We would now like to begin information meeting for fiscal 2019 by Eisai Co., Ltd. Because of COVID-19 infection situation today, we are live streaming the presentation in today's information meeting. Let me introduce the presenter today, Mr. Haruo Naito, President and CEO. Without further ado, Mr. Naito, please begin the presentation.
I am CEO of the company. This year, we have to hold information meeting in this style. We are not able to have discussion face-to-face with you. It is quite regrettable, though we like to make utmost efforts so that our thought and our beliefs of Eisai, it can be communicated to you. In usual years, I would like to present my rather unskillful drawings of annual zodiac sign, and this year, the first zodiac sign of the 12 signs, mice, the year of rat. I tried to draw a rat here. Please look at the slide. Eisai is currently running under a 10-year medium term business plan called EWAY 2025.
Where this name EWAY came from is, as you can see in this description of the slogan in English, "Converting knowledge into business, we make decisions, we make solutions through Eisai's way." EWAY is taken from this Eisai's way. Today, the first year of this plan, starting from FY 2016 through this fiscal year, FY 2019, which is described as EWAY Current, and we'd like to provide you our review on that period for four years. In the next half or six years from fiscal year 2020, the next fiscal year to 2025 as EWAY Future, we'd like to provide our analysis. First, EWAY Current. Strategic intents under EWAY 2025 are to be reviewed here on this slide. As you can see at the top of this slide, we wanted to have therapeutic areas of focus.
We wanted to transform business portfolio, and we wanted to use the term richie and innovation. What we mean by richie is, for example, please imagine that you are going to build your house, which location you would like to choose? Probably the location which is not so crowded, with a nice view, and with good water works, and land which is resistant to any disasters, and you would like to choose such land on which you want to build a house. Based on exactly the same concept, the place or areas where we should make our innovation or concentrate our innovation efforts, we would like to choose such location. That is the concept behind richie. Based on such concept, we wanted to concentrate therapeutic areas of focus and transform business portfolio.
As a result, two business groups, Neurology Business Group and Oncology Business Group, have been created with our focus of efforts. In each of the business groups, which are respectively described as end-to-end organization, covering from discovery through marketing. That is how these groups have been established. During the EWAY Current period, in each group, we have obtained very powerful global partner. With this business group structure has progressed to partnership model. I believe that this is the general or major trend of EWAY 2025. The first case of partnership model, which is with Biogen. Strategic partnership was originally concluded in March 2014. This was expanded through revision in October 2017. At that time, Eisai opted in aducanumab. Under this strategic partnership, there are three candidates in pipeline. First, aducanumab, which is now under preparation for filing.
BAN2401, as has been reported. Large-scale phase II trial, Study 201, has been successfully completed. Currently, open-label extension study of Study 201 is ongoing. Toward filing, this is going to be the last pivotal study, a phase III study, Clarity AD, is steadily ongoing. More recently, so-called early-stage AD or preclinical AD is targeted in this study, called AHEAD 3-45 study. Through collaboration with ACTC, we are currently making preparation for the study, and screening of patients are about to be started. As for elenbecestat, to our regret, development has been discontinued. With Biogen, we are also cooperating on the multiple sclerosis business. Biogen is a global leader in MS business area. Biogen's MS products are being co-promoted by us in Japan, and in Asia, excluding China, we are marketing, commercializing the MS products of Biogen under this strategic partnership.
As you can see at the bottom of this slide, close cooperations are deployed from CEO level through various levels in the organization. Close communication has been maintained. In order to maintain this strategic partnership, we believe that the frank communication between the two parties, in addition, in advance communication, will be essential conditions for smooth operation. For example, Michel, CEO of Biogen, and myself at the CEO level, at any time, anywhere, using our cell phones, we have established a relationship which allow us to have close communication through cell phone. Next, in oncology area, we are partnering up with Merck. This strategic partnership was concluded in March 2018. What is presented on this slide is that the strategic collaboration has been progressing steadily because we believe that this information would support such collaboration.
Various milestones that have been set forth during this period are as follows. This means that our collaboration, when collaboration progresses steadily, these milestones can be achieved. Currently, the last one, sales-based milestone payment for FY 2019, is yet to be received. However, for all others which have been already achieved, we expect that the last milestone payment will be also received. I believe that you can understand that our collaboration has been steadily progressing. Except for the last milestone payment, the total payments received is, as you can see at the bottom line, is over $1 billion and $425 million. At the very bottom of this slide, in FY 2017, we received $450 million as reimbursement for R&D expenses. Commercial arrangement is rolled out in 18 countries across the globe, and in the latter half of FY 2019.
The first approved indication of KEYTRUDA plus LENVIMA combination in 2019 was launched for endometrial carcinoma under the name LEAP studies. A very large scale pivotal studies in seven cancer types or 11 indications in the basket trial have been initiated, which includes a basket trial as well. From CEO to CEO level and throughout various levels of operations, we have very smooth and close cooperation and communication maintained throughout the period. Here is the slide which provides the overview of LEAP study, HCC first line study, through to the last one that has been recently incorporated in this LEAP study, HCC combination with TACE for seven types of cancer in 11 indications. This is very large-scale study.
On the right-hand side, you can see the description of basket trial, which corresponded to phase II trial, particularly among which gastric cancer, we have obtained a promising favorable data and gaining attention to this. The top three of its LEAP study have been designated as Breakthrough Therapies, and the summaries comments are provided at the bottom. In total, approximately 8,200 patients with cancer are to be enrolled in this very large scale LEAP study as whole, which is ongoing steadily, covering all such types of cancer. We believe that KEYTRUDA and LENVIMA combination can be established as backbone therapy. We have high expectation to that. Another partnership has been formed with Nichi-Iko, which is also strategic partnership, which was concluded in March 2018. Under this partnership, through our transformation of the business portfolio, transfer of [Element AI] was completed in April 2019.
