Eisai Co Ltd

TSE:4523

Earnings Call Transcript 2022-Q4

[Operator]

It is now time. We will begin presentation session on financial results for the fiscal year ended March 31, 2022 of Eisai Company Limited. This session is held online or through telephone lines. Those of you who are participating via online, please download materials from the website and please advance the slides yourself. Those who are connected online, please continue to watch the session.

Presenter is Representative Executive Officer and CEO, Mr. Haruo Naito.

[Haruo Naito, executive]

This is Naito speaking. Now I'd like to utilize presentation slide deck to report it to you on the results for fiscal year 2021. As you see in the headline, we increased revenue and profits through expansion of partnership model and the global brands. Please look at the right-hand side of this slide.

Revenue grew 17% year-on-year. At the very bottom, profit for the year has attributable to owners of the parent, which was 14% up from the previous year. So we achieved double digit growth, both in revenue and profit. Having said that, in November last year, we announced that we were making upward revision of our guidance of operating profit to JPY 78 billion from which, as you see, we ended up at JPY 53.7 billion. Although 4% increase was recorded from a year earlier, however, compared to the JPY 78 billion, the result was decreased which is quite regrettable to us. But the reasons for this gap is converged into one because of the subsequent event occurred to ADUHELM, which I would like to explain in more details later.

Another big point regarding this fiscal year under review, as you see in the headline, partnership model, and a second line from the top, other business revenue. Compared to the previous year, this increased by more than double. Considering our assets of Eisai, we are utilizing such assets for generating revenue, but for example MORAb-202 and Lenvima milestone payments received, these have progressed steadily to reach JPY 129.9 billion. Cost of sales due to the improvement of mix are reduced by 1.9 point steadily.

Please look at the expense side, R&D expenses and SG&A expenses respectively increased. As you see in the footnotes, all these were related to increased expenses associated with ADUHELM, which I would also like to explain in more details later. In SG&A expenses, in line with the increase of the sales of Lenvima, there is an increased of share, the profits with partner. This is included. But this is rather we believe a proactive investment in SG&A.

As a result of this, revenue was JPY 756.2 billion up 17% from a year earlier. Operating profit JPY 53.7 billion, 4% up from a year. And profit for the year attributable to owners of the parent was JPY 48 billion, up 14% from a year earlier. ROE was 6.6% and the 5-year average is about 10%. At the Board of Directors meeting held today, year ended dividend was resolved to be paid as ADM per share. So full year dividend will be JPY 160 per share.

At the very bottom, you see the metrics for financial structure. Net DER improved by 0.05 point. And shareholders' equity ratio is 60.4%. The balance sheet itself as a whole has expanded due to weaker yen. Therefore, ratio seems to be decreased. However, a JPY 748 billion level has been maintained, which is the largest shareholder equity in history.

First, take a look at the breakdown of revenue migration. On the left-hand side, JPY 645.9 billion was recorded as revenue for the past one year and in FY 2021, JPY 756.2 billion was recorded with increase of JPY 110.3 billion. Organic growth in global brands were achieved in this genre as well and secondly, payments received related to Lenvima and thirdly, business options utilizing in-house assets.

And these are 3 categories of factors for increasing the revenue. Firstly regarding the global brands, in-house developer brands, on the right-hand side, total of revenue generated by 4 global brands increased by JPY 78.7 billion. So JPY 280 billion was achieved with the total of 4 products. We reached this high level.

Particularly please look at the Lenvima, this increased by JPY 58.4 billion to reach JPY 192.3 billion in revenue. And below that, on the other hand, a domestically marketed Lyrica and Banzel in the United States because of the impact of entry and the progress of generics, revenue decreased for both.

The net total of a global brand increased on a net basis by JPY 38.7 billion and in the middle, you can see Lenvima related payments received. And during the year under review, we achieved the 2 milestones and milestone payments were received as such. First one is based on the calendar year. And this milestone was received in the previous year. Therefore net variance of JPY 13.8 billion was recorded. And another milestone is based on the fiscal year. This milestone was also achieved. Therefore, JPY 34.7 billion was received by the company.

And the last bullet point, it's about lumpsum payment for specific option rates for renewal of contracts, which was recorded in the previous fiscal year which was not recorded in this fiscal year '21. Therefore, there was a net decrease. And the third category, business options particularly JPY 49.6 billion recorded at upfront payment related to MORAb-202 with BMS. As a result, revenue increased by JPY 110.3 billion.

Next, breakdown of operating profit migration. As you see on the left-hand side, revenue increased by JPY 110.3 billion. First, cost of sales increased by JPY 13.5 billion. Please take a look at the right-hand side. Impairment losses related to sales rise for ADUHELM of JPY 8 billion, which was accounted for.

