It is now time. We would like to begin financial results presentation for the Third Quarter Fiscal 2021 by Eisai Co., Ltd. This presentation is live streamed. We apologize that this is only live streaming and telephone conference only. Those of you who are participating via telephone line, please download the presentation material from the website and click to move the slide forward. First part, financial part, will be presented by Dr. Yanagi, CFO, and the second part, operational part, it will be presented by Mr. Ivan Cheung, President of Neurology Business Group, and Dr. Owa, President of Oncology Business Group. Ivan Cheung will be presenting in English. If you are listening to a Japanese channel, you will be listening to Japanese interpretation. If you are listening to English channel, you will be hearing Mr. Cheung himself. Now, without further ado, I would like to ask Dr. Yanagi to start the presentation. Thank you very much. This is Yanagi speaking, CFO. I would like to present the Third Quarter of Fiscal 2021 consolidated statement of income. Please turn to page two. Through expansion of partnership model and global brands, double-digit growth in revenue and profits is continued. First, top -line revenue. Revenue was JPY 565.3 billion. This was 13% increase year-on-year. Double-digit increase was achieved. Drug price revision in Japan and the generics of Lyrica impacted. However, these were more than offset by strong growth of Lenvima, one of the global brand. There was also JPY 45 million of upfront payment on MOR202. Other business revenue includes the licensing-related revenue. Excluding this, increase was 4% year-on-year. Lenvima has low cost of sales, and Lenvima is growing, and licensing revenue was also recorded. Cost of sales as a result was 22%. In comparison to global standard, the figure is a favorable figure. As a result, gross profit was JPY 441.2 billion, which was a growth of 17%, double-digit growth from the previous year same period. This 17% increase, within that, margin, the increase of expense, is contained at 14%. As a result, we were able to achieve significant increase in both revenue and profit. As for the breakdown of the expenses, R&D expenses was JPY 123.3 billion. This was a double-digit growth at 14% year-on-year, and this is 21.8% of the sales. Mainly on Lenvima and global brands, we are investing resources proactively, including partners reimbursement. On a gross basis, R&D expenses was JPY 175.9 billion, which was 31.1% of the sales. In comparison to other global pharmaceutical companies, we are one of the companies that is very proactive in making R&D investments. As for SG&A expenses, this was an increase of 20% at JPY 255.9 billion. As a percentage of sales, it may look somewhat abnormal at 45.3%, but this is also including shared profit of Lenvima paid to Merck. This positive expense, if that is deducted, actual SG&A expense is JPY 190.4 billion, which is 33.7% of the sales, which is within the global range. Excluding share of profit, SG&A expenses grew 16%. This also includes other health-related items. Other income and expenses include divestiture of rights for Zonegran. Operating profit as a result was JPY 74.6 billion, about 30% growth year-over-year. OP margin is above 13%. For your reference, for the nine months, ROE is 11.2%. Excess equity spread exceeding 3% was ensured, creating value. As for the balance sheet, we are still net cash positive. Effectively debt-free at more than JPY 1,200 billion in cash. Net DER is -0.26x. Equity ratio is 62.9%. For future investment and for shareholder return, we have sound financial position to achieve both at the same time. Now please turn to page three. This is the breakdown of revenue migration. Left box at the very top is the revenue for the nine months from last year at JPY 498.3 billion. Below this chart, for this fiscal year, for the nine months, revenue was JPY 565.3 billion, which was a growth of JPY 67 billion. Excluding licensing, pharmaceutical business total was growing at 4%. On the right side, we have breakdown of the increased global brands. Total of four global brands exceeded JPY 200 billion, JPY 205.7 billion. This is increase of JPY 51.9 billion from the previous year. LENVIMA grew strongly at JPY 103.8 billion. Correction, JPY 141.1 billion. Growth, it grew by JPY 37.4 billion. This more than offset the impact of generics of Lyrica. Other business options are listed below. BMS upfront payment, $450 million is included here. As for LENVIMA-related milestone in calendar year, sales target is achieved, and milestone for that is recorded. $200 million was from last year. In this fiscal year, it is $300 million, an increase of $100 million. With that, revenue grew by JPY 67 billion. Next slide, please. This is page four, showing the breakdown of operating profit margin. Please turn. The left box at the very top is operating profit from last year. For the nine months, operating profit was JPY 57.7 billion. Below that, for fiscal 2021, from April to December, in the nine months, operating profit for this fiscal year was JPY 74.6 billion JPY 16.9 billion. JPY 7 billion positive FX effect was observed. In the pharmaceutical business, growth was 6%. In our core business, the pharmaceutical business, we were able to increase both revenue and profit. Right side shows factors for increase and decrease. Revenue had already been explained on the previous page. Regarding R&D expenses, LENVIMA in R&D cost increased by JPY 2.8 billion, but there was a regulatory milestone for approval of RCC in the U.S. of $75 million is included. Therefore, on a net basis, for LENVIMA, more than JPY 10 billion is invested, and we are also proactively investing in lecanemab. On the other hand, turning to SG&A expenses, as explained earlier, there are costs related to Aduhelm, and there is also LENVIMA profit sharing, which is also included in SG&A expenses. Last year's profit sharing was JPY 47 billion, and for this fiscal year, profit share was JPY 65.6 billion. As LENVIMA revenue grew, profit sharing increased by JPY 18.6 billion. At left, bottom, for your information, R&D expense breakdown is given. From partners, we have reimbursement. In last year, it was JPY 46.8 billion. In this fiscal year, JPY 52.6 billion. JPY 123.3 billion is R&D expenses on the, profit and loss accounting-wise. But on gross basis, JPY 175.9 billion is invested in R&D. With a partnership model, we are able to spend 1.5x the, R&D expenses on P&L. With the growth of global brands, we