ESALF - Eisai Co Ltd (ESALF) Q2 2023 Earnings Call Transcript

2023-11-07 16:25:19 ET

Eisai Co Ltd (ESALF)

Q2 2023 Earnings Conference Call

November 07, 2023, 01:00 ET

Company Participants

Haruo Naito - CEO

Lynn Kramer - VP & Chief Clinical Officer, Alzheimer's Disease and Brain Health

Yasunobu Kai - Former Senior Group Officer

Akiko Nakahama - VP and Chief Portfolio Officer

Masatomi Akana - IR Officer

Satoru Yasuda - Former VP & Head, Regional Cooperation

Conference Call Participants

Seiji Wakao - JPMorgan Chase & Co.

Fumiyoshi Sakai - Crédit Suisse

Kazuaki Hashiguchi - Daiwa Securities

Miki Sogi - Sanford C. Bernstein & Co.

Hidemaru Yamaguch - Citigroup

Shinichiro Muraoka - Morgan Stanley

Presentation

Operator

Thank you very much for participating in earnings announcement session for Q2 Fiscal 2023 by Eisai Company Limited. Presentation is held in hybrid format, including in-person attendance and virtual attendance. Those of you who are attending in person, please make sure that you have the handout materials, including the slide presentation, flash report. And those of you who are participating online, please continue to watch the presentation.

Let me introduce the presenter, Representative Corporate Officer and CEO, Mr. Haruo Naito. Mr. Naito, the floor is yours.

Haruo Naito

Let me begin our presentation on the financial results for the second quarter of fiscal year, 2023. First, let me review the consolidated statement of income. As you can see in the subtitle, we achieved increase in revenue and operating profit through steady growth of LENVIMA and Dayvigo. And also costs were controlled within so-called financial discipline. That means to say, costs were controlled within the growth of the gross profit.

So, operating profit was increased by about 6 fold when compared to the level recorded last year. This was the characteristics of the first half results. If you look at top line, these numbers include growth of global products and onetime revenues and impacts of weaker Yen and then revenue grew by 4% year-on-year. And cost of sales was reduced by 4.3 percentage points. This was due to an improvement of product mix and revenue recorded onetime.

Now turning to R&D expenses or commitment to expenses. The allocation of resources into R&D expenses were almost at the same level as last year. SG&A expenses, in terms of the ratio, the ratio reduced by 2.4 points from a year earlier because LENVIMA continued to grow, therefore, the expenses regarding shared profit of LENVIMA paid to Merck increased, but other SD&A expenses were well controlled. As I said earlier, total expenses were almost flat from a year earlier, and this was well controlled within the growth of in gross profit within 10% from a year old earlier. Therefore, operating profit increased by 6 fold.

Profit for the period because there was the shrinkage of the tax charge recorded last year because of the impact of repayment of paid-in capital from a consolidated U.S. sub to the company. Therefore, we ended up at ¥24.2 billion for the profit for the period, and we have resolved on the ¥85 per share as the dividend. And we do not think that there is any change to the full year dividend of the full year dividend of ¥160. There are no changes in the financial metrics as described at the bottom.

Now a breakdown of the revenue migration, LENVIMA increased by ¥23.2 billion year-on-year and Dayvigo, particularly in Japan, revenue increased by ¥5.8 billion year-on-year. And in others, you may notice minus ¥16.8 billion. As you see in the footnotes, this was because of the expiration of the co-promotion agreement in Japan for HUMIRA. But overcoming these negative factors, we achieved growth.

In addition to these, there was a onetime revenue recorded because of the transfer of all future economic rights for the SYSTRAN, therefore, top line grew by ¥14.9 billion with 4% year-on-year.

Operating profit is explained here. First, frontline business or pharmaceutical business, there was increase of operating profit by ¥12 billion. And the ratio improved from 49.1% in the previous year to 52%. If you turn to R&D expenses. In the last year, there were expenses related to ADUHELM, which was reduced in the first half. This was a big factor. And group headquarters, management costs and other expenses. In this area, there was a reduction in the ADUHELM-related expenses, which was another factor for increasing the profit and ¥12.1 billion in the other business was added. Therefore, there was an increase by ¥26.2 billion operating profit, which recorded 598% year-on-year growth.

