Eisai Co., Ltd.

It is now time. We would like to begin fiscal 2020 financial results presentation by Eisai Co., Ltd.

Presentation will be livestreamed and will also be distributed over telephone line. Those who are participating via telephone line, please refer to the slides after downloading the slides from our website.

And please click to advance the slide. I would now like to introduce the presenter today, Representative Director and CEO, Mr.

Haruo Naito. Mr.

Naito, please.

Thank you. This is Naito speaking.

We'd like to give you a presentation on financial results for fiscal year 2020. In the year under review, we have been affected by COVID-19 pandemic in a variety of ways.

Given that backdrop, what we have focused on during the year is, as you can see on this page, to secure the product or products and secure the stable supply of products. Needless to say, pharmaceutical products are directly linked to the lives of patients, therefore, it is never allowed to stop supply.

In our case, we have 9 manufacturing sites globally where manufacturing is done, out of which if even 1 of 9 manufacturing sites is down, and then it will impact the stable supply of our products. As shown in this table, the plant in Vizag in India and Bogor in Indonesia, they are still suffering from the pandemic.

But at both plants, operations were suspended for 3 days or up to 10 days. But regarding other manufacturing sites, utilization rate was kept at 100%.

Overall, smooth and stable supply was maintained. That's what I'd like to report to you first.

And that was supported by the securing of the raw material intermediates and final products, appropriate level of inventory has been maintained. During fiscal year 2020, 8.1 billion tablets in total or up 109% year-on-year, such a stable supply of so many tablets have been maintained during the year.

Now turning to the P&L where I would like to report to you the consolidated statement of income. Revenue was JPY 645.9 billion, which was 93% of the previous year.

And operating profit was JPY 51.8 billion. We announced a downward revision to our guidance earlier, and we believe we have ended up at almost in line with that revised forecast.

However, our results ended up well below the original plan for which I would like to apologize today. Looking at the revenue top line, which was 93% of the previous year.

And one line below it, other business revenue is presented, which stood at JPY 59.9 billion, which was 51% year-on-year. That means that this other business revenue was almost halved from a year earlier.

Products such as Lenvima was expected to clear certain threshold to gain the sales-based milestones of onetime payment, and that means that these were significantly below the plan or from the previous year. And we believe that this was a big factor for delaying the progress in achieving the revenue.

Regarding Lenvima, the sales itself will be explained later, but the sales itself grew steadily with 20% increase from a year earlier. Unfortunately, however, there was a delay against the original plan.

Therefore, in accordance with the plan, milestone -- or sales-based milestones were scheduled or expected and which we could not receive during the year. Therefore, revenue in other business halved almost, therefore, resulting in the revenue, as you can see in the top line.

And by segment information, you can see the sales has increased. And also, the profit also increased by 3% as well.

And the sales increased by 20%. Therefore, the core businesses have not been hampered or compromised.

R&D expenses, JPY 150. 3 billion.

Including the partners' reimbursement, R&D expenses in total was JPY 208.4 billion. LEAP study for Lenvima and the multiple AD-DMT projects are ongoing.

That means that we have made ample investment of our resources into these priority projects. SG&A expenses was JPY 281.4 billion, which was 43.6% of revenue, which means the expansion from a year earlier.

And it includes the shared profits of Lenvima paid to partner. JPY 60.2 billion was incurred related to the shared profit for Lenvima in fiscal year 2020.

We believe that this was rather proactive investment and increasing SG&A expenses for the growth of Lenvima. And for preparation of the environment for launch of AD-DMT, we made investment as well.

As a result, operating profit was JPY 51.8 billion. Profit for the year was JPY 42.5 billion.

ROE was 6.1%. At the bottom, you can see the financial structure.

So-called equity ratio was 64.5%. For the first time, equity -- or shareholders' equity, over JPY 700 billion has been obtained.

Net DER was minus 0.27. So that means that our business has been run substantively debt-free.

And rating has been upgraded to -- from single A to AA-. So based upon this strong financial integrity, year-end dividend of JPY 80 per share has been resolved at the Board of Directors meeting held today, and the full year dividend is JPY 160 per share.