In April this year in the United States, CMS, Center for Medicare & Medicaid Services, made a final decision of reimbursement for ADUHELM. Their final decision was quite tough decision related to the reimbursement for ADUHELM. Given this decision, what is already on a BS sales rights, all of the sales rights had to be impaired in the amount of JPY 8 billion. This is due to so-called a subsequent event towards the end of fiscal year '21, we had to recorded this loss.

Please look at R&D expenses, which increased JPY 21.4 billion. Please take a look at the bullets one by one. Increase in the expenses for Alzheimer's disease pipeline, JPY 8.3 billion, out of which sets JPY 7.6 billion for lecanemab and JPY 0.7 billion for ADUHELM.

In GI specialty pharma with EA Pharma has a pipeline and pipeline was reevaluated proactively and out of which 4 themes has had to incur impairment losses in the amount of JPY 7.3 billion. Lenvima related R&D expenses are negative JPY 0.4 billion. As you see in the footnote, the regulatory milestones in the United States and Japan for approval of RCC amounted to JPY 11.2 billion.

Receiving this, the expenses for R&D for Lenvima decreased year-on-year. SG&A increased by JPY 84.8 billion. As I said earlier, SG&A investment were made proactively in terms of the shared profit for Lenvima paid to Merck, increased by JPY 30.5 billion.

On the other hand, increase in expenses related to ADUHELM by JPY 37 billion, which includes impairment losses on inventory and idle capacity charges. These too are included. In the third quarter, JPY 6.6 billion and JPY 2.4 billion were recorded respectively, and in terms of the JPY 16.7 billion recorded in Q4 as impairment losses on inventory and JPY 3.2 billion in Q4 for idle capacity charges because of the final decision of the NCD. As subsequent event, the impairment losses on inventory as well as idle capacity charges had to be accounted for towards the end of the fiscal year 2021.

As I have been telling you in November last year, we announced that we made a upward region to JPY 78 billion in operating profit and the gap between that number and the actual result. The top one, the ADUHELM related impairment losses for a sales rights of ADUHELM and also impairment losses on inventory for JPY 16.7 billion recorded in the fourth quarter and the idle capacity charges of JPY 3.2 billion in the fourth quarter. The total of these accounted for the gap between the JPY 78 billion and a JPY 53.7 billion for which we feel very regrettable.

And the other is JPY 11.7 billion is mainly due to the divestiture of a rate of Zonegran in EU. As a result, operating profit was JPY 53.7 billion to increase by JPY 2.2 billion from a year earlier. In the bottom left, you can see the R&D expenditures. We receive reimbursement from partners and in fiscal year 2021, JPY 240.3 billion was invested and this amount account for 31% of sales. So this means that we have continued to invest amply into R&D.

As I said, in fiscal year 2021, expenses were incurred for ADUHELM. There was a significant burden. Once again, I would like to recap the amendment we reported to you, which was made in March this year to collaboration agreements. This amendment to the agreement what was the impact on the expense side. For calendar year 2022, that means from January 1 through December 31, 2022, Eisai's share of ADUHELM related expenses is capped at USD 335 million.

As I have explained including such subsequent events for the fiscal year 2021, expenses related to ADUHELM included in the fourth quarter results was USD 225 million. So fiscal year 2022, that means starting from April 1 through December 31, in the fiscal year, expenses related to ADUHELM is capped at USD 110 million to be incurred in this year. So there is no further expenditures. For fiscal year 2021, there were a lot of expenses related to ADUHELM. And it was quite difficult to foresee in the size of the expenses. Therefore, we believe that it caused a lot of inconveniences to shareholders but for this current year 2022, we believe that there is an increased uncertainty for this current fiscal year.

So all in all, here is a transition of costs related to ADUHELM. For fiscal year 2020, total costs was JPY 29.7 billion. Pink portion is R&D expense and the green portion shows SG&A expenses. In a current fiscal year 2021 under review and in the COGS, which includes the JPY 8 billion as impairment losses related to sales rights, JPY 10 billion in R&D, and SG&A including all those expenses JPY 57.4 billion was recorded and in total, JPY 75.9 billion was spent for ADUHELM. We take this gravely. There have been a lot of lessons learned from ADUHELM. We would like to utilize such experience as learnings for lecanemab going forward.

So regarding these expenditures, we would like to come up with the conclusion and direction going forward out of this experience. As I said, for this fiscal year, from April through December, there is a capped amount of $110 million as costs related to ADUHELM, JPY 13.8 billion based on the current ForEx and starting from January 1 to 2023, there will be no further share of expenses related to ADUHELM for Eisai.

Now turning to lecanemab. First, as we have reported to you on May 6, in the United States based upon the accelerated approval pathway, we completed rolling submission to FDA and a PDUFA date will start to be counted. And the last module which was submitted was CMC part. Lecanemab is at last is going to make a great first step. And by this completion of our submission, we believe we have made a significant first step already.

And for this drug, as a pioneer of Alzheimer's treatment at Eisai, we like to deliver this AD-DMT to people living with AD and their family as quickly as possible. We have such a strong sense of mission. Utilizing accelerated approval pathway, we think that this will be realized.

