Thank you very much for taking your time to attend Eisai Q2 fiscal 2022 financial results presentation. The presentation session is held in hybrid format, including in-person at the venue and online distribution. Presentation flash report and reference materials are distributed to those who are attending in person. Those who are calling in, please download the presentation material from our website and please click to advance the slides. Those of you who are watching live streaming, please continue to watch the screen. I would now like to introduce the presenter today, Representative Corporate Officer and CEO, Mr. Haruo Naito. Now, I would like to start our financial briefing session for the second quarter of FY 2022. The first page, on the right-hand side of this slide, for the first half of this fiscal year, you can see the P&L results. The top line, revenue, was almost flat from a year earlier. To the right, you can see the amount of Forex impact. For revenue, the impacts of weaker yen was positive and negative impacts of weaker yen for profit. P&L results are being reported now, but first thing that I needed to mention is related to operating profit, JPY 5.3 billion, which was only 9% of the level recorded last year. We'd like to take this opportunity to apologize for this. Reasons for this profit level is something that I'd like to explain first today. The main reason for this is here related to the revenue in other business, the third line from the top, which was 10% of a year earlier at JPY 6.1 billion. Last year, JPY 62.9 billion was recorded in other business in revenue. Last year, there was the revenue for partnership for MORAb-202. Therefore, there was the license income. Therefore, as a reaction to that, for this fiscal year, other business revenue significantly decreased. This accounts for the reasons why there was over 90% reduction in operating profit for this fiscal year. The decrease in the revenue in other business was also due to the items of business development, which were anticipated to be recorded in the first half, which were delayed to the second half. We can say that these items will be realized in the second half for sure. The revenue in the other business will recover to what was expected at the beginning of the year for the full year. Therefore, this decrease in operating profit is one-time, and we are sure that the profit level will recover in the second half. The second line from the top, pharmaceutical business revenue, because of the weaker yen, it grew 18% from a year earlier. Excluding the Forex impact, it grew 106% or 6% up from a year earlier. Our overall main business, which is a pharmaceutical business, the revenue has stayed steady and strong. R&D expenses accounted for 22.7% of revenue. We have continued to make strong and positive investment in R&D expenses compared to the peers of the global top-tier companies. AD related and lecanemab R&D expenses have been made proactively. We have prioritized investment and resource allocation to these areas. Including partners' reimbursement, the R&D expenses ratio in the revenue was over 30%. This suggests that we have been making proactive investments in R&D expenses. SG&A expenses, because of the strong impact by weaker yen, particularly the next line, shows expenses regarding shared profit of LENVIMA paid to Merck. If you look at this was expanded by about 1.5-fold from a year earlier. This is the shared profit of LENVIMA paid to a partner. This shared profit of revenue, in line with the expansion of revenue of LENVIMA, it is expected to increase as well. This is the proactive investment. We believe that this will lead to the further strengthening of our collaboration relationship with partner. Excluding this shared profit in the SG&A expenses, excluding the impact of weaker yen, decreased slightly from a year earlier. Therefore, SG&A expenses have been well controlled. That is our understanding. As a result, operating profit was 9% of the recorded amount of last year at JPY 5.3 billion. Profit for the period, as we reported in the financial briefing session for the first quarter, in order to correct the maldistribution of the funds, we received the repayment of the paid-in capital from a consolidated U.S. sub to the company. Thirty-one point eight billion yen was recorded as the profit for the period because of the reduced tax expenses. We have been able to maintain the very robust and healthy balance sheet and financial structure, based upon which, at the board of directors meeting held this morning, we have resolved to pay JPY 80 per share as the dividend for the first half. Next page. I have said that the pharmaceutical business has been steady, and the driver for such steady growth is these four global brands as you can see here. In particular, LENVIMA grew 40% from a year earlier to reach JPY 128.2 billion. For Fycompa, HALAVEN, Dayvigo, for all of these products, we have been able to exceed the levels recorded last year. For Dayvigo, significant growth was achieved in Japan, which was about double the revenue from last year. For global brands, total revenue was JPY 183.3 billion, which was up about 40% year-on-year. Next. By region as well as the current status of pharmaceutical business and OTC business as well. For the left half, as I said earlier, the revenue of the pharmaceutical business grew steadily, and also segment profit of pharmaceutical business, excluding the impact of weaker yen, up 15% from a year earlier. Therefore, we have been able to grow the profitability as well as revenue in these segments. On the right-hand side, you can see the growth of revenue by segments. In all five regions where we do businesses, we have been able to achieve the growth over last year. Particularly Americas and EMEA, we could achieve double-digit increase in revenue. In Americas, over 40% growth in revenue was mainly driven by the growth of LENVIMA. Because of this impact, if you'll turn to the left-hand side, bottom left pie chart, this shows the share of the sales composition by region at Eisai. The blue portion at the bottom, Americas share, is shown here, which increased by five percentage points. Next. This is the financial forecast for full year. In the second half this year, we are ushering in the era of lecanemab. We are entering a very crucial period with a very tense, and we have braced up ourselves with a strong resolve. We're expecting to have revenue of JPY 760 billion. R&D expenses and SG&A expenses will be controlled securely. The revenue in the other businesses which have been delayed to the second half, we are confident that we will recover in this