In China, Nichi-Iko's generic products are to be developed through collaboration. Comprehensive strategic partnership in China had been concluded in September 2019. API is being manufactured at our Vizag plant in India. We initiated the supply of API to Nichi-Iko. The real aim of this partnership was to provide Eisai and Nichi-Iko products packaged with integrated product package, which is showing the progress as well. Here, you can see the status of EWAY Current. We have summarized the figures for the period. The starting year of the period, results for FY 2015 are provided. At the top half, you can see consolidated P&L and ROE, EPS and so forth. In the middle, revenue by region. At the bottom, revenue by focused area, namely neurology and oncology business areas.
You can see the forecast for this current fiscal year 2019 at the time of Q3 result announcement. As you can see on the right-hand side, CAGR is provided. Revenue grew on the average by 5.5%, and operating profit was increased by 20.6%. EWAY Current has shown significant growth overall. If you look at the yellow box at the bottom, because this provides you the summary, please look at the R&D expenses. For example, under FY 2019, JPY 148 billion was spent for R&D activities on P&L. Actual expenditure in a pipeline development, R&D resources, was JPY 188 billion. Therefore, exceeding by about JPY 40 billion, the R&D expenses on the P&L statement. This gap is the reimbursement from partners. Based on the partnership model, we have been able to invest huge R&D expenditures. Please look at the COGS rate.
There has been about 10.5 percentage points improvement or decline. There are various reasons, major reason was because of the growth of in-house products such as LENVIMA. Because of this improved product mix, we could reduce the COGS rate and also increased profitability. Please look at revenue by region, at the right-hand end column, CAGR. Under EWAY Current, the fastest growing region was Asia and Latin America. That is followed by China. Asia and China's growth was most conspicuous in this EWAY Current period. Revenue by focused area and CAGR for oncology was 9.5%, which we believe has drawn the growth of the overall business. Going back to the top box, ROE. Our FY 2019 forecast is 15.6%. ROE was actually targeted to achieve 15% or over in FY 2025. Therefore, that target is expected to be achieved well ahead of schedule.
Similarly, operating profit FY 2019 forecast is set at JPY 110 billion. As for this as well, JPY 102 billion was originally set as a target for FY 2020, which is expected to be achieved ahead of schedule. Overall, EWAY Current has been quite steady. I would like to talk about EWAY Future. The most important aim under this EWAY Future is to address Alzheimer's disease area. I would like to provide you with demography for AD, Alzheimer's disease. On this slide, AD demography is provided in this table. These figures are based on various economic calculations on our own, this is the very basic figures for supporting our simulation. These figures are constantly updated. On the vertical axis, you can see the comparison of 2020 and 2025.
On the horizontal axis, you can see six regions from U.S. through region total. The total population above 65, AD-ALL, MCI, mild AD, combining the two early AD figures are provided. AD-ALL means amyloid-β-positive patients are counted as AD-ALL. I believe there are various ways to interpret these numbers. For example, early AD. In the yellow box, please look at the early AD, the right-hand side. Globally, the region total early AD population is estimated to be 38 million. At the very bottom, in 2025, this number is expected to increase to 44 million, about 44 million in the world. The number of people living with AD or AD-ALL in this chart by region. In China, right from the middle, 11.6 million in 2020, and in 2025, this number is expected to increase to 14 million.
Based on current number as well as this estimate, the number of people living with AD is expected to be the largest in China, followed by Asia, EU, ALL, and Asia. Above 65%, the ratio of people aged 65 and over. In Japan, currently, the ratio is 28%, and it is expected to increase to 30% in 2025. Therefore, the ratio of people aged 65 or over is estimated to be the highest in Japan. Going forward, AD-DMT, the disease-modifying treatment for AD, Alzheimer's disease, is to be promoted in the market going forward. What is most important for us is to be explained here in this rather busy slide. Please look at the headline on this page. How much disease understanding is obtained, for which how much preventative actions are being executed in daily lives.
As the metrics for measuring that, cognitive function checkup, how much such checkups are being conducted in daily lives. Consultation with physicians, how much cognitive checkup is being conducted. By establishing all these, AD-DMT will be able to exhibit its real value. We believe that these associated activities are going to be critical for us. Chasm. I would like to use this term, chasm. I think that this is not a term which you are familiar with, what does it mean? As you can see, a little below the headline, a hurdle which has to be overcome to promote understanding of disease, making it possible to make a habit of checking cognitive function in daily living.
Chasm is used in that sense, and how through our efforts, how we can resolve various chasms that are the biggest challenge for us for the time being. Chasm. In daily living domain and medical domain, please look at the gray horizontal line. The bars below that shows the number of people belonging to that category. People aged 40 to 79 years old, and 65.91 million people are represented in the left-side bar, out of which, how many people understand the disease or dementia? How many people understand what MCI is? The number respectively are represented in blue portion of the bars. As you can see, the number of people who understand that the diseases are decreasing. There are such chasms. Furthermore, in daily living, like diet, exercise, or sleep, et cetera, people pay attention to those daily life activities like preventative actions.