The second point. Having said that, still we are of course pursuing to obtain full approval. I would like to explain this later but we needed to submit and review the data from Clarity AD. But under the current accelerated approval, the data separate from Clarity AD, will have been reviewed in the current ongoing process. Therefore, what will be remaining for the review period towards the full approval will be related to on the Clarity AD data. Therefore, there is a potential to shorten the review period towards the full approval.

At the same time at Eisai, perhaps in lecanemab, that mean formulation will be a subcutaneous injection, which will allow patients to do self-injection. Under certain circumstances, we are currently proactively developing this formulation as well. And after achieving certain level of efficacy, those could be reduced or perhaps frequency of dosing can be reduced. Maintenance new regimen is being developed as well.

All of these can be possible based upon when first approval, and as a supplemental submission can be filed only after getting an approval. Therefore, getting an accelerated approval is very significant to allow us to conduct to the supplemental submission going forward. And we believe that this is a great benefit for accelerating review process.

Next, Clarity AD confirmatory study, which is called the Study 301, I'd like to give you an update on this study. As we have reported to you, we are expecting to see the primary endpoint readout around September 2022. Study is currently steadily ongoing and 62% of the subjects enrolled had MCI due to AD. And average CDR-SB score is 3.2, an average age is 72 years old. All of these were in line with the plan.

Third bullet. Approximately, 70% of subjects in bold, are ApoE4 carriers. In Study 201, higher efficacy were suggested in ApoE4 carriers, compared to non-carriers. We think that this is one of the positive aspects of the subjects enrollment. When it comes to discontinuation rate, when considering the statistical power to be secured, this is very important metrics. Discontinuation rate is 14.3% compared to the expected rate of 20%. This rate is significantly lower than that.

After completing 18 months administration, already, many patients have started to roll over into 301 Open Label Extension study and 96% of patients enrolled in the original study, core study rolled over into 301 OLE study. This suggests that patients enrolled in the study had a quite high level of satisfaction. Study is ongoing steadily as planned.

For this Clarity AD study, it's a very -- based on a very robust design to confirm efficacy. First, hierarchical testing. Primary endpoint is CDR-SB and key secondary endpoints are amyloid PET upon agreement with EMA, but with FDA, ADAS-Cog, ADCOMS, ADCS-ADL-MCI, these are key secondary endpoints. And as prespecified scheme, it has been already decided to conduct a stratified randomization.

What kind of stratification it is? ApoE4 carriers are non-carriers, to be randomized equally to active arm and placebo arm and MCI due to AD and mild AD, SoC combination group and non-SoC combination group. And by region, stratified randomization will be conducted. Region, meaning North America, Asia Pacific and EMEA. 3 geographic regions. So for these metrics, stratified randomization will be conducted, and a subclass analysis will be conducted. And this has been already determined.

Third bullet point. We are going to obtain large-scale biomarker data. Amyloid PET is from over 800 subjects, tau PET data from over 350 subjects, CSF biomarkers of over 450 subjects and plasma biomarkers, which are going to play significant roles. A beta 1-42 and A beta 1-40 and plasma A beta 42/40 ratio, NfL, p-tau including p-tau181, all these plasma biomarkers will be measured on all subjects, which we believe are very important knowledge and data regarding biomarkers, which will support the treatment policy in the modern AD treatment area.

And fourth bullet point. For this particular study, there is a safe independent data in the safety monitoring board, which is monitoring safety profile. And currently, they have not shown any concerns. Of course, we believe that the board is monitoring closely ARIA and others. Incidence of ARIA-E, which was 9.9% in Study 201, and we anticipate that incidence of ARIA-E in this study will be similar to that of Study 201. And in this study, there was a spread of COVID-19 infections. Therefore, there were patients who had to miss 3 or more dosings, and we had to treat them as a dropout.

In order to mitigate the impact of dropouts, we added 200 subjects, all based upon agreements with agencies. Therefore, the total number of patients enrolled amounted to 1,795 subjects. Enrollment has been already completed 1 to 1 between active to placebo. So approximately 900 subjects per arm. It is a very large scale Phase III study of AD-DMT. And as I said earlier, dropout rate or discontinuation rate is lower than expectation. And the data variability in this double-blind study is also in line with assumptions.

Therefore, we believe that this study is expected to have a very high statistical power at 93%. This is the 93% powered study. That means they too conduct the test trials, 100x out of which 93x a CDR-SB primary in the point, it is possible to prove the hypothesis with high statistical significance in this Clarity AD study. As a result, we are very confident now in carrying out this study. Now with the Clarity AD study towards full approval, we have time line for submission within fiscal 2022 in the U.S., and we have already received a breakthrough therapy designation and fast track designation.

In Japan similarly, submission begin in fiscal 2022 and the rolling submission is already underway with prior assessment consultation system. In EU as well, submission is scheduled in fiscal 2022. And we aim for submission towards full potential approvals in Japan, U.S. and EU in fiscal 2022.