Next, here is the breakdown of changes in revenue by using this waterfall chart. In the middle, the beige-colored box, you can see the increase and decrease in global brands.

As a total, there was an increase by JPY 24 billion in the total global brand sales, mainly led by increase by JPY 22 billion or a 120% increase from a year earlier in Lenvima; Fycompa, up; and Halaven, down. But from this fiscal year 2020, Dayvigo was launched during the year under review, and it contributed by JPY 3.1 billion to revenue.

By region, in Japan business, which decreased revenue by JPY 15.2 billion because of drug price revision and COVID-19 impact. But in the latter half of the year, there was a market entry of the generics of Lyrica, which is one of our mainstay products.

We believe that these were the factors for the decrease. In Americas business, through the growth of Lenvima, this increased revenue by JPY 14.9 billion.

Even with the COVID-19 impact, particularly in the first half of the year, sales and marketing in-person activities could not be done. So that was the impact they had in Americas.

In China business, revenue was increased by JPY 8.1 billion. China was the country where COVID-19 pandemic broke out for the -- first in the world, but it was a country which could recover from the pandemic earlier than other countries and contributed to the growth of the business.

From March 1, Lenvima and Fycompa, these 2 products have been added to the National Reimbursement Drug List. And JPY 8.1 billion has been recorded as the increase because of this effect of the NRDL inclusion.

And EMEA or Europe, that has been significantly impacted by COVID-19. Most of the offices continue to be closed.

But through the digital utilization, revenue was increased by JPY 1.6 billion. In Asia and Latin America, there was impact of termination sales contract of Humira in Taiwan.

As I have been saying, the most or biggest downside or downward impact was brought about by the milestones or payments related to Lenvima received from partners. As you can see in the pink box, you see the decreasing factors.

First, during fiscal year 2019, what about the Lenvima-related milestones or payment received? There were option rights-related onetime lump-sum payments.

It depends on the year's business. But for fiscal year 2019, there was JPY 21.6 billion.

And there were 3 sales-based milestones acquired or received during '19. On a calendar basis, from January through December, JPY 800 million was received.

And for the fiscal year, a JPY 750 million achievement. And there was another threshold of fiscal year, JPY 1 billion achievement.

There were 3 sales-based milestones. All in all, JPY 76.2 billion payments were received.

But on the other hand, regarding 2020, fiscal year 2020 option rights, JPY 12.9 billion. And the sales-based milestone on a calendar year base, JPY 1.2 billion.

JPY 20.7 billion was received. That was the only sales-based milestone we received.

As I said earlier, Lenvima grew 20% year-on-year, but compared to the original plan, which could not be met. So in addition to this, there were calendar year-based milestone which would not -- could not receive in full.

Therefore, compared to fiscal year 2019, there was a significant drop in the payment receipt -- received from partners. And regarding the tazemetostat-related payment, which was according to the contract, in 2019, there was the -- it decreased to JPY 16.4 billion.

Therefore, the revenue was JPY 645.9 billion for the year. Next, I would like to explain the breakdown of changes in operating profit from a year earlier.

The biggest factor for decrease is in the middle in the right, JPY 42.6 billion related to Lenvima-related payments. And this has affected the operating profit as a whole.

And this was the greatest factor for the decreased OP. On the left-hand side, global brands added 27 -- JPY 23.7 billion to operating profit.

For Dayvigo, in the U.S., launch was in June; and in Japan, it was in July. And recalling the launch in June in the U.S., actually, that was the timing when the COVID-19 impact was most significant, therefore, our sales reps could not visit clinics at all.

And after the launch, over 200 reps were newly hired and we were making such preparations. Therefore, preparation-related costs were incurred and included in this number, adding up to minus JPY 14.7 billion.

Lenvima-related R&D costs and the increase in shareholder profit of Lenvima paid to partner and the AD-DMT will be explained in detail later, but we have 4 AD-DMT candidates. Alzheimer's disease-modifying therapies are being developed.

And related to this and the preparation for the environment incurred some costs, and therefore, the total JPY 18.4 billion was spent. And we ended up in JPY 51.8 billion in OP.

