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

Thank you very much for taking your time out of your busy schedule to attend the press conference by Eisai Company Limited. We would like to begin information meeting for fiscal 2024. We are holding this meeting in hybrid format, both in person here as well as online. Presentation materials are distributed to those of you here in person, materials are also available on the website. I would now like to introduce the speaker today, Mr. Haruo Naito, Representative Corporate Officer and CEO. Mr. Naito, the floor is yours.

Now I'm showing you the drawings of the zodiac sign for this year. This is my hobby of drawing the cartoon like this. Actually, similar drawing was presented 24 years ago. At the time, Aricept was approved in Japan and was about to be launched. At that time, Eisai was passing through this the gateway to success. That was the feeling I had when I drew this drawing at the time. Again, in 2024, with LEQEMBI, we would like to go through this gateway to success. So that is the feeling that I had for this drawing. And here, you have the subtitle. We are determined to change the future of AD. First, let me talk about our articles of incorporation. The articles of incorporation, it's something like constitution for companies. This comes at the top of the hierarchy of documents. And this requires the special resolution by shareholders. That means that more than 2/3 of the shareholders are attending the General Meeting of Shareholders are necessary for determining articles of incorporation. This signifies the importance of this and in these articles, we have included the corporate concept. We started since 2005 to present these articles of incorporation as such, I believe that we have incorporated the concept, which is one of the leading concept among the companies in Japan. First, social goods, which can be translated to impact. Now we like to realize social goods effectively. And what the impact is, is as follows. Those impacts are in the form of relieving anxiety over health and reducing health disparities. And the second point is about our business model. As a pharmaceutical company, we have been promoting business model as in full value chain of the pharmaceutical company, but for the future model as you see here, we like to pose ecosystem as a business model. That means that we like to empower people not only in the medical domains, but also those people in the daily living domain by providing solution in order to support them to realize their fullest life through an hhc ecosystem. And the third point is what we hear a lot these days, DE&I, diversity, equity and inclusion. This is represented here in this point. Now when it comes to impact to be realized, what should we consider? We have listed the keys here. We would like to realize impact effectively. In order to do so, we needed to quantify impact. If possible, it's better to represent the impact in monetary values. Then over time, we will be able to compare to what it was in the past and also we can compare ourselves with other companies return or financial performance and impact should be represented in monetary values so that these can be important KPIs. We believe that this will be a very important key factor for realizing effectiveness and impact-weighted accounting method, which has become a buzz word these days, and we are considering to implement this accounting method in a wider area. So we would like to start applying impact-weighted accounting method to human capital investment efficiency, which is shown here. Quantifying impacts and translating them into monetary values, it can be the first step for realizing effectiveness and efficiency. And the second point here is, first, the integration of multi talents and technologies are seem to be indispensable for pursuing effectiveness. And while we are working on the impact or that means we are working on the social issues. Therefore, it's not that Eisai is trying to pursue returns alone. But rather than that, compared to such a company which is pursuing on the return, we believe that we will be able to gather a lot more diverse talents and technologies. For example, we are collaborating with Gates Foundation or WHO. What is not experienced by other companies in the pharmaceutical industry, we are able to have encounters with diverse people. And through collaboration with them, we are able to be engaged in a much wider scope of our business and activities. On the right-hand side, you can see the same thing. Those in order to empower the people in the daily living domain to realize their fullest lives, we are not able to do sufficient contribution on our own. Inclusive of public organizations, I believe that we needed to collaborate with those organization or people with a well-established governance. For that, I believe hhc ecosystem is very important. Through this, we like to realize effective realization of impact. Here, I would like to put particular focus on talents to explain what we are considering and how effectively we are able to realize impact. On the left, you see global talent. In early 2000s, when we thought about globalization, we tended to keep focus on the West, over the U.S. and Europe. And now we have expanded area to India. In India, we have large-scale manufacturing plant, and we have a wholly-owned subsidiary as an independent company and the operation there is getting on track. So beyond India going forward, we would like to go further to the West. As you see here, Africa or Middle East. We believe that these regions will be the source for greater potential for growth in the future. And the picture you can see here was taken about 2 weeks ago at the opening ceremony for Eisai Pharmaceutical Africa, which was opened in South Africa, where a Japanese Ambassador to the country, Ambassador Ushio attended. And we are preparing the talents in Africa and in Middle East, Israel and as well as KSA or Saudi Arabia, we are making preparation for -- we are establishing the subsidiaries there. And we are looking towards the West in order to enrich and reinforce our global talents. In the middle, you see what we are doing at headquarters in Japan. We are seeing a steadily increasing number of those people who are mid-career hiring. In about 15% -- 16% of total employees are hired mid-career and those are very active in digital area, legal and compliance and finance and accounting and corporate venture investment with a relatively high retention rate. And as I said earlier, human capital investment efficiency stands at about 82% now. And in FY 2025, we would like to increase this level up to -- sorry, the current level is 80%, and we'd like to increase this level up to 82% in FY 2025. And on the right, talent in Technology and a new business model. Under Eisai's logo, it will be difficult to attract such digital talents. But for hhc Ecosystem, we believe that digital technology will play a central role. Therefore, we established a new company subsidiary, there are technologies specializing in this area. And in order to acquire people, we acquired shares of Arteryex. This is so-called Eco hiring. And in different entities under our group, we are trying to attract those specialists talents. And these are working well and steadily. Actually, the number of applicants for these companies are now increasing rapidly. In other general business domains in marketing area, omnichannel marketing and data lake is used for AI in order to make the AI to recommend make the next recommendation and also KPIs are generated from the business analytics for the management's dashboards. In these areas, we are reinforcing talents. To quantify such impact, as we have been explaining several times, there are several examples, one of which is about the DEC tablets for -- as a treatment for lymphatic filariasis, the DEC tablets are made in -- at the plant in India. Since 2013, Eisai has provided 2.3 billion tablets free of charge. So how long we may continue doing this? There is no return. Using this simple formula, you were able to calculate the impact. For DEC tablets, Eisai, JPY 160 billion at the bottom is the annual social impact we are generating through the DEC tablets provided by us. So in parallel with the financial statements, we would like to show clearly these impacts and value them as well. And next, I would like to talk about the recent case of the impact of LEQEMBI being quantified. And if you look at on the left-hand side of the numerator of this QALY. Quality-adjusted life year gained times WTP threshold. These are the same core of the impact generated by LEQEMBI. What is QALY? That is explained in the middle. QALY equals the length of life of AD patients going forward and quality of life level for each year of the length of the life. These 2 are multiplied to calculate the QALY. So that means the QALY is a measure of the value of health outcomes for the 80 patients lifetime. If taken LEQEMBI is not added and if they are treated with standard of care in the United States, the QALY is calculated at 3.7, but adding LEQEMBI to the