Next, about Lenvima. Please look at the bar charts on the left and the bar chart in the middle shows fiscal 2021 results, JPY 192.3 billion. This was 144% year-on-year. In particular, in the United States, it exceeds JPY 1 billion and achieved a high growth of 144%. On the right side, HCC is noted here. It is a very large market, and Lenvima Mono once again captured a top market share and newly added indication of combo AC/RCC are also showing smooth growth, and we are now positioned to take a top share.

And with omnichannel, we are enhancing adverse event management. This fiscal year, continuously in the United States, we expect the market to grow to JPY 145.5 billion. The second point is China. It was at JPY 35.8 billion, 187% year-on-year. DTC and HCC are the 2 indications in China. With HCC, we have achieved top market share. NRDL, National Reimbursement Drug List has listed Lenvima and access is rapidly increasing, which is also supporting the rapid growth.

In China and in Japan, key opinion on leaders of HCC and others are very active and such exchange is also helping increase of access. In fiscal 2022, forecast is JPY 23.5 billion, 66% growth year-on-year. Lenvima achieved results of 34 years of partnership with Merck, which started in 2018. We believe the partnership has been very effective.

Over the past 4 years, I would like to show you the summary of the history of the alliance. 6 indications for 5 cancer types were obtained. DTC, HCC, RCC, EC and cynic carcinoma. And turning to the right, how many patients have we been able to make contributions to? The number has grown by 30x to 140,000 patients in comparison to fiscal 2017 and the latest figure for the number of capital is JPY 57 million. At Kawashima, new facility for anticancer drug construction was completed in 2020 and globally, stable supply is insured from this new facility.

LEAP studies will be presented in the later slides and the regulatory studies are ongoing, counting more than 20 studies. In next 4 years, we have much expectations for Lenvima. LEAP-002 on the left, this is HCC1L combo, LEAP-001EC first-line combo, LEAP-006 non-small cell lung cancer first-line combo. These 3 indications will be yielding results ahead of others. And all of these cancer types are very important cancer types, and we have much expectations. Towards fiscal 2025, we aim to continuously obtain results.

Today, I would also like to discuss that Lenvima clinical studies for pediatric indications are steadily ongoing. With the U.S. and EU regulatory agencies, we have already reached agreement to start clinical studies for these pediatric indications. As for formulation for pediatric use that are required for submission, in-house development is underway for oral suspension formulation. And with the pediatric indication approved, we also have expectations that patent expiry will be extended by 6 months.

Lenvima-KEYTRUDA have been given to many patients and human biological analysis has been conducted. As a result, Lenvima-KEYTRUDA is known to cause resistance. And to unlock resistance, we are looking for drugs with that potential and novel CBP/beta-catenin, E7386 potentially that can unlock resistance to Lenvima plus KEYTRUDA.

On the left side, you see cancer big 4. These are undruggable -- so-called undruggable targets that are difficult to engage and in oncology 4 are known. One of the 4 is beta-catenin the subject today and that they are KRAS, MYC and P53. As for KRAS, it has become more druggable in recent years. As for E7386, regarding cancer big 4, one of the big 4, beta-catenin will be approached by E7386. In that sense, it is quite innovative. As shown in the middle, it is a medium-molecular peptidomimetic.

What it does is that the resistance to Lenvima plus KEYTRUDA is known to be caused by the elevation of Wnt pathway and the elevation of Wnt pathway is -- has involvement of protein-protein interaction of CBP beta-catenin, E7386. It will engage CBP and it will inhibit this protein-protein interaction to prevent elevation of or activation of Wnt pathway. So this is quite a potentially innovative breakthrough compound.

Including outside experts, clinical POC has already been confirmed. And Wnt pathway DNA in a patients with mutations in Wnt pathway APC or beta-catenin mutations, partial response has been confirmed. AXIN2 gene expression down regulation or increase of FGF21 protein are biomarkers and changes in these biomarkers have been observed. And that there is a high likelihood that there is efficacy. So clinical POC has been confirmed for this theme.

Including Lenvima-KEYTRUDA, there are doublet options. And with E7386, there will be triplet option, and we would like to pursue the option of triplet option. This is in vivo data. This is RCC in mouse. Lenvima and PD-1 antibody and adding E7386 on the left side, in 8 out of 8, complete response -- in 7 out of 8, complete response was observed. And adding PD-1 antibody in triplet as shown on the right side, similarly, a complete response was observed. And currently with the Merck, we are conducting discussions, and I believe, more or less, we are seeing a similar vision.

I am coming to final 2 slides. First, balance sheet is the strongest in the history of Eisai. Net cash has increased by JPY 50 billion close to JPY 240 billion level. As I mentioned at the outset, net DER improved by 0.5 points. Shareholders' equity increased by JPY 47.2 billion to reach a level close to JPY 750 billion. As for the ratio of equity because of FX impact, it has declined slightly, but we have achieved a historically high level of shareholders' equity. And therefore, we believe that we have the strongest balance sheet ever. With this, we are able to make growth investment and achieve stable dividend payout at the same time. We have high confidence we are able to achieve both.