And you can see the R&D expenditures, including the reimbursement from partners, on the right-hand side. Next, AD-DMT or Alzheimer's disease-related treatments.

We are aiming to make changes in AD treatment on this page. Aricept was launched in the U.S.

in 1997 and in Japan in 1999. We believe that it was a new historical step in AD treatment.

We take pride on that. Dr.

Kazuo Hasegawa, who is called the father of treatment of dementia in Japan, and according to his speech, he said, "With no available treatments for Alzheimer's disease at that time, they felt helpless. However, Aricept provided patients, their families and doctors a sensible hope for fulfillment."

And overall initiatives in diagnosis, treatment of care have been advanced a lot. We believe that the benefits for patients and their families have increased.

And from this fiscal year '21 and beyond, we believe that we are at the turning point to enter into the era of AD-DMT. We are at such a timing.

We have 4 AD-DMT compounds in our pipeline. We believe that in the world, Eisai is the only pharmaceutical company which have 4 AD-DMT compounds.

We needed to develop them fully. And biomarker research and new modality researches have to be advanced at the same time in order to have a new historical step in the AD treatment again.

A core concept in this pathway is brain health panel concept -- concept of brain health panel. Conventionally, Alzheimer's disease was considered to be a snapshot damage or impairment of the cognitive function.

This was a target in treating this disease. But more recently, Alzheimer's disease may have started even much earlier from a healthy state.

And through very long patient journey, disease will continue to progress. So this disease is now regarded as a continuum of disease.

It is now understood as a new concept. And at each phase of disease continuum, there are various pathophysiological aspects or changes in pathophysiology in a continuum.

And biomarkers, as explained here, can be utilized for understanding such aspects. And this has become the core of the concept of this disease.

That is called the concept of brain health panel. Now turning into the contents.

On the left-hand side, genetics information. ApoE, for example, and various genetic polymorphisms related to the cognitive decline rate and amyloid accumulation rates, these have been identified.

Therefore, as a biomarker, these have to capture into brain health panel. On the right-hand side, imaging.

PET, amyloid beta PETs, tau PET and MRI, these all have very high precision and high resolution now. Information taken from imaging should be added to brain health panel.

CSF. Today, regarding the changes in the neurogeneration, CSF is expected to provide the broadest range of biomarker information.

More recently, protofibrils can be measured by CSF. So just focusing on CSF and a lot of biomarker-related information can be captured.

On the left-hand side, blood comes. Clearly, by the advance of the blood biomarker development, disease continuum AD can be transformed dramatically.

Aß40, amyloid beta 42 and pTau or other tau-related information can be obtained one after another. The items which can be measured through blood are increasing, and this constitute an important portion of brain health panel.

And EEG and physiological information and digital or personal health record in daily activities can be registered in brain health panel. The progression in the AD disease continuum, the intervention or treatment can be achieved and brought about through this information.

Now turning to the first of our AD-DMT candidate, aducanumab. FDA in the U.S.

had set PDUFA date at June 7, and it is only less than a month from today, and we are just focusing on the outcome on the PDUFA date. Whatever outcome comes, we are preparing to address it, and we are putting most priority on that.

And in EU and Japan, the MAA and the submission have been filed and which are all under review. At the bottom, we are reporting to you that in other markets, such as Brazil, Canada, Australia, Switzerland, MAA has been submitted.

Next, the second one is lecanemab BAN2401, anti-amyloid protofibril antibody. Top left, one remaining regulatory study, Clarity AD, which is a Phase III study, the summary of the study is provided.

Clarity study, of course, was affected by COVID-19 during fiscal year 2020. For example, some patients cannot -- could not come to clinics, therefore, they could not be administered with the investigation drug.

So through consultation with the authorities, we increased the number of patients to be enrolled to 1,795, which have been already completed. And remote diagnosis and other measures were utilized in order to complete the enrollment of expanded number of samples, which has been completed.

In accordance with our plan, we expect that readout of a primary endpoint is targeted for second quarter of fiscal year 2022, next fiscal year. And the continuum or more upstream preclinical AD Phase III study, together with ACTC, which is an academia consortium in the United States, with AHEAD 3-45 is being conducted smoothly.

