leveraged. Eisai possesses that. Clinical samples are held in large quantity, and that can be turned into an advantage after that challenging experience. Thank you. Next question is from Nomura Securities. Mr. Kohtani of Nomura Securities. Thank you. This is Mr. Kohtani of Nomura Securities. Do you hear me? Yes. I think this is the same question I must repeat regarding the lessons that you have learned from aducanumab. The FDA approved aducanumab, saying that seems to be effect. However, it is not available for use now. Compared to your expectation, there was a higher hurdle from the general public. At the financial results briefing session, I think this question was asked, and this is a question I would like to ask you, Mr. Haruo Naito. What is the lessons that you learned from aducanumab, and how are you going to utilize that lessons for lecanemab? Could you please give us your CEO's opinion on that? Utilizing several slides today in my presentation. First, data is important. We needed to keep transparency in data. Publishing in peer-reviewed journals, whether or not such data are published in such peer-reviewed journal is a very important point. I believe that is a very important lesson that we have learned. At the outset, I said we needed to create a facilitating environment. Regarding the data to be captured, we needed to publish that data promptly in peer-reviewed journals. That will lead to the further adoption by major medical institutions, and such fact of a publication may become a key. In terms of a pricing proposition. These could be important data sets. Lessons learned. The major lessons learned is to keep transparency in data, and we needed to proceed with the publication of such data. Honestly speaking, I agree with you. Aducanumab is still. Well, part of the data related to ARIA-E has been published, but the peer review journal has not published the data for aducanumab. These are to be published by physicians. How much acceleration you are able to make is unknown. Principal investigators, once that data becomes available, we needed to ask the principal investigators to publish and prepare a paper immediately. Have you asked such cooperation from PIs? I believe that the data to be published in the well-known and prestigious journals, and that will be the quickest way for improving this situation. Have you prepared for that? Yes, we have. I am not able to give you information today, but at which time point are we going to publish the data? We have come up with a schedule as well. As you, Kohtani-san pointed out, at such timing, accomplishing the publication securely is already targeted in our timeline. That's what I can say. Thank you. This is my last question. On page 23, there is the list of the lecanemab clinical trial, Clarity AD and OLE. I think everyone knows this, but AHEAD 3-45, DIAN-TU, Tau NexGen. Is this the trial that you're collaborating with physicians? If your therapy or antibody has been selected to be included in the regimen, but this is not a trial that you are running on your own, so how is it going to be competitive? That's what I'd like to gantenerumab and donanemab are catching up now. In my understanding, still, not only treatment, AHEAD 3- 4 5 covering the prevention area is not conducted by competitors. What is going to be the differentiating advantage for you once a trial for lecanemab succeeds? As you said, AHEAD 3- 4 5 is conducted at an academic consortium, ACTC, which had selected lecanemab to be included in the regimen without need of titration. ARIA-E incidence is also low. ACTC, in the trial covering preclinical space, they didn't want to have a possibility of causing side effects. This was one of the top priorities in evaluation by ACTC. That has been cleared by our drug. This is the regulatory study. This is the pivotal study for a regulatory submission, and this trial is ongoing on track with accumulation of patients enrolled. DIAN-TU is, as you know, led by the cohort, is a cohort study led by Washington University. Just because there is a drug, it does not mean that the drug will be selected for sure to be included in this trial. They are selective, and we were selective. Anti-tau antibodies, we were selected. For amyloid beta antibodies, lecanemab has been selected. In Tau NexGen protocol is of course anti-tau antibodies are the main targets to be evaluated. With one single group, anti-amyloid beta antibodies are to be administered in advance. Professional academic researchers have agreed to select lecanemab. That means that among various antibodies, excellent profile has been shown to be held by this drug. Gantenerumab and donanemab, these other antibodies, do you think that, these can pose as the differentiating factors against them? Yes. As you may know, because of the binding portion is different from other antibodies, therefore making difference in the incidence of ARIA-E and the period for titration can be very long. Therefore, I believe that these are very strong, differentiating factors against others. Thank you very much. Understood. Next, Akama-san from Nikkei newspaper, please. Akama-san