Based on fiscal soundness, long-term investment and maintaining a dividend payout will be achieved in ROE 10% level on 5-year average is to be achieved by fiscal 2022 above shareholders' cost of capital, positive spread is to be achieved, and we have high confidence of achieving that. This page gives consolidated financial forecast for fiscal 2022. Year-on-year revenue is 93% year-on-year at JPY 700 billion, and that is because other business revenue will be 57% of this fiscal year for a number of reasons. Organic business and actual business revenue does not decline. It doesn't mean that revenue will be declining in actual business. As for expenses, R&D expenses, SG&A expenses have achieved a JPY 40 billion reduction. Operating profit is JPY 55 billion or a 2% increase. And profit for the year, JPY 46.5 billion, 2% growth; EPS of ROE 150.85 of 6.1%, a dividend of JPY 160 to be achieved with high confidence. Thank you very much for your kind attention.

[Operator]

[Operator Instructions] First question is from Citigroup Securities, Mr. Yamaguchi.

[Hidemaru Yamaguchi, analyst]

This is Yamaguchi of Citi speaking. Please explain this first regarding lecanemab, accelerated approval pathway is done. And I believe that PDUFA is not accepted. Therefore, PDUFA is not officially activated. But in 8 months from today, that means in January next year, PDUFA cog for this accelerated approval will be set. Is this correct understanding?

[Operator]

Regarding this question, from Neurology Business Group President, Ivan Cheung is going to respond.

[Ivan Cheung, executive]

Thank you very much for your question. This is Ivan Cheung. And as you mentioned, we just completed the BLA rolling submission. So of course, we are waiting for the FDA to provide us with the acceptance of filing letter, which will contain the PDUFA action date. Is it going to be 8 months? Would that be a little bit shorter? We don't know at this moment. And of course, as you know very well, as we wrote in the press release, we are seeking a priority review. So I would say, shall that happen, which we, of course, I'm hopeful for that to happen. Latest January, hopefully, a little bit faster, but we'll find out soon once we get the letter from the FDA.

[Operator]

Second question is related to your guidance of the performance. Please clarify the other business revenue, and excluding MORAb, I think that the revenue seems to be flat. And Lenvima milestone for this particular year is considered to be staying flat. Is this correct understanding? And ADUHELM, as you explained, $110 million as the max and capital expenditures related to ADUHELM, it is already included?

Mr. Masaka, who is in-charge of Planning is going to respond to your question.

[Teruyuki Masaka, executive]

Thank you very much, Yamaguchi. I am in charge of Planning. This is Masaka speaking. Regarding the other business, what is contributing to the enhancement of corporate value, the alliance for the development with a high probability of success and outlining and such strategic real options are being considered. And as we pointed out, MORAb milestones, we are making efforts to attain such milestones. And secondly, for expenses related to aducanumab, these are included in the company's guidance.

[Operator]

Next, Mr. Kohtani from Nomura Securities.

[Motoya Kohtani, analyst]

This is Kohtani from Nomura. I have 2 questions. First question is about lecanemab. Recalling aducanumab in Phase III study, variability above expectation was observed and that was a bad omen. And in the lecanemab study, the dropout ratio number was given at 14%, and it is lower by wide margin from the expected at 20%. But it was a 14.5% in aducanumab after administration of 78 a week. And this is a very specific question, but at ADPD tau PET sub-study results were presented by Eisai and Clarity AD study enrolled 311 patients are included in this sub-study. And it seems that tau accumulation was limited to moderate in most of the patients, which was a good news. But in about 8 patients, tau accumulation was about 4x as much as other patients. Clinical implication was explained to be unknown, but there are patients who have this much tau accumulation. Other disease may be included? Or are they fast progressor with abnormally fast pace of progression of AD? Those are the concerns. So in a nutshell, in the lecanemab studies, different disease patients may have been included. Is that a possibility and statistically, have you been taking measures against this? That is the first question.

[Operator]

That question will be once again addressed by Ivan Cheung.

[Ivan Cheung, executive]

Thank you very much for the question, Kohtani-san. This is Ivan Cheung, Eisai. You mentioned at the ADPD presentation, the tau PET baseline of the 311 subjects in Clarity AD, as you mentioned, just a small, very, very small number of the individuals appear to have a higher tau PET accumulation level at baseline. Vast, vast majority of those subjects in that presentation at ADPD, you can see have only a moderate level of tau accumulation. One thing I do want to point out Kohtani-san, the primary endpoint of Clarity AD. The primary endpoint of Clarity AD is to detect a statistical significant benefit of the mean value of CDR Sum of Boxes, the mean value. That is the key point.