How many people understand the purpose of the preventative action? How many people individualize those actions? How many people execute them? How many people make it a common practice? By raising the bar or degree, and then gradually the number of people who do these actions is decreasing. As you can see, there are various chasms represented in yellow arrows towards the right. Further, after conducting preventative actions, and then how many people have been undergoing the cognitive checkups and habituated checkups? Gradually, one by one, you can see the number of people who conducted these checkups are also decreasing. There is a huge gaps or chasms that have to be resolved. Towards the right, in medical domain, although patients, people are consulting with the physicians, however, not going through the cognitive checkups. We have identified a great chasm here as well.
We would like to address these chasms. I'd like to recap the chasms. In the middle of this page, chasms are presented, little awareness or perception of disease, or chasm of preventative behaviors are not performed as common practice, or chasm as cognitive function checks are not performed, or chasm where convenient diagnostic tools for early AD are not widely used. We are able to identify these four types of chasms. For each of the four chasms, we would like to provide certain solutions. First, for the chasm of little awareness or perception of the disease or dementia, of course, we'd like to promote the disease awareness activities, but utilizing our own media, such as e-65, sodan.e-65.net. This will be utilized more actively, and I believe that younger people belonging to this 40 to 79-year-old population will have their very important role to play.
Therefore, we'd like to proactively promote the disease awareness activities utilizing these channels as well. In the middle, in daily lives, such as diet, exercise, and sleep. Preventive behaviors, which will be explained in details later. Easiit, we have this platform named Easiit, through which we'd like to prepare brain performance app so that patients and their families can utilize the data, and we would like to have the two-way communication going forward. On the right-hand side, the checkups of cognitive functions, Cognigram, and for nonmedical use, Cogstate Brief Battery. We have signed an agreement for using these. We would like to utilize these in Japan. Nonmedical use, Cogstate Brief Battery, has been named NouKNOW. We are registering this trademark now. As you can see in the schema, which looks like a combination of the human face, and this is the logo of NouKNOW.
We would like to utilize this utilizing cards. This provides the simple, convenient cognitive function checkup, which will only take 10 to 15 minutes. In daily lives, you can conduct this testing simply on PCs or tablets, and we would like to promote the use of this tool. As you can see in the middle, the chasm of a convenient diagnostic tool for early AD. This will be resolved, and using the same algorithms as NouKNOW, Cognigram for medical use is also available. We would like to consider using this in a medical domain as well. Next. What is Alzheimer's disease? I'd like to share with you this pathology of this AD that is described as AD continuum, continuous disease pathology, and biomarker panel that is described in headline Alzheimer's disease.
As you can see at the top of this slide, starting from people with no pathological changes to preclinical AD, MCI due to AD, mild, moderate, severe ADs. There is a continuum of progression of this disease. Therefore, we believe that it is right for us to consider this disease as a continuum. Based on the treatment guideline and the diagnosis for a disease stage to be correctly conducted, there are various biomarkers being developed. That is called ATIN in a vertical axis in the middle of this page. A stands for amyloid, T stands for tau, I for inflammation, N for neurodegeneration. Of course, those people with no pathological changes in daily lives, they can use NouKNOW or a simple Cognigram can be utilized in various way. A, for example, A for amyloid, even with blood, amyloid β 42-40 ratio can be measured nowadays.
Amyloid PET and CSF, which is a very important measurement. Next, tau. Some part of the tau can be measured by blood, and tau PET is being developed, and CSF can be the source of measurement as well. A can be tested mainly by CSF. N as well can be tested mainly by CSF. Some N can be measured by PET as well. Gene, please look at the brown band. Of course, ApoE4 or other associated genotypes are recognized as important factors. About 2.1 million SNPs can be analyzed so that polygenic risk score for Alzheimer's disease can be calculated, which is now possible. Therefore, gene-based information is getting more and more important. What I have mentioned is described at the bottom. Simple confirmation of brain performance for diagnosis utilizing ATN in a biomarker will eventually be possible.
Diagnosis and efficacy evaluation in AD continuum is based on biomarker panels, which can comprehensively understand the disease pathology. Currently, the CSF testing will be capable of evaluating these biomarkers with a high degree of sensitivity and versatility. We believe that a CSF testing carries the highest potential. What will be the future progress of AD diagnosis? That is summarized on this page. In terms of PET, there are various PET tracers under development. More precise information may be obtained. For example, for preclinical AD, to diagnose disease stages using new PET probe, that diagnosis may become possible, and that is going to be included in AHEAD 3-45 study. Tau PET tracer may be available. Aβ-tau included imaging biomarker panel may be the type of information that we are able to use. I have been stressing the importance of CSF test.
FDA has given Breakthrough Device Designation to amyloid measurement using CSF from two companies. I may sound repetitive, as an overall biomarker panel for AD, currently CSF is considered most powerful. Looking at blood at left bottom, using MISSION AD sample with Sysmex, Eisai is looking at the ratio of Aβ42 to Aβ40 using blood sample. We are making utmost effort, we believe that significant progress is made towards submission. We are engaged in various efforts. Regarding FDA Breakthrough Device Designation from FDA, this diagnosis was granted that designation. In this area, we have seen major progress in the past one or two years. As for genetics, SNP-based polygenic risk score system may be used for onset determination and prognosis determination. Going forward, using blood and genetics in combination, diagnosis and efficacy evaluation of the drug may become the mainstream approach.