And AD-DMT is the -- lecanemab is the only AD-DMT which is conducted -- or studied in the clinical trial under this consortium. Lecanemab, we conducted Study 201 with over 1,800 subjects, which was a large-scale, placebo-controlled Phase II study, double-blind study.

And here is the summary of the results from Study 201 and the re-dosing study or Study 201 open-label extension study, which has been initiated. On the horizontal axis, this is the time axis.

The core study of 201 was 18-months study for core portion, and that was followed by about 2-year gap period. And after that, OLE study was initiated, which started from OLE baseline.

And the red line shows the active arm, and the blue line shows placebo arm. During the 2-year gap period during which the amyloid beta reduction was maintained in the group which was administered with the active drug, and the gap between the amyloid accumulation between placebo arm and active arm was not narrowed.

That means that the AD-DMT effect was sustained. At OLE baseline onward, for placebo arm, active drug was administered.

Blue line in the OLE study period, in relatively early period at around 3 months, already a significant or conspicuous amyloid reduction was observed. In around 12 months -- in 12 months, about 80% of subjects with the drug, the amyloid level was reduced to negative levels.

Therefore, robust effect was confirmed. And in the right-bottom corner, here is the instance of ARIA-E in the OLE study.

Incidence was 8.9%, which was consistent with the rate of 9.9% observed during the 201 core study. Now the third DMT is related to tau, tau antibody E2814.

On the left side is a schematic diagram. Tau antibody -- there are various different tau antibodies, but E2814 binds to MTBR in tau, MTBR or microtubule binding region.

So it is a specific antibody. Regarding MTBR-tau fragments, as shown in this schematic diagram, will control tau propagation in intercellular space.

It is a tau-propagating species, and so it is related to tau propagation. And as shown in the schematic diagram below, it also promotes accumulation of tau.

And this antibody E2814 specifically engage MTBR region. At right top, Phase I study summary is given in dose-dependent manner.

E2814-bound MTBR-tau is increasing. And in 2 different populations, Phase II studies are planned: first is in DIAD, the so-called familial background Alzheimer's disease population; and the other is sporadic AD population.

In these 2 different populations -- and the reason for selecting these 2 different populations are as shown in these diagrams. When we look at the behavior of biomarker representing propagation and accumulation of tau, these 2 populations are showing similar behavior, almost identical behavior.

And that is why we've decided to test in these 2 populations. Regarding DIAD, academic consortium DIAN-TU is managing DIAD population.

And therefore, in collaboration with DIAN-TU, as the first tau-related therapeutic investigational drug picked up by DIAN-TU, we are planning to -- we are preparing for a Phase II study. And the fourth AD-DMT is synapse regenerant E2511.

This is our orally administered small-molecule drug developed in-house. As shown on the left, this compound engages with TrkA.

And as shown on the left, synapse survival signal will be activated. And as shown in right, damaged synapse, restoration and regeneration will be promoted.

In that sense, it is a drug with EPOCH-making mechanism, first-in-class that have never been tried before, maybe achieved as a disease-modifying therapy. These are disease-modifying therapies.

For A-beta, tau and synapse, with these composite treatments, we hope to make advances, major advances in treatment of Alzheimer's disease. Now I would like to turn to oncology.

We aim to reinforce immuno-oncology treatment. There are 3 bullet points.

First, combination of Lenvima and KEYTRUDA. And we are conducting LEAP studies, and LEAP studies are advancing.

We aim to develop Lenvinma and KEYTRUDA combination as cancer backbone therapy. There are cancers that are resistant to the combination treatment of Lenvima and KEYTRUDA.

To overcome that treatment resistance mechanism, we have 2 in-house-developed compounds that we would like to further develop. And there are also cancers that show limited efficacy to IO -- where IO treatment shows limited efficacy.

And we would like to address this with new modality. About LEAP studies, on the very left, 5 approved cancer types are shown.

There are 3 monotherapies and 2 combination therapies that are approved. And Lenvima approval was given in 74 countries, and number of prescribed patients is over 130,000.

In the middle, LEAP studies development underway are shown. For 14 cancer types, development is underway.