treatment, 0.64 QALY will be gained. That means that 0.64 will be added. So simply put in the Alzheimer's disease patients, the quality could be increased by adding LEQEMBI by 17%. This is the value of LEQEMBI or impact by LEQEMBI. In Japan, although we use different numbers for the calculation. However, the incremental portion of QALY was exactly the same as 17% in Japan as well. And when we would like to monetize or translate this into monetary value, we needed to put price stacks. And the price stack is represented in willing to pay threshold or WTP threshold, which is provided at the top. If you are relieved from Alzheimer's disease for a year, how much would you be willing to pay? Its range is from 1 to 3x of the GDP per capita is usually applied in the United States, AD or any such a serious disease, about $200,000 will be applied as WTP. So with this time price tag added and then the impacts could be represented in the monetary value. And then per patient -- per annum, the value was calculated as USD 37,600. And from this, we calculated drive to USD 26,500. And in December last year, JPY 50 billion was financed through issuance of sustainability linked loan. And at that time, KPIs used for the evaluation less than annual value created by LEQEMBI. $37,600 in the U.S. and the annual value in Japan, 4.6 million -- about JPY 4.6 million per year. So sustainability linked loan could be fluctuating big. The interest rate for the sustainability-linked loan could fluctuate based upon these numbers. So when it comes to the financing, these values could be impactful. That's what I wanted to say today. Next, I would like to share with you successive upside events for LEQEMBI. Whatever business you are engaged in, in principle, you need to gain trust from the society, from the market. And in our case, we have to gain trust from patients and HCPs. So trust comes first. I'm sure this is applicable to any businesses, then where can we gain trust? Trust is based upon transparency and explicability. Only after we can gain these, we will be able to gain trust, transparency in terms of the data transparency, pricing transparency. These are considered to be very important. And in the Clarity AD trial at the CTAD held in San Francisco in 2022, data from Clarity AD studies were published. And also on the same day, that data was published in New England Journal of Medicine. So doubly, we were -- we ensure the trust. And when launch was made and then pricing was explained at the press conference by myself in January. And the simulation models were published in several papers in peer-reviewed journals and also for the pricing, we have explained based upon the transparency. In Japan and as well as in the United States, there is no controversy regarding the pricing level. So once we are able to ensure the transparency and society is ready to accept that. So if we consider the wider scope of transparency, we can think about the Board for business management, Board consisting of the independent directors as the majority of the membership of the Board with the transparent and objective view. And then the Board -- existence of such Board can ensure transparency. Therefore, that will be the basis for us to gain trust. And game changer or key factor one for increasing the value -- value of LEQEMBI. First, to increase the number of NAS in the United States. You may wonder what NAS is. NAS stands for Neurology Account Specialist. In the go-to-market system in the United States, there are various functions, but we believe that NAS can play a central role in that. The MR specializing in the neurology. In this case, because NAS means the MR or a sales reps specializing in specific areas. But if you look that at the bottom, there are many stakeholders in the United States. There are about 4 functions or 4 types of field force with different functions are engaged. And in the end, information gathered in the field will be integrated at the NAS, and NAS will be representing the company in communication with the customers or health care providers. Therefore, NAS can play a role as a command center. And this NAS will be increased by 30%. We are in the midst of recruiting candidates. As we reported at the last meeting, we have already identified areas with large potential. So we are prioritizing those areas for assigning NAS. About half of the increase of NAS will be head count of our people at Biogen. Therefore, this will lead to the enhancement of collaboration with Biogen Inc. Next, Key factor 2, for increasing the value of LEQEMBI is to change dosage and administration. IV, long term for 18 months and 24 months. And after this long-term administration IV, and we are trying to get approval for the IV maintenance treatment. And at that time, the dosage will be about halved. With this dosage and administration, we would like to get approval for IV maintenance treatment, which -- for which we are about to submit soon. And in parallel, SC-AI, subcutaneous injector formulation will be utilized in the future. We would like to make such switch. And we anticipate that at the same time, almost at the same time, we will be able to get approval for this SC-AI. And in FY 2025, we would like to get approval for SC-AI for the entire treatment period from the initial through maintenance treatment of LEQEMBI. We believe that these could be a very significant key factors because under the current pathway infusion, it's quite burdensome process. For the sake of infusion, people, in some cases, have to drive a car for several hours to get to the infusion center. And it requires a lot of workload by nurses. So by simplifying the infusion process or in the case of SC-AI, patients can administer treatment at the home or facilities such as the nursing care facilities, the patients themselves or caregivers will be able to administer. Therefore, this means that the pathway could be simplified significantly. So I believe that they -- very impactful. Key factor number three is the wider usage of blood-based biomarker or BBBM. There are 2 things here. First, Triage. This might be an unfamiliar word, but I think it is beginning to be used more commonly, this means that it can be used in prescreening and this has already started. And confirmatory use for confirmatory testing in place of PET/CSF. A Beta deposition confirmatory testing with BBBM. There are these 2 types of usages. And for triage use, the major objective is that the current BBBM already is able to precisely detect A Beta negativity. In prescreening, BBBM will be used and [ AB ] negative people will not have to proceed to PET/CSF. This will streamline and simplify PET/CSF related process. In confirmatory use without PET/CSF by drawing blood, confirmatory testing can be done. This will also be addressing the most burdensome part of the pathway. PET is costly. CSF is invasive procedure. It can be replaced by simpler inexpensive BBBM if that is achieved in a major way, there will be an advancement of diagnosis and transformation of AD, $40 million investment, $50 million investment to C2N was announced on Wednesday. For confirmatory purposes, C2N is the top runner of BBBM. One of the challenges of C2N is throughput, specimen samples in large volume cannot be processed because mass spectroscopy is used for analysis. And there has to be a very large number of mass spec machines to process large number of specimens. And we would like C2N to invest in these equipments, and that is the reason for equity investment. We are making investment to support BBBM. Key Factor 4 is primary care physicians or PCPs. Primary care physicians are expected to make full-scale entry into diagnosis and treatment of AD in around fiscal 2027. SC-AI that I've mentioned in BBBM, if they are combined, this will be possible currently in the AD market. It is a specialist market without neurologists, nothing can be started. The diagnosis and treatment are dependent on specialists. But with SC-AI, if treatment can be done at home or care center and if A Beta deposition can be confirmed easily with BBBM, then PCPs, primary care physicians can complete diagnosis to treatment. Alzheimer's diagnosis and treatments in -- will be very convenient. And something that is very readily available. PCPs for entry into diagnosis and treatment will bring about such a major change. Key factor 5 is preclinical AD. MCI -- this preclinical AD is a stage before MCI. Cognitive function deterioration is barely starting in preclinical AD stage, but A Beta accumulation has already started. This is the stage before MCI, perhaps 5 years to 10 years before MCI stage. Here, there are many people who are at this stage around 2030, it is expected that it will be over 400 million people who will be in that stage. And the number of people in this stage will be almost equal to early AD stage people. AHEAD 3-45 study is conducted currently jointly with ATCT (sic) [ ACTC ], which is a clinical trial consortium in the United States, comprising around 6 major universities. Led by ATCT (sic) [ ACTC ], Eisai together are conducting Phase III study, administration period is 2 