We would now like to begin information meeting for fiscal 2019 by Eisai Company Limited.
Because of
COVID-nineteen 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.
Haruo Naito speaking. I am CEO of the company. This year, We have to hold information meeting in this
style. Therefore,
We are not able to have discussion face to face with you. It is quite regrettable, though We would like to make utmost efforts so that our thought and our beliefs of Eisai, it can be communicated to you. As in usual years, I would like to present my rather unskillful drawings of annual zodiac sign. And this year, the 1st zodiac sign of the 12 signs, MICE, the year of RACT. Therefore, I tried to draw a wrap 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 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. So e Way is taken from this Eisai's way. Today, the 1st year of this plan, starting from FY 2016 through this fiscal year FY 2019, which is described as e way current, and we like to provide you our review on that period for 4 years.
And in the next half or 6 years from fiscal year 2020, the next fiscal year 202025. As EWAY future, we'd like to provide our analysis. First, EWAY current. Strategic intents under IWAY 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 Ritchie and Innovation. What we mean by Ritchie 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 waterworks 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 RICI. Based on such concept, We wanted to concentrate therapeutic areas of 4% to transform business portfolio. As a result, 2 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 Iwei current period, in each group, We have obtained very powerful global partner. With this, 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, and this was expanded through revision in October 2017. At that time, Eisai opted in aducanumab. Under this strategic partnership, there are 3 candidates in pipeline. First, aducanumab, which is now under preparation for filing.
BAN2401, As has been reported, larger 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. 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-three forty five study.
Through collaboration with ACTC, [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] We are currently making preparation for the study and screening of patients are about to be started. At for LMB Cestat. To our regret, development has been discontinued. With Biogen, we are also cooperating on the multiples closest 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. And as you can see at the bottom of this slide, close corporations are deployed from CEO level through various levels in the organization, and the 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 co established a relationship which allow us to have close communication through cell phone.
Next, in oncology area, we are partnering with Merck. This strategic partnership was concluded in March 2018. What is presented on this slide is that This 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: And 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, [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] For all others have been which have been already achieved and that we expect that the last milestone payment will be also received. Therefore, I understand 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 1,425,000,000 alerts. At the very bottom of this slide, in FY 2017, we received $450,000,000 as reimbursement for R and D expenses. Commercial arrangement is rolled out in 18 countries across the globe and in the latter half of FY twenty nineteen.
The first approved indication of KEYTRUDA plus LENVIMA combination in 2019 was launched for endometrial carcinoma. Under the name LEAP studies, very large scale pivotal studies in 7 cancer types So 11 indications in the basket trial have been initiated, which includes basket trial as well. And from CEO to CEO level and throughout various levels of operations, We have very smooth and close cooperation and communication maintained throughout the period. And 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 7 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 promising favorable data and gaining attention to this. And the top 3 of 8 LEAP study have been designated as breakthrough therapies, and the summary 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 a 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 Eco, which is also a strategic partnership, which was concluded in March 2018. Under this partnership and through our transformation of the business portfolio. Transfer of Elemet Eisai was completed in April 2019. In China, niche eco's generic products are to be developed through collaboration and comprehensive strategy partnership in China had been concluded in September 2019. API is being manufactured at our Vizag planned in India, and we initiated the sale supply of API to Nichi Eco.
And the real aim of this partnership was to provide Eisai and Nichiko products packaged with integrated product package, which is showing the progress as well. Here, you can see the status of e Way current, and 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 and L and ROE, EPS and so forth. And in the middle, revenue by region and at the bottom, revenue by focused area, namely neurology and oncology business areas.
And also, you can see the focus for this current fiscal year 2019 at the time of Q3 result announcement. And 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%. EA Current has shown significant growth overall. And if you look at the yellow box at the bottom, because this provides you the summary, Please look at the R and D expenses.
For example, under FY 2019, JPY 148,000,000,000 was spent for R and D activities on P and L. But actual expenditure in our pipeline development, R and D resources was 188,000,000,000 yen therefore, exceeding by about 40,000,000,000 yen the R and D expenses on the P and L statement. And this gap is the reimbursement from partners. Based on the partnership model, we have been able to invest huge R and D expenditures. Please look at the COGS rate.