line as well. Operating profit will be JPY 55 billion. Profit for the year will be JPY 58 billion. JPY 160 per share as dividend, based on the robust balance sheet or financial structure, will be achieved. Now, today, I would like to talk about Alzheimer's disease as well as the current status of lecanemab. If I may recap, Alzheimer's disease, what AD is. First, this disease is a progressive and fatal neurodegenerative disease which accounts for approximately 70% of elderly people living with dementia. AD begins with slow cognitive and functional deterioration, and then eventually leads to total loss of independence in the later stage. AD progresses from an asymptomatic preclinical stage to mild cognitive impairment, or MCI, to dementia, and ultimately to death. In the United States, AD is the sixth leading cause of death. Very, a critical disease. Pathophysiologically, amyloid plaques, neurofibrillary tangles with tau, neural and synaptic degeneration, or neural inflammation are confirmed in AD. One out of three people diagnosed with MCI progress to AD within five years. One out of two people diagnosed with AD are mild AD, according to some reports. What is most conspicuous about this disease is that this disease pose a significant economic burden on healthcare system and the people living with AD and their families. Burden of taking care of the patients, particularly for families. Informal costs or invisible costs are estimated to exceed the healthcare expenditures or, nursing care expenditures provided by the public service. Also bringing about the economic burden on the families, such as restricting the working hours of the family members who have to take care of their family as patients. Next, in late September, top line results for Clarity AD for lecanemab, and I would like to give you the update since then. First, we initiated communication with FDA, PMDA, EMA, these three major regulatory authorities. We have been able to make and continue smooth communication with them. By the end of March next year or within the end of fiscal year 2022, we are aiming to complete submission for full approval in Japan, U.S. and EU. CMS managing Medicaid, Medicare, we have started negotiation with CMS as well. For AD DMT accelerated approval, CMS has made a very tough decision on the reimbursement. However, for full approval and so-called data with high level evidence, if these have been brought forward and this decision can be overturned, this statement was also issued by CMS. We believe that Clarity AD data meet the requirements to be high level evidence prescribed for by the CMS. We are aiming to secure full reimbursement coverage in the United States, and we would like to continue to have constructive dialogue with CMS going forward. The second bullet point is related to the review under accelerated approval pathway in the United States, which is ongoing on track. PDUFA action date has been set for January 6 next year, so we expect that we will obtain approval by this date. Regarding the results from Clarity AD, how we are going to publish the results. We are preparing to submit for timely publication of the results in a peer-reviewed journal with high impact factor, which is ongoing steadily. This publication shall be co-authored by 12 eminent experts in the field of the dementia who are also investigators in Clarity AD, and seven experts from Eisai. On November 29, CTAD conference will be held in San Francisco. On the first day of the congress and in the first session in the evening, 75-minute lecanemab session will be held. I would like to share with you what will be presented then. The session will be chaired by Professor Takeshi Iwatsubo of the University of Tokyo. Professor Iwatsubo is the president of Japanese Society for Dementia Research. Presentation one will be talking about the study design of Clarity AD. Eisai Inc.'s Michael Irizarry will report. Michael played the central role in preparing the protocol for all the lecanemab related studies. Next, regarding the efficacy of lecanemab from Yale School of Medicine, Professor Christopher van Dyck will make presentation. Professor Christopher van Dyck, as you may know, has experience in most AD-related clinical research projects, and he is the leading authority in the AD field. Regarding safety profile of lecanemab, Dr. Stephen Salloway, who is the leading authority in the safety research of AD, will make presentation on safety and imaging CSF plasma biomarkers. Bateman from Washington University will make presentation. He is the leading authority on these biomarkers related to AD, and he is the leader of the DIAN-TU. For presentation five, which will discuss context of Clarity AD results. The overall data from Clarity AD will be discussed to explain what clinical meaningfulness are included in such data for patients and their families. This is going to be the overall presentation. The speaker will be from Toronto Memory Program. Dr. Cohen will speak. Dr. Cohen is in the front line of a clinical practice as the behavioral neurology expert. Dr. Cohen has rich experience in real world. Therefore, she is appropriate for talking about the meaningfulness and significance in the real world. She believes that it is very important to have such a clinical real-world meaningfulness. Lastly, there will be panel discussion and Q&A. For Clarity AD, there will be multifaceted discussions on the Clarity AD as a whole in detail the data sets at this conference. As we have been telling you, what we believe as very important as regards to lecanemab is to secure transparency of data. I'd like to report to you today that we are making steady progress towards transparency of data. If I may recap what we may have said, I would like to talk about the origin and characteristics of lecanemab. On the left-hand side, you can see the origin and the development since then. Of course, AD DMT that started from this publication of the amyloid cascade hypothesis by Professor John Hardy in 1992, which was published in Science. In 2001, from Uppsala University, Professor Lars Lannfelt researched familial Alzheimer's disease in Sweden, and he found Arctic mutation. On the right-hand side, mutation was found in 22 of amyloid of that beta, APP. In researching this Arctic mutation, he found that amyloid beta protofibril were formed significantly, and amyloid beta protofibril was found to be playing a central role in neurotoxicity. After that, in 2005, based on this Arctic mutation, the creation of the mouse-derived antibody was started. Since then, Eisai participated in the joint research. In 2007, that mouse-derived antibody was