years. This is a very large trial. Towards target patient number steadily, patients are being enrolled. BBBM is already used as prescreening test in this study. After the launch of LEQEMBI, there are many discussions of the effectiveness of LEQEMBI, and there is greater attention paid to AHEAD 3-45 study, we aim for approval in fiscal '28. Key Factor 6 is Tau. Another major pathology of AD is tau. It is said that tau is the other major pathology in AD. You see schematic diagram within synapse, the tau will be aggregated. Similar to A Beta deposition, there is tau deposition. This is set to be the cause of Alzheimer's disease. Tau within the cell is difficult to trap. However, tau is propagated in intracellular space. It is known that it propagates in intracellular space and MTBR tau is the species of tau that propagating in intracellular space. Elimination of these species by binding with antibody is the concept of E2814, and MTBR has 4 regions as shown at the top from R1 to R4. And the center of the toxicity are R2 and R4 and the antibody will be binding to these species. We believe that it can be a flagship drug on the par with LEQEMBI, we believe that E2814 has such a potential. The origin of this academia lies in the academia UCL, University College London in the United Kingdom. Currently, development is mainly led by Washington University in St. Louis through collaborative research. Washington University was featured in the recent TV program, the other day, DIAN-TU or DIAD familial Alzheimer disease cohort is managed by Washington University with global headquarters located at the university. Familial Alzheimer's disease patients data reside at Washington University in large number. Clinical trials are also conducted or can be conducted. And up to Phase II studies have been carried out. As shown on bullet number 4, sporadic AD, in comparison to sporadic AD, tau related to biomarker profile has been confirmed to be equivalent in DIAD. In biomarker study, a proof of mechanism of E2814 was achieved. And this is a tau antibody. That is the focus of attention these days. We aim for U.S. approval in fiscal 2030. And we would like to develop with that aim. This is showing a time line of various key factors in 2014 is not included in the population of AD. PCP participation, clinical AD, additional indication, these will be a major game changers and various events leading up to those will also be important steps. LEQEMBI aim to change the future of AD. First of all, the factor 1, Eisai aim to overcome 2 major pathologies. AD pathological finding is shown in the central photograph. Lecanemab will be removing A Beta's aggregation shown on the left side and right side. Tau aggregation will be removed by E2814. PET detected time of onset is shown for each. These 2 major pathologies, if they can be overcome, the future of AD will be transformed in a major way. AD can be a curable disease -- a treatable disease with a possibility of curing insight. With these 2 drugs, we believe that we are able to open such a pathway. We hope to be able to do so. Factor 2, to change the future of ADs earlier time to initiate treatment. During the days of Aricept, treatment started in mild AD stage. 25 years later in LEQEMBI -- with LEQEMBI, initiation of treatment is starting at 1 stage earlier at MCI. At the time of Aricept, as I recall, there was no concept of MCI. But if we are able to obtain indication for preclinical AD, we can move the treatment 1 step earlier, earlier the start of the treatment, greater the efficacy. AD treatment is such that the earlier the initiation of treatment, the greater the effect size that is known. And this will lead to greater efficacy or if the pathology is eliminated in preclinical AD, progression to severe state may be prevented or even a cure may become possible. Factor 3 is, as I have mentioned, to simplify the diagnosis and treatment pathway, as you see at the top half, very heavy loaded pathway is existent without a specialist on neurologist, we are not able to run this pathway. But this amyloid beta testing could be done by BBBM or infusion can be changed to SC-AI so that administration can be possible at homes and nursing care fastly. That means that pathway could be significantly simplified. And PCPs and attending physicians of the patients will be able to treat them. So tremendous innovation can be brought about to AD treatment. The patients don't have to spend a lot of time to visit hospitals. So this is considered to be a very important factor 3 for changing the future of AD. Now I would like to share with you the current LEQEMBI efforts. Currently, we are putting focus on the followings. We like to first promote establishment of the diagnosis and treatment pathway because there is no such pathway. Traditional approval was obtained in April 4 LEQEMBI and rushing into the market, there was no pathway. We are the ones who needed to work together with medical institutions to create pathway. We are now engaged in such very significant effort. Let me discuss this more in detail today. And another key focus is that we needed to promote understanding that the earlier initiation of the treatment is important, and also continued treatment is important even after amyloid plaque removal, is achieved, and this may yield the best outcome for the patients. We would like to share the deeper understanding of that. We have solid data supporting this. When it comes to the early initiation of treatment, 60% of patients enrolled in the Clarity AD was MCI patients. So the largest population of MCI patients were enrolled in the trial in history. And the Tau-PET subsidiary was conducted. Please recollect it. Low-tau subgroup study results were presented at the CTAD, low-tau means the patients are in the earliest stage of MCI. These patients with the treatment of LEQEMBI could slow significantly the decline of cognitive functions or, in some cases, improvement was shown. For the first time in treatment of AD, there were responders who demonstrated improvement. So that was the nature of the study results. So the significance of starting treatment early, it could be supported by sufficient data or evidence. After removing amyloid plaque and amyloid beta turns negative, is it all right for patients to discontinue treatment. Amyloid beta, as everyone knows, AD is a neurodegenerative disease. So AD is a progressive disease? So even after amyloid beta turns negative, can we really say that you were able to discontinue treatment? Do we have sufficient evidence to say that? We have sufficient data, which suggests it is important to continue treatment. What is it? In Phase II study, Study 201, OLE, open-label extension trial provided that data because it was OLE. Therefore, all the patients in the study received the active drug. And those patients who turned the amyloid beta negative, in which LEQEMBI, there was a gap period of 2 years where they didn't receive any treatment. And even during that time, biomarkers were tracked and amyloid beta deposition started to be seen amyloid beta 42/40 and P tau has showed there was the start resumption of the accumulation of amyloid beta and CDR-SB also shown -- has shown the deterioration. And another is Study 2301 open-label extension, a Phase III study. And the core study period was 18 months, but open label is now extended to -- is now at 24 and 30 months. And data from that suggests that the efficacy is sustained. There was no placebo. Therefore, Adonis data with patients with the similar conditions were used to show the clear difference with the placebo. This was not published by ourselves, but academicians, academic specialists made a presentation on this. So the improvement could be sustained at 24 and 30 months. So that data was presented at the academic conference and we have such data for supporting the continued treatment. Then establishment of the diagnosis and treatment pathway. You may wonder what we are doing here. But establishment of the pathway in the United States requires so much effort, as you see here. Let me talk about it one by one. Starting from the yellow box on the left, in the AD market in the United States, we have IDN, integrated delivery network consisting of a large hospital network and community practices, neurology specialist clinics in community. So these are the 2 major markets. For both segments, you needed to get P&T, pharmacy and therapeutics approval. We also have the similar scheme in Japan. So that is the place where the certain therapy will be adopted or not. And then data presented and pricing is presented and then at this P&T committee, they will decide to adopt LEQEMBI as a therapy to be used by the medical institution. That is the first step. As you see here, there are multiple stakeholders, professionals are engaged. After getting approval for adoption of the LEQEMBI and next, it's the criteria for eligible patients, MMSE and PET/CSF or either both could be used for amyloid beta testing, APOE4 to be what is the methodology and infusion outside or in the hospitals and area monitoring, which MRI to be used, 1.5 Tesla or 3 Tesla.