are able to increase both revenue and profit. That is the gist of profit and loss statement. That concludes my presentation on the results from the first nine months of this fiscal year. Next, on neurology business, Ivan Cheung will present. This is Ivan Cheung from Neurology Business Group. Let me first give an update on Aduhelm, and then I'll explain the tremendous progress being made with lecanemab. As you can see in the top blue box on slide five, our top priority for Aduhelm continues to be enhancing the AD community's understanding of Aduhelm's clinical data. Our partner, Biogen, is on track to initiate the phase IV post-marketing confirmatory study called ENVISION this year in May and is in the final stage of publishing the phase III data from EMERGE and ENGAGE. We are encouraged by Biogen's action to reduce the price of Aduhelm based on feedback from stakeholders, and we are pleased that the J-code is now in place for Aduhelm. The critical matter now is how to improve drug access to Aduhelm, and we urge CMS to reconsider its draft NCD with a proposed CED for monoclonal antibodies directed against amyloid by the April final decision, which I'll go into more details on the next slide about Eisai's position. In Japan, with regard to the outcome by the first committee on new drugs to continue the deliberation on the application of aducanumab, we're working closely with Biogen to actively engage with the PMDA to agree on it, on the additional data requirements so that we can pursue the most expedited path going forward. In Europe, with regard to the negative opinion adopted by the CHMP, the reexamination process has been initiated. Next slide. Slide six, please. On January 11, CMS released the draft NCD with a proposed CED that applies categorically to all monoclonal antibodies directed against amyloid and recommends restrictive coverage to only patients in randomized controlled trials approved by CMS or supported by NIH. Eisai strongly opposes this draft NCD for a number of reasons, as you can see on the right-hand side in the green box. First, we're greatly concerned that this action severely limits and delays access to FDA-approved therapies and directly calls into question the FDA's role in determining safety and efficacy of new drugs. Second, the proposed CED exacerbates health inequities by restricting coverage to only individuals willing and able to enroll in randomized controlled trials in selected medical facilities. Third, application of CED for investigational therapies that are not yet approved by the FDA prejudges clinical trial data and labeling. The assumption that drugs in this class are identical is wrong and unscientific. Last but not least, it's unacceptable to the AD community why AD treatments are the only ones being discriminated against with such restrictive CED, unlike other diseases such as cancers and HIV. We strongly encourage CMS to reconsider its proposed decision on this NCD. During the 30-day open comment period, Eisai will make a formal response. CMS final decision is expected to be issued by April 11th. If we look at the case of lecanemab, we deeply believe that CED is not reasonable, necessary, or appropriate based on Study 201 data, low rate of ARIA, and the anticipated data readout from Clarity AD confirmatory trial later this year. With that, let's go to slide seven. Now let me turn to lecanemab, and I'm very excited to report that we've made significant progress in the rolling BLA submission under the accelerated approval pathway. We remain very much on track to complete this BLA by the beginning of fiscal year 2022 in order to enable potential approval within calendar year 2022. Both the non-clinical module and the clinical module were already submitted to the FDA, and we're having ongoing interactions with the FDA regarding these submitted modules. The clinical module is primarily based on clinical, biomarker, and safety data from Study 201 core and OLE. As shown in the yellow box, we saw uniquely differentiated data in terms of amyloid clearance at just three months of treatment all the way to 18 months and low rate of ARIA. In addition, blinded safety information from the confirmatory phase III trial Clarity AD were included in the clinical module submitted to the FDA and will be updated for the FDA during the upcoming day 120 safety update. We are confident about the size of our safety database submitted for this BLA based on our interaction with the FDA. Meanwhile, in preparation for potential approval and launch before the end of this calendar year, we are working intensely on additional publications from Study 201 and mechanism of action and health economics value of lecanemab for the AD community. Looking further ahead, we continue to aim for a primary endpoint readout from Clarity AD by the end of September this year in order to enable submission for full approval to the FDA within fiscal year 2022, which I will explain in the next slide. Slide eight, please. I'm equally excited to report a tremendous progress from Clarity AD, our confirmatory phase III trial for lecanemab to support full approval in the United States and the basis for submission for approval in Japan and Europe within FY 2022. As you can see in the yellow box on this slide, this trial successfully completed enrollment of 1,795 subjects in March last year, and more than 620 patients have already been transferred to the open label expansion OLE study, representing about 95% of the eligible patients from the core study. The lower than expected discontinuation rate in the core study and the strong participation rate in the OLE study indicate high level of engagement from patients and their caregivers for this particular trial with lecanemab, even during the period of the COVID pandemic. In addition, we are very encouraged that ongoing reviews of Clarity AD by our independent DSMB have not identified differences in the safety profile of lecanemab, including ARIA, from what was seen in Study 201. Furthermore, we are very proud that approximately 25% of the total U.S. enrollment in Clarity AD consists of African Americans and Latinx people living with early AD, which mirrors the diversity in the U.S. Medicare population. Turning to China, a country with a large rising AD population, I'm glad to report that we completed enrollment for the additional cohort of subjects required for registration there during the previous quarter. Last but not least, we are on track to incorporate less frequent IV dosing regimen guided by blood