from Nikkei, please. Thank you. This is Akama from Nikkei. Can you hear me? Yes. Please go ahead. Thank you for taking my question. I have one question. This is, an old question. In June 2021, FDA approval was granted. At the time, it wasn't foreseeable that Aduhelm would be in this kind of situation. Is that the correct understanding? For Eisai, is that Aduhelm will be in such a situation today. Back in June 2021, was it something that was difficult for Eisai to foresee? That is the first question. Thank you for your question. When accelerated approval was given, the advisory committee had a major debate. The majority, it seems that the majority had opposition views. I was closely following the discussion, but these were discussions held remotely. It seems that it was difficult to conduct the discussions. That is my impression. No matter what the voting is at the advisory committee, in principle, irrespective of the voting results at advisory committee, in principle, FDA should be able to give its own decision. Accelerated approval, given the majority opposition in advisory committee, even despite that approval, accelerated approval was given, and I did not anticipate obstacles. FDA taking its independent decision, I respected that. Advisory committee debate has lingering effects, and various opinions were issued, and there were countering opinions. In the Ministry of Health or Department of Health, survey or study was to be conducted, and a huge debate began. As for MCD by CMS, at least as far as the drug approved by FDA is concerned, the restriction that the drug will not be made available unless a patient is enrolled in RCT, such a strong limitation to be given. Unfortunately, that was beyond our expectations. At the time, I thought that as the first approved drug ever, Aduhelm, will be supported by many patients and many HCPs and will be introduced into the market. That was the expectation back in June 2021. You may blame that on my incompetence. However, such a controversial development, unfortunately, was beyond our expectation, to be honest. Thank you very much for that, very detailed explanation. I have a second question, if I may. Looking at competitors, I think, they are following closely. Eli Lilly, of course, is starting with, BLA submission, and, Roche is also conducting clinical trials. This may be also somewhat repetitive, but how can you differentiate lecanemab? How will Eisai utilize disadvantages of other, drugs? I don't think, there are disadvantages. The target is protofibril soluble substance. Because of that target, insoluble plaque is not targeted, and that leads to lower incidence of ARIA-E. However, A-beta reduction effect is faster and more potent in comparison to other drugs. In the end, these two other drugs also reach A-beta negative, but the speed of reaching A-beta negative. Well, this is not a head-to-head comparison, so there is no way of telling. According to literature, we can say that lecanemab is the fastest. The biggest advantage is lower incidence of ARIA-E and no need of titration. The first dose is the effective dose. Onset of the effect is early, and that is by far a major advantage. Subcutaneous injection formulation is being developed. By around 2024, with subcutaneous injection formulation, it may be possible to inject lecanemab at home or at work. Looking at the data of progression, when it is in the maintenance stage for a patient, let's say after A-beta turns negative. In the maintenance period, on a bi-monthly, should 10 milligram be given or dosing can be less frequent or dosing, dose can be reduced. Such regimen is also being studied. Optimal dosing scheduling, we hope, we will be able to show that eventually. With the other competitors, we believe we are a step or two steps ahead. Looking at this antibody, lecanemab, in comparison to other antibodies, absolutely there are no disadvantages. Thank you very much. Next is from JP Morgan Securities. Mr. Wakao. Mr. Wakao of JP Morgan Securities, if you are ready, please. This is Wakao of JP Morgan Securities speaking. My first question is about Biogen's commitment to lecanemab. Could you please tell me n ow, the agreement for lecanemab has been changed, but both companies continue to try to maximize the value of lecanemab. Once lecanemab is approved and launched, Biogen, including the sales and marketing, will continue to maximize their efforts. I'm not sure whether this is appropriate to say, but are they continuing to make efforts to maximize the value of lecanemab based upon the agreement? Royalty rates and sharing of the profits will be larger for Biogen. Aducanumab is in such a state now, so it's very difficult. Lecanemab will be more focus area rather than aducanumab. Regarding the commitment of Biogen to lecanemab after launch, are they also making commitments to sales and marketing of lecanemab? The performance with lecanemab as drug is very understood, very well understood by Biogen. Also the fact that this is a very advantageous candidate drug, that is also understood by Biogen. Maximization of the value of lecanemab shall be done, and