So in such a large and highly powered study, as you heard from CEO, Naito in terms of the size, in terms of the lower-than-expected dropout rate, in terms of the well-managed variability of a Clarity AD, a very small number of outliers are very much unlikely to impact the main primary objective of the study, which again is the mean value of CDR Sum of Boxes. To your question from a statistical approach perspective, as you know well, there are various statistical approaches with pros and cons in terms of managing outliers in any clinical trial. And all those approaches are well considered in the comprehensive statistical plan in Clarity AD with feedback from health authorities. But again, I would like to emphasize that the appropriate statistical approach is being deployed to, first and foremost, focus on detecting statistical significant benefit of the mean value of CDR Sum of Boxes.

[Motoya Kohtani, analyst]

Well, certainly, the number of such patients may be very small, but aducanumab ENGAGE study, 9 aducanumab and 5 placebo that was a very small imbalance and that affected. So inclusive of that, you are not concerned about potentially fast progressors included?

[Ivan Cheung, executive]

Thank you very much.

[Motoya Kohtani, analyst]

Moving on to my next question. Since you have presented this, I have a question on Page 15. To be honest, declining to the right-hand side, I do not recall seeing this pattern of graph. So I have a question. This is a mouse model, and RCC is planted and the drug was given on day 1 and was decline observed in this way? Usually, we don't see such declining curve. Usually, it is a suppression of tumor growth in majority of the cases. And I believe that what you are trying to say is that this is unusual, which was observed. And I would like to confirm by adding Wnt. Why is there synergy with Lenvima and KEYTRUDA? Could you also comment on that?

[Operator]

Thank you for that question. That question will be addressed by Dr. Owa, Oncology Business Group President.

[Takashi Owa, executive]

This is Owa speaking. First, as Kohtani-san rightly mentioned, this is a mouse model and mouse cancer is planted. So this is allogeneic strain of cancer in PD-1 antibody or Lenvima, likewise, a dramatic tumor shrinkage model is very unusual, as you pointed out. And therefore, Lenvima plus PD-1 antibody combination is shown in green line, and there is a small shrinkage, but it is almost level. Lenvima and the 7386 in combination similarly is showing not a dramatic shrinkage but in triplet, 7 out of 8 showed a complete response.

Such a data to the extent that I know, [indiscernible] CTLA-4, there are many IO combinations in all of the IO combinations in preclinical data, I don't think in mouse model such result is shown in other IO combinations. So I believe that this relates to your second part of the question. I believe this wouldn't be possible without the clear difference from this combination in PD-1 antibody resistance, the immune call status is because T cells are not able to come into the microenvironment of cancer. There is a barrier in that this is a mesenchymal fibroblasts. And Wnt pathway is involved in the maintenance of this. So by inhibiting Wnt pathway, T cells are able to get into 2 more micro environment, a more potent fashion.

And if there is a PD-1 antibody present, then without a T cell cytotoxic cell, these agents will be coming. So it will be more cytotoxic. As for Lenvima and the E7386, there is a synergistic effect. Mesenchymal fibroblast also include parasites. These are different from endothelial cells in terms of origin and these cells also protect vasculatures. In vasculature inhibitor Lenvima, cancer peripheral cells are not adapt, although vasculature may be attacked. And so a nutrient, that will be supplied by vessels but with the Wnt, peripheral cells are also suppressed. And then genetic effect is also suppressed. So the triplet combination for Lenvima and KEYTRUDA can be a very important combination because of Wnt. And I believe that is why synergy is expected.

Wnt pathway importance is noted by Merck and Eisai, amongst are those who are responsible for science. And this is almost established as a common recognition.

Usually, we see PDX data. So immune block the mouse is used. But in your case, Mr. Kohtani, may we take question from the next participant. When time allows, we will come back to you.

[Operator]

Next question is from JPMorgan Securities, Wakao-san. From JP Morgan Securities, Wakao-san.

[Seiji Wakao, analyst]

This is Wakao of JPMorgan. I have a question about lecanemab first. The patients enrolled in the study are quite favorable, and we can have a high expectation to the study. And on the other hand, Biogen aducanumab for Alzheimer's sales and marketing infrastructure is going to be closed. What can be the potential impact of that? Because they are closing their assets, aducanumab. Suppose that aducanumab will be successfully launched in the United States. That means that Eisai needs to create from scratch the infrastructure for marketing. Is this the correct understanding? What will be remaining with aducanumab? But on the other hand, there are assets which will be closed, and there are things that you are required to build from scratch.

[Operator]

Ivan Cheung is going to respond.

[Ivan Cheung, executive]

This is Ivan Cheung. The first point I want to explain is that for lecanemab globally, and of course, in the U.S., since Eisai will be taking the lead on the commercialization activities. We believe for the time being, we have the capabilities to ensure a steady and appropriate preparation for a lecanemab. And as you know very well, in the United States, for example, the accelerated approval pathway has a specific access implications from the CMS. And of course, this fiscal year, for example, our goal is to make sure we disseminate our clinical data to the public, gain public trust and also prepare the patient journey in the United States. So that ultimately, when the full traditional approval comes based on Clarity AD, we will be very much ready when the full coverage and access will be available in the United States.