In the bottom half for Leqembi, total R&D and SG&A expenses invested in Leqembi while it was at the ¥45 billion level for the first half. Today, I would like to focus on the Leqembi in my presentation.

First, the approval or regulatory status, including submissions after approval in the United States on September 25, Leqembi was approved in Japan. And currently, now deliberation is being made at the social insurance Central Medical Council. As regards to the NHI price listing, once it is completed, we would like to launch the product here. We are making separation. EU and China, the review processes are ongoing steady as expected. Therefore, we anticipate to get approval by the end of this fiscal year.

And in the bottom half, as you see, the 25 countries and regions such as EU are listed in these countries and regions, submissions that will be achieved. Already in countries and regions until Hong Kong in color-shaded boxes, these are the countries and regions where we have already achieved a submission. Therefore, globally, in order to provide a Leqembi patients with AD opportunities are expanding globally.

Now, turning to the approval in Japan. Following full approval in the United States, Japan was the second country where Leqembi was approved. In this home ground, market for Laser this was a very significant approval for us. indication for use and dosage and administration and warnings in this contents are almost the same as the content in the package insert in the United or prescribing information in the United States. In the Japanese label, there are contraindications. And these 3 contraindications are identical to the exclusion criteria in our Phase III study, Clarity AD. So these 3 items are listed as contraindications in Japan.

In the bottom of this slide, all case surveillance is going to be conducted. Considering the number of patients as well as the duration of the surveillance will be determined of subject to the negotiation with the regulatory authorities, but this is going to be the first innovative drug in Japan as well as in the world originated in this country. Leqembi is such a drug, therefore, there needs to be a secure introduction of this drug into the Japanese market in terms of efficacy as well as safety, such as ARIAÂ management, such management must be done securely so that we can minimize any potential accidents or events. This innovation needs to be securely grown and developed in Japan. That is perhaps the judgment by the public authorities. Therefore, such all case surveillance is determined to be introduced.

Therefore, we are currently making preparation for such surveillance. Going forward, at the time of NHI price listing, there will be optimal usage guideline to be issued. So, by the end of this calendar year 2023, we plan to launch Leqembi in this market.

On this slide, in near future, how Leqembi is going to be evolved as option of treatment, that is described in the top half. In the bottom half, diagnosis which is expected to play a very important role in AD treatment so how a diagnostic advancement will be made. So landscape is described here. Firstly, if you look at top half treatment advancement with Leqembi, in FY 2023, IV formulation was launched.

And shortly, maintenance therapy for intravenous dosing will be filed for approval. So what we intend to do here is after a certain period of the initial treatment, now after turning into the amyloid beta negativity and that amyloid beta level needs to be maintained. That is the purpose of having this maintenance therapy by reducing the frequency from biweekly to monthly dosing.

This IV maintenance therapy should be provided. Therefore, we are planning to submit for approval of this therapy. I would like to explain this later in detail. Even after amyloid beta level is reduced but gradually, there will be inception of the accumulation of amyloid beta in the brain. According to 201 or 301 study OLE study, we have found such facts or data. Of course, that is shown by PET, particularly amyloid beta 40-40, biomarkers suggest that even after removing amid better in the brain, but there will be, again, re-accumulation of the amyloid beta.

Therefore, the significance of maintenance therapy is very important, very high. So following that, the subcutaneous formulation or SC formulation, this will be administered using auto-injector. Submission will be filed by the end of this fiscal year for this formulation. Utilizing excellent auto-injector, we expect that the burden on the patient will be minimal. Therefore, without needing to visit the hospital, they are able to do self-injection at home or other locations. Therefore, it will increase patient convenience and eliminate lack of accessibility based on patients' geographical locations.

And in 2026 or so, even before MCI, at the earlier stage of AD so-called the preclinical AD, where people are cognitively normal, however, having signs of amyloid accumulation. Such patients at high risk. Currently, the Phase III trial is ongoing, targeting such patients based upon the results of which 20 clinical AD indication will be filed in submission.

And if you turn to the bottom half, this is about diagnostics. On October 13, this year, there was a great advancement. CMS, which is in charge of the Medicare reimbursement in the United States before amyloid PET was only reimbursed only once in lifetime. However, such restriction of the number of times when the PET test can be conducted is lifted. So that the determination was made. Therefore, restriction of the amyloid PET was eased very much. And we expect that this listing of this restriction will lead to the increased number of patients who are treated with Leqembi. We are sure about that. But actually, there is a delay of about 2 months. But with a time lag of 2 months, we believe that there will be increase in the number of patients treated with Leqembi using amyloid beta PET.