then as a result, 50% of profits will be brought about from that. Jointly, lecanemab, the more maximization of the value is achieved, and then what will be shared between the two companies will be maximized and increased further. The CEO and other staffers below, the CEO all understand this very well. Therefore, I don't think that they will reduce the efforts for maximization of the value of lecanemab. Understood. Thank you very much. Second question is re-in... Well, you talked about the commitment and also we have a high expectation to the lecanemab, but based upon the track record of lecanemab so far. Because of the past situation, I would like to ask this. Amyloid beta approval, and there is a necessity for presenting the clinical effect efficacy. The CEO also explained very well the efficacy side in clinical setting. In terms of that, lecanemab, regarding the data which will become available by the end of September and the suppression of the progress of the disease, what will be the level of values that you will need to obtain in order to penetrate the understanding of this CDR-SB? CDR-SB. What will be the level of CDR-SB? I believe that there is not a consensus formed regarding the level of CDR-SB to be achieved. What is the opinion of Eisai based upon the lecanemab data? -0.5 or so was the data. Do you think that statistical significance is obtained and then it will be a success and can be commercially successful? Or with the statistical significance and then published in the peer-reviewed journal, do you think that there is not much big issue regarding the data? In the designing of the Clarity AD, we agreed with FDA. In study 201, CDRSB data was the basis for that discussion. The statistical significance needs to be demonstrated with a power which has been incorporated in the design agreed between Eisai and FDA. Therefore, if we are able to proceed with the trial according to the protocol, that result will be obtained. What is the target in the data? Even if FDA grants an approval, but in NCD there is a term, clinical usefulness. Even with a statistical significance, how much expansion can you expect in the access to the drug is not foreseen. The target set by Eisai in recent discussions, do you think that if the target is achieved and then access shall be also expanded accordingly? Do you think in that way? Yes, of course. That is correct. Understood very well. Thank you very much. I'm looking forward to it very much. Next, Morgan Stanley MUFG Securities, Muraoka-san, please. Can you hear me? Hello. This is Muraoka from Morgan Stanley. Can you hear me? Yes. Please go ahead. Thank you for taking my question. I have a question. Aducanumab. At this time, you have changed the royalty scheme. That I understand. This may sound opportunistic, but aducanumab phase IV is underway, and if there is undisputed results from aducanumab studies in the future, then in the future, is there room for negotiation to increase the take for Eisai under this revised collaboration agreement? The answer is no. The royalty scheme is fixed for the future? That is correct. I see. Thank you. One more question. This is a hypothetical question, and I know that this is a rude question, but Clarity AD results expected in September, if it does not show statistical significance, if that is the result, then what is your plan B at Eisai to the extent that you're able to share with us, please? As I have been saying, large-scale phase II study or phase I study was conducted as placebo-controlled comparative study. Based on that data, phase III study is designed and to show sufficient statistical significance, a number of patients are enrolled. I believe that I'm confident that, or I firmly believe that we will be able to show results. Beyond that, this is not a shareholders' meeting, but beyond that, I'm not able to answer a hypothetical question. That is not something that I anticipate. Thank you very much. Thank you. That is all. Next question is from Daiwa Securities, Mr. Hashiguchi. Mr. Hashiguchi of Daiwa Securities. Yes, this is Hashiguchi speaking. Thank you very much. My question is related to page 32. You introduced the algorithm to predict the effect of the therapy. Regarding this algorithm to be provided, and what kind of regulatory rules are needed to be met, including the differences among regions, could you please tell us pathway to realize this algorithm? And at which timing do you think this algorithm will be realized? And also the progress made to date and also regulations related to that. Could you please elaborate on these? Of course, when data is to be utilized, then we need to obtain the informed consent. That is the precondition. This is for lecanemab. For lecanemab, there needs to be a regulatory approval. After going through such milestones for getting regulatory approval, without doing so, we won't be able to utilize data for this kind of service. Your concern, Mr. Hashiguchi, about the regulations and how to handle the data, we will make sure that we will not do this wrongly, and we will put focus on the compliance with regulations. As Mr. Naito