And then based upon this policy or protocol of the particular site will be determined. And then pathway will be built. So how many chairs for infusion will be placed and where did they have to be placed? And how much should be purchased? And all the conduct in the pathway, needed to be covered by the insurance. So reimbursement have to be confirmed as well. It's also a cumbersome process. And Medicare's regional offices or MAC is the counter part -- their counterpart may be private insurers after confirming the coverage. And then at last, going to the trial stage, a few patients will start to go through this pathway. For receiving the treatment. And once there is no problem, infusion as well as the infusion reaction can be monitored?

Well, after confirming those, then lastly, full-scale introduction will be done. So that large number of patients can go through this pathway. So when we entered the market for the first time, there was nothing like this. We needed to play a role as a pioneer to develop all these. And that's what we have been doing so far. Eisai is the standard bearer in the AD field. We are determined to forge a path for new treatments. We do not have a path before us but we are going to create path behind us, like in the poem written by Takamura Kotaro, with that determination, we are working on the establishment of this pathway. At the end of March, the number of doses administered at the end of the March, it's just a checkpoint, a passing point. Even if there is a slight delay, as long as pathway is established steadily, we are not concerned at all. I am not concerned at all. This is what I wanted to convey to you strongly. Or rather this mountain of Alzheimer's disease, this mountain is now shaken and being moved. In that sense, I believe that U.S. field force is doing a great job. I would like to use data to support what I have said. The IDN, as I said earlier, IDN, I believe, is playing the leading role in the treatment for AD. Harvard and Duke and all other big medical centers are under IDN. Even in a single IDN, in some cases, 10 or 20 hospitals are covered. So LEQEMBI is used and adopted and prescribed. So that is very important to find the status of IDN. Therefore establishment of the pathway at IDN is the most important. And 80 was the target by the end of -- end of this fiscal year, and there are about 100 IDNs in the United States and the progress rate will be about 90% because 72 will have established a pathway. And in neurologists, we have conducted a questionnaire.

Do you think that you have established the pathway in the AD treatment you were engaged and the 80%, about 80% of them said that they have established pathway?