humanized successfully, and then gave rise to the lecanemab, which was the first only amyloid beta protofibril antibody with high affinity and selectivity for protofibril, which is explained on the right-hand side. In this diagram, a snake-like figure shows APP, amyloid precursor protein. Currently, there are four AD DMT antibodies in clinical stages. The regions of affinity held by these four antibodies are shown in this diagram. As you can see, each of the four antibodies are recognizing different regions of APP, respectively. Lecanemab, as you can see in the bottom right corner in red characters, when amyloid beta is in the monomer state, lecanemab recognizes 1-16 of amyloid beta. But when amyloid beta aggregates and forms protofibrils, it recognize 20-34. Therefore, as a result, protofibrils are more easily recognized and leading to high affinity. So this is the unique characteristics of lecanemab. Next, for success of lecanemab Clarity AD, we believe there are four Rs. At Eisai, we believe that these four Rs, four right elements needs to be realized in order to have success in drug discovery. This is what we have believed in. Regarding these four Rs, four rights, I'd like to explain. Right hypothesis, right dosage and administration, and right target population, and right endpoint. This may be compared to jigsaw puzzle. Once there is a perfect combination of these puzzles, we have experienced success in drug discovery and development. In this Clarity AD, for right hypothesis, amyloid beta protofibril playing a central part of neurotoxicity in AD. If we can suppress this, then we will believe that it will lead to the improvement of the clinical symptoms. Right dosage, 10 milligrams per kilogram bi-weekly without titration. This dosage and administration were identified. This dose and administration, as we have reported to you several times, was based on the results from phase 2 study, Study 201. Study 201 took as long as 6 years. Five doses were compared in control study against the placebo. Therefore, it took as a result in total 6 years. It gave us a lot of frustration. From the results of the study, we derived this dose and administration. We believe that this was the one of the key success factors. Now, right population, MCI, and mild AD, and right endpoint. Over the past 20 years. Regulatory authorities have reviewed CDR-SB in the past. This was designated as the endpoint, primary endpoint. We believe that these four Rs led to the success in Clarity AD. This is a busy slide, but what we consider to be important is shown in this slide. Clarity AD success and origination of lecanemab related importance. The beginning of the lecanemab drug discovery was Arctic mutation discovery. This is a familial mutation. Starting with that discovery, pathology, functional genetics were understood. What is at the center of that pathology is Aβ protofibril, and clearance of Aβ protofibril was suggested as potential treatment. Highly selective Aβ protofibril antibody was developed. In not only familial Alzheimer's disease, but sporadic Alzheimer's disease which show similar pathology are also targeted. In sporadic Alzheimer's disease, effectiveness was shown. In drug discovery and development of lecanemab, this approach was taken, and we believe that this will be a new page in the chapter of drug discovery in neurology area. E2814 development is underway. This is anti-tau antibody. Similar pathway is followed by E2814. This anti-tau antibody is looking at dominantly inherited AD mutation carriers. From that analysis, it was found that within CSF, there is an MTBR region containing tau. This was discovered to be increasing from early stage. MTBR tau clearance was expected to result in slowing down of clinical deterioration in not only DIAD, but in sporadic Alzheimer's disease. With that thinking, development is underway. Specific tau antibody specific to MTBR was developed. The familial Alzheimer's disease trial is conducted by DIAD, but we are also conducting in-house phase one study. Sporadic Alzheimer's disease with similar pathology, tauopathy treatment, is what we would like to target. Toward maximization of value of lecanemab, multiple studies are ongoing. First, regarding development of new administration methods, I would like to report that these developments are underway. Currently, administration is intravenous dripping. Patients will have to come to the hospital and receive IV drip for a certain duration of time, which can be burdensome. At home, for self-injection, to enable self-injection, new administration method is developed. Clarity AD open-label extension study is conducted, and auto-injection included subcutaneous administration sub-study is carried out. We aim to file for regulatory submission in fiscal 2023, as shown in the second bullet. Development of maintenance dosing regimen is also underway. Currently, it is bi-weekly, but after obtaining certain efficacy, switch to monthly or once every 12 weeks or longer interval administration maybe are considered in Study 201 OLE study. As shown in the middle, we are beginning to collect evidence from long-term administration. The two OLE studies are planned for up to five years and four years each. In addition to early AD data that we have collected thus far, for moderate AD, what efficacy we can observe in terms of data can be collected. DIAN-TU Tau Next-Gen study also plans to have long-term administration. As shown at bottom, now as for earlier stage in preclinical AD, asymptomatic AD, will be targeted. This is a PET finding of borderline or slight increase in PET finding. These so-called preclinical AD, a stage before MCI, will be targeted in phase 3 study called AHEAD 3-45 study. This study is underway and 54 months of administration is planned. On a broader base of patients, we are planning to make a greater contribution. Next, regarding amyloid diagnosis, this chart shows the current status. The top part is a very busy chart. In Japan and the United States for MCI and AD, PET CSF blood biomarkers are used for amyloid or tau, and whether regulatory approval is given or not is shown, and whether reimbursement is given or not is shown. Regarding regulatory approval, circles or crosses are found in the cells, and you can see that the situation is mixed. As for reimbursement, currently, for most of the diagnostics, crosses are the majority. They are not reimbursed. AD DMTs are approved and launched. At that time, there should also be regulatory approval for amyloid diagnostics, and reimbursement should also be granted to amyloid diagnosis. This is a crucial factor in providing AD DMT to