The diagnostics shipment is drastically increased. That is the information we have caught. Now at CTAD held in Boston recently, there was great presentations about blood biomarkers. As you can see here, blood biomarkers included 2 types of the tests, so-called screening or triage. Perhaps we believe triage is more appropriate name. Therefore, recently, triage test is more used nowadays. So the combinational blood biomarker test has very high precision or accuracy for amyloid negativity, therefore, using black biomarker tests, we can identify the amyloid negative patients. Therefore, this may reduce the number of patients who need PET or CSF, thus simplifying the diagnosis pathway.

This triage test will be used more widely in maybe next year. That is our expectation. Based upon that, confirmatory test is anticipated, PET or CSF, it can be replaced by blood biomarkers. To that extent, large biomarker will gain the trust in the actual clinical setting. That situation will be realized in around 2026. If that becomes a reality, then PCP or so-called primary care physicians will be able to prescribe the therapy to patients. That is, therefore, the advancement made in the blood biomarker technology is going to be a very critical factor for the future. Since the full approval obtained in July, we have been making preparation for the launch in the markets in the United States. So the current status and also our anticipation of the revenue towards the end of this fiscal year, I would like to explain these now. At the end of this fiscal year, we are expecting to make contribution to 10,000 patients in the United States. Towards that, there are 3 momentums as you see on this slide.

Firstly, on the left-hand side, we are enhancing go-to-market structure. Currently, those people who are in the field, so-called sales reps or other people with different functionalities comprising go-to-market structure, which is being even more enhanced for the expansion of the number of patients treated with this therapy, we believe that this is going to be a big one momentum. In the middle, you can see progress of market readiness. In AD market, this is not well established market. For example, cholesterol lowering or the C3 therapy or diabetes therapy or rheumatoid therapies in such disease areas, there are established markets, this is the market.

As a pioneer, we are making great efforts in order to create and ramp up the market itself. Of course, with the cooperation of the sufferers of the medical institutions and the health care providers in order to establish the market properly, we are currently in the midst of the efforts being made for building up the market. Such results will be explained later, but the steadily and also rapidly, we are seeing the buildup of the efforts and achievements. What do we need to do? That is listed here. For example, the simple cognitive function test at PCP and what is expected to play an important role in the AD treatment. IDN integrated delivery networks, mainly comprising of the large hospitals, P&T pharmacy and the therapeutic committees need to approve the therapy.

That process needs to be passed and also the number of neurologies ready for Leqembi once the prescription needs to be increased, amyloid beta testing, including PET, CSF and blood biomarker ApoE4 testing and readiness to accept patients at the infusion centers and area monitoring must be done through MRI. These factors have to be in place so that AD treatment market can be built up. So these are the efforts we are doing. And we are seeing a very rapid ramping up of the market, but we are not able to say this is completed yet. We are currently in the process of building markets.

And the third momentum is data expansion. At the recent CTAD, Clarity AD open-label extension studies results, tau-PET sub-study and subcutaneous sub-study, very important data sets were presented CTAD, which will be explained later in more details. Based upon these situations, if you turn to the bottom half, how many patients are currently being treated with Leqembi? This is our estimated numbers. Currently, approximately 800 patients with AD are treated with Leqembi. That is our estimate. As you see in the graph, of course, compared to the level at the time accelerated approval, the number of patients treated is increasing dramatically. And on the right-hand side, this is what we simulate towards the end of this fiscal year, at the end of March because of the PET NCD lifting, as I said earlier, we expect to see a rapid increase in the number of patients treated to reach 10,000 level.

So the first momentum, we are enhancing go-to-market de-structure in the United States. Let me explain about this first momentum. When it comes to so-called AD treatment, on the right-hand side, there are various stakeholders, there are multiple professionals such as neurologists. And as I said earlier, throughout the United States, there are about 120 large networks, mainly comprising of large hospitals in medical networks, IDN, integrated delivery networks, and there are hospitals in communities where PCPs are existent or community-based practitioners or general neurologists in communities and infusion centers, which are providing therapies actually to the patients and the PET/MRI buffers and health care professionals and also reimbursement processors are also very important stakeholders. They are all related.