In fiscal 2021, first-line for RCC and for endometrial carcinoma first-line for following previous systemic treatment. And in HCC first-line, we are especially focused on these in fiscal 2021.

The top 2 will be discussed in more detail. HCC Phase III is also underway with a good progress.

And we believe that we are making full-out efforts so that we can file at the earliest possible timing. And in fiscal 2025, we target to achieve JPY 500 billion from Lenvima.

RCC first-line Phase III study, full data is shown on this page. Regarding RCC first-line in the United States from FDA, priority review status was granted.

PDUFA date is August 25 this year. Data is shown, including PFS -- median PFS.

Lenvima-KEYTRUDA combination is achieving medium PFS of about 2 years, a very long period of time of progression-free survival. And ORR on the right is also showing high rate.

CRR is as high as 16%. Complete response rate is 16%.

And this shows a possibility of very robust option for RCC treatment. Already, it is included in a guideline.

Endometrial carcinoma following prior systemic treatment is shown in the bottom half. And in all-comer population, the previous treatment was chemotherapy -- or control is chemotherapy, but PFS and OS are far superior to results in chemotherapy group.

And therefore, in this cancer type as well, it may become a new treatment option that can completely replace chemotherapy. Based on these, I would now like to discuss commercial prospects of Lenvima.

As I mentioned earlier, in fiscal 2020, Lenvima revenue was JPY 133.9 billion, 120% growth year-on-year. This year's forecast is JPY 172 billion, 128% year-on-year growth.

Key drivers of these will be, among others, RCC first-line, which I just explained. This is a combination with KEYTRUDA.

We already have indication of combination with everolimus in the second-line. And this is also to be transitioned into first-line.

In NCCN guideline, it is -- combination with KEYTRUDA in first-line setting is recommended as Category 1 treatment option. In endometrial cancer, conditional approval is already obtained.

But based on overall survival, we would like to transition to full approval. In endometrial cancer treatment, especially in the United States, this is going to be an innovative treatment option for the first time in the United States in 50 years.

To health care professionals, regarding this option, thorough information needs to be provided as to how this drug should be used. In this respect, unfortunately, we were impacted by COVID pandemic last fiscal year.

And we may not have been able to fully communicate information related to conditional approval, especially adverse event management guidelines. We have already started to make efforts to thoroughly communicate this information to health care professionals.

With this, we would like to maintain sufficient time where patients adhere to Lenvima regimen. When there are adverse events, there are guidelines for drug holiday or drug withdrawal.

And there should be good compliance with that guideline. HCC monotherapy in combination with KEYTRUDA, now we are seeing emergence of competition, which is a combination of 2 antibodies.

Right now, there is not sufficient evidence of that competition. For example, as shown in the parenthesis, case refractory BCLC-B type and NASH derived type, which is increasing in the U.S., this is HCC due to nonalcoholic NASH shown in footnote.

And we would like to make a proposal related to these and would also like to convey the benefit of Lenvima being an orally administered drug to maintain our competitiveness. And combination first-line study is underway, so we would like to continue to make efforts in this area.

As for regions, the biggest market, Americas, is the market where we are seeing very rapid progress in terms of vaccination. And normalization or returning to a new normal life is beginning to be seen, and restriction of visitation to clinics will be gradually lifted.

And in more full-fledged fashion, we will be able to provide information to health care professionals. And in Americas, RCC, EC, HCC, DTC, with these 4 types of cancers, including additional indication, we will continue to make strong efforts.

And with this, on a full year basis and on a calendar year basis, in 2021, we would like to make sure to achieve good results. And by region, the second largest region is China.

As I mentioned earlier, the drug was listed a National Reimbursement Drug List, NRDL, which led to increase in access and supply of the drug is increasing at rapid pace. 144% growth in volume over the previous year is the forecast for fiscal '21 for China.

Lenvima-KEYTRUDA combination efforts are made. And as we make these efforts, we have come to understand better mechanism of treatment resistance.

There are enhanced FGF signal and enhanced Wnt signal. And regarding enhanced FGF signal, we have small-molecule compound developed in-house, E7090, which received SAKIGAKE designation in Japan.