Such paradigm shift may occur. What will be the value brought about by AD-DMT? At the very top of this slide, cost for dementia is estimated, and where the cost is incurred is estimated. As shown at right, we have number of statistics, but JPY 220 trillion is expected to be the total cost in 2030 globally. There are low-income, middle-income, and high-income countries, and a breakdown is given in the middle. About 80% will be spent on care in all of these countries, social care cost, long-term care cost. On the right side, this is care cost by family members, which is called informal care cost. This is rather difficult to calculate, but such cost is also included. About 80% of the total cost is related to caregiving. AD-DMT may affect and may bring about impact on this care aspect.
On the left side, aducanumab EMERGE study result is shown. ADCS ADL-MCI. This is based on the assessment by caregivers, whether deterioration of ADL was slowed. Aducanumab demonstrated 40% reduction in the deterioration of ADL. This is a robust data. The care part, which accounts for a large portion of the cost, there may be beneficial impact from aducanumab. At the very bottom of page, this shows the possible effect of delaying the onset of disease by five years.
AD-DMT will have to prove such efficacy or effect, but possible cost reduction is estimated by various reports. First, in the U.S., if such a treatment method is introduced, $367 billion reduction is expected in five years' time. Similarly, in Japan, if such a treatment method is introduced, JPY 2 trillion reduction in care costs is expected in fiscal 2025. In summary, shown at the bottom of the page, AD-DMT is expected to contribute not only to delaying disease onset and slowing cognitive decline, but also to reducing social costs such as medical, nursing, and informal care costs. AD-DMT is also expected to reduce the burden caused by disease onset by extending the time without symptoms of dementia, so huge value can be brought to the society.
Since Aricept, day and night, we have been making efforts to develop the next generation AD drugs, there were successes as well as failures. The basis of our development has been Aβ hypothesis. Based on Aβ hypothesis, when it comes to drug discovery based on that hypothesis, Eisai is at the forefront in the world and has accumulated the most experience without a doubt. Based on that experience and track record, we have updated our understanding of Aβ hypothesis as shown here. First, the current state of Aβ hypothesis is shown in this schematic diagram. The middle part, the red dot, shows the aggregation of amyloid-β and dissociation of amyloid-β. Amyloid cascade is shown. In the middle, there's tau. Tauopathy involvement is shown. Below that, as a result of these tau, nerves are attacked, resulting in neurodegenerative disease.
The state of neurodegeneration is also included in this schematic diagram. Earlier, I mentioned ATN, and this is the graphic representation of that. Based on this hypothesis, we have engaged in drug discoveries, and there are five findings or knowledge that we have obtained. At the left top, we have lentiviral vector and experience of BACE inhibitor. Amyloid precursor protein, APP, at the very left, is cleaved by BACE enzyme, and Aβ monomer is created as a result. This is the start of the cascade. The hypothesis supposes that this initial stage should be stopped. Right now, we understand that BACE inhibitor is involved in multiple substrates, resulting various effects. If we are to develop BACE inhibitor in the future once again, then high selectivity to APP will be necessary to develop such a compound. Aβ monomer generation will be suppressed.
The pharmacologically active substance that is a BACE inhibitor, it is without doubt that it's pharmacologically active, the middle part, the aggregate, that is the main cause of the neurotoxicity. These aggregates are not much removed by BACE inhibitor, so the timing to use BACE inhibitor will have to be quite early when monomer starts to aggregate, or after removal of aggregates in maintenance therapy stage. Those may be the appropriate timing for use of BACE inhibitors. The box two at right top. This is the biggest achievement in drug development based on amyloid-β hypothesis. amyloid-β aggregates at the middle part shows oligomer and protofibrils, or plaque may also be included in amyloid-β aggregates.
By reducing or removing Aβ aggregates, there is a less decline of cognitive function and benefits in activities of daily living, as demonstrated in large-scale studies, phase II study of BAN2401 and phase II studies of aducanumab. This is a major achievement showing that Aβ hypothesis is the correct hypothesis. In the area of Alzheimer's disease drug discovery, this is an epoch-making accomplishment in our view. At left bottom, there's box three. The Aβ aggregates that do the most evil, it should be removed. Target engagement is necessary. Antibodies with such target engagement will be strongest. With monomer antibodies or BACE inhibitors, aggregates cannot be removed entirely, and speed of breaking up the balance or dissociation is shown to be slow.
In the fourth box at the bottom, in order to understand the overall picture of amyloid-β hypothesis, not only A, T biomarkers at the top, but I biomarker and neurodegeneration biomarkers will also be needed to understand inflammation and neurodegeneration. In box five, there are various aggregates known to be neurotoxic, and soluble aggregates, protofibrils included, may be most neurotoxic according to some papers that have been published recently. Treatment focusing on soluble aggregates is considered to be important. aducanumab and BAN2401 studies are ongoing and are under preparation. I would like to discuss them. First, for aducanumab, under the name of EMBARC study, patients who are enrolled in the past studies will be included in a redosing study. Redosing study is under preparation. For BAN2401, there is remaining one phase III study, Clarity AD study. This is moving ahead smoothly.
In fiscal 2020, by the second quarter, we expect to achieve last patient in. 1,566 subjects will all be enrolled according to our expectation by the second quarter fiscal 2020. In the first quarter fiscal 2022, final readout of primary endpoint is targeted, and progress so far has been steady towards that goal. There is open-label extension study of large scale Study 201. In preclinical space, we have AHEAD 3-45 study. Under one protocol, two cohorts will be considered. Early stage A3 and next stage A45, two cohorts. These two cohorts are included. Academia group in the U.S. with rich experience, ACTC. We are jointly conducting this study. This is a co-development. Biomarker panel will be used as endpoints, including CSF and blood as possibilities for biomarker panel.