For them, there needs to be a proper and total explanation and education, in some cases, so we have deployed people in charge of those tasks in the field. If you look at the left-hand side, these are the field deployed personnel at Eisai, there are 6 types of professionals. And integrating these at 1 point or 1 stop, in the middle, you can see neurology account specialists nurse who are professional in the neurology area, the specialty MR or sales reps are located in the middle of this structure. And the health system account executive on the left-hand side, they are in charge of calculating health economics.

In many of the medical institutions in the United States, the Leqembi value is calculated to the same, whether it is positive for the patients and the benefits and the costs are analyzed to seek the balance. So that information is required. Therefore, that is provided by the top one in this list, HFAE. And the second one is access and reimbursement managers for CMS, suppose that a patient would like to know the procedures for getting reimbursement for the Leqembi or PET or ApoE4, whether it is possible to get reimbursement for ApoE4. So that information is provided by ARM and IDN adoption and approval by P&P, they are playing a very important role.

Clinical educators are medical for medical staffers other than physicians, they are in charge of educating or providing information to those non-physician stuffers and regional thought leader reads liaisons. In regions, there are opinion readers and also there are many different patient groups, and they like to be aligned with them. Medical science liaisons are, needless to say, to provide the cutting-edge data such as data presented at CTAD recently. They are very busy now.

They needed to explain such data to the physicians throughout the country and patient navigators, for those who are insufficiently covered by the insurance and also low-income people. They provide care and also explanation will be provided regarding the patient assistance program or free of charge treatment.

So, all these information will be concentrated, integrated as a nurse. And that will be the centralized point of contact to have the relationship with stakeholders on the right-hand side. So now the go-to-market structure is being built as such. So in the bottom half of this slide, I tried to explain this in text. I have been to the United States 5 or 6x this year. And AD diagnosis and treatment situation in America is now well understood by myself, an Alzheimer's disease diagnosis and treatment status is explained in this text. Let me re-read it. Modern AD diagnosis and treatment require the involvement of multiple stakeholders as described on the right-hand side, sharing the same direction and the establishment of a collaborative system. Procedures such as simple cognitive function test, including digital methods at PCP, primary care physicians, a network of referrals to neurologists, such network is important. And amyloid beta test at neurologists such as PET, CSF and blood biomarker adoption and ApoE4 test at a neurologist. These have to be conducted.

Now turning to the stage of infusion, infusion for treatment is necessary. Therefore, the infusion facility may be available at the same hospital or facility or external infusion centers will be chosen as an option. And ARIA monitoring, which will be done through MRI after infusion. This may be conducted at the same facility or other locations. These need to be conducted in a sequence that proceeds efficiently and promptly for the AD diagnosis and treatment.

Furthermore, at HCPs and the medical institutions reimbursement procedures are indispensable and essential procedures. And furthermore, supports are provided to patients themselves if they are in need or a patient navigator or patient assistant program, if they need them, we are providing support to them. So in this go-to-market structure, we are currently working on establishing these processes so that AD proper and appropriate market is being built.

In the bottom, IDNs, will play a significant role in AD treatments, such as Duke University, where most university hospitals are included in the IDN, integrated delivery network and state run hospitals and also private hospitals are belonging to IDN. IDNs will need to establish such processes, as I mentioned earlier. As a prerequisite, each IDN has P&T or the pharmacy and therapeutics committee, it is necessary to receive P&T committee approvals at IDN. So there is one step here. So, as the basis of these efforts, there are Leqembi data or communication with the patient groups in regions through medical science liaison, MSL mainly conducting these tasks or HSAE, which is described at the top, and these are going to form indispensable base for all these efforts. Very broad ranging and multiple steps need to be done in order to build a healthy sound AD market, which is, we believe, very important. We are currently in the midst of these efforts, and we are making utmost efforts, and we are seeing the steady achievements derived from these efforts.