So for this fiscal year, we believe we can have a very efficient approach in terms of commercial preparation activities and between Eisai and Biogen for lecanemab, we don't believe the recent actions taken by Biogen on their end, will have an impact on the lecanemab preparation. Of course, as we have done between both companies, all the insights and know-how are being, of course, fully leveraged going forward for lecanemab.

[Seiji Wakao, analyst]

And regarding cancer area, MORAb-202. This year, I believe that the pivotal study is going to be initiated. I think you explained that last year at the briefing session. And have there been any updates on this MORAb-202 pivotal study, it will be initiated by the end of this fiscal year. Is this correct?

[Takashi Owa, executive]

This is Dr. Owa speaking. I'm in-charge of oncology. For MORAb-202, next month, starting from third through 7th of June, ASCO, 2 presentation posters, oral presentations will be conducted. And the summary of Phase 1 will be presented and also optimal dosing and schedule. The consideration of [ such ] will be presented. These 2 presentations will be done. And for multiple types of cancer, we are proceeding with the clinical studies. So the possibility of studying pivotal study is already there. But when it comes to the clinical study, we never know what will happen. So proactively, in line with the plan to start the pivotal study, we will proceed. Why have I not been able to explain this? Based upon the ASCO, you will find out what we have been considering in the meantime. So based upon that plan, we are going to proceed.

[Seiji Wakao, analyst]

Okay, I will check on ASCO presentations.

[Operator]

Next, from Tokai Tokyo Research Center, Akahane-san.

[Takashi Akahane, analyst]

I have only one question. It's about Page 5, ADUHELM. I was able to understand and it will be down to half this year and JPY 125 to the dollar and then JPY 13.8 billion this morning. So at JPY 125, what will be the impact of FX this fiscal year?

[Operator]

That question will be addressed by Mr. Dr. Yanagi, CFO.

[Ryohei Yanagi, executive]

This is Yanagi, CFO, speaking. Regarding foreign exchange rate, our assumption is JPY 125 to the dollar. And we have updated given the recent yen depreciation, overall, we do not disclose clear numbers. But from the earnings results of fiscal 2021, please make estimations. Regarding the sensitivity from the recent financial status, revenue will increase by JPY 2.6 billion for JPY 1 for every yen depreciation, but it is a JPY 600 million down for profit. And for other currencies, it will be favorable. So overall, yen depreciation assumption was included this time in comparison to the previous fiscal year.

So there is an upside on the top line. But on the operating profit, it's more or less value neutral. And conservatively, we have made these forecasts. Please consider this in a more conservative fashion. In the previous fiscal year, ADUHELM costs would have increased with the yen depreciation, but now this demerit has declined because of a smaller number of -- well, I'm not so clear on your question. In the fiscal 2021, there was ADUHELM related JPY 225 billion expense. And with the weaker yen, expense will increase between JPY 110 and JPY 125, it will increase by JPY 2 billion. So in the previous year, the burden is large. But this year, despite yen depreciation, the expense is smaller, so it's about negative JPY 600 million. And that's correct in terms of U.S. dollar sensitivity.

Overall, it will be value neutral at profit level. As for ADUHELM position, certainly, in the previous fiscal year, in comparison to JPY 125 to the dollar this fiscal year, it may have been lower, smaller, but from the initial level towards the end of the fiscal year, yen depreciated. So it has increased in yen terms. But for this fiscal year, it is estimated -- it is forecasted at JPY 110 million and the exchange rate applied here is JPY 125 to the dollar. And as for PL, research and development and Biogen payment, these are dollar-denominated liabilities, but there are also royalties from overseas, which are credit side. And so top line is increased about on OP, it's value neutral. And on the OP level, it may be slightly positive, but we are taking a conservative look in terms of foreign exchange impact.

[Operator]

We have used up the time already. So I'd like to designate it to last persons. From Nikkei Newspaper, Nikkei Shimbun [ Oni Sishang ].

[Unknown Analyst]

This is Onishi of Nikkei. I have 2 questions. First question is regarding the current situation. Regarding Russia with Ukraine and China as well, any impact by lockdown in China or because of the invasion by Russia into Ukraine, have there been any impact on the operations?

[Operator]

I would like to ask Dr. Yanagi, our CFO, to respond to your question.

[Ryohei Yanagi, executive]

Yes. This is Yanagi speaking. I am CFO. First, regarding the situation surrounding Russia, because of the depreciated Russian ruble, there was an impact of FX. And the operations itself, it's based upon the HHC in order to deliver contribution to patients. Based upon that company policy, the delivery of drugs are ongoing without any hitches. The uncollectible debts are not existent and there are no problem in funding as well. And for the consolidated results by the end of March, we didn't have to come up with a different accounting treatment or there was an option not to include the materiality related issues. But without doing so, we could complete the accounting closing processes. Financing, closing and audit and funding and delivery above therapies to patients and contribution to patients in any areas, there were no problems, significant problems in Russia.