There has been about 10.5 percentage points improvement or decline. There are various reasons, But 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 increase profitability. Please look at Revenue by region and at the right hand end column, CAGR. And under eWAY current, the 1st growing region was Asia and Latin America.
That is followed by China. And 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
strong
the growth of the overall business. Going back to the top box ROE, Our FY 'nineteen 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 110,000,000,000 yen As for this as well, 102,000,000,000 yen was originally set as a target for FY 2020, which is to be achieved ahead of schedule.
Therefore, overall, eWAY current has been quite steady. Next, I would like to talk about eWAY future. The most important Aim under this e way future is to address Alzheimer's disease area. First of all, 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, and this is the very basic figures for supporting our simulation. Therefore, these figures are constantly updated. On the vertical axis, you can see the comparison of 2020 2025. On the horizontal axis, you can see 6 regions from U. S.
Through region total. The total population above 65, ADO, NCI mild AD, Combining the 2 early AD figures are provided, ADO means amyloid beta positive patients are counted as ADO. And I believe there are various ways to interpret these numbers. But 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 38,000,000. And at the very bottom, in 2025, this number is expected to increase to 44,000,000, about 44,000,000 in the world.
And the number of people living with AD or ADO in this chart by region in China, right from the middle, 11,600,000 in 2020. And in 2025, this number is expected to increase to 14,000,000. Based on current number as well as this estimate, the number of people living with ID is Expected to be the largest in China, followed by Asia and EU all in Asia and above 65 percentage. 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. And 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 and for which preventative actions are, how much preventative actions are being executed in daily guides. And as metrics for measuring that, cognitive function checkup, how much such checks ups are being conducted in daily lives and consultation with physicians how much cognitive checkup is being conducted. By establishing all these and then ADDMT, we'll be able to exhibit its real value. Therefore, we believe that these associated activities are going to be critical for us. CASM, I would like to use this term, CASM.
I think that this is not a term which you are familiar with, but 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. So CASM 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. So Chasm, in daily living domain and medical domain, please look at the gray horizontal line. And the bars below that It shows the number of people belonging to that category.
People aged 40 to 79 years old and it's 65,910,000 people, represented in the left sidebar, out of which, how many people understand the disease or dementia or how many people understand what MCI is. The number, respectively, are represented in blue portion of the bards. So as you can see, the number of people who understand that the diseases are decreasing. So there are such chasms. Furthermore, in daily living, like diet, exercise or sleep, etcetera.
People pay attention to those daily life activities like preventative actions. How many people understand the purpose of the preventive action? How many people individualize those actions? How many people execute them? And how many people make it a common practice.
So by raising the bar or degree and then gradually the number of people who do these actions is decreasing. So as you can see, there are various chasms represented in yellow arrows towards the right and then further conducting after conducting preventative actions. And then how many people have undergone have been [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] Undergoing the cognitive checkups and habituated checkups. And gradually, 1 by 1, you can see the number of people who conducted these Checkups are also decreasing, so 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.
So we would like to address these chasms. I would like to recap the chasms. In the middle of this page, chasms are presented Little awareness or perception of disease or CASM of preventative behaviors are not performed as common practice or CASM as cognitive function checks are not performed or CASM where convenient diagnostic tools for early AD are not widely used. We have been we are able to identify these 4 types of CASMs. For each of the 4 chasms, we would like to provide certain solutions.
First, for the chasm of little awareness or perception of the disease for dementia. Of course, we'd like to promote disease awareness activities by utilizing our owned media such as logo, sodan.elogo.net. This will be utilized more actively. And I believe that younger people belonging to this 40 to 79 year old population We'll have there a very important role to play, and therefore, we'd like to proactively promote the disease awareness activities utilizing these channels as well. And in the middle, in daily lives, such as diet, exercise and sleep, Preventative behaviors, which will be explained in details later, is it We have this platform named EZIT, through which we would 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. And on the right hand side, the checkup of cognitive functions, Cogonigram And for non medical use, cognistate brief battery, we have Signed agreement for using these, we would like to utilize these in Japan. And non medical use Kogostate Brief Battery is now has been named No No. And we are registering this Trademark now. And as you can see in the shima, like it which looks like a combination of the human face, And this is the logo of NONO.