Now regarding the metrics of market readiness. Firstly, the number of neurologists ready for one-stop prescription has been increased by about 1.8 fold compared to the level recorded in June. And also amyloid beta test in combination of PET, CSF and blood biomarkers at the end of August, it was increased by about 1.3x. And going forward, it's going to be increased by about ten fold because of the limitation of the amyloid PET coverage was listed. Therefore, we believe that this number is going to be increased sharply. And the number of P&T committee approval for Leqembi was increased by about six fold compared to the time of accelerated approval, at approximately 60% of our top 100 IDNs our target IDNs, the P&T committee, Leqembi approvals were obtained. Therefore, once these are in place, we believe that the number of prescriptions will increase sharply. Many patients are still waiting for the therapy.

Now turning to revenue from Leqembi as shown in the middle. In the first half of 2020 through fiscal 2023, revenue was ¥400 million. This is as planned. And we believe we did a good job. But I understand that there are some voices of disappointment in the market. And I'm concerned that, that is reflected in the share price, but we don't think the situation is such that there should be a disappointment that leads to sales of our shares. We are accumulating results, which resulted in ¥400 million revenue. Please do not see this as a negative surprise. On the left side, this is weekly average revenue. In comparison to the time when accelerated approval was given currently, the level is approximately 11x. And I checked the recent data and the growth achieved is at a faster pace than shown here. As I mentioned earlier, we have 3 momentum, and we are making progress. At the end of March this fiscal year, we expect to achieve contribution to 10,000 patients and achieve a ¥10 billion level revenue, mainly in the United States. And I would like to convey to you that we are confident of achieving these objectives.

Regarding the third momentum, expansion of data at CTAD, new findings were presented. There are 3 Phase III Clarity AD OLE study data in tau- PET sub-study data, subcutaneous sub-study data. Those are the 3. And the details of these 3 data will be explained later. But one conclusive message is the importance of early triage treatment and long-term treatment after the removal of amyloid plaque. We believe that the importance of these was confirmed. And furthermore, subcutaneous administration, treatment option, expansion potential was suggested. First, lecanemab session at CTAD had Dr. Chris Van Dyke presents a mode of action.

Lecanemab/MOA characteristic includes not only rapid removal of plaque, removal of protofibrils. So dual action mechanism of action was introduced by Dr. Van Dyke. Leqembi with this dual action continues to support the function of a preneurons by removing soluble highly toxic protofibrils that can cause neuronal injury and death even after plaque removal. Chris sent this message strongly. And it was also observed that lecanemab delayed tau pathology progression. I will come back to this later, but especially in early stage, according to Dr. BRAC, the Backstage is determined and typical early BRAC region is a tau pathology progression in temporal and it was observed that this progression was delayed. Dr. Sandi's conclusive message was that lecanemab removed plaque and it also has a DOE action of removing protofibrils and delayed tau pathology progression.

The 3 studies that I will be describing are targeting a third population and analysis of these data are also very important. So it may be somewhat tedious, but please be patient. First Clarity AD4 study is shown at the center and purple box at the right is open-label extension of that study, those who hope West are given active drug in the continuation study, those who were originally randomized to placebo will be receiving lecanemab in open-label extension study. And the sample size is very large at 1,414 and tau PET sub-study within the Core study on 342 who received the tau imaging and placebo and lecanemab, were almost one-to-one randomized. And the subcutaneous sub-study right below had about 320 patients that are conditioned from Core study.

Those included patients who transitioned from IV administration or those are transitioning from IV administration to subcutaneous. As for sample size 72, these are lecanemab-naive patients. And these are naive patients for given subcutaneous lecanemab in de novo setting. And there were those who transitioned from core study directly to subcutaneous and also those from outside of the Core study. And the sample size in total for subcutaneous sub-study was 394 patients. And please keep in mind this study design.

First of all, about OLE, right chart shows our overall results very well. Please focus on this chart as I will be going over 3 bullet points. In OLE study, the graph shows up to month 24. But CTAD presentation also included preliminary results up to month 30. CTAD, Dr. Lisa presented these results. And the first bullet, of course, study active drug group, is the top green line in the graph and OLE study active drug group. Patients were given placebo in the Core study but are receiving active drug after transitioning to OLE study, that is the second line in the graph. And the divergence between these 2 groups were maintained, the divergence did not diminish the same gap was maintained. Therefore, the earlier, the start of the treatment, the greater the treatment efficacy that was what was suggested. And the importance of early start treatment was demonstrated.Â

The second bullet point is about the bottom blue line in the graph, there is no placebo in OLE and ADNI data matching similar baseline characteristics that was used for modeling. And matched ADNI participants and active drug group. At the very top, if you compare the 2 lines, CDR-SB difference continues to become greater. And once again, long-term treatment significance was demonstrated. And the third bullet point, and please look at the second line in the graph, those who were given placebo in the core study and who switched to active drug in OLE. In 6 months' time, the efficacy in this group was demonstrated. The conclusion is that based on 24 months OLE data, importance of early start of treatment and significance of long-term treatment were demonstrated.