Subcutaneous administration route of study is also under consideration, as shown at the bottom of the page. As for aducanumab, we are actively engaged with the FDA and regulators in Europe and Japan. We are making progress. In the U.S., with FDA, we have been having discussions with a view towards completing a regulatory filing as soon as possible. As for aducanumab EMBARC study that I explained earlier, this is a redosing study, and protocol has been submitted to FDA, and it will be initiated soon under open label study. Biogen and Eisai are working together for go-to-market model, and we are establishing commercial teams and are in very close collaboration in preparing for aducanumab. This is the pipeline related to AD. For each of A, T, I and N.
For A, we have two compounds or two antibodies, and in T, we have one antibody. phase I is ongoing for antibody that affects the entire spectrum of tau. In I, druggable product is being considered with G2D2 in Boston. In N, synapse-related projects or themes are being pursued. One of which is from Tsukuba Research Laboratories. This is a small molecule, and we believe that phase I can start soon. Beyond A, T, I, N, or outside of A, T, I, N, we have, for example, DAYVIGO. Japanese researchers looked at orexin receptor biology, and this is a superb insomnia drug. DAYVIGO is already approved as an insomnia drug. DAYVIGO, for ISWRD, it was studied in phase II study, which was finished. A PDE9 inhibitor, also an in-house developed compound, is in phase II, III study for dementia with Lewy bodies.
We also have collaboration with Keio University called e-KID. This receives funding from AMED. Keio Medical School owns various samples. Using these samples, we can conduct multi-omics analysis to obtain various information, and it can be used in in vivo study in reverse translation methodology. In the world, no one has attempted to analyze protective mechanism of brain in this way. There are various protective mechanisms of brain. We would like to identify drug discovery signature based on protective mechanism of brain. This is also underway steadily in collaboration with Keio University. Next, I would like to turn to cancer or oncology. Here, we consider this as a cancer continuum. This is a continuum of disease. At the top, as shown in this blue arrow, there is precancerous condition, ultra early cancer, early cancer, and then advanced cancer in this continuum.
In each stage, there are various events that lead to canceration, proliferation or infiltration, recurrence, metastasis, and treatment of refractory state. In each stage, there is cancer evolution or gene alteration. With liquid biopsy, we are to understand this so that we can target them as a drug discovery target. That is the strategy in cancer continuum. In monotherapy setting, we have a strategy, and we also have combination therapy strategy. In monotherapy strategy, neoantigen induction. This uses special technology from H3 Biomedicine in Boston. Splicing modulator is used as payload in ADC to induce neoantigen. Such research is underway jointly with BMS. The research has been initiated. Next, Wnt/β-catenin signaling pathway modulation also has a large potential.
As shown in the middle of the page, we have assets including eribulin, and eribulin is used as payload in ADC MORAb-202, and there is liposomal formulation and a parent compound of eribulin, halichondrin, is turned into a formulation E7130. These target microenvironment of cancer, and we have such a grand platform. As for combination therapy, what is representative is LENVIMA and KEYTRUDA combination used in LEAP study that I explained earlier. We would like to establish this combination therapy as the backbone therapy in cancer. All of the monotherapy candidates can become good partners for combination therapy. Amongst them, I would like to select two as next flagship candidates. First, as shown in this pink box, Wnt/β-catenin signal pathway modulator E7386. This is in phase Ib. β-catenin is called one of Cancer Big 4. It is difficult to create drug based on this.
Out of such difficult druggable candidates, there are such four areas. Out of that Cancer Big 4, it was quite significant that we are now able to target β-catenin pathway. CBP and β-catenin will cause protein-protein interaction, and there is a translation or transcription. This protein-protein interaction will be inhibited to stop transcription. That is the mechanism. Including for HCC and in various other cancer types, it is known that this mechanism is useful. Protein-protein interaction inhibition is not simple. At multiple point in time, inhibition effect should be shown by a compound. Very high level of medicinal chemistry capability is required, and we have been able to progress successfully in this area. We consider this a very important location or niche in cancer treatment. In case of HCC continuum, we have E7386. This addresses early phase of HCC by inhibiting transcription.
In the later stage disease, LENVIMA plus KEYTRUDA combination may be used to treat HCC. Such regimen may be possible. As for gastric cancer, ER, estrogen receptor alteration-related drug is what we are considering. H3 Biomedicine discovered H3B-6545 is considered. This is in phase II. Hormone positive breast cancer account for several tens of percentage of breast cancers. The majority of them are ER+ . This is a typical endocrine therapy, including aromatase inhibitor, and about 30% will exhibit therapy resistance. ERα mutation occurs that make patients therapy resistant. What is called SERM or SERD, these hormonal therapy, there will be resistance to even SERM and SERD. This is a very difficult gene mutation to address. There is covalent binding with a wild type and mutant type, so breast cancer proliferation can be suppressed. Such an epoch-making profile is shown by this drug.
As shown at the very bottom, this is the possible regimen for breast cancer treatment. Hormone therapy, molecular target treatment may be used at a certain timing. During that wide period of time, ERα gene mutation addressing drug may be used. This may bring about a paradigm shift in breast cancer. We believe that this has a potential for such an epoch-making treatment. Now turning our eyes away from R&D, I would now like to look at the origin of Eisai. What is our philosophy? What are our processes in our operations? What we consider to be most important is the ability to empathize by spending time with patients. Based on the empathy, we will understand the anxieties held by patients, and we will develop strategy and possible solution to remove anxieties.