We would like to utilize this. Utilizing cards, this provides the simple convenient The 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. And 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 NONO, Cogonigram for medical use is also available.
So we'd like to consider using this in the medical domain as well. Next, What is Alzheimer's disease? And 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.
And 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 NOLO, our simple Combinogram can be utilized in various way. A, for example, A for amyloid, even with blood, Amyloid Beta 40:40 ratio can be measured nowadays and amyloid PET and CSF, which is a very important measurement. And next, tau.
TAO, some part of the TAO can be measured by blood and TAO PET is being developed and CSF can be the source of measurement as well. I can be tested mainly by CSF. NN as well can be tested by mainly by CSF. And some N can be measured by PET as well. In gene, Please look at the brown band.
Of course, APOI4 or other associated genome Types are recognized as important factors and about 2,100,000 SNPs can be analyzed for 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. And what I have mentioned is described at the bottom. Simple confirmation of brain performance for diagnosis utilizing ADI and Biomarker will eventually be possible. And diagnosis and efficacy evaluation in AD Continuum It's based on biomarker panels, which can comprehensively understand the disease pathology.
And currently, the CSF testing will be capable of evaluating these biomarkers With a high degree of sensitivity and versatility, we believe that SCSF 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-three forty five study and TaupeTracer may be available. So A beta tau included Imaging Biomarker Panel maybe 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 2 companies. I may sound repetitive, but as our overall biomarker panel for AD, currently, CSF is most is considered most powerful. Looking at blood at left bottom, using MISSION-eighty sample with Sysmex, Eisai is looking at the ratio of A beta42 to A beta40 using blood sample. We are making utmost straightforward, and we believe that significant progress is made towards submission.
We are engaged in various efforts. Regarding FDA breakthrough device from FDA. This diagnosis was granted that designation. And so in This area, we have seen major progress in the past 1 or 2 years. And as for genetics, SNP based polygenic risk score system may be used for onset determination and prognosis determination.
And going forward, So 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 up right and we have number of statistics, but 220,000,000,000,000 yen is expected to be the total cost in 2,030 globally.
And there are low income, middle income and high income countries, and the 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. And 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. And 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. And aducanumab demonstrated 40% reduction in the deterioration of ADL. This is a robust data.
And so the care part, which accounts for 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 5 years. And AD DMT will have to prove such efficacy or effect, but possible cost reduction It's estimated by various reports. 1st, in the United States, if such treatment method is introduced If such a treatment method is introduced, USD367,000,000,000 reduction is expected in 5 years' time.
And similarly, in Japan, if such a treatment method is introduced, 2,000,000,000,000 reduction in care cost 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, but to 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 ARRISEPT, Day and night, we have been making efforts to develop the next generation ADA drugs.
And there were successes as well as failures. And the basis of our development has been A Beta hypothesis. Based on a beta 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 doubt. And based on that experience and track record, We have updated our understanding of A beta hypothesis as shown here. First, the current state of A beta hypothesis is shown in this schematic diagram.
The middle part, the red dot, It shows the aggregation of amyloid beta and dissociation of amyloid beta. Amyloid cascade is shown. And in the middle, there is tau. Taupathy involvement is shown. And below that, As a result of these, how nerves are attacked, resulting in neurodegenerative disease.
The state of neurodegeneration is also included in the schematic diagram. So earlier, I've mentioned ATIN and this is the the graphic representation of that. Based on this hypothesis, we have engaged in drug discoveries. And there are 5 findings or knowledge that we have obtained. At the left top, we have elenbecestat and experience of base inhibitor, Amyloid precursor protein, APP, at the very left is cleaved by base enzyme And A beta monomer is created as a result.
This is the start of the cascade. So the hypothesis supposes that this initial stage should be stopped. And right now, we understand that base inhibitor is involved in multiple substrates, resulting in various effects. If we are to develop base inhibitor in the future once again, then selectivity high selectivity to APP will be necessary to develop such a compound.