The second data is data set is from tau PET sub-study. There are 3 figures and comments for each figure are given on the left side. First, overall status, tau PET sub-study included low tau PET group and intermediates plus high-tau PET group. There were analysis for these 2 subgroups as well as sub-study all group analysis. Red is intermediate high-tau PET at the top and blue low-tau PET at the bottom in the middle is tau PET sub-study all. And in all groups or subgroups, amyloid reduction was observed. And lecanemab efficacy is suggested to be not affected by the accumulation of tau. Figure 2, this was much talked about, low tau PET population, that is to say, amongst the MCI population earlier stage, most likely early 80-stage patients. In such low tau population, as shown in the left chart under Figure 2, in 76%, CDR-SB score was maintained. In placebo, it was maintaining 55%. And in 60%, as shown on the right side, improvement was observed, whereas it was 28% in placebo. Sample size is not very large, but the p number shows statistical significance.

And in early stage, administration of lecanemab suggested a possibility of improvement. This was much talked about at CTAD. And this is also somewhat related to pathology as shown on the right chart. In tau PET, temporal lobe to frontal lobe, various parts of the brain are captured in image to measure the improvement through measurement of tau accumulation after Leqembi administration. And in early BRAC-stage patients, in temporal lobe in early stage, it said that tau accumulation will start in a temporal lobe, medial temporal and part of the temporal lobe, where a tau will accumulate early on in these regions, there was a significant suppression of tau pathology that was observed. And p number is close to significant. And lecanemab tau pathology suppression effect was observed. And so in addition, by administering in early-stage patients, efficacy was observed.

The third data set is from subcutaneous administration sub-study. As shown at the top, safety is assessed in this population. So safety population numbering 394 was examined. And there is a PK population numbering 65, as shown on the right. To analyze PK profile, there were 65 patients who were analyzed who switched from IV to subcutaneous. And for PD, which is to analyze a decrease in A beta, PD population shown on the left were those patients who were given lecanemab in subcutaneous form for the first time in these naive patients.

First, PK pharmacokinetics SC administration in comparison to IV administration showed 11% higher AUC, but it was within the acceptance range of bioequivalence at 90% confidence interval, meaning that PK bioequivalence was demonstrated and Centiloid reduction in SC Group, in comparison to IV Group, had a higher amyloid removal by 14%. And this was also comparable at 90% confidence interval.

So in PK as well as in PD, SC bioequivalence to IV was established. And so we believe that we are able to file submission for SC administration. As for safety, first systemic injection reactions not localized but systemic injection reactions often times with injectable drugs, such reactions are observed and systemic fatigue may occur after vaccination, but such incidence rate was significantly low in a subcutaneous sub-study. As for ARIA incidents, in SC population, since the sample size was very small, confidence interval was very broad. However, frequency, onset timing and severity were similar between SC and IV in clinical and imaging evaluation. The range for SC patients was very large and sample size was small, so the ratio was affected by a number of changing for selling subject. It is difficult to have a direct comparison, but it is considered similar. And IIA predictor for IV was considered to be Cmax. However, in SC, AUC is considered to be a better predictor for incidence of ARIA-E.

Overall, we believe that we are able to file for submission for SC administration, and I believe next week, we are scheduled to begin consultations with FDA on this possibility. There are great benefits from SC administration, depending on the patient situation, we will have expanded treatment options. That is to say, at home or in a care home, administration is possible. Infusion will no longer be necessary, and it will lead to overall cost reduction it will lead to a better convenience and allow for a longer treatment. This is an overview of the pipeline. Pathology and the disease stage are shown on vertical and horizontal axis. We have pipelines covering different areas and 2814 and anti-NTBR or tau antibody, NTBR or tau is involved in propagation of tau as a tau species. And this is the focus of attention these days. And it will be trapped in the cell cleft by E2814, DIAD cohort-based study is done after treatment with lecanemab. By giving E2814 antibody, what happens is observed in Phase II/III and there is also a monotherapy study ongoing, 2 studies are currently ongoing, and there is much attention paid to E2814.