That is a cycle that Eisai uses as a rule or way of doing things. What do we mean by empathy? As shown at the bottom of the page, empathy is status of intersubjectivity of feelings with other persons, which may create mutual trust. For example, the fourth photograph, right top photograph, shows John Collins, who is responsible as a global lead of LENVIMA in our U.S. entity. A few years ago, he visited Japan and visited pediatric cancer hospital ward in Tokyo, spending about an hour and a half, and this is when they are saying goodbye, and both of them are in tears. John Collins does not understand language, this shows that it is possible to transcend generations and language differences. This shows the ability to empathize. Number 6, the left part of the photograph.
This is Elaine, who's responsible for finance function in Europe. Elaine visited a group home for mentally handicapped, and there is a language barrier. By spending time over many hours, they are able to smile together. They were able to establish such a relationship, and Elaine was very moved by this experience, and I recall that she cried afterwards. Looking at photograph number one, these are medical reps in Miami, in our U.S. operations, and they visited Puerto Rico when Puerto Rico was hit by hurricane. They prepared relief supplies. The left corner photograph shows that our medical rep visited Puerto Rico and were able to confirm the safety of our patients. I think this also shows the ability of our employees to empathize. Using this methodology, we are applying this methodology to AD strategy, and what happens is shown here.
For a long time, since the days of Aricept, we have been spending time with people living with dementia and their family as part of our hhc activities. As a result, we were able to understand three anxieties. The first is when will the symptoms manifest themselves? Secondly, what needs to be done to avoid the manifestation of such symptoms? The third is not wanting to be burden on the family members. To address these anxieties, we designed dementia ecosystem platform. We would like to implement this platform. We are at a stage finally to implement this to see whether we are indeed able to address the anxieties of patients. This platform is called Easiit, starting with E for Eisai. Welfare, et cetera, are the notions that are represented in this name, Easiit.
First, there are patients and their families. There's an arrow going to and going from people living with dementia and their families. There is a NouKNOW and other cognitive function checkup. There is information related to sleep, diet, and exercise, and such information can be included in Easiit. AD-DMT and latest information data set, biomarker set, and cohort study covering healthy subjects to MCI. We have such data set and based on these data sets, algorithm can be developed, so appropriate advice can be given. In this way, we are able to return information to patients and their families about prevention and treatment. That loop is at the center of this platform. Of course, we are in compliance fully with Act on the Protection of Personal Information and other requirements. Professional versions can be shared and built for medical institutions.
Easiit role covers not only medical or medical part that is shown in green, that is quite important. Societal part is also where Easiit maybe made good use of. For example, private insurance companies are trying to design appropriate insurance products for dementia, and collaboration with Easiit may lead to designing of good insurance product. In fitness clubs, there are many people who are interested in exercise that may help prevent decline in cognitive function. In automobile, there's a concern about safe driving by elderly people. In retail, how people who are senior or with dementia can work is an important issue. In nursing home, support and optimal care may be designed. In all of these areas, Easiit may be able to offer collaboration. We believe that Easiit will be able to provide superior benefit than when it is addressed on a stand-alone basis.
We believe that this will develop into socio-medical innovation. Our ultimate objective is to realize societal innovation through dementia ecosystem. Under the title of Eisai Future Aspiration, figures are shown. The top table is overall CAGR, and region balance is shown in the lower chart. In the middle is EWAY Current up to fiscal 2020. This is information that I explained earlier. Under EWAY Future, we expect that there is an enormous growth opportunities. For example, revenue is expected to grow on average 20% globally. In terms of profit growth is expected to exceed growth in revenue. Neurology and oncology businesses are expected to grow at faster pace than 20%. Especially neurology is expected to show very strong growth. As for the region balance, in the middle, the current situation is shown, and EWAY Future is shown under the column FY 2025.
That is represented in graphic form in these line graphs. As you can see at a glance, Americas will come to have a very strong importance. EWAY Future, about half of the performance is expected to come from the Americas. Total region will be showing strong growth, but Americas importance will be very strong or high in EWAY Future. As shown at the bottom, we aim to achieve remarkable growth with expansion of LENVIMA and potential AD-DMT during EWAY Future. Americas region is expected to be the major driver for the whole company. I have two last slides, and key points of Eisai are summarized in these two boxes. We are pursuing partnership model that I have explained earlier, and partnership model has been and will be the core of our business through Eisai.
As shown in Easiit example, medical innovation, not only medical innovation, but it will be transformed into societal innovation. That evolution is already underway in Japan to address Parkinson's disease, insomnia, and epilepsy. In these three areas, we have already begun to implement this. Transformation of medical innovation to societal innovation is the task of Eisai Future. This is my last slide. This is Mount Everest. This picture was included in Eisai booklet that we made in the first year of Eisai from the base camp in 2016. We have been steadily making progress climbing this mountain. Where are we now? There is a mouse indicating.
Where we are, I believe, at a point slightly before the attack camp, and we are about to complete the building of the attack camp so that we can approach the summit, attack the summit. We are determined to approach the summit in 2025 and achieve the objectives under EWAY. I would like to ask for your continuous support and guidance. With that, I would like to conclude my presentation. I thank you for your kind patience.
We would like to open Q&A session. Today, we would like to take questions from participants who are taking part in this conference through telephone system. We are currently taking questions and registering questions. Please hold on a minute. There has been access from first person to ask a question. Mr. Yamaguchi of Citigroup Global Markets Japan. Are you ready, Mr. Yamaguchi?
Mr. Yamaguchi, can you hear me? Yes. Please, have the floor. Thank you.