A beta
monomer Generation will be suppressed. The pharmacologically active substance, That is a base inhibitor. It is without doubt that it's pharmacologically active. But The middle part, the aggregate, that is the main cause of the neurotoxicity, but these aggregates are not much removed by base inhibitor. So the timing to use base 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 base inhibitors. And the BOX 2 at right top, this is the biggest achievement in drug development based on A beta hypothesis. A beta aggregates, the middle part shows oligomer and protofibrils Our plaque may also be included in A beta aggregates. By reducing or removing A beta 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 a beta hypothesis is the correct hypothesis.
In the area of Alzheimer's disease drug discovery, this is an epoch making accomplishment in our view. In left bottom, there is Box 3. The A beta aggregates The most evil should be removed. And Target engagement is necessary. Antibodies with such target engagement will be strongest With monomer antibodies or base inhibitors, aggregates cannot be removed entirely and speed of breaking up the balance or dissociation is shown to be slow.
And In the 4th box at the bottom, in order to understand the overall picture of A beta hypothesis, Not only AT biomarkers at the top, but eye biomarker and neurodegeneration biomarkers will also be needed to understand information and neurodegeneration. In box 5, There are various aggregates known to be neurotoxic. In soluble aggregates, protofibrils Included, maybe most neurotoxic according to some papers that have been published recently. So 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. 1st, for aducanumab, under the name of EMBARK study, patients who are enrolled in the past Studies are now will be included in a redosing study and redosing study is under preparation. For BAN2401, there is remaining 1 Phase III study, CLARITY AD study. This is Moving ahead smoothly, in fiscal 2020, by the Q2, we expect to achieve last patient in 1566 subjects will all be enrolled according to our expectation by the Q2 fiscal 2020. And in the Q1 fiscal 2022, final readout of primary endpoint is targeted.
And Progress so far has been steady towards that goal. And there is open label extension study of large scale study 201. In preclinical space, we have ahead 3, 4, 5 study under 1 protocol, 2 cohorts will be considered early stage A3 and next stage A45, 2 cohorts. These 2 cohorts are included. Academia Group in the United States with Rich Experience, ACTC, and we are Jointly conducting this study, this is a co development and biomarker panel will be used as endpoints, including CSF and blood as possibilities for biomarker panel.
And Subcutaneous administration route of study is also under consideration as shown at the bottom of the page. Now as for aducanumab, we are actively engaged with with the FDA and regulators in Europe and Japan. And we are making progress. And in the United States, with FDA. We have been having discussions with a view towards completing a regulatory filing as soon as possible.
As for aducanumab Embark 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 preparing for aducanumab. This is the pipeline related to AD for each of ATINN. For A, we have 2 compounds and in 2 antibodies. And in T, we have 1 antibody.
Phase 1 is ongoing for antibody that affects the entire spectrum of tau. And in I, Draggable products, product is being considered with to day 2 in Boston. And in N, Synapse related projects or themes are being pursued, one of which is from Tsukuba Research Institute. This is a small molecule, and we believe that Phase 1 can start soon. And beyond ATIN or outside of ATIN, we have, for example, Dave Vigo, Japanese researchers looked at orexin receptor biology, and This is a superb insomnia drug.
DayVigo is already approved as an insomnia drug. And DayVigo For ACE Board, it was studied in Phase II study, which was finished. PD-nine inhibitor, also an in house compound in house developed compound, is in Phase II, III study for dementia with Lewy Bodies. We also have collaboration with Keio University called IKID. This receives funding from Amed.
Keio Medical School owns their samples. Using these samples, we can conduct multiomics analysis to obtain various information and 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. And we would like to identify drug discovery signature based on protective mechanism of BRAIN.
And 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 proliferation or infiltration, recurrence metastasis and treatment of refractory state. And in each stage, there is cancer evolution or gene alteration. And with liquid biopsy, we are to understand this so that we can target them as a drug discovery targets. That is the strategy in cancer continuum. In monotherapy setting, we have strategy and we also have combination therapy strategy.
A 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 study research has been initiated. And next, Wnt Beta catenin signaling pathway modulation also has a large potential.
As shown in the middle of the page, we have assets including eribulin, And erbulin is used as payload in ADC MORAB-two zero two and there is liposomal formulation And parent compound of Erbiline, 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 Then bema and KEYTRUDA combination used in lip study that I explained earlier, we would like to establish this combination therapy as the backbone therapy in cancer. And all of the monotherapy candidates can become good partners for combination therapy. Amongst them, I would like to select 2 as next flagship candidates.