mentioned, informed consent. With whom, from whom do you need to obtain informed consent? Data on hand or data from U.S. ADNI shall be utilized. Even for that purpose, the consent has been already taken from those patients in the past. Do you think that you need to obtain consent again? Or do you mean that informed consent needs to be obtained from those from whom data will be newly obtained? Mr. Hashiguchi, I would like to call upon specialist in this area to answer your question. Regarding this question, in charge of clinic, Japanese clinical side, Mr. Ogawa is going to respond. Do you hear me? I am in charge of clinical development in Asia and Japan. My name is Ogawa. Thank you for your question. Regarding the development of the algorithm, as you pointed out, various different regions have different regulations. Informed consent was mentioned by Mr. Naito. The data that is being obtained so far will be utilized. Within what is specified in the informed consent, we are going to utilize the data. That is what we meant to say. Mr. Naito said that is important to obtain informed consent, U.S. ADNI or J-ADNI or clinical trials for lecanemab. Such consent to use the data for algorithm development has been already obtained. Mr. Hashiguchi, I think you are asking questions which are too technical. I am trying to explain the overall direction of the business. Could you please ask such technical question on a different occasion? Yes, understood. Thank you. The next person with a question is the last person in the queue for question, but we still have some time for questions. If you would like to ask question, please, raise your hand. Right now we have Sakai-san from Credit Suisse. Mr. Sakai from Credit Suisse, please. Thank you for taking my question. Mr. Naito, what is your view? Or that is not a good way to start my question. Even before approval of Aduhelm, and I think, this is not, limited to Alzheimer's, but value-based medicine has been always the focus for Mr. Naito. You always also kept in mind, patient access as the priority. The philosophy, was it, put to good use in the lessons of Aduhelm? The price is $56,000, as I understand, and I do understand that this is something that is not controllable by Eisai. Half is held by Biogen. What is value based? Among our HCPs, there is confusion, and there is also a negative reaction from HCPs, I think. Based on that, if lecanemab has a very clean data, then it will not be a problem. Price setting, especially in the United States, since it will be a trailblazer, it will be important. In Japan and in Europe, the public health drug price setting is also important. About lecanemab price setting, the lessons from Aduhelm, do you think that you will be able to apply the lessons from Aduhelm? Mr. Sakai, what you pointed out is quite correct, I think. For example, in rheumatoid or in cancer, there are antibodies and there is a certain price. At certain price, these products are accepted in the society, but such argument is not understood. Alzheimer's disease is a disease that can happen to anyone. Many people have people who are close to them who are living with Alzheimer's disease. The devastating effect of AD is well understood. Therefore, it has to be treated with a medicine. The price range, what is the appropriate price range? This is very sensitive. Beyond comparison with the drugs for other diseases. Now, there are several models and based on models and from clinical trial data, how much a delay in onset was achieved, including such parameters, the value of the drug is calculated, as far as calculation applying formula is concerned. The price should be below what is suggested from such calculation formula because Alzheimer's disease is such an urgent pressing matter which can happen to anyone. Unless otherwise, I don't think it will be socially acceptable. That is my thinking. I hope this answers your question. I believe in a way this is related to ESG. This can be a very important factor in ESG. You also have to achieve at the same time return for shareholders. This is difficult to achieve both at the same time. I think Biogen is under enormous pressure from shareholders, much more so than Eisai, if I may say so. The change in collaboration agreement may have been triggered by that, I suspect. In that sense, you have a successful track record of having developed Aricept. You have an outstanding track record. The stakeholders, including shareholders, they have high hopes on our company for 30 years. My question is, this is related to page 40 on capital efficiency. I don't know if I should pose this question to Mr. Naito, but PBR is around 3.5 times. This is much higher than one time, but it's moving in a very choppy way. Alzheimer's disease and oncology, these are risky areas. Mr. Naito has taken on the challenge of these risky areas. In this information meeting, I think what you have indicated is that you will continue to take on the challenge of developing in these difficult therapeutic areas. Sakai-san, as you rightly mentioned, expectations from shareholders include tangible and intangible expectations. For