Thank you for the opportunity. I think I have two questions. My first question is about your presentation about aducanumab, the timing for filing for approval for aducanumab. At the beginning of the year, that was as you explained earlier. Now we are in early March. Could you please elaborate on the timing for filing in the U.S., and also the filing is planned in Europe as well as in Japan. What will be the timing for filing there? Timing may be different by region or simultaneously filed in all the regions. I think that you have a hotline communication, close communication with the counterpart president. Could you please give us the update on the timing of filing? Thank you for your question.
As I said earlier, in Japan, the U.S., and Europe, with three regulatory authorities, we are currently progressing in our consultation with them. In U.S., continuous and constructive consultations with FDA are currently ongoing. For completion of submission is now aimed at, and we believe that preparations for early completion of filing is being made steadily. Once our filing is accepted by the authorities, we would like to immediately make press release as we have been doing so. This time as well, when the filing dossier has been accepted by the regulatory authorities, we'd like to inform you of as such without delay. I would appreciate your understanding. You mentioned acceptance. The timing from submission to acceptance will be different between Japan and U.S. In Japan and Europe, sorry.
In Japan and the U.S., when it comes to acceptance of the filing, once the simultaneous submission is made, then the acceptance can be done first in Japan. Regarding the regulatory process, I believe that this is sensitive issue, I would like to refrain from making comments on specific timing. I hope you understand this.
Understood. Thank you. Second question is about amyloid β blood testing. I think Eisai is working with Sysmex, I think on different types of technologies which are also being developed. Do you intend to completely work together with Sysmex to the end, would you like to opt for other types of technologies if they seem to be better than Sysmex? Could you please give us your comment?
I don't know whether it is appropriate to say that we will work with Sysmex towards the end, but at least we would like to collaborate with Sysmex so that HISCL, which is an excellent system developed by Sysmex. The blood-based diagnostics method will be developed, which will be adopted on this system. We are working with them to develop that. AHEAD 3-45 study, blood samples will be secured and obtained. What kind of method will be utilized regarding what will be the most realistic method through our consultation with ACTC, which is academic consortium, to decide which method to be used.
Thank you very much. This is the easy question. Modality is now a buzzword, and I think that companies are increasing modalities in order to promote the drug discovery process. I think that you are focusing on the medicinal chemistry.
Some are based on the antibody, but beyond this, and I think that you are also utilizing computers, the cells and genes. What about the future potential for expanding modalities for Eisai?
I don't think that modality is something that we should stick to as a result of our other efforts, and I think modalities can be changed. Intratumoral STING agonist can be administered directly into tumors, in our case, and longer tubes can be used for administering drugs. We are utilizing those. It really depends on the needs of the therapies. For example, nucleic acids are very proactively being developed. Such, it's not because there is a modality called nucleic acid, because there is a need for compounds based on the nucleic acid. I think that is the order we should focus on.
Thank you very much.
Thank you for the question. Next, we have Mr. Hashiguchi from Daiwa Securities. Mr. Hashiguchi, please.
The first question. Hello? It seems that you were cut off. Yes. Thank you for taking my question. I have a question about page 18, line one, line two. aducanumab regulatory topic. Line one and line two show different descriptions. What is the reaction from the authorities as of now? Does that mean that the U.S. authorities' reaction is different from EU and Japan? Does that mean that early submission is not possible in some of the regions?
Thank you very much for your question. As I have been saying, this is a delicate matter when it comes to regulatory issues. In the end, it will be determined by the judgment and decision of the authority. I hope that you will be able to understand based on the description presentation given today.
Next question is about page 26, Eisai Future Aspiration. Although revenue is expected to grow on average 20%, operating profit grows only on average 25%. This is quite unlike pharmaceutical industry. What is the change that you expect in the revenue structure? Based on Merck partnership, what is your projected revenue inclusive of that? Could you address this?
LENVIMA 2025 based on partnership with Merck. For our projection, as I have been saying, more than JPY 5 billion, or more than JPY 500 billion, is the rough indication. To report a JPY 5 billion OP will result in enormous improvement in profitability. In our view, between the top line and the profitability, we do not think that there is much discrepancy. I hope that helps your understanding.
Turning to page five, you have milestones and one-time receipts. In fiscal 2025, could you comment on your expectations about milestone receipt, et cetera?
We will be making earnings announcements. We would like to consider touching upon these pieces of information on those occasions.
BAN2401 subcutaneous study possibility that is mentioned on page 18. What are you considering? Is it a technological aspect or formulation aspect, or when do you expect to finalize your decision about go or no go?
This is not an economical consideration, but more of a technological consideration. I do not expect that too long a time will be necessary before taking a decision.
Thank you very much. Next person is from Nomura Securities, Mr. Kotani. Mr. Kotani from Nomura Securities, please have the floor. Are you ready?
Thank you. This is Kotani of Nomura Securities speaking. Can you hear me?
Yes.
Page 26 of the slide deck, an Eisai future is presented here. I believe that this is what is already visible right now is included in Japan and Europe. You are not saying that aducanumab will not be sold, and in the U.S., you are preparing for filing, therefore that portion is included. I think at the previous occasion last year at the briefing session, I think the perception I had at the previous meeting, I think this is rather more conservative. Why a 20% growth for sales revenue and a 25% growth is projected for operating profit? Did you multiply these factors by probability of success? How did you come up with these projections? Could you please explain this?
Thank you very much for your question. The complete success of LEAP study and AD-DMT are two products to be approved and launched.