patients. Currently, we are also engaged in consultations with the authorities regarding PET, as shown in the middle. Imaging authentication facilities are increasing in number, and especially regarding amyloid PET, enhancing the number of related staffs will have to be achieved. Regarding CSF, lumbar puncture procedure is necessary. Through training sessions, conferences, it is important to make lumbar puncture procedure skill widely acquired. As shown at the very bottom, going forward, patient number is expected to grow the most in Asia, especially in China and in India. In Asian region, we believe that patient number will be increasing by wide margin. Therefore, in this region, low cost, convenient BBB, blood-based biomarker, will become essential. By accumulating real-world evidence, tests that are as precise as amyloid PET or CSF will have to be established as BBB, blood-based biomarkers. We would like to do our best in that respect. Now, at Eisai itself, we have subsequent projects for Alzheimer's, which I would like to report now. Regarding Lecanemab, I have already reported to you so far. Next, as I mentioned earlier, we have anti-MTBR tau antibody E2814. This is in the middle of this schematic diagram, and tau will be propagated in the. There are green parts on both sides of MTBR tau, and antibody that has affinity to these are developed, which is E2814. By stopping the propagation, the accumulation of tau in the neural cells will be stopped or inhibited. That is the mechanism. E2511 and E2025 both aim to restore synaptic function. E2511, by activating TrkA, aims to restore synaptic function by regenerating damaged axons. This is a small molecule oral drug. E2025 is an antibody. It is an anti-EphA4 antibody. When EphA4 is activated, synaptic retraction and tau phosphorylation occur. By suppressing this activation, dendrites are to be regenerated to restore synaptic function. Both of these themes aim to restore synaptic function. These are themes that come after proteinopathy. These themes target activation of neuronal cells. Next, further upstream, we have collaboration with academia, which is advancing. There is an exclusive collaboration between Eisai and academia. One is with Keio Medical School in Japan. This is called EKID, Eisai Keio Innovation Lab for Dementia. This receives full funding support from AMED and from 2017 for 10 years. Project is underway. Keio Medical School, Keio University School of Medicine, as you know, has centenarian samples. Samples of people over the age of 100, 110, 120. Data from these people are collected, complete with medical records. Some of them have APOE4 positive data, but even at the age of 120, did not experience onset of Alzheimer's disease. Such samples are also included, and these are quite a precious assets. In addition, related to Keio, we have high quality clinical samples. Based on these, research is conducted. Analysis using multi-omics is carried out, and iPS cells and human organoids are also used with cutting-edge technologies and facilities. By AMED, there are three milestones established. The first milestone was achieved in fiscal 2021, which is brain clearance enhancement. A related target signature was discovered. At Eisai itself, synthetic research will be initiated and preparation is made. Milestone 2 is brain homeostasis improvement, and milestone 3 is a neural network activation. As shown on the right side, we have collaboration with University College London, UCL, in the United Kingdom. For more than 30 years, we have engaged in collaboration with UCL in various forms. We are having a full-fledged collaboration with UCL in neurodegenerative diseases area. DRI, U.K. Dementia Research Institute, is a consortium of seven universities, and leading-edge research is conducted. UCL is a core research institute of that consortium. Anti-MTBR tau antibody that I've mentioned earlier is an antibody that was found as a result of the UCL discovery. Small molecule TREM2 function coordination for treatment of AD. For Parkinson's disease, there are 2 small molecule compounds. One is related to mitochondrial homeostasis, and the other related to lysosomal function. These projects are being launched. As for Eisai R&D at Eisai itself, starting from the second half of this fiscal year, business groups such as Oncology Business Group, Neurology Business Group, from discovery to development, we have these two organizations. As shown here, DHBL structure will be the structure that we will be shifting into. Deep Human Biology Learning, DHBL structure. The target remains the same, AD and refractory cancers. However, drug discovery approach will be changed significantly. As shown at the top, there is a green box and blue, pale blue boxes. Genome and various human biology data based drug discovery hypothesis will be pursued by these groups. In addition to integrated analysis of genome based on these five angles, protein integrity, homeostasis, microenvironment, dynamics, et cetera. These are upstream of biology angles. From these angles, we would like to aim at drug discovery. The basis of the hypothesis is the genome information. In the middle, there are pink bars, and here are where the hypothesis will be tested. What we consider world-class is our chemistry capabilities, and that will be utilized to the maximum. There will be discovery, validation and using the chemistry, optimum modality selection, will be aimed at in this pink bar part. In the blue part, ultimately, we have to also prove in clinical development our hypothesis and highly advanced statistical methods. We would like to utilize advanced statistical analysis method. With AI/ML of past data, for example, clinical trial without placebo arm may be designed or the number of participating patients may be reduced by substantial margin, or the duration of the time for clinical study may be shortened substantially. By conducting such studies, we would like to prove the hypothesis. Only we will be able to have high-quality clinical data, biomarker and cohort data from these efforts, and they will be fed back, and this cycle will be repeated. Now, there are two last slides. Another important aspect of dementia is realization of inclusive society. People living with dementia should be able to live in comfort and with a sense of security. We have to build such a society. From quite early on with various local governments, we have been cooperating with local governments in our efforts in this respect. On the left side, employment support in Gifu Prefecture and in Oita Prefecture, in Taketa City, we are conducting ikiiki driving and health classes. Elderly people, if