biomarkers and subcutaneous formulation into the OLE study of Clarity AD later on this year. To get there, though, within this quarter, we'll first introduce less frequent IV dosing regimen into the OLE phase for Study 201, and we'll complete the phase I study of our subcutaneous formulation. Overall, as you can see, we continue to be confident about the outcome from Clarity AD and very much look forward to a data readout in September. Next slide. Slide nine, please. We have a clear vision that the specific role for lecanemab in this new AD DMT era is to create the simplest patient journey. As shown in the pink box on the left, we envision a simpler diagnostic pathway through digital cognitive tests such as Cognigram in the comforts of people's homes and simple blood tests for amyloid confirmation. Moving to the green box in the middle, we envision a simpler treatment process because lecanemab is the only anti-amyloid beta antibody that requires no titration and the upcoming availability of a subcutaneous formulation to allow self-injection. Moving to the yellow box on the right, we envision a simpler monitoring system driven by lecanemab's favorable safety profile, such as low rate of ARIA, and because of our extensive works with blood-based biomarkers to guide when to reduce frequency of dosing and when to stop dosing for lecanemab. Although not all these elements will be available by the initial launch in the U.S. under the accelerated approval pathway, we very much look forward to putting this together, the simplest patient journey together that is only made possible with lecanemab at a time of full approvals across major markets. Next slide. Slide 10, please. This is my last slide, and it summarizes why we believe lecanemab will emerge as the most comprehensive therapy in the new AD DMT era. Our conviction in lecanemab is rooted in four pillars. Number one is the early AD indication, which we believe lecanemab has a uniquely differentiated profile and could potentially be the first therapy to receive full approvals across major markets. Number two is the preclinical AD indication, which we believe lecanemab could be first to market. Number three is lecanemab's patient-friendly dosing approaches. Number four is lecanemab's position as a backbone therapy in combination regimen. I already explained about number one and number three, so let me update number two and then number four further. In preclinical AD, as shown in the upper right box, our phase III AHEAD 3-45 trial in collaboration with ACTC is enrolling well in over 100 sites globally. This cutting-edge trial has what we believe the most modern biomarker characterization for the A3 population versus the A45 population, and also dosing paradigm tailored to the A3 population versus the A45 population. With regard to the combination regimen as shown in the lower left box, we believe lecanemab potentially has the best profile in terms of both efficacy and safety, as well as dosing approaches to become the backbone therapy in combination regimen. Lecanemab was selected as the base anti-amyloid therapy in a DIAN-TU Tau NexGen phase II/III study for DIAD subjects, which is now actively enrolling into both the symptomatic tangle-positive cohort and the asymptomatic tau accumulation cohort. We're continuing to evaluate other proposals to potentially combine lecanemab with other novel agents to further combat this devastating disease. This concludes my presentation. Thank you very much for your kind attention. With regard to the oncology business, Dr. Owa would like to report to you our oncology business. First of all, with regard to the Lenvima sales revenue, please take a look at the left-hand side bar graph. FY 2021, the third quarter, JPY 141.1 billion global sales was achieved, which is 36% year-on-year growth. Japan-originated blockbuster of Lenvima has been achieving the very powerful growth. When you look at the sales in Americas region, in the same time previous year, the sales was JPY 62.2 billion, which grew to JPY 82.6 billion, up by JPY 20.4 billioA, driving the overall growth. As for China, centered around the HCC indication, achieved 84% of the growth year on year. Also for EMEA as well as Latin America, and Europe as well as in Latin America and Asia, 40% of the increase was achieved. For the important contributions of Lenvima to the patients is the approval for this Lenvima in combination with Keytruda. Here you see the two processes that are currently ongoing. One is the advanced endometrial carcinoma. That is following the prior systemic therapy in U.S., in Europe, as well as in Japan. Last year, in July, November and December, the approval is granted. In response to this, in January of this year, the pivotal phase III study, the 309 study was published in New England Journal of Medicine. In Asia and Latin America, based upon this pivotal study, we are currently in the submission phase. For China, the phase III is the LEAP-001 study. The first-line study is currently ongoing. For the second one is the advanced RCC for the first-line. In the United States, as well as in Europe, the approval is granted in August and November. Currently in Japan, this is currently under review by the health authority. Actually, tomorrow on February 4, this is going to be reported in the special new drug committee to be organized tomorrow. In Asia and Latin America, in January, it was granted the approval in Taiwan and also in another country. This is under review. With the contribution with Lenvima and other indications in the for the calendar year, we expect we achieved $114 million of the sales for Lenvima and achieved the sales milestone and have received $300 million for milestone payments. For other milestones, I can report to you that we are pretty much on track. The next slide. As you know that in order to maximize the patient contribution in oncology field, we really need to capture the position as the standard of care and for Lenvima to really achieve the leading positions. We are aiming at all of these the cancer indications. One is the hepatocellular cancer. This unresectable HCC patients would be the target. This is going to be the Lenvima monotherapy to be followed by TACE. This is the conversion therapies being looked at in this study and which was reported in January 20 at ASCO GI meeting. As you can see that the response rate is as high as 94.6%, and the complete response rate was 66%. Very high level of the response rate was reported. Also Lenvima in combination with