Community practices still staying at the 60% progress rate. But IDN, which is the most impactful influential in the AD treatment, 90% is the progress rate. Therefore, in terms of that -- our work is scaled from 0 to 1, I believe that we believe that 90% of progress rate is an achievement. Now turning to Japan. I believe that we are making a smooth introduction with LEQEMBI to the market because we are feeling very strong passion from neurologist in Japan for AD treatment. They are fully complying with the OUD. As you see at the very bullet at the bottom, the -- all-case surveillance is [indiscernible], therefore, all these facilities are collaborating for all-case surveillance. There are about 300 facilities, which are scheduled to cooperate for all-case surveillance. University hospital and medical -- national medical institutions, a number of facilities that plan to adopt LEQEMBI 85 and completed established -- 76 completed establishment pathway and 35 have started prescribing and the progress rate is about 40%. And the core hospital actually, many core hospitals have established the pathway and the progress rate is about a little less than 30%. In Japan, it's just 50 working days after the launching the same. So establishment of pathway introduction of the LEQEMBI prescription progressed faster than expected and approximately 3,500 physicians had a safety training for ARIA. And usually, it would have taken a lot more time to start prescribe prescription, but I believe that these physicians have a strong passion at about 100 medical institutions, they accelerate the introduction of LEQEMBI by about 2 months. Now third country where LEQEMBI is being launched is in China. Manufacturing of LEQEMBI for China is now being promoted in a full-fledged manner. We believe that in July, a launch will be achieved. A pathway in China is going to be very different from those in Japan and the United States. First, the screening will be conducted through collaboration with other industries, insurers and the medical examination industry and nursing home industry. With these industries, we they will be able to play very important roles in pathway and commercial insurance forms a big industry in China. They are about to launch dementia care insurance. And this includes the benefits to reduce burden of cost of drug. With the power of the insurance industry, we expect them to provide opportunities for disease awareness and for screening. And the medical examination industry is expanding rapidly. They are expected to conduct the cognitive function test and APOE4 testing and the initial MRI testing. Nursing home is also growing and where we expect them to conduct disease awareness and education and early screening. And from -- for diagnosis from initial stage, BBBM will be utilized. PET and CSF availability is very low in China. There are several broad-based biomarkers, which have been obtained approval. Based upon this, they are going to replace the amyloid beta testing with this BBBM-based testing to be included in the pathway and also IV infusion and MRI or ARIA monitoring will stay the same. But online platform will be run. As we have been reporting to you several times, there is an online platform for dementia called, Yin Fa Tong, which was established jointly with Jingdong Health under the Jingdong Group, which is Chinese GAFA, and about 350,000 people are now using Yin Fa Tong, and about 6,000 physicians, specialists are registered on the platform. And this is the online platform, which is expanding and growing very rapidly. As you see in the arrows, amyloid beta test sites and infusion centers or specialists can be introduced on this online platform and towards the right, this is to provide online reminder for follow-up consultation, LEQEMBI administration or MRI testing through in fact, and we like to establish this kind of pathway. Why do we think it is important? Because China is, I'm sure, a huge market to roll out to other countries in Asia and Africa. For example, in India, this model here can be a powerful model or a mainstay model for other countries in Asia, such as India. So we'd like to establish such model here in China. Expanding potential. Early 80 patients, estimated number currently is 180 million. In 2032, this is estimated to expand to 240 million. Yellow and orange part are characteristic. China, Asia, Latin America regions. In these regions, about 70% of early AD patients are located. And we have to do business in these regions to be successful. As for estimated number of AD-DMT eligible patients, currently a little less than 20,000, mostly in the United States. AD-DMT eligible patients who can be treated with AD-DMT. Currently, there are about 17,000 to 18,000 mostly in the United States. In fiscal 2026, we estimate that to be about 400,000 people -- close to 400,000. In fiscal 2032, 3.32 million people through a series of upside events that I've discussed, through which AD treatment will become more widespread and with the simplified pathways, we expect patients receiving AD-DMT will increase, not only LEQEMBI, but other AD-DMT included. This is the simulated revenue of LEQEMBI. You might be interested in what happens at the end of this fiscal year. At the forefront, in Japan and the United States, all our efforts are being made and we would like to update you at the earnings report. But we are seeing a rapid ramp up, both in the U.S. and Japan. And in fiscal 2026, close to JPY 300 billion and in fiscal 2032, JPY 1.3 trillion is the estimated revenue through simulation. LEQEMBI's EAD part is shown in red and PAD part is shown in pink. Preclinical is calculated with a certain assumptions and potential of JPY 1.6 trillion in revenue for fiscal 2032 is simulated. I would now like to turn to the topic of Lenvima. In May last year, the U.S. court issued a decision favorable to Eisai for a patent suit filed by us in August 2015. The decision was favorable to Eisai. And since then, in August 2023 and this suit is against 2 generic companies. And usually, in patent lawsuit, there are 2 contentious points. First is whether a patent is infringed or not by generic manufacturers. And the second point is whether the patent in question is valid or whether there is inventiveness, which is a patent requirement. Regarding infringement, the party is stipulated to infringement. And therefore, remaining issue is the validity of the patent. We believe that we are very quite confident regarding the patent requirement being met, including inventiveness and specialist report, IPD Analytics made a report that recently on February 14, 2024, I will quote, "Eisai appears to have the advantage in defending the validity of the 393 and 547 patents. These 2 patents are high-purity Lenvima patents. And this is the state of the patent litigation concerning Lenvima. Based on this, up to fiscal 2022, revenue is simulated earlier, there can be part is included in blue zone. Blue indicates other brands including Lenvima and certain LOE extension is taking into account potential of that is taken into account. And there are also 5 studies ongoing for Lenvima, and that is also taken into account. The Dayvigo BB-1701, MORAb-202, these are oncology ADCs using eribulin, Halaven as payload E7386. This is immuno-oncology resistant cancer treatment. E2814 is tau antibody that I've explained earlier, E2086 is Orexin receptor biology antagonist, rather antagonist is Dayvigo and E2086 is agonist. This is developed for treatment of narcolepsy and et cetera. And we estimate the sales to be JPY 2 trillion in 2032. The period is divided into 2 phases and I would like to invite the CFO, Mr. Shomon, to explain this part.