1st, As shown in this pink box, Wntbeta catenase signal pathway modulator E7386. This is in Phase Ib. Beta katenin It's called 1 of Cancer Day 4. It is difficult to create drug based on this. Out of such difficult druggable candidates, there are such 4 areas.
And Out of that cancer before, it was quite significant that we are now able to target beta catenin pathway. And CBP Embetacatinib 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. And 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. So 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 rich in cancer treatment. In case of HCC continuum, we have E7386. This addresses early phase of HCC by inhibiting transcription.
And 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 Operation related drug is what we are considering. H3B biomedicine discovered, H3B-six thousand five hundred and forty five is considered. This is in Phase II. Hormone positive for breast cancer account for several tens of percentage of breast cancers, and majority of them are ER positive.
So this is a typical endocrine therapy, including ALMUTASE inhibitor, And about 30% will exhibit therapy resistance, ER alpha mutation occurs that make patients therapy resistant. And what is called CIRM or CIRD, these hormonal therapy, there will be the resistance to even CIRM and CIRD. So this is a very difficult gene mutation to address, but 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. And as shown at the very bottom, this is a possible regimen for breast cancer treatment.
Hormone therapy, molecular target treatment may be used at a certain timing. And during that wider period of time, ER alpha gene mutation addressing drug may be used. So 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 and 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.
And 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 the feelings with other persons, which may create mutual trust. For example, the 4th photograph, right top photograph Shows John Collins, who is responsible as our 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, but this shows that it is possible to transcend generations and language differences. And so this shows the ability to empathize.
Number 6, The left part of the photograph, this is Elaine, who is responsible for finance function in Europe. Elaine visited a group home for mentally handicapped, and There is a language barrier, but 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.
And looking at photograph number 1, 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 And the left corner photograph shows that Our medical rep visited Puerto Rico and were able to confirm the safety of our patients. And 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. And as a result, we were able to understand 3 anxieties. The first is when will the symptoms manifest themselves? And secondly, what needs to be done to avoid the manifestation of such symptoms?
And the third is not wanting to be burden on the family members. To address these anxieties, we designed dementia ecosystem platform. And we would like to implement this platform. So we are at a stage finally to implement this to see whether we are indeed able to address the anxieties of patients. And this platform is called EZIET, starting with E for Eisai.
Welfare, etcetera, are the notions that are represented in this name, EZED. First, there are patients and their families, and there is an arrow going to and going from people living with dementia and their families. And there is a no no and other cognitive function checkup and There is information related to sleep, diet and exercise and such information can be included in EZIT. And AD, DMT In latest information, the data set, biomarker set and cohort study covering healthy subjects to NCI. We have such data set.
And based on these data sets, algorithm can be developed, so appropriate advice can be given. So in this way, we are able to return information to patients and their families about prevention and treatment. And that loop is at the center of this platform. Of course, we are in compliance fully with Personal Information Protection Act and other requirements. And professional versions can be shared and built for medical institutions.
Is it role Covers not only medical or medical part, that is shown in green, and that is quite important. Societal part Is also where is it maybe made good use of? For example, private insurance companies are trying to design appropriate insurance products for dementia and Collaboration with IZIP 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. And in Automobile, there is a concern about safe driving by elderly people.
And in retail, How people who are senior or with dementia can work is an important issue. And in nursing home, support and optimal care may be designed. And in all of these areas, is it and maybe able to offer collaboration. And we believe that EZIP will be able to provide Superior benefit than when it is addressed on a stand alone basis, and 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 eBay Future Asian figures are shown. The top table is overall CAGR and region balance is shown in the lower chart. In the Middle East, eWAY current up to fiscal 2020. This is information that I spring earlier. And under eWAY in future, we expect that there is an enormous growth opportunities.
For example, revenue is expected to grow on average 20% globally. And in terms of profit, Profit growth is expected to exceed growth in revenue. And 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. And 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 America's importance will be Very strong or high in eBay future. As shown at the bottom, we aim to achieve remarkable growth with expansion of VENVIMA and potential AD TMT during EVA Future. And Americas region Both art is expected to be the major driver for the whole company.