they have to give up a driver's license, it will be very difficult to lead daily life. How it is important for elderly people to be able to drive for as long as possible, and that is what is dealt with by these classes. Two boxes in the middle show dementia screening in Bunkyo Ward or space creation project, where a house is rented. Together with our neighbor, Atomi University, we are engaged in this project. On the right side is Kakekomi-dera Shichikenchō Center for dementia care promotion in Shizuoka City. People can consult about any questions regarding dementia by going to this center. This is the last slide. For 25 years since the approval of Aricept, people living with Alzheimer's disease and their families kept asking us, "When will the next drug come out?" We have never forgotten the serious expressions in their faces and sparks in their eyes, not even for a moment. Just the other day in August, in the United States, there was a relocation of a U.S. entity to Nutley. We had an opening ceremony, and we also invited people living with Alzheimer's and their families. At that ceremony, the families asked, "When will the next drug come out?" I answered that we will be able to provide information of the results at the end of September. The person living with Alzheimer's who was right next to us was looking at me quite intently and asked me, "Are you sure?" This is quite momentous. It is very strong expectations. I felt a very strong sense of responsibility to fulfill that expectation. We are doing our utmost to obtain approval of lecanemab. Drugs are able to show value only when drugs are taken by people who need the drug. We are determined to do our utmost to realize that, to realize access. We are working with various parties to find ways to help people living with dementia and their families live safely with peace in mind. What Eisai can do may be limited and small, but we are working with industry, government, and academia towards this end. Thank you. Now we'd like to open the floor for Q&A session. First, we would like to take questions from those who are in this venue, and afterwards we will take questions from those who are participating online. Please utilize microphone and state your name and affiliation before asking a question. Please raise your hand if you have any questions. To the left in the venue, and the gentleman in the second row, please. This is Kohtani of Nomura Securities. Thank you very much for your presentation. On page eight, a primary endpoint was discussed, so I wanted to ask you a question. I understand CDRSB is globally used as primary endpoint for AD, but there is only one company that uses very different endpoint. Now, turning to ADCOMS, I think Eisai used ADCOMS as primary endpoint in phase 2 study. As regulatory agency did not agree on it, you changed it to CDRSB. ADCOMS is a composite of MMSE, ADAS-Cog 14, and CDRSB, and it includes cognitive and behavioral endpoints as per required by the regulatory authorities. Could you recap why ADCOMS, which is similar to CDRSB, was not accepted? If the agency's position has not changed, do you think it is likely that iADRS, which is a composite of ADAS-Cog and ADCS-ADL, will not be accepted by agencies? CDRSB has been used widely and for many years. For regulatory authorities, they wanted to evaluate based on CDRSB. That was the main reason. ADCOMS, as you know, this is the composite score created by Eisai. As the secondary endpoint, ADCOMS was admitted. CDRSB was set as the primary endpoint, and there are four secondary endpoints. As an overall data set for all these endpoints, we believe that very important result were derived. Am I answering your question? iADRS is different from ADCOMS. Do you think that there is a higher chance that the regulatory authorities will accept that, FDA? I did not understand what it is. iADRS. As you know, this endpoint is related to dressing as well as cleaning of the room and preparation of meals, take a walk. For payment at the time of shopping or whether or not the person could go for shopping. There are 18 items in the activities of daily living which are evaluated, rated by caregivers. This endpoint is very important endpoint. As we reported earlier, this has been shown to have the remarkable suppression of the decline of the clinical symptoms. If with such a clear efficacy and then clear decline of the s uppression of the clinical decline, and then this shows the clear efficacy of the drug. To see that context, this is the last session for the overall summary. This endpoint will be discussed as a very important endpoint. This is only my surmise, but in our discussion with various key opinion leaders about top-line results, this sub-endpoint, as we are sure, will be taken up by them as a very important endpoint. Therefore, we believe that this is a very important second endpoint. ADCS-ADL, I think that is what you are referring to. Well, I don't want to spend a lot of time. Well, I don't want to confirm what is written in the weekly magazine, but this is a news in the United States. That news, after lecanemab, there was a person, patient, who passed away because of the cerebral hemorrhage. That person said that it was related to lecanemab, but this will be judged by the DSMB. According to your publication, your opinion is different. The MI and also other stroke and several falls were reported, and anticoagulants were prescribed additionally. According to this report by the company, could I have your take as a company on this matter? May not be related a lot, but I mean, amyloid beta antibodies is related to ARIA-E and ARIA-H. What is the mechanism relating to the cerebral hemorrhage? Lecanemab and then nine cases of mortality after ARIA-E. Well, there were no such reports related to such events. I think that you can more strongly negate that possibility. As for this case, this is related to the personal information of the patient. Therefore, I am afraid I'm not able to mention any detailed background. For this particular case, when this happened, the company of course securely followed up on this case, and we reported to the regulatory authorities. An independent data monitoring committee made a deliberation and came up with a judgment. They said that there was no need for amendment, significant amendment of the protocol. Once again, you needed to emphasize the notes to be taken. That was the instruction from the committee. Based upon which we have continued. For the overall progression of this clinical trial as well as the requirements for regulatory submission, we do not believe that there has been any significant impact. Thank you