Thank you. I am Shomon, CFO. I would like to go over financial figures up to fiscal '32 dividing the period into Phase I and Phase II. Left side is between fiscal '22 to '26. This is the first phase where diagnostic and treatment pathway for LEQEMBI will be developed globally and this is the preparatory period. We will not fall into short-termism and will be proactively making expenditures in the LEQEMBI R&D and global commercialization and to enlarge Lenvima Dayvigo sales and to promote sales and to develop -- to invest in research and development of our next-generation pipeline of 2 ADCs using [indiscernible] and also into anti-MTBR Tau antibody, we will be spending R&D spending of about 20% of sales. As a result, in fiscal '26, revenue of JPY 1 trillion, operating profit margin of around 10%, ROE of a 10-year average of 8% are estimated. Next, between fiscal '27 to fiscal '32. This is the second phase where pathway will be simplified and significant advancement is expected for AD treatment. This is the period to reap in the result of the investment. During this time, we expect resource reallocation to be stable and profitability to be enhanced throughout this period. R&D spending and SG&A will be enlarged, but it will decline as a percentage of sales. As a result, fiscal '32 estimation of revenue is over JPY 2 trillion, operating profit margin at 20% level, ROE of 25%, January average of ROE of 15%, DOE of 15% are estimated. As for shareholder return, we will continue our policy of not basing it on short-term PL, but on medium-to-long-term balance sheet management and financial soundness on a continued stable basis. So far, we have used a majority -- in the majority of our dividend to return value to shareholders but because of rapid growth in performance, we will maintain the -- and enhance dividend while at the same time, utilize your buyback to manage ROE. And if we feel that market valuation is extremely low at the right conditions, we expect to carry out share buyback. As a way of returning value to shareholders, we did not deny the possibility of share buyback. But on this point, we would like to take stock once again. In terms of ROE management, we believe that it is one way of implementing ROE management decision effectively. And unfortunate circumstance of our value not being properly evaluated by the market and if the Board believes that is the case, then we would like to be able to exercise the option of share buyback. And that possibility is taken into consideration, and that is what I'd like to convey to you today. I have 2 more slides, and please bear with me for a bit more future model dementia ecosystem, how will it look like? The red part in the middle is the platform where we would like to serve as a platformer. This shows dementia platform. MCI dementia-related challenges are faced by users shown on the left. And there are solutions from Eisai and others that can address these challenges, and there are platform partners on the right side. And we believe that we can be the platformer. And the reason for that is LEQEMBI Aricept in E2814, promising tau antibody, we have the ability to develop these real medicines. That is one of the major reasons to consider that we have the potential to become the platformer. And through that, we have gained data. And with the data, we are able to develop predictive engine to predict when the onset is and to predict the course of treatment, and we are able to deploy services accordingly. Because of these 2 abilities, we believe Eisai can be a platformer. And as for the users of the platformers, they are healthy people, patients, caregivers, doctors, HCPs, medical institutions, they will purchase services and services will be provided. Platform partners on the right side include partners from other industries including insurance companies, automotive companies, food companies and testing companies. Products and services from these companies can be put on the platform. There can also be some public sector partners, but these product services can be put on the platform and we are able to collect usage fee or advertisement fee. This is the final page, conclusion. By accumulating talent and technologies that efficiently generate returns and impact. We will continue to create fundamental treatments for 2 major diseases, Alzheimer's disease and refractory cancer that reduced vitality in modern society. Furthermore, we will be transforming into a disease ecosystem platform that provides appropriate solution packages for people in all stages of life beyond drugs. Thank you for your patience.

Now we would like to open the floor for Q&A session. After receiving questions from this venue, we would like to receive some questions from those who are attending online. Before asking your question, please mention your name and affiliation. If you have any questions in this venue, please raise your hand. The person in the first row, please.

This is Yamaguchi of Citi. Let me just check on the understanding of the facts because I'm asked from investors all over the world. So I needed to find an answer. As you see, there can be -- submission will be done by the end of this fiscal year. That means that in this month, and again, the approval timing is roughly presented here. The timing for submission can be possible by the end of this month. This is first question. Dr. Lynn Kramer, are we going to -- yes, we'd like to have Dr. Kramer to respond to this question.

Yes. This is Lynn Kramer, the Chief Clinical Officer of Eisai. Thank you for the question. We are on track for filing the SC formulation this month and the IV maintenance dosing. So both of those filings are going in.

Yes, as scheduled. Yes, as planned. Then in your presentation, you mentioned BBBM changed from Triage used to confirmatory use. You'd also talked about the timing, perhaps in fiscal year 2026. And according to the presentation by the Sysmex and I believe that they have a preparation and also AC is also obtained. And assuming that it will need further several years and what will be the trigger of bottleneck for getting this approval. So perhaps Dr. Kimura is going to respond to that question.

Thank you for your question. My name is Kimura. I am Global AD Officer. Could you please speak into the microphone? Black-based biomarker to test the amyloid beta accumulation today, perhaps [indiscernible] made a presentation to explain this, not only through Sysmex but also C2N into which we made investment, PET and CSF have shown a very high agreement with this BBBM. And also the [indiscernible], very high agreement. And data in the publications, which are available now are based on the clinical data or clinical trial data or cohort data such as those from [indiscernible], very strictly controlled trial data are used. At the time of social implementation of these technologies, some people are concerned that the various types of test centers under various conditions and if measurement is done and then the data could be reproducible or not, particularly it would be okay at the testing. However, pre-analytics application of getting the blood and how the blood will be preserved and to be stored at a testing sensor, all those pathways could be really managed well and we are collaborating with Sysmex. We believe that robustness in those processes have been confirmed that we need to support that based upon the real-world data. Maybe that is the request from the society and from the academia. In fiscal year 2026, we believe that we can use BBBM for confirmatory use because of the accumulation of the real-world data, which will be convincing enough and then this will allow us to switch from PET CSF to BBBM. So time will be necessary in order to accumulate the data in the field, and that will suffice.

Next question from attendee seated on the fourth row, please.

I'm Wakao from JPMorgan. First about Lenvima patent litigation. Conclusion, I don't think has been reached. When do you expect the conclusion? And when conclusion is reached, I believe that there are various options, including settlement and will be releasing that information. And as for patent extension on Slide 31, how many years of patent extension are incorporated in the assumption?

Legal aspect will be addressed by Mr. Takahashi. And if there's additional comment, Dr. Owa will make additional comment. First, Mr. Takahashi, please.

Thank you for your question. I'm Takashi, General Counsel. When is the conclusion expected? That was the question. The litigation itself is such that a trial date is yet to be set. On the other hand, as it was mentioned in the question, as for the possibility of settlement. Are we going to wait for a decision? Or we going to settle? Of course, it is not certain yet. If the settlement proposal is reasonable, we can take it into consideration the possibility of settlement. If such an event occurs, we will immediately inform you.