example, tangible way in revenue, in terms of revenue. In the end, sales equals price multiplied by a certain number. Even if the price is high, the number multiplied by is if it's low, the sales will not be large. We have to look up price sensitivity, and we have to establish appropriate price and maximize the multiple N. That is the basic principle. Lower price does not necessarily mean that the tangible revenue. It doesn't mean that we are not meeting the expectations of shareholders by providing a tangible form of revenue. Rather, I believe that maximization of revenue at the appropriate price level is the way to satisfy shareholders' expectations. Regarding the latter part of the question, I think that is the nature of the pharmaceutical industry. Because of the high risk, sometimes it yields higher returns. Sometimes it's all or nothing. That is sometimes described as volatility, and sometimes you criticize us for that volatile performance. I think this is a link to the nature of the business we are in the pharmaceutical industry. Of course, the management has to make efforts and show their capabilities to level the performance and reduce volatility. People who come to pharmaceutical companies must take on the challenge of unmet medical needs. Otherwise, we don't have raison d'être. Please support us in that respect. Please understand the nature of the pharmaceutical industry, and I hope as an investor, Mr. Sakai, you will support Eisai. Mr. Hashiguchi, I hope that you will support Eisai, understanding the nature of the pharmaceutical industry. Mr. Naito, thank you for that answer. It's been a while since I was able to hear such an enthusiastic comment. Thank you. Maybe I have spoken too much. No, no. Thank you. Thank you very much. It's the limited time available, so we'd like to ask Mr. Shimoyama of Sophia University to be the last person to ask. This is Shimoyama speaking. Do you hear me? Yes. first time in the past one year to talk with you. In 2020, since November 2020, when advisory committee was held, I have been watching Eisai through financial results briefing. Aduhelm has been discussed much, and I was impressed during this period of time. I think you have just touched upon oncology area of Eisai. The track record of performance grows in oncology, which impressed me a lot after Aricept. It was very difficult to launch other Alzheimer's disease treatment. You talked about HALAVEN and LENVIMA. These are the two drugs that have been approved. Now, there has been a lot of discussions about Aduhelm. Still, we have seen the growth in revenue of Eisai, and that has been mainly driven by LENVIMA. I am now covering the business in oncology. You said that the pharmaceutical companies need to take on the unmet medical needs. I have two questions. In Eisai, I think in 1987, you started research on oncology at Eisai. When Mr. Naito was at Tsukuba Research Laboratories, research on oncology was started at Eisai. What was the trigger for you to consider starting research in this area? What was the belief of Mr. Naito when starting the research? Thank you very much, Mr. Shimoyama. I think there was a group which was specializing in the immunology, which was not making any drugs, and they were just spending a lot of money. There were a small group of five or six people. They did not leave the company, even they were like Hachiro Sugimoto. Because of their persistence, which stimulated me on the extension of immunology, there was a potential business of oncology. Maybe I was convinced by them. I think that was how we started the research in oncology. After that. Well, sorry, taking time in important information meeting. Dr. Takashi Owa. Very edgy people are available in oncology research. They are very stubborn, and they stick to their own belief, and they continue on research to pursue and explore excellent compounds. Thank you very much. My second question. You said that on the extension of immunology, I think it was interesting. Within yourself, Mr. Naito, I think after approval was granted, when did you started to think that LENVIMA was going to be prominent? The first approval was granted for thyroid cancer. The population of patients with thyroid cancer is very limited to about 1,000 in Japan. When did you think that this is going to be promising with expanding populations who will be indicated for this treatment? This is because of the Merck deal. Deal with Merck. When we were approached for deal, I thought that this drug could be very prominent and promising. Understood. Immune checkpoint inhibitors and combination with such inhibitors may be promising. That's what you thought at that time as well? Well, Merck is a company which is drawing respect in the global pharmaceutical industry. If Merck recognized value in this drug, we thought that we are sure, we can be sure that there is such a promising value in that. Thank you very much. Understood. I'm sorry, now the time is ended for information meeting. With this, we'd like to conclude the meeting today. Thank you very much for taking time out of your busy schedule to participate in this meeting.