Keytruda and the Lenvima in combination with TACE and also MK-1308, that is Lenvima and also the pembrolizumab. The fixed combination therapy is being studied. First of all, for RCC and after getting the approval in the United States in January last year, the first-line market share has been expanded rapidly. Also in Europe, as the EU as well as at ESMO, Lenvima or lenvatinib and the Keytruda combination therapies are now newly recommended for the first-line. Also HIF-2 alpha inhibitor that is called belzutifan and also MK-6482, a combination therapy. Again, they're all currently being studied in phase III studies. The third indication is endometrial cancer. Now NCCN guideline is being recommended in the second-line with the category 1 evidence for in combination with Keytruda. Also in Japan, including DNA mismatch repair enzyme deficient patients, that is for all-comer, the basis the approval is granted. Also the first-line LEAP-001 study patient enrollment has been completed. The study is progressing and ready to come up with the top-line results. Here on this slide, you see four of the LEAP studies that have already completed last patient in. One is the LEAP-002 for HCC, the first line, and also LEAP-006 studies and third, non-small cell lung cancer and also, LEAP-001 studies, that's endometrial cancer and also a LEAP-003 studies, melanoma studies. They're all looking at the PFS or the overall survival as the primary endpoint. That is to say that, this study design can really replace the current, the first line therapies. After achieving the, last patient in and there was no, judgment of futility, given and it is progressing very rapidly. That is to say that there was no judgment that this would not be able to achieve the primary endpoint. This shows how hopeful this study is. As for this final readout, as is reported in ClinicalTrials.gov, and the LEAP-002 study is expected to come out in July this year and also two years in two years time and in April. The report is expected OS. Also we are expecting some interim analysis for some of the studies. Based upon the disclosure rule, once we get the positive results from these studies, we'd like to keep you informed. From 2022, the very important LEAP study data expected to come out one after another. Therefore, I think that we are ready to make a very strong step forward into the future. In this slide, the oncology pipeline, following the LENVIMA KEYTRUDA combination therapy is indicated. The key to that is that through this LENVIMA KEYTRUDA combination studies that we have been able to collect the various clinical data, and we have been able to better understand the mechanism of resistance to IO therapy. We'd like to learn from that, especially the CBP pathway. FGF pathway has been very much drawing attention. The first one is E7386. This is the medium molecules CBP beta-catenin inhibitors. Inhibiting the protein interactions and Eisai's chemistry is really putting all our efforts into this oral agent. Already the clinical POC has been established. One is that the clear tumor shrinkage effect has been demonstrated from the various carcinomas. Also very important pharmacodynamic, the biomarkers changes have been identified from the genes as well as from serum. The gene biomarker is AXIN2, the biomarker. The protein is the FGF23, the biomarkers. Based upon these biomarkers, the Lenvima in combination with E7386 or the Keytruda in combination with E7386. Two of these phase I-B studies are currently being carried out for some of the carcinoma. The next asset is E7090. That is the new type five bound FGFR1/2/3 inhibitor. With regards to E7090, the clinical POC has been confirmed in phase I study, so very clear, the tumor shrinkage effect has been obtained. Six of the FGFR2 positive bile duct carcinoma patients and 5 PR was reported. Another important pharmacodynamic biomarker is FGF23 and dihydroxy vitamin D and phosphate. The clear elevation of these biomarkers, serum biomarkers, have been confirmed. Based upon this, FGFR2 fusion-positive biliary tract cancer pivotal studies are currently ongoing. Fulvestrant, exemestane in combination with E7090 is being carried out for the patients who are ER-positive and HER2-negative breast cancer patients. This is my last slide, and here we are discussing the update of MORAb-202. MORAb-202 is the very first Eisai's ADC, the antibody-drug conjugate. For this MORAb-202, the antibody part is Eisai-created farletuzumab, and that is the target antigen, the folate receptor alpha. This is like for lineage-dependent cancer like serous cancer, endometrial ovarian, so endometrial, so peritoneal cancer. We see the high level of expression of folate receptor alpha and of course for payload is irinotecan. Irinotecan has a very unique bystander effect. Based upon this compound profile, this can demonstrate a certain effect. That is to say, in the form of ADCs, it is internalized into the cancer cells. With the enzyme, the linkers would be truncated, and then irinotecan would be accumulated at very high level, having this cytotoxic effect. From the dead tumor cells, it will be efficiently released. For the cancer microenvironment, especially this mesenchymal cancer-related fibroblast, it does have a very strong suppressive effect. It does have a very unique bystander effect. With this kind of very superb drug profile, we have entered into this strategic partnership with BMS. Based upon this alliance partnership, we are currently discussing this BMS so that we can start the pivotal study in 2022. As for the MORAb-202, the patients who have been heavily pretreated, especially ovarian, endometrial, triple-negative breast and non-small cell lung cancer patients, we have been able to demonstrate a very clear anti-tumor effect in order to optimize the efficacy and safety through the right dosing regimen. That we would like to get ready to move into the global pivotal study for this compound. Thank you. Next, with regard to the full year, the financial forecast, I'd like to ask Dr. Yanagi to present. Once again, Yanagi, the CFO, would like to go over the consolidated financial forecast. Please refer to slide 16. Here you see the FY 2021 financial forecast. With the continued growth of Lenvima and also the continued investment into R&D in a financially disciplined manner would continue. The sales revenue is JPY 730 billion, which is 13% growth from the previous year. Including the license income and also with this growth of Lenvima, we have seen these product mix improvement. We