Thank you for your question in what part -- how much was incorporated in this graph, we are not able to discuss that. I understand that is incorporated in this graph. But in what way -- When we are able to do so, we will convey that information to you. Why is that information incorporated in this timing? In the first quarter or earnings call, you've mentioned that high purity patent, you're confident that you can include that in the numbers up to 2035, I was suspecting that there was a development that you're not able to disclose that warrant some calculation. I'm not able to discuss that, but we believe that as far as guidance is concerned, if we consider April 2026 LOE, which is currently the case, it can be misguiding and therefore, possibility of extension of LOE is incorporated to a degree. Why is the timing of now? That is the reason.

The second question about SC maintenance regimen, I understand, but initial treatment. Was this scheduled to be submitted before the end of the fiscal year. It seems to be taking time. And according to what I've heard from IR people, dose change is also being considered. Lynn, please address that question. Dr. Lynn Kramer will answer that question.

Yes. Thank you for that question. We are planning to submit first, the maintenance dose as is listed here in the middle and then the initiation dose. We believe that the initiation dose will be at a lower dose and we'll optimize the patient experience with lower volume injection and so forth. So that's the reason why the 2 are at a different timing and it has a number of benefits for the system and patient pre-optimization. So thank you.

So as pointed out, there is a possibility of changing the dose. The reason for changing the dose is that due to possibly a negative comment from FDA -- no, no, no. That is not the case. Lower dose offers a greater benefit in our view.

Final question. You've also talked about possibility of share buyback. Currently, your share price is very low. Clarity AD study, if it succeeds and although you're in the middle of developing pathway, the number, share price has come down to a level lower than the pre-announcement days. And over the short term, is there a possibility of share buyback? Is that a correct understanding? Mr. Shomon, would you like to address that question?

This is Shomon, CFO. Thank you for your question. We are considering various matters but nothing has been decided yet. When we have the right conditions.

The person in the first row, please have the floor.

My name is Hashiguchi. I'm from Daiwa Securities. I have 2 questions. First question is regarding the PCP to be playing the central role in the pathway, regarding that future vision. According to the current guidelines, they are not -- it's not that they are not allowed, but rather they should not be engaged in those processes. I think that there are several reasons but was one major reason is the AE or ARIA monitoring and control and safety issue. That process is not established well. Therefore, I think that is the major reason. So suppose that for the PCPs to play a central role and then you needed to identify the patients with potentially high risk of ARIA. And even their PCPs will be able to see the signs of the risk and are able to respond to such a risk. And I think that such monitoring methodology needs to be established. How do you think? I'd like to get your take.

I believe your point is very important. As for ARIA, understanding ARIA, which is an online training program that Eisai has offered in the United States. We have been going through these programs very thoroughly. And so far, serious incidence of the ARIA has not been observed. By educating HCPs regarding the risk of ARIA and homozygous patients with higher incidence of ARIA is communicated to the attending physicians before starting administration. That is required under the current label that I believe has been implemented so thoroughly in the field. As Hashiguchi pointed out, I believe that this is a very important point. So more than ever, we needed to establish the knowledge or expertise as regards to ARIA so that PCPs will be able to get that enough level of awareness and also ready to take a response to whatever incident may occur. But thinking about the current situation, I believe that these will be possible.

My second question is the ramp-up speed by region. On Page 28 and 29, the eligible patients and also sales or revenue by region based upon these graphs. Relatively speaking, Japan seems to be expanding or ramping up the LEQEMBI introduction rapidly. And after that, stabilizing. And in China, the ramp-up speed is not so fast but it will take up speed later on. So could you please explain the factors behind these differences?

In China, although I couldn't touch upon this today, but there is a national drug reimbursement list. The timing to be listed on that is estimated to be in 2027. If that is the case, as you are aware, the number of accesses could be expanded by several folds, but there may be discount, usually 80% or in some cases, 95% discount may be allowed. Therefore, the price will be dropping significantly. But we'd like to have LEQEMBI listed on the NRDL even if we see a decline in the prices, but with the expansion of the number of accesses, we believe that we can make up for the decline in the price. That is the case in China. For us, this is the innovation derived from Japan. We feel really strong support for this. So I believe that the ramp-up speed is faster in Japan.

[indiscernible] could you please give us your comments if there are any regarding the ramp-up speed in Japan?

Yes, thank you for your question. I am incharge of LEQEMBI commercial in Japan. My name is Yusa. I would like to respond. Regarding the ramp-up speed in Japan, that was explained by CEO. On 20th of December, LEQEMBI was launched in Japan. It's only a little less than 50 business days after the launch, but faster than our expectation, pathway is being established and also introduction of LEQEMBI is being made in prescription. As we mentioned earlier, this is a very progressive disease and particularly MCI is included in the scope of eligible patients. That is very important. With the conventional therapies without diagnosis of dementia, the treatment could not be started but with the diagnosis of MCI, patients are now able to get the treatment. So we are not able to keep patients waiting. So physicians and HCPs, medical institutions are thinking together in order to establish the pathway. As has been explained earlier, coordination in the medical institution is really cumbersome in Japan as well. In reality, those hospitals, which have a step pathway and started the prescription, have established a working group in the hospital and they are discussing how to start administration of LEQEMBI. They are frequently holding such conference. MRs or specialist MRs from Eisai are participating in such meetings in order to collaborate for establishment of pathways. Thank you. Next question, please.

Fum Sakai from UBS.

About Japan, you have just described the situation. My question is on the United States. I believe U.S. is more advanced after the patient is diagnosed as MCI, how long does it take until the actual treatment begins currently. And as Mr. Naito, CEO, as you mentioned, once pathway is established, how fast can patients be rolled in and be on treatment. If you have some numbers, please.

Mr. Yasuno will address that question.

Thank you for your question. Can you hear me?

Yes.

This is Yasuno speaking. I'm responsible for the United States. Patients visit medical institutions and until they start receiving the treatment depending on the medical institution, depending on the region, it can vary. But before we had a launch, we thought that it may take between 6 months to 1 year I believe many people believed that it may take 6 months to 1 year. But steadily, pathway treatment -- diagnosis and treatment pathway are being developed. And the time is around a few months before the start of the treatment. It can be as early as 1 to 2 months before patient receives treatment in several months. And in some regions, it is a little longer but sadly, the duration is becoming shorter. It's your ideal 1 month between diagnosis to the start of the treatment.