And highly active, highly selective small-molecule or E7090 can be applied to unlock treatment resistance mechanism. That is what we would like to achieve.

And regarding enhanced Wnt signal, we have E7386, middle molecule category of drug. This is CREB-binding protein/beta-catenin inhibitor.

This is a protein-protein interaction inhibitor. This is a very difficult chemistry to achieve.

And development led to this E7386, which is very difficult to obtain chemically. And with these 2 compounds, we believe that we can further strengthen Lenvinma-KEYTRUDA combination therapy.

Last topic related to oncology is cancer with low sensitivity to IO treatment, including breast cancer and ovarian cancer. We would like to approach these with new modalities.

Shown on left is MORAb-202. This is an ADC, payload is eribulin.

Antibody is developed by former Morphotek. Farletuzumab, this is anti-folate receptor alpha receptor antibody.

Our in-house-developed linker is used. Every component of this ADC was developed by Eisai.

And this may be the best-in-class ADC using anti-folate receptor alpha receptor antibody, and we will continue to develop this for such cancers as ovarian cancer. On the right side is a drug developed by H3 Biomedicine in Boston, 6545, for estrogen-dependent breast cancer.

Right now, there are other compounds in this area, and these are all called third degraders. 6545 is not a degrader, it is an antagonist.

And it has potent binding through covalent binding to target. So this is similar to new modality.

This is a product of very precise organic synthesis. With this, estrogen-dependent breast cancer -- we would like to target estrogen-dependent breast cancer, aim to make change in AD treatment, aim to reinforce IO treatment, aim to transform to ecosystem platform model, including DX investment.

In fiscal 2021, we will be making robust investment based on long-termism. We aim to maximize corporate value through contribution to people in order to generate sustainable value.

This is the forecast PL for fiscal 2021. Revenue, JPY 681 billion.

And in fiscal 2020, other business revenue declined, but we plan to achieve growth here to achieve the top line result. SG&A, 47.1%.

SG&A expense will grow by that margin. In fiscal 2021, regarding R&D expenses and SG&A expenses, JPY 500 billion for Lenvima.

This is a big fish. And AD-DMT, there are 4 AD-DMTs that I introduced today, these are also big-fish items.

And we have to be able to catch these big fish, and we have to strengthen our capabilities to be able to fish. And we are making advanced investments to strengthen our powers.

And operating profit, JPY 58 billion, 112% increase. And ROE percentage forecast is 6.7%.

5-year average ROE since 2017 was 10.1%. And over medium term, equity spread is ensured.

And based on healthy financial condition, JPY 160 annual dividend was approved at today's Board meeting. That concludes my presentation.

We would now like to enter questions.

[Operator Instructions] Now the first person, Mr. Yamaguchi from Citigroup Securities.

This is Yamaguchi speaking. I have 2 questions.

The first question is about the precondition assumptions for your guidance. Lenvima milestones year-on-year, a little less than JPY 40 billion will be recovered.

And R&D increased by JPY 10 billion, so SG&A will be increased. But the operating margin seems to be rather low.

Other than these factors, do you think that there are any factors in profits comparing in last fiscal year and this year, like what happened in last year will be lost and so forth? Any changes from last year?

Could you please share them with us? In SG&A, aducanumab in the U.S., I think costs have been incurred.

How much of such cost incurred is -- are included in this SG&A line? These are the 2 questions.

Thank you for your questions. Mr.

Yanagi, CFO, is going to respond to your questions.

Mr. Yamaguchi, thank you very much for your question.

This is CFO Yanagi responding to your questions. First, regarding the fiscal year '21 company guidance, are there any extraordinary or specific line items which may affect the income or profits?

We do not expect any extraordinary large items, but as you pointed out, which shall be included in the other business, including milestones by segment. If you look at the guidelines, over JPY 100 billion was recorded in '19.

But in '20, a JPY 60 billion level was recorded. And furthermore, in FY '21, it's going to be a little less than JPY 100 billion.

So as you pointed out, milestones to be received from Merck will be changed. So that is the difference.