would expect the level parallel to Q3 and also the very low cost of sales that can be achieved. As a result, the gross margin would achieve the double-digit increase. With this 130% growth in the sales revenues, we can expect very good operating income. The gross margin increase is going to be above this. Operating income is expected to be JPY 78 billion, which is 50% higher than the previous year. There is no change to the forecast from the previous announcement. ROE in this period is 8.4%, creating the positive equity spread. With the strong balance sheet, we are confident we can continue with the dividend of JPY 160 with this good positive financial discipline. Now, lastly, I'd like to go over the last page 17, and I'd like to share this with you as my concluding remarks. You have already heard from the presentations on Neurology and Oncology Business from Ivan Cheung as well as Dr. Owa. For the respective businesses, we have witnessed the very steady growth, and the pipeline is becoming ever more enriched. On top of that, I have tried to explain some of the financial numbers, but we have had the first nine months of very favorable performance. There is a very favorable the forecast for the full year for 2021. Based upon the strong balance sheet, we do have a very solid the financial fitness. Based upon that, we would like to continue with the mid- to long-term proactive investment into the future under these conditions. When we look at the current share price, I must say, unfortunately, this is very much dissociated from the intrinsic value of a company, and it is pretty much towards the green. However, under this COVID-19 pandemic, which is really becoming the major social issues around the world. However, in the field of dementia that we are working on, again, almost in line with this COVID-19 pandemic, and this will pose the most major challenges for us. We are really working for this very serious challenge that is in front of us. As Ivan Cheung mentioned, we have complete confidence into the lecanemab that we have in this field, and we have discussed the scientific aspect, strategic aspect and regulatory aspect related to this project. But at the same time, this social goodness based upon the corporate activities is something that we want to pursue. From this perspective, ESG, we believe that ESG lecanemab is something that can really contribute to the patients. Not only that, it can really alleviate the concerns and the burden for the caregivers and their family members. When you think about access to medicines and, again, for the emerging markets that really represent the predominant population of the world and for all of these aspects, we believe that we can bring about tremendous goodness to them. We think that we can create a great societal impact. This is pretty much in line with ESG spirit. This is going to bring about the mid- to long-term corporate value creations. This is a great potential of lecanemab that we're expecting. Based upon that, we believe that the current share price is showing some disassociation from this intrinsic value that we can bring about. We want to continue with our first. We would like to achieve the milestones one after another, and then we'd like to fulfill our accountability. Through that, we would like to continue with the efforts to achieve the mid- to long-term corporate values and sincerely hope that you will also extend the mid- to long-term support to our company. With this, I'd like to conclude this financial presentation. Thank you very much. We will now move on to Q&A session. We will be taking questions from those who are participating via telephone line. Please press asterisk one if you wish to ask question. Moderator, I will be connecting those who have questions. First question is coming from Mr. Yamaguchi, Citigroup Securities. Mr. Yamaguchi, Citigroup Securities, please. Can you hear me? Hello. Thank you. Can you hear me? This is Yamaguchi. Yes, we can. Please go ahead. Thank you very much. I have two simple questions. First is about the progress in the financial performance and full year forecast. Dr. Yanagi, CFO, presented various aspects. Up to Q3 progress has been strong. I think in the company's forecast, in comparison to original forecast, milestones might have seen upsides. As for full year forecast, up to Q3 performance was strong. Why is there no reflection of that in the full year forecast? Full year forecast is unchanged. Thank you for your question. Dr. Yanagi will respond. Mr. Yamaguchi, thank you very much for your question. This is Yanagi, CFO. As you rightly mentioned, full year forecast, operating profit forecast is JPY 78 billion. For the nine months, JPY 74.6 billion is the amount of the operating profit. Progress rate has been very high as you pointed out. As Mr. Yamaguchi pointed out, in comparison to the business plan of the company, performance is an outperformance, outperforming a strong performance. This time, we have decided not to make upward revision on the full year forecast. Continuously for Lenvima and DTC and DMT in a disciplined fashion, investments will continue. In the fourth quarter, there are some uncertainties in terms of market environment. In consideration of these factors, this time we concluded that the change will not be a material one. Because of the principle of materiality, although we expect some upside, we decided to keep the forecast unchanged. There are also very proactive investment and market condition changes, but with confidence we would like to achieve these numbers, the full year forecast. With Biogen under collaboration, Aduhelm is pursued and expenses are absorbed, and we are achieving these strong results. As it is noted in the flash report with Ajinomoto, we have EA Pharma, which is a joint venture and a structure reform. It has been absorbed. That impact has been absorbed. We are taking all of these into consideration, and you might consider this somewhat conservative, but we have kept the forecast, full year forecast unchanged, which we believe we are able to achieve confidently. Secondly, I have a question regarding timing. In Ivan Cheung's presentation about lecanemab, regarding accelerated approval timing. In the beginning of fiscal 2022 was the wording that was used. According to the guidance so far, the guidance was as before June 2022, so it may be in the same April to June quarter, 2022. Between April to June 2022, you plan to file submission and that remains unchanged or is it brought forward closer