very much for the clear explanation. Next, question, please. Yes, attendee, seated in the second row on the window side. I'm Sakai from Credit Suisse. I have two questions. First, PDUFA date, January sixth. I think this remains unchanged. After that, you will file a full package submission. I think it will be in three months' time, around by March, and then official approval is expected. If approval is given on PDUFA date and when you file a full package, until a full package approval is given, there is some lead time. What do you plan to do during that time? As you know, that period of time is such that for accelerated approval product, CMS has quite stringent limitations in terms of reimbursement. For Medicare, we will have to follow that limitation. In markets other than Medicare, prescriptions may be written, and we will respond. As necessary, we would also like to start patient assistance program. Does this answer your question? Does that mean that basically it will be reimbursed, Medicare and Medicaid reimbursement? Do you expect that to start next year? The current NCD decision determination change occurs only after there is a full approval. That is my understanding. Thank you. Next question. The person in the first row to the left. Thank you very much. My name is Hashiguchi. I am from Daiwa Securities. I have two questions. First one is related to the SC formulation for lecanemab. By the end of the fiscal year 2023, you are aiming at filing a submission. In which regions? And the data sufficient for filing, what kind of data do you think will be required? Based upon the concept of the regulatory authorities. Are you saying that you are expecting to file by the end of the fiscal year 2023? Or regarding the discussion about the conditions to be met with the regulatory authorities are yet to come? Ivan Cheung is going to respond to your question. Thank you very much. We have had very productive conversations with various regulatory authorities, including the FDA, so that we now have confidence with a plan to file within fiscal year 2023. As you may remember, we've already reported out the bioavailability phase 1 result. Right now, in the OLE portion of Clarity AD, we are enrolling individuals into the subcutaneous cohort, which will give us the necessary TD and PK information as well as safety information. As you may remember, we reported out previously that we believe the subcutaneous formulation could further reduce the ARIA-E because of the, well, Cmax of the subcutaneous formulation, while maintaining the same C-average for this formulation. The plan is quite clear now with the regulatory authorities on the data package requirement, and we will file within FY 2023 to the major authorities. Thank you. My second point is related to your plan of the revenue in other businesses. You have revised down your forecast this time. Does this reflect any changes in your strategy? You mentioned that there were some business development-related events. Are there any changes in such plan, the BD events or changes in the number of BD projects? Although the number of projects has stayed unchanged, but the value of such BD projects have changed. Regarding this question, Mr. Kosaka is going to respond. This is Kosaka speaking. I am in charge of strategies. Thank you for your question. Could you please stand up? There are several BD projects with the probability of success are being discussed. Timing of the realization and whether or not that these will be carried out are being discussed. Based upon that, we have also factored in the strong and the robust growth in the real business. We have made up this plan. As we have reported, JPY 55 billion operating profit will be realized based upon the realization of these projects. Mr. Hashiguchi, as you know, there are innate risks in each of the one-time events. What was planned in the first half have been delayed to the second half, but with a very high chance we will be able to realize this. The numbers that we have presented are baseline, the minimum that we would like to achieve. Please understand as such. If possible, we would like to aim at further upside with the one-time revenue. I hope that you will take these numbers as such. As a follow-up question, if possible, I would appreciate if you could answer this question as well. According to the original plan, the sales milestone of LENVIMA were not included. This time, the revenue projection for LENVIMA has been revised upward. According to your explanation, the sales milestones are also included in the plan. Is this correct understanding? As for LENVIMA sales milestone, we will continue to pursue sales milestone for LENVIMA in the second half. We have had various discussions. We are continuing to pursue this. Thank you very much. Next question, yes, attendee seated in the front row on the window side, please. Thank you very much for the presentation. I'm Onishi from The Nikkei. I have two questions regarding the earnings results. In the latest quarter, it is down by 90%. What were the causes, and why do you think that you'll be able to achieve recovery in the second half? That is my first question. That question will be answered by Mr. Yasuno. I'm Yasuno, CFO. My apologies, I was not able to hear your question very clearly over here. Could you repeat your question? The first half operating profit was down by 90%. Why do you think that you are able to achieve a target in the second half? Could you elaborate on the factors behind this? Thank you for your question. On that point, and generally about profitability, I would like to supplement. Regarding the second quarter, a low level of operating profit was the result. As for the reasons, as our CEO just explained, in the first half, we expected business development related milestone, but these were postponed to the second half of the year. This is a temporary factor, and as a result, this will be realized in the second half. Therefore, we have no concerns about the full-year result. As for profit, in comparison to the previous year, profit declined. In the previous year, we had a large revenue from business development. That business development did not occur in the first half and overall profit declined. As for the overall structure, right now, as you know, we are investing actively for future growth, including research and development investments. The percentage of R&D to the revenue in the first half was 22.7%. This is the actual basis. As announced today, on a four-year basis, the forecast is 21.9%. Among global top-tier companies, this is a high level. Over short term, this will be pushing down operating