We have been going through all the necessary processes to date. And after that, we haven't had any information on the material changes in the situation. In China, regarding the lockdown in Shanghai and so forth, causing inconvenience among citizens of China. But for us, at Eisai's operations in China, in Suzhou, we have a plan there we are manufacturing there, and we are also delivering our products from there. Of course, within Shanghai, there is a certain level of confusion. But when it comes to the delivery of products and sales and the financing, funding or AR and AP settlements and payments, there are no problems. And therefore, of course, we believe that we have to continue to closely monitor. But in China, in Russia, we do not believe that there are any significant issues. So please feel assured.

[Unknown Analyst]

My second question is not related to the financial closing. And we heard that Dr. Yanagi is retiring after June. So I'm interested in hearing what you are going to do after this? And if you could give us your comments from CEO?

[Haruo Naito, executive]

During the tenure of Dr. Yanagi, his contribution was very significant. He created this today's Eisai financial strength and the capital policy and the dividend policy have been positively promoted. We do not think that at this trend, he will be stopped. Capital policy and dividend policy will continue to be held by us. On top of that, the successor who has experience in finance, accounting and IR and recently the person was serving as the top of U.S. Eisai, which is the most important subsidiary of us, and he is believed to be contributing to creating further stronger financial structure of the company. In terms of timing, Yanagi-san is going to retire. After his retirement, we believe that he will continue to serve as adviser to the company. Please be assured. And regarding operations in Russia, I would like to supplement. In Russia, anticancer therapies and antiepileptic drugs, which are directly connected to the lives of patients. Such drugs are being delivered and supplied from Russia. If we stop that for any company in pharmaceutical industry, particularly for us at Eisai, who believes in the HHC, we believe that this is not something that we are able to do. So centering on the continuation of a stable supply, we are still continuing on the stable operation there.

[Operator]

This will be the final question. [ Mr. Nushan ] from Tokai Tokyo Asset Management.

[Unknown Analyst]

I have a question for Dr. Owa about 7386. You've answered a question from Kohtani-san, and I listened to your answer. KEYTRUDA plus Lenvima plus this drug, the triplet can be the strongest combination that I was able to understand. But aside from that, the 7386 checkpoint inhibitor overall sensitivity can be enhanced by 7386. Will that be a commercial value that you will be pursuing to drive from 7386? And what is the percentage of target patients? What is the ratio of target patients and at what stage? Well, for example, LEAP-006 is non-small cell lung cancer. And before trading will biomarkers be used to screen patients and for those screened target patients, 7386 used as a second line. And Merck, is it correct to understand that Merck is not jointly developing 7386?

[Takashi Owa, executive]

This is Owa speaking. First, about the potential of E7386, what we have through Merck alliance, Lenvima-KEYTRUDA and so these are prioritized, but I believe that there is enormous potential for 7386. And this year at ASCO as well as at AACR, IO resistance will be a big topic. That is what I expect. Immuno-oncology is now standard of the standard, king of the king, but it is not able to cure. There are patients who are not cured and when we investigate Wnt, other causes are found. And the checkpoint inhibitor has developed a very large market, but there are IO therapy resistance problem, and they are looking for new therapy. So including IO-resistant cases, Wnt modulator 7386 may be used. And in that case, KEYTRUDA is the champion of checkpoint inhibitor. This is the biggest selling IO therapy, where the business opportunity lies is with Merck. We believe that we can see the biggest business opportunity there. And as for the development, what is important is right now, KEYTRUDA and 7386 doublet is developed ahead of others.

In this combination, Merck is providing a KEYTRUDA at 0 cost but clinical trials are led by Eisai. And Lenvima deal started in a similar fashion. So we would like to be able to show good data in series, and I would like to maximize value working with Merck. If that is possible, that will be our dream. And that is how with that expectation we are developing.

[Unknown Analyst]

What is the ratio of a patient out of cancer patients? How many will be target patients?

[Takashi Owa, executive]

If there is a Wnt pathway mutation beta capitation or APC mutation, that those will be -- but these apply to all cancer types. So I believe it's about 10% to 15%, but it is not only about mutation, IO therapy failed patients. I believe 30%, 40% of those failed patients have elevated Wnt pathway. So second line or IO is given in adjuvant or first-line patients who fail those therapies will be in large number. So what percentage? I'm not able to address in that sense, but I believe millions of patients can be target patients.

[Operator]

With that, we would like to conclude today's earnings presentation session. Thank you once again for taking your time out of your busy schedule, and we ask for your continued support.

[Statements in English on this transcript were spoken by an interpreter present on the live call.]