to April? Is there possibility that filing might be somewhat earlier, closer to April? That question will be addressed by Ivan Cheung. Mr. Cheung. Ivan, can you hear us? Please wait for a moment. Can you hear me? Please wait for a moment. Yes, I can hear you. Thank you very much for the question. Compared to the last time when we made the statement about completing the BLA within the first half of this calendar year, as I mentioned earlier, we have made significant progress with this rolling BLA, which gave us more confidence to complete this BLA earlier. Hence, the beginning part of the first quarter of fiscal year 2022 is our updated target. Thank you. Thank you very much. That is all . Thank you. Next question. Mr. Kotani from Nomura Securities, please. This is Kotani, Nomura. Can you hear me? Yes. I have two questions. First is lessons learned from Aduhelm. In January, draft NCD was announced by CMS, and it's like a second FDA. I don't think CMS has authority to make such decisions. What have led to these very complex issues? Personally, I think there are three problems with Aduhelm. First, one study succeeded, but one study failed, and most of the people were not able to understand the picture fully. The second is the pricing of Aduhelm. If price was to be halved in December, that should have been the starting price. The third is researchers, experts. Almost no researcher expert is supporting Aduhelm. With a quality study, complete and perfect data are expected. Secondly, appropriate pricing should have been the starting price. The third is in peer-reviewed journals, papers have to be published. Unless there are papers, experts, researchers have no basis to make judgment on. It may be difficult for you to answer, but regarding Aduhelm, there have been a series of confusions. What lessons are learned, and what can you apply as lessons learned in lecanemab development? On the three points I raised and on other points, could you share your view with us? Regarding a safety profile, you've mentioned that safety profile is expected to be same as Study 201, which means that ARIA-E incidence is about 10%. The question will be once again addressed by Ivan Cheung. Thank you very much for your question. I believe you have two questions. On the first question, thank you for your advice. Much appreciated. I think, firstly, we should understand that the circumstance for lecanemab is a bit different from the circumstance of Aduhelm. As you may remember, the accelerated approval of Aduhelm basically became public at the date of approval. The AD community was not prepared for the accelerated approval outcome. For lecanemab from day one last year when we initiated the rolling BLA, it is well known that this will be an accelerated approval. I think, that's the first major difference. The second major difference is the phase III confirmatory trial readout is only several months away later on this year. These are the two major differences in the circumstances. I'm saying this because one important point, as you pointed out, is the public's transparent understanding of the clinical data and the regulatory situation. For lecanemab, as you pointed out with regard to the publication, the accelerated approval application for lecanemab is based on Study 201, and the results of Study 201 was already published almost a year ago in a peer-reviewed journal for the public to go through all the data. That's the first point. The second point, I agree with you that how to ensure the most optimal and appropriate access to as many eligible patients as possible is critically important in this space of Alzheimer's disease. For lecanemab, I would say that we are confident how we're gonna do that and get it right. Third point, I would point out. I mentioned on my slide nine earlier. For lecanemab, because of its differentiated profile, we have this vision, and we believe it's our responsibility in Eisai, it's lecanemab's specific responsibility to create the simplest patient journey for this new AD DMT era. We believe this is critically important for the society. Now, to your second question on ARIA-E in Clarity AD, what I can say is, in Clarity AD, we have independent safety monitoring board and mechanism in place where we check the timing, frequency and severity of side effects. If there is any deviation compared to what we saw in Study 201, then such reporting must occur to the FDA. So far, that hasn't occurred. That's why we remain confident that the safety profile of lecanemab, including ARIA, remain consistent of what we saw in Study 201, and we're very encouraged by this situation. Thank you. Thank you. About the last point, I would like to ask about the Lenvima sales in the United States. When you look at the Q3, it is increasing by as much as JPY 10 billion in the United States. I think that the first line is- The share is really increasing. To what extent the share of the first line is really expanding and that kind of information would be very helpful because this is a highly competitive area. For the HCC, the LEAP-002 study, there are some preceding the compound that we do have the benchmark to compare with that. The most latest the share conditions and also how to distinguish from the competitive regimen. For the HCC cabozantinib and Opdivo combinations, COSMIC studies, the results have already come out last year, and they were not able to show the OS the benefit. You are using in combination with Keytruda and so it was non-inferior to Sorafenib. COSMIC-312 was not the positive studies. What do you think about your current conditions? Thank you very much. Owa would like to respond to your questions. As to the progress in the United States, as you have pointed out, the growth of the HCC is very significant. As for the specific market share numbers, I do not have the specific number with me, so I cannot share that with you. If you can refer to the number of script versus the previous year, that is, by the end of the calendar year, December. When you look at the new script, there is a twofold of increase. There is the market increase in the number of script. In terms of the share, as you know that in the field of RCC, the TKI class, Lenvima, is really the market leader. Immune checkpoint therapies, the Opdivo and the Keytruda competing with each other. Our strategy is that Lenvima in the TKI field, that's the kind of positions that we would like to overcome. We don't know the exact number. Definitely the Lenvima market share is growing, and they're coming closer