I Have two last slides and key points of e Way 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 eWAY. And as shown in EZ example, medical innovation, not only medical innovation, It will be transformed into societal innovation and 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 and transformation of medical innovation to societal innovation is the task of eWAY Future.
This is my last slide. This is Mount Everest. And this picture shows this picture was included in eWAY booklet that we made in the 1st year of e way from the base camp in 2016. We have been steadily making progress climbing this mountain. And where are we now?
There is a mouse indicating where we are. We are, I believe, points are 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. So I would like to ask for your continuous support and guidance.
And with that, I would like to conclude my presentation. I thank you for your kind patience.
Now we would like to open Q and 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. Now 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 the mid early March. And 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? And timing may be Difference by region or simultaneously filed in all the regions. And I think that you have a hotline communication, close communication with The counterpart, President, sir, 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 3 regulatory authorities. We are currently progressing in our consultation with them. In United States, Continuous and constructive consultations with FDA are currently ongoing. So for completion of submission is now aimed at, and we believe that Preparations for early completion of filing is being made steadily.
And once our filing is accepted by the authorities. Then 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 as such without delay. I would appreciate your understanding. You mentioned acceptance. So the timing from submission to acceptance will be Difference between Japan and U.
S. In Japan and Europe sorry, in Japan and the U. S, when it comes to acceptance of the filing, then once simultaneous submission is made and then acceptance can be done. First in Japan, regarding the regulatory process. I believe that this is sensitive issue.
So I would like to refrain from making comments on I hope you understand this. Understood. Thank you. And second question is about amyloid beta blood testing. I think Eisai is working with Sysmex, and I think on different types of technologies which are also being developed.
And do you intend to completely work together with Sysmex to the end? Or Would you like to opt for other types of technologies if they are 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 like to collaborate with Sysmex so that Cisco, which is an excellent system developed by Sysmex, the blood based diagnostics So a method will be developed, which will be adopted on this system. We are working with them to develop that.
Now HET-three forty five study, Blood samples will be secured and obtained. So what kind of method will be utilized regarding what will be the most realistic method with through our consultation with ACTC, which is academic consortium, to decide which method to be used. Thank you very much. This is an easy question. And the modality is now a buzzword, and I think that companies are increasing modalities in order to Promoted drug discovery process, and I think that you are focusing on the medicinal chemistry.
Some are based on the antibody. But beyond this, 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 over other efforts and the same modalities can be changed. Intratumoral STING agonist Can be administered directly into tumors, in our case, and long tubes can be used for administering drugs.
So we are utilizing those. So it really depends on the needs of therapies. And for example, nucleic acids were very proactively being developed. And as such, it's not because there is a modality called nuclear acid because there is a need for Compounds are based on the nucleic acid. So I think that is the order we should focus on.
Thank you very much.
Thank you for the questions. 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 question about Page 18, Line 1, Line 2, [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] Aducanumab regulatory topic. Line 1 and Line 2 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 have been that our 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. So I hope that you will be able to understand based on the description presentation given today. Next question is about Page 26, e Way Future projection.
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. As for our projection, as I have been saying, more than $5,000,000,000 or more than 5 100,000,000,000 is the graph indication.
And to report 5,000,000,000 OP will result in enormous improvement in profitability. In our view, between the top line and profitability, We do not think that there is much discrepancy. So I hope that helps your understanding. Turning to Page 5, you have milestones and onetime receipts. And in fiscal 2025, could you comment on your expectations about milestone receipt, etcetera?
We will be making earnings announcements. So we would like to consider touching on these pieces of information on those occasions. Now BAN24 2,401 subcutaneous study possibility that is mentioned on Page 18, What are you considering? Is it the technological aspect or formulation aspect? Or when do you expect to finalize your decision about Go or Nogo.
This is not an economical consideration, but more
of a technological consideration.
And I do not expect consideration. And I do not expect that much time will be necessary, too long a time will be necessary before taking a decision. Thank you very much.
Our next person is from Nomura Securities, Mr. Ko 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 and e Way future is presented here. And I believe that this is [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] What is already visible right now is included in Japan and Europe.
You are not saying that, that kanama will not be sold. And in the United States 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. So 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 ADT DMT, the 2 products to be approved and launched. The success in this, these are already utilized as the given successes for simulating this aspiration.
[SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:]
Well, In Japan, China and Europe, I don't think that there has been there have been much A projection of growth. LENVIMA with HCC is expected to grow further. So 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.
[SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] In the value, a value can be very huge. So in all regions, Unless we maintain very high growth ratio, we won't be able to reach this level. [SPEAKER UNIDENTIFIED COMPANY REPRESENTATIVE:] Understood. My second question is, I wonder which page I'm referring to, but I think it was on Page 12. Koganogram, I'm sorry, I am not well versed in this, but I believe that this is very critical point for aducanumab to be approved.
And I think the first bottleneck will be the neurologist lack of neurologist. And on the next page, ADIN, I think that it will not be possible to Diagnose all the Alzheimer's diseases and then there needs to be a medical testing. Of course, it will be time consuming. And in Japan, such Neurologists who are experts in dementia not maybe reaching the 2,000 physicians, so they will be overwhelmed by the flow of patients. So, CogonyGram, do you plan to get approval on this CogonyGram?
Do you suppose that CogonyGram will be Approved as a medical device and compared to the existing scale like CRSB, The MMSE, I think that these will be interoperable with the existing scales. Comnigram is already approved as a for medical use by FDA in the United States. And for us, Nono and the Comigram are almost the same. And before selecting the 2, over 160 various convenient and simple cognitive function Diagnostics tools were screened before reaching the decision to choose these 2, covering Consistent with daily living domain through medical domain, I think the body of these two devices will be able to provide the information covering these 2 domains. And regarding the development in this country, in Japan, we are Yet to start.
Understood. The last question, I would like to To summarize, this year, I think that you are not able to discuss specifics about aducanumab, but on Page 4, Study 201, OLE12401 extension study, AIC or CTAD, Do you think there will be a potential to see the data in LENVIMA, LEAP-five, gastric cancer or other Cancer types, I think the presentation will be made on these type of types of cancers. But other than these, and 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 2 years or so from today, the study will be completed.
I think that we'll be ready to report to you on the results. Kotani san, what was your question? The other question? For Olenbema, LEAP-five, Part of the basket trial will be become available. I think that's what you mentioned at the last presentation meeting.
And other than that, for LENVIMA, Newstral or readout of the clinical studies may become available. So could you please elaborate on this? So perhaps I need to call Doctor. Owa to respond to your question. Mr.
Kotani, thank you very much for your question. My name is Owa Speaking, Anu from the Eisai's Oncology Business Group. Lead 005 study readout timing as you questioned. The study itself is ongoing steadily. And in total, 180 patients are planned to be enrolled and which we believe is taking place very steadily.
And the timing for readout will be readout. We have to secure the considerable time for the follow-up and the OR and the Determined response rate will be very critical. So interim rather than interim unconfirmed data, but I that the determined finalized ORR will take a considerable time to have the data. So other than that, read out timing. For example, in the overview slide of Lipo study, HCC, Additional announcement is planned 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. Tsuno to complement my explanation. Tsuno speaking. Thank you for your question.
Regarding the open label extension study, And last patient in has been done and 2 year administration is planned. In 2 years from today, And I believe that overall study results will become available for announcement. And the additional baseline data had been reported last year. And baseline for all patients as well as the interim data in the mid point of the 2 year period may be announced. That is the current status.
So that means that you have just finished the enrollment of patients. So OLE or update on these studies may be 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, so 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, but that risk Will be after 2025, and I understand that this is not a forecast.
This is only a simulation, but 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. And 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. And 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. And regarding LENVIMA, Disease Education Outreach and So we have to engage in interaction with the medical community. And It is taking time to come to an agreement about price.
And Unfortunately, we were not able to conclude negotiations at this time, but we would like to make sure that patients who need LENVIMA will be able Access LENVIMA, we have reviewed the mechanism of the pricing entirely, and the Free pricing duration will be longer. And so that it can be applied more flexibly, we have changed our pricing strategy. And we would like to make sure that we contribute to patients and improve patient access. That is all. Sorry, one more point.
So LENVIMA IP risk, you are not saying that there is no LENVIMA IP risk, but It's that it is not reflected here. Looking at the 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 maintained 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.