But having said that, it was less in fiscal year '20, but it will be returning to the cruise level or pace in '21. So it's not extraordinary item.

But overall, the status of the development, new products and business development beyond budget or adaptive budgeting process, in which we would like to consider the potential of various real options so that we can provide a best estimate as of now. That's what we have presented today.

So these are not to be considered finalized. Please consider that there are items which are not fixed and others which are already fixed.

And another item is -- ultimately, which is related to OP margin, but as we said, aducanumab-related SG&A expenditures, for this item, as we explained earlier, the real options are being considered in order to maximize our contribution to future patients. So we are making the proactive investment to maximize that, and for example, which includes the issues related to access and diagnosis and those preparation-related costs for environment for launch.

And more specifically, numbers are not disclosed related to line item. But the earnings call suggested that fiscal year, calendar year difference is considered as well, and it's only level of the tens of billions of yen SG&A shall be invested.

Overall, P&L structure for fiscal year '21, to maximize the value of Lenvinma, R&D expenditures shall be invested. At high level, we think that it may peak -- reach the peak.

And R&D expenditures for lecanemab will also reach the peak. Therefore, 23.5% of the sales will be spent for R&D expenditures.

SG&A as well, for maximization of value of Lenvinma and for next-generation AD-DMT and maximization of the contribution to patients in the future, we are making proactive investment of 47.1% of the SG&A ratio. So in both, it's about 70%.

So almost the OP margin is on the single digit, although the double-digit growth is to be planned for the profit growth. However, the one single-digit growth number is recorded in the profit line.

But we are going to maximize the value for the medium to long term. And the SG&A and R&D expenditure ratio, we believe that we are peaking out in fiscal year 2021, and these will be converging to the average of the global pharma.

And OP margin going towards 20% level, and we expect that the OP margin will continue to improve. They're not going into short-termism, but from the medium- to long-term perspective, we are making proactive investments to maximize the future corporate value.

If I may add further, such proactive investment and stable dividend payment shall be sustained both based upon the financial integrity. We have maintained such 65% of the equity ratio and JPY 190 billion level on net cash.

And the credit rating has been put to AA- and stable dividend and such productive investment can be sustained. And customer contribution to patients as well as the maximization of the corporate value can be maintained from the medium- to long-term perspective.

This is Naito speaking. If I may go into details, I would like to add just one point.

For Lenvima, the full year annual sales-based milestones, we said that we lost some of the expected milestones during fiscal year 2020, but this is not the end. In the 2021 as well, we have same target threshold in sales where we will be allowed to try to get those milestones even during the year.

Thank you very much.

Next, Mr. Kohtani from Nomura Securities.

This is Kohtani from Nomura speaking. First question, regarding Lenvima.

Lenvima-KEYTRUDA RCC first-line data was shown. I think we shouldn't be comparing with other clinical trials.

But in VEGF inhibitor in combination with a PD-1 antibody, there are 4 trials, including Lenvima, and patient background is similar. Risk category, gender and age are quite similar.

So ORR, CRR, PFS and DOR, in all of these, your drug, Lenvima, exceeds other drugs. And in adverse event, hypertension or hand-and-foot syndrome are less frequently occurring.

Is there any factor leading to this? And LEAP-002 study for HCC was also discussed.

And I think anytime, interim analysis result is expected. Melanoma, LEAP-004 interim analysis, it was 21% and CBR was 65%.

Until the end of the completion of data analysis from the full trial, will submission not be possible?

Thank you for your question. Dr.

Owa, responsible for oncology, will respond.

Thank you, Mr. Kohtani, for your questions.

First, about RCC, what you pointed out is correct. And if we intentionally find a weakness, we may be able to find a weakness, but this may sound boastful, we cannot find a weakness, any weakness as far as I know.

But well, is there any problem with the safety? But QOL-related data will be presented one after another at the academic conferences, and please keep paying attention to these.

As for CER once it is obtained, there may be relapse or recurrence of cancer. There is such concern.

But how CRR is sustained, we are following in detailed fashion, and we will be providing information one after another. And so please keep paying attention to what we will be able to provide in terms of information.