Since -- as it was just mentioned, it's a progressive disease and earlier treatment is what you're advocating. Do you have any target internally of the time that it takes between diagnosis to treatment target may not be the right word. How long is considered ideal between the time of diagnosis to the start of treatment. Mr. Yasuno, can you address that?

As soon as possible is what we would like to achieve target is when patients visit the clinic and receive testing and when results are available, smoothly we would like to see the start of the treatment. And we will be making utmost efforts to achieve that. What is the status in Europe? CHMP's decision may be imminent? Is it going to be in March? EU status will be addressed by Dr. Lynn Kramer.

Yes. Thank you for that question. We have what's called a SAG meeting, scientific advisory meeting with the CHMP, the EU health authority on next week. And we will be able to have a better understanding in March of when approval might occur. So we will have to update you after having that meeting. And the following week, we have a second meeting with the CHMP to determine the next step. Thank you.

Does that mean that it is being delayed because of this SAG meeting?

Delay, I do not know if this can be characterized as SAG. CHMP meeting will be held within this month and the results will be conveyed to us within this month. So even if there is to be a delay, I don't think it will be as long as a quarterly delay.

And the person in the front row, please up the floor.

My name is Mamegano BofA Securities. Thank you for this opportunity. You have updated the revenue simulation for the medium to long term. I have a question about that. In fiscal year 2032, JPY 1.3 trillion is projected. And key factors that you mentioned, if they go well, as you anticipated, and then this number could be achievable. But this number could be seen as a little bit challenging. But do you think that in a business as usual course, do you think it's pretty achievable number. So in near future, and in recently, you have that establishment of diagnosis and treatment pathway is being established smoothly only for LEQEMBI. Pathway is being established smoothly or steadily. So the number of patients on treatment is behind the plan a little bit, but you will be able to catch up going forward. Then do you think that these numbers are achievable.

Yes, before that, each event, there is a simulation to see the increase in the number of patients. Can I have that slide? This is what you mentioned all the events, upside events and accordingly, we are expecting to see increase in the number of patients on LEQEMBI treatment. At each event, we have applied a very strict calculation of how much increase we are anticipating for each event, like 20% for this event or 40% for this event. So we accumulated this incremental portion of the number of patients to make these numbers. Therefore, it's not the reckless or numbers without a grant. We have made these calculations and multiplied by price to make the sales projections. So please understand these numbers are quite logical numbers. For these events, PCPs to be engaged in the treatment and diagnosis -- can we say that, for sure, in a full-scale manner, BBBM will be allowed to be used and SCAI will be introduced and then without doubt, we believe that there will be a transformation of the healthcare in AD. I believe that there will be great benefits. And with the additional indication of a preclinical AD, it will be also impactful based upon these upside events, based on the reasonable estimation of the increase in the potential patients on treatment, we came up with those numbers you mentioned.

We will be taking the next question, please.

Ueda from Goldman Sachs. About AD pathway development I have a question. You are making a great effort to develop pathway and what kind of competitive advantage is this going to lead? I'm sure there will be companies following with this competitive drug. Do you think that the competitors coming in will be disadvantageous or advantageous? As for the competitors coming in, Mr. Keisuke Naito will answer.

About the competitors coming in. Thank you very much for your question. As for the development of the pathway and so overall, setting aside the competitors coming in, we are strengthening pathways. As for more options, although it will mean that we have competition. But for patients and families, it will be beneficial to have more options. And for companies developing pathway, even a bigger market. So I believe that it will have a positive effect. So in terms of the impact on a pathway that is my response to your question. In Pharmaceutical business, people will not forget who initially drilled the water well. That is the experience on a number of occasions. For example, we were a late comer in contrast media, but we were not able to take away the market away from the more established earlier entrants. I think you are concerned that our share might be eroded but people will not forget who took pains and made efforts. So I think we have unwavering advantage there.

Next, about Lenvima patent. Inventiveness that you've mentioned with regards to patent requirement, could you elaborate more on this high-purity patent? If it is valid, I think it will be difficult for generics to develop products, evading the infringement. General Counsel will address that question.

Thank you for your question. As for the patent, this patent is about containing the level of impurity to below certain level. And as you rightly pointed out, if this patent is valid, the entry of generics can be prevented. Thank you for your question.

Although we have used the time, but we have one person raising hand online. Mr. Muraoka from Morgan Stanley.

This is Muraoka of Morgan Stanley. Thank you very much for calling me to speak. There are only 2 questions. One is about ARIA. This is about the science. When it comes to the ARIA monitoring, after resolving various issues, and I think that the monitoring ARIA will pose the next issue, MRI is currently used. I understand, but methodologies to simplify this process. Do you have any ideas, which are visible?

Dr. Kimura, could you please respond.

Yes, I am a Global AD Officer, Kimura speaking. Thank you for your question. For ARIA monitoring, as you said, currently, MRI is used for monitoring ARIA and the first initial test is conducted for monitoring. Now at Academia, what is happening at the academic societies is based upon the clinical trial for lecanemab and other companies trial, which are generating the samples and the data and the real-world data will be used. And with the ARIA, if it occurs and what biomarker movements we will see and which biomarker will move. And based upon the genetic testing what will be the patient profile, which -- who will pose the higher risk of ARIA. So based upon this, research will be continued. And ARIA incidence is low and also controlled in the field. Therefore, I don't know how fast this research will proceed. But in the future without using MRI, but the monitoring could be conducted based on the biomarker, blood, or genetics and risk will be captured and also even before the onset, the monitoring could be possible. Thank you for your question.

So specifically, which markers could be used. Are there any specific names of the biomarkers, which can be used as candidate markers?

BBB should be broken and also the blood vessels markers raised as the candidate, but we needed to use the human samples to verify these candidates. So we have not identified the specific ones.

Last question is about the share buyback. Based upon the balance sheet, JPY 280 billion in cash is recorded on your balance sheet. So if you decided to do the share buyback, to what extent do you think it will be allowed to buy back your shares?

We would like to refrain from answering that question.

Then with this, we would like to conclude today's information meeting. Thank you very much for your participation. [Statements in English on this transcript were spoken by an interpreter present on the live call.]