The success in this, these are utilized as the given successes for simulating this aspiration. Well, in Japan, China, and Europe, I don't think that there have been much projection of growth. LENVIMA with HCC is expected to grow further. Inclusive of all those factors, do you still stick to this projection? Region balance under the column titled FY 2025. This shows the mix of regions in the total. In the value, a value can be very huge. In all regions, unless we maintain very high growth ratio, we won't be able to reach this level.
Understood. My second question is, I wonder which page I'm referring to, but I think it was on page 12. Cognigram. I'm sorry I am not well-versed in this, but I believe that this is very critical point for aducanumab to be approved.
I think the first bottleneck will be the neurologist, lack of neurologists. On the next page, ADIN, I think that it will not be possible to diagnose all the Alzheimer's diseases. There needs to be a medical testing. Of course, it will be time-consuming. In Japan, such neurologists who are experts in dementia, not maybe reaching the 2,000 physicians. They will be overwhelmed by the flow of the patients. Cognigram, do you plan to get approval on this Cognigram? Do you suppose that Cognigram will be approved as a medical device and compared to the existing scale like a CDR-SB, the MMSE?
I think that these will be interoperable with the existing scales. Cognigram is already approved for medical use by FDA in the United States. For us, NouKNOW and Cognigram are almost the same.
Before selecting the two, over 160 various convenient and simple cognitive function diagnostics tools were screened before reaching the decision to choose these two. Covering consistently daily living domain through medical domain, I think the value of these two devices will be able to provide the information covering these two domains. Regarding the development in this country, in Japan, we are yet to start.
Understood. The last question. I would like to summarize this here. I think that you are not able to discuss specifics about aducanumab, but on page four, Study 201, OLE 12401 extension study, IC or CTAD. Do you think there will be a potential to see the data? LENVIMA LEAP-005, gastric cancer or other cancer types. I think the presentation will be made on these types of cancers.
I think that there are some outcomes or data that may be important for you. Do you have any plan to make presentations or announcements on the data?
For OLE Study, currently, I don't think that there is a current plan for making presentation or announcements. I think in two years or so from today, the study will be completed. I think that they will be ready to report to you on the results. Kotani-san, what was your question?
The other question. For LENVIMA LEAP-005, part of the basket trial will become available. I think that's what you mentioned at the last presentation meeting. Other than that, for LENVIMA, new stroke or read out of the clinical studies may become available. Could you please elaborate on this?
Perhaps I need to call Dr. Owa to respond to your question.
Mr. Kotani, thank you very much for your question. My name is Owa speaking. I'm from the Eisai Oncology Business Group. LEAP-005 study readout timing, as you questioned. The study itself is ongoing steadily. In total, 180 patients are planned to be involved, which we believe is taking place very steadily. The timing for readout, we have to secure the considerable time for the follow-up and the ORR and the determined response rate will be very critical. Rather than interim unconfirmed data, I think that the determined finalized ORR will take a considerable time to have the data. Other than that, read out timing. For example, in the overview slide of LEAP study, HCC additional announcement can be possible by the end of this fiscal year. That is all I have.
Regarding the OLE study, I'd like to ask Mr. Yasuno to complement my explanation.
Yasuno speaking. Thank you for your question. Regarding the open-label extension study, last patient in has been done and a two-year administration is planned. In two years from today, and I believe that the overall study results will become available for announcement, and the additional baseline data had been reported last year. Baseline for all patients as well as the interim data in that midpoint of the two-year period may be announced. That is the current status. That means that you have just finished enrollment of patients, so OLE or update on these studies may be difficult by the end of this fiscal year. Is this correct understanding?
Yes, that is correct. Thank you. Understood.
Thank you.
Next, we have Mr. Sakai from Credit Suisse. Mr. Sakai from Credit Suisse, please.
We are almost running out of time. This is going to be the last question that we will entertain. Mr. Sakai, are you ready?
The earlier mentioned aspiration on page 26, that other people also had a question on. I have a question also related to LENVIMA. I believe LENVIMA IP will expire around 2025, 2026. That risk will be after 2025. I understand that this is not a forecast, that this is only a simulation. The expiry of IP of LENVIMA is not reflected here. Is that the correct understanding? That is the first question. I also have another question on LENVIMA. This is somewhat outdated, but last year on China's reimbursement list, LENVIMA HCC was not included. It was not listed up. What is the current situation? What happened afterwards, and why was it not listed? Could you follow up on this?
Turning to your first question, IP risk is not included. Turning to your second question, as you may be aware of, in the listing on the national reimbursement price, we have to negotiate with the government. Regarding LENVIMA, disease education outreach, we have to engage in interaction with the medical community. It is taking time to come to an agreement about price, unfortunately, we were not able to conclude negotiations this time. We would like to make sure that patients who need LENVIMA will be able to access LENVIMA. We have reviewed the mechanism of the pricing entirely, the free pricing duration will be longer. That it can be applied more flexibly, we have changed our pricing strategy, we would like to make sure that we contribute to patients and improve patient access. That is all.
Sorry, one more point. LENVIMA IP risk, you are not saying that there is no LENVIMA IP risk, but it said it is not reflected here. Looking at Mount Everest, after climbing to the summit, then the rest is just coming down from the summit. What is the correct idea that we should have?
There are various IP-related challenges that we face, but we do not consider them to be the major factors affecting the results. Until the expiry of the IPs, we believe that we are able to maintain our IPs.
Thank you very much.
It is now time. We would like to conclude information meeting of Eisai Company Limited. Thank you very much for staying until the end of the meeting.