And as for HCC, anytime, we may have a result from interim analysis, as you correctly pointed out. I'm very much looking forward to seeing that data.

Now lastly, about melanoma trial, thank you for raising that. In view of our recent FDA position with ORR data alone, it may not be sufficient to file submission.

But LEAP-003 study for first-line is underway and is making good progress. In combination with that, we would like to consider melanoma in both first-line and the second-line setting.

Follow-up question about the VEGF inhibitor and PD-1 antibody combination, various other data are also coming out. So in HCC, it seems to be very effective -- in RCC, it seems to be very effective, but not so in HCC or melanoma.

Is there any scientific reason?

The answer: I don't think so. Vascular regeneration, we have scoring biomarkers at least for cancer types included in LEAP studies.

Regarding VEGF, we have selected a biomarker that is sensitive to VEGF. And in other TKI that Mr.

Kohtani may be aware of, FGFR inhibition in advanced way is not achieved by other drugs in comparison to Lenvima. So I do not have any concern that the effect may be insufficient for these cancer types.

I have a question regarding aducanumab, but I don't think there will be an answer forthcoming. So instead, on 2401, I have a question, and there's solanezumab from Lilly.

So aducanumab safety-related issues, this is because of ARIA-E concern that highest dose was not reached in many patients, and therefore, patients who advanced quickly. And I think there is also a lack of reproducibility in CDR-SB.

And when we look at BAN2401, if we see whether these apply, ARIA-E is 10%, very low. So highest dose is achieved.

And second point, at the other day at the earnings session, it wasn't disclosed, but to fast-advancing patient, it's also applied. So the rest is reproducibility of CDR-SB 0.5 and 1.0.

So what is 0 and 1 point -- what is 0.5? And what is 1.0?

It has to be determined in a very precise manner. So clinical -- clinicians training will be very important.

And Eli Lilly's results added new DRS valuation item because of some questions about this. And how are you training health care providers in measuring CDR-SB?

So this is a question regarding reproducibility of CDR-SB for your drug.

Neurology Business Group President, Ivan Cheung, will respond.

Thank you very much for your question. This is Ivan Cheung.

And you're correct, training of all the sites and the staff working at the site on these endpoints, such as CDR-SB, is a core component to the excellent conduct of any Phase III large-scale trial. And that's why we spend a lot of time and effort in, first of all, securing the highest-quality sites around the world and also conduct a very detailed training on -- with all the sites.

And last but not least, also having ongoing monitoring efforts to make sure that we don't see any, for lack of a better phrase, outliers or underperforming site with regard to this matter. We are probably one of the very few companies in the industry who know how to do this.

And we are confident in the Clarity AD trial for BAN2401, for example. Thank you.

Thank you very much. Next is Mr.

Sakai from Crédit Suisse Securities.

I have only one question. Aducanumab PDUFA date scheduled in June, I know everyone is aware of this, and the outcome will be given reflecting on that.

And what sort of corporate actions are you envisioning to be taking going forward? Until the outcome is seen, it will be difficult for you to decide on the actions.

But based upon the result to be seen going forward, I think that there will be some kind of a release or announcement from the company. But what are you currently considering?

I know that this is based on the collaboration with Biogen. But are there any plans or ideas regarding how you are going to take course going forward?

Thank you very much, Mr. Sakai.

This is Naito speaking. For instance, for diagnosis and PET and TFS and blood, if we just take the diagnosis portion, there are various players.

Therefore, with these players, we needed to keep close communication so that we can take appropriate regulatory actions. And our processes aiming at getting approval for reimbursement, we have to make those preparations.

As has been shown by these areas, in various areas, we needed to prepare sound foundation or structure or capabilities. Because we are the company which is dealing with 4 AD-DMT compounds, we believe that this is something that Eisai must cope with, and we are going to cope with these initiatives going forward.

Understood. Anyway, you are waiting for the results, conclusion from PDUFA -- on PDUFA date.

So I am also looking forward to it.

Now it is time to finish. I'm sorry to call the day.

But however, now we'd like to close the conference. We would like to close today's briefing session for the financial results.

Thank you very much for taking time out of your busy schedule to participate in this call.