profit. We would like to continue 20% R&D spending to revenue level for the short term and would like to bring it to around 15% over the medium to long term. In AD, oncology, and neglected disease areas, centering around these areas, in important projects for future growth, we would like to continue to make investments. As for another type of growth investment, as our CEO mentioned in the second quarter, expense regarding shared profit of LENVIMA paid to Merck increased. This is a positive expense. To advance partnerships, investment is made such as this. In the future, this will be leading to enhancement of operating profit, and this is an investment for growth, and we are confident that this will lead to achievements. If I may repeat, the low level of profit in the second quarter is temporary. Pharmaceutical business lately is showing robust growth. In addition, in the second half, strategic option we expect will be realized. Therefore, we have no concerns in achieving the full-year forecast. As CEO mentioned, that is considered as a baseline, and we would like to aim to achieve an upside. If I may add another point. We expect the strategic option realization in the second half. Regarding business development and strategic option and milestone receipt, these one-time revenues, we consider these one-time revenue as a result of our investment in R&D and commercial investment. We consider this to be returns on our investment and reward for our efforts in actual business. Inclusive of these, we believe that profitability is not necessarily low. I'm sorry I'm long-winded, but over medium to long term, our main organic business should achieve high profitability. We aim to achieve higher profitability in main organic business by digitalization. All operations will be made smarter. That will be one of the key measures. In R&D, AI machine learning will be utilized to improve agility of clinical research and reduce time required for clinical research. We believe these will contribute to improved efficiency in R&D spending. Thank you. I have a second question regarding FX in Americas. I believe in revenue and in profit currency level is working positively. What are your views on the current level of exchange rate? Once again, Yasuno speaking. Thank you for your question. On a full-year basis, we have announced in our forecast the exchange rate assumed is JPY 143 to the dollar. That is the basis of our full-year forecast. Is this high or low? It is difficult to say. I don't think anyone has the right answer. But currently, that is the assumption that we have adopted. As for dollar yen exchange rate and its impact on our business results, this is included in the reference material. When a yen depreciates by JPY 1 to the dollar, JPY 1.6 billion plus in revenue and negative JPY 1.2 billion in operating profit. That is the impact. I think we can take all the questions from those who are raising hands. We will take two. Well, there are three. Okay, we will take three questions from the venue, and then we will go to those who are participating online. The next question. My name is Susumu Shimoyama, author. We haven't been able to participate in the announcement of the results of Clarity AD, and congratulations. It started from the research on the familial AD, and lecanemab was discovered and developed, and I'm glad to hear that today. In familial Alzheimer's disease, those people living with familial AD. Well, they have cooperated for research. Still, they were not able to participate as subjects in the clinical trials. To resolve that issue, DIAN, the international research cohort was created, and then DIAN-TU were combined so that those people with FAD can participate. I think that's what Professor Lars Lannfelt mentioned. For lecanemab, the familial and the hereditary AD, MCI or mild familial AD were not included in this trial. Once approved, and then indication, do you think indication will include a familial AD or milder cognitive impairment or milder dementia, do you think that these will be included as the population who will be indicated for this lecanemab? Thank you very much. Indications to be granted from regulatory authorities will decide. Well, for Aduhelm, the Alzheimer's disease was simple indication, therefore covering very broad indications. That's my understanding. Then sporadic as well as familial AD may be included in the indication. Of course, amyloid beta confirmation will be necessary as a condition for that. Thank you very much. Next question, please. Thank you very much for that presentation. I'm Miyazaki from BS TV Tokyo. I have three questions. This is in relation to your earnings results. On a full-year basis you expect to achieve forecasted results. Today at Keidanren there was a press conference, and increase in wage was requested. I think that was the gist of the press conference by Keidanren. What are your views? I believe the message was that to increase wage by increasing base salary. This fiscal year, what did you do in terms of base salary? Even with the increase in wage, do you think you are able to achieve full-year forecasted results? Mr. Masaka is calling in, who is responsible for human resources development. Will respond to your question. This is Masaka, CHRO. Can you hear me? Yes, we can. Ms. Miyazaki, thank you very much for your question on wage increase and base-up or base salary increase. Regarding base increase in salary, on a year-end form basis to increase base salary, that is not considered at the moment. For this fiscal year, we have not increased our base level of salary. As for increase in wage, in addition to regular increase in monthly wage, we also have a performance-linked bonus. A bonus and increase in remuneration will have a personal performance reflected. We have adopted a total compensation to reward the performance by our people. The level of performance in expertise area, competitive area, we would like to review these areas. Follow-up question. One-time payment. With a one-time payment, you are planning to increase compensation to maintain motivation and to retain people. Is that the correct understanding? That question will also be answered by Mr. Masaka. Thank you for that question. One-time compensation is also not considered. In the future, for expertise areas, we plan to conduct a review of the compensation structure. Thank you very much. The second question from the venue, please. My name is Hyodo. I am from Toyo Keizai Inc. I have one question. Aricept indicated for the dementia with Lewy bodies. The result of a reexamination, what will be the potential impact on your business performance? Against