to that target when you look at the number of scripts issued. This is my first response to your questions about RCC. As for the HCC cabozantinib and nivolumab, the combination COSMIC studies and also LEAP-002 study to be compared. As for the cabozantinib and Lenvima, from my perspective, I believe that they are completely different compounds in TKI, especially for the HCC, FGFR pathway is extremely important for the in terms of the tumorigenicity as well as the cancer proliferations. This, cabozantinib does not inhibit the FGFR. We believe that lenvatinib can really achieve the distinction there. Also for the lenvatinib, REFLECT study's non-inferiority result. Anti-tumor effect of lenvatinib in the real -world setting, we believe that we have been able to demonstrate the very strong effect, so Lenvima. The Lenvima and Keytruda combination therapy, we believe, can be the standard of care in this field because of the very long the overall survival extension. Again, this is published data, but in July of this year, the final analysis is expected to come. Currently, we have not really corrected the information in ClinicalTrials.gov. Again, we expect that very long overall survival data is expected, just as we have seen with RCC. Thank you. The next question is Akahane. Mr. Akahane of Tokai Tokyo Securities. Can you hear me? Yes, please start. I have two questions. I have one question regarding Aduhelm, and the second question is about the financial performance regarding aducanumab approval and insurance coverage. Not about this, but strategically, what you're doing in terms of lobbying activity, et cetera. Looking at the appendix, the expense is JPY 32.1 billion, and after the second quarter, it was JPY 14 billion or so. You are spending much on lobbying activities and educational outreach activities. What are your strategies in terms of lobbying activities and outreach and education? Expense is growing, but what is the strategy? Thank you very much for your question. That question will be addressed by Ivan Cheung. Thank you very much for an important question. In the United States, both Biogen and Eisai for many years very much involved in many projects with patient advocacy groups in terms of education, in terms of supporting communities. Those efforts are of course very much a big part of the activities for Aduhelm. Of course, critically important for both Eisai and Biogen to continue outreach to members of Congress, to the CMS, to really explain our perspectives and our position on why improving drug access to Aduhelm is so important for the Medicare beneficiaries, in terms of equitable and a fair access to an FDA approved therapy, the first AD DMT approved by the FDA. All these are extremely important activities that have been going on every day, you know, for the past many, many months. Thank you for your question. Thank you very much. The next question is about the performance, financial performance. For these activities, JPY 32.1 billion is spent. In the fourth quarter of last year, it was 3.5 billion, and there is also a milestone payment for Study 201 at 49.6 billion. Is that why you assume that in the fourth quarter, revenue and profit will not grow so much, or are you simply being conservative? Thank you for your question. Mr. Masaka, Executive Officer, will respond. Mr. Akahane, thank you very much for your question. Simply put, the 78.5 billion operating profit forecast is as a result of the one-time expense and growth offsetting each other. LENVIMA growth and strong growth is expected as positive factor. As for a negative factor to strengthen our business foundation, we are incurring restructuring costs and strengthening our foundation, and there is also aducanumab-related expenses. Taking all of these into account comprehensively, our forecast remains at JPY 78.5 billion for operating profit. The next question is, Mr. Hashiguchi from Daiwa Securities, please. Thank you. I am Hashiguchi. I have two questions. Yes, go ahead. Your partner at Biogen, with regard to Aduhelm, these situations—they have indicated that they are going to work on the very significant structural reform, but you haven't referred to that. Of course, I know that you have lecanemab, but how should I understand the difference in the policy between the two companies? Do you have different perspective on lecanemab or the environment surrounding the area other than AD? Would that be very different between the two companies? Or, could you please explain the difference in terms of such policies, differences between the two companies? With regard to the questions, Dr. Ivan Cheung is going to respond. Thank you very much for the question. In the United States, as you said, Biogen takes the lead on Aduhelm commercialization, and Eisai takes the lead on lecanemab commercialization. With regard to Aduhelm, majority of the people deployed for the launch belong to Biogen. The restructuring of the cost structure for Aduhelm going forward in terms of people, you mentioned a restructuring. In terms of people, that is really what Biogen needs to work on from that perspective. Not that much on the Eisai side, and that's why we didn't talk about that earlier. Now, for lecanemab, we will be taking the lead, so we will be deploying majority Eisai people, Eisai talents, to do that. From a policy standpoint, we clearly understand the stages of the launch. First stage is the accelerated approval launch, and then the second stage will be the full approval launch. Which these two we expect to happen pretty close within a year. This is our approach to the launch, which we believe is critically important. Once again, the three points I mentioned earlier in the previous question. One, around the transparency and understanding of our clinical data. Two, about how to really improve drug access. And three, creating the simplest patient journey with lecanemab. These are the three key points, we'll be working on. Thank you. Thank you. One more question. It's about page eight. Lower part of page 8. OLE study of lecanemab and points to be confirmed. Dosing frequency is to be reduced with a new dosing regimen according to this slide. In comparison to other anti-amyloid beta antibody, I believe lecanemab has shorter half-life without sacrificing efficacy. To reduce dosing frequency, I would assume it's not easy. Using blood biomarker is also mentioned. Could you elaborate on the use of blood biomarkers? That question will be addressed by Ivan Cheung. Thank you very much. A great question. At the CTAD Congress last year in November, we presented the five year trajectory of blood biomarkers, both Aβ42/40 ratio and p-tau181. The concept here is after the initial 18 months of treatment, not only the brain amyloid level measured by PET, but also the blood biomarker levels are coming down to a level near amyloid negativity. After 18 months, we don't believe you have to keep giving the bi-weekly dosing to maintain that plateau level of, in this case, the blood biomarkers. The concept is in that post-18 months maintenance stage to maintain the blood biomarker level at that low level. We don't believe, because of all the work that we have done so far in the PK/PD modeling, you have to give bi-weekly. You can give a lower frequency. Actually, as mentioned, as written on slide 10, we also have the OLE phase for Study 201. So we're gonna be first testing this new, less frequent dosing regimen in the Study 201 OLE, which is happening very soon within this quarter. We'll test a couple different less frequent dosing regimen, and based on that, we'll pick the one or more to go into the OLE phase for Clarity AD. So those are the steps. To answer your question specifically, we have confidence based on all the work that we do. After 18 months, we don't have to give bi-weekly, for sure. Thank you. Thank you. That is all. The next question from Nikkei, Mr. Akama. Are you ready? Thank you. I am Akama from Nihon Keizai Shimbun. I have two questions. The first question is to Dr. Yanagi. About the potential lecanemab that you have emphasized at the very end of your presentation. So far, for the Lenvima cliff in the year 2026 and including the potential of Aduhelm, I think that you have built up the story to go over this. Now that Aduhelm is faced with this kind of situations. Now, of course, as a growth story, you have to really wait for the full-fledged growth of Lenvima. As with the lecanemab growth on the stand-alone basis, would you be able to go over the offset that you would achieve? The lecanemab would be able to go over the offset. This is the first part of my question. Thank you. Dr. Yanagi would like to respond to that question. Hi, Mr. Akama. Thank you very much, Mr. Akama. Maybe since you have covered many different points, and I think you were referring to somewhat of a bigger picture, I probably have to respond to you from a little bit of a bigger picture. My concluding remark was pretty much a sort of qualitative statement, and I think your question is referring to that. That is to say, that of course, I refer to the big potential lecanemab. For the scientific aspect or this marketing aspect, if you're looking for a set quantitative data, perhaps, Ivan Cheung should be responding to you. Just in terms of storyline images and then related to the latter half of your question. Now, when you think about the Lenvima patent cliff, and again, that would it have the kind of potential that would be able to overcome this offset from the Lenvima's. And it's not really apples-to-apples as a comparison. Lenvima, including the social contributions, and we are really expecting to achieve the very big sales with this compound. Of course, when it comes to lecanemab, again, it is not even launched in the market. The full, the formal, the sales forecast is something that we have not disclosed. I'd like to refrain from making any comments on that. When you think about the very innovative potential, so next generation AD DMT is exactly the kind of solutions to the social challenges which is tantamount to the COVID-19 challenges and for the patients, for the family members and the economy of the societies. Again, it can really have the enormous potential to overcome those great challenges. Of course you cannot really make apple to apple comparisons, but from a little different dimensions. Again, the kind of things that you could never really take for granted for the conventional drugs. That much of upside is something that we are expecting from this product. That is, really, the point I was really trying to make in the concluding remarks. As for this peak sales forecast for lecanemab, if that is what you're after, then of course I would like to refrain from responding to that. However, all of these, an unimaginable social challenges, that's where we are really trying to bring the impact investment. I think this is a compound that has, that much of the great potential. That's how I would like to respond to your questions. Second question. This may be, perhaps, to be addressed by Mr. Ivan Cheung. Lecanemab, before the end of fiscal 2022, you plan to file your submission in Japan, EU and U.S. What about China? I believe study is making progress. Before the end of fiscal 2022, is it difficult to file submission in China? If so, what is the timing for China? Ivan Cheung will answer. Thank you very much. It's a great question. As I explained earlier, we are very glad that we completed enrollment of the additional cohort in China in Clarity AD in the previous quarter. So, this is an 18-month duration trial, and that's why a submission for approval in China within fiscal year 2022 will not be possible. Obviously, fiscal year 2023 will be a very important target for us to see how we can take the earliest action in terms of regulatory filing in China. We're still working on the timeline, but please be assured that China is an extremely important market for lecanemab. I believe Clarity AD is the first phase III AD DMT trial to complete enrollment in China. We are very proud of that. Thank you. Regarding a study in China, is there a possibility that this may move along faster than Aduhelm? With regard to Aduhelm, it's public information that the EMERGE and ENGAGE phase III program did not enroll subjects in the country of China. As a result, the Biogen team is continuing to have conversation with the Chinese authority on the path forward for Aduhelm in China, of course, seeking the most expedited and reasonable path forward. That is still not yet determined. As a result, while we have a rather, I would say a rather clear timeline for lecanemab in China, the timeline for Aduhelm in China is still not certain. Unfortunately, I'm not able to answer your question. Thank you. Thank you. Unfortunately, we have run out of the time, so we'd like to end the Q&A session. With this, we would like to conclude today's financials, the presentation. We would like to thank you very much for joining with us for this session. I'd like to ask for your continued support. Thank you.