the placebo, there was no significant difference in the primary endpoint. Could you please give us what you think about this result? Mr. Naito, please. Well, Mr. Ogawa will respond to the second question regarding the dementia with Lewy bodies. Did you hear? For that question, Mr. Ogawa is going to respond. I am Ogawa. I am in charge of the development in neurology area in Japan. Thank you for your question. There is no significant difference obtained in the endpoint. On the other hand, we have conducted the various studies and trials in the development. Overall, the improvement in the cognitive function was observed in those programs. Partial amendment is to be made to continue. There haven't been any further requirements from the regulatory authorities. Based upon this evidence, we would like to have a discussion and communication with prescribing doctors as well as the patients. Regarding the impact on the business performance, Mr. Ujiie, he's going to answer your question. Thank you for your question. As has been explained earlier, we have not received any additional requirements from the authorities. Therefore, the impact, potential impact may be minor. Thank you very much. We would now like to take questions from those who are calling in. If you have a question, please press star and one or asterisk and one. We have Yamaguchi-san from Citigroup Global Markets Japan Inc. Yamaguchi-san from Citi, can you hear me? Yes, this is Yamaguchi from Citi. Yes, please go ahead. Thank you for taking my question. I have two questions. First, regarding CTAD presentation that will be on the following day, morning Japan time. Maybe I should ask the CTAD conference itself, but do you think that non-registered audience will be able to listen? I'm sure many people are very interested in the presentations. I would like to ask Ivan Cheung to answer that question. Thank you very much. This is Ivan Cheung. You can be sure that we are making the appropriate arrangement to make sure that such important event can be viewed by all the interested parties. We'll follow up with everyone on this topic. Don't worry. Thank you. Thank you very much. Next q uestion is from J.P. Morgan. Mr. Wakao. Mr. Wakao from JP Morgan, do you hear us? This is Wakao of JP Morgan speaking. Thank you very much for this opportunity. From me, I have a question about lecanemab. Communication with CMS has been started. Now, for full coverage, could you please give us your feeling that you have felt so far? Well, regarding the results of the secondary endpoints which will be announced on the CTAD, that data have not been submitted to the authorities, but there may not have been any progress in that. But if there is anything, please share it with us. Also, the traditional approval will be obtained, and then there will be discussion to be initiated, for a full coverage. What is going to be the timeline? According to Biogen, they said that it will take about nine months-12 months. Have you started communication or Aducanumab, which was delivered for NCD, and then I thought that this could be accelerated further. Regarding this question, Ivan Cheung is going to respond. Thank you very much for your question. You are correct that we have been in conversations with the CMS. For example, we have already shared a number of important information and will continue to do so very shortly, including of course the most important item, which is the Clarity AD data. We are actually very reassured by the collaborative tone of the CMS in reviewing the Clarity AD data in an expeditious manner. With regard to timeframe, as you know well, of course the CMS will require full approval to make that official decision. We do believe this will be on an expedited process. The timeframe you mentioned is a standard timeframe post full approval in general, but in this case is very different. You may remember that even though the NCD is for the class, the lifting or amending the CED will be on an individual drug basis. Once again, I can reassure you that the conversation and the action plan with the CMS has been very proactive on both sides. We are obviously confident with the Clarity AD data, which you will see more at CTAD, hitting primary endpoint or the key secondary endpoint as early as six months, all highly statistically significant and more, such as the expected safety profile. All these elements, of course, will be under consideration for the CMS. Also, this trial is very unique because it has a rather well-represented population from a diversity perspective, from a comorbidity inclusion perspective to reflect the Medicare population as much as possible. We have confidence to have a positive outcome with the CMS upon a full approval to lift or amend the CED to drive wide access in the Medicare population in the United States. Thank you very much. This will be the final question. Muraoka-san from Morgan Stanley. Can you hear me? Hello, this is Muraoka from Morgan Stanley. Can you hear me? Yes, we can. Thank you for taking my question. I have two questions. First, about next fiscal year, I would like to understand how you plan to spend your money. I believe to improve access next year you will be proactively spending SG&A. Do you plan to make major investments? That is my first question. The second question is about the manufacturing of lecanemab. I believe it is already announced that Biogen will be manufacturing lecanemab, but is it sufficient? Is there any plan to outsource contract to outside the manufacturing of lecanemab? Thank you for the questions. Regarding the next fiscal year plan, Mr. Ujiie will respond. Thank you for your question. Right now, access strategy, commercial strategy are carefully considered at this stage, and we are currently not at a stage to describe a clear numbers, but necessary investments will be proactively pursued with our partner. Thank you for your question. Regarding the manufacturing of lecanemab, Ivan Cheung will respond. Thank you very much for the question. You are correct that drug substance will be manufactured by Biogen at the state-of-the-art facility in Solothurn. As you may know, that facility has flexibility to scale up going forward as necessary. At the same time, of course, for manufacturing planning for such important therapy for patients, additional backup sites will of course planned accordingly. We have no concern for the capacity to manufacture lecanemab. Thank you. With this, we'd like to conclude today's session. Thank you very much for participating in this session out of your busy schedule. Thank you very much. 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