At CTAD, MTBR-tau 243 biomarker was presented as a new biomarker. And this is a biomarker specific to tau neurofibrillary tangles in AD. And in DIAD patients, when E2814 is administered, it was confirmed that MTBR-tau 243 decreases, and that helped increase attention to E2814. In Japan, basic Actonel dementia to promote an exclusive society was enacted. And Prime Minister Chida himself is inserting leadership to promote inclusive society and digital tools towards that end are developed. First, Quick-Carter, you may have received various health checkups and there are different formats of data with Quick-Carter, if you take the record by quick clicking the camera, it will be recorded in the app.

And chronologically, for example, systolic blood pressure change can be shown in this app. NOUKNOW is now installed in Quick card. And self-check simple NOUKNOW function is available at 60 local governments, institutions, companies have adopted and 100,000 per year in excess of that number of tests using NOUKNOW are expected. NCI risk prediction tool is another tool. For example, such a screen will come up, what is the level of risk of cognitive function that declined in 2 years for you? And it says risk is not high, but improving such in such behavior is recommended to further reduce the risk. Such screen can come up, and this is close to being commercialized. Natural Cores treatment prediction tool is also under development right extreme column is Societe tool. Frequency of visits to physician may differ for dementia patients, it may be an interval of 2 weeks to several months. And in the meantime, in between physician consultation, how ADL changes in the patients is difficult to thoroughly describe during the consultation. And this change can be recorded on the app so that it can be understood at a glance. That is the purpose of Societe.

The screenshot example is shown, and there are 10 types of ADL. For example, use of home appliance. This is a very important item. How will kind of person use the home appliance? And this is an example. It says score of 2.1%, and this is a decline from the previous score of 2.6% and total score is 19.4% out of passable 30 and below 20 points will lead to alert. And on the right side, the trend of this total score is shown and at a glance attending physician will be able to see the recent trends in the patient instantaneously. And this will lead to a better efficiency of treatment and effectiveness of treatment.

We would like to roll this out nationwide. This is full year PO forecast. Today, we have announced an upward revision guidance. Top line was about ¥27 billion. I hope my number is correct, revision is by ¥29 billion for top line. We will be making adequate spending on leqembi operating profit. This is a revision by how much? ¥1 billion. We made a ¥1 billion upward revision for operating profit. And profit for the year, there was an increase -- we expect increase in interest income. And we made ¥4 billion upward provision for profit for the year. So we gave guidance on upward provision today. That concludes my presentation.

Question-and-Answer Session

Operator

Now we would like to start Q&A session. If you have any questions, please raise your hand and please mention your affiliation and then before asking a question. Due to the interest of time, please limit the number of questions you can ask at one time to one question.

Seiji Wakao

This is Wakao. I'm from JPMorgan. I have a question about this 10,000 patients to be at probability of achieving this number. Could you please explain the factors for achieving this? Because this is the novel drag. And because of this initial movements, I think this will affect the share price trend. Therefore, could you please explain the probability of achieving 10,000 patients? On Page 9, amyloid beta tests being conducted. It's increased by tenfold recently. So could you please explain what do you mean by this increase compared to the level of June? And then this should have been 8,000 and then simplify the tests are received to identify patients with a potential early amyloid Alzheimer's disease and the amyloid beta test will be conducted. And therefore, a large number of patients should go through this test. So 10x increase, do you think it will become one prospect or factor for achieving the 10,000 patients? Regarding your question, I'd like to ask Mr. Yasunobu to respond.

Yasunobu Kai

Thank you very much for your question. I am in charge of Americas business. My name is Yasunobu. And regarding your question, I would like to respond. But before that, I would like to recap the situation being activated in the United States, the commercialization activities, which are becoming much more and more active day by day in the United States. Let us explain.

First, as our CEO explained today, in the United States, Leqembi in the United States is growing as per in the plan and also the monthly plan is exceeded and also targets towards the achievement of the full year target. After the full approval in July, the number of physicians ready for the Leqembi treatment and number of amyloid beta tests conducted and also number of IDNs, which has decided to adopt leqembi are all expanding. All these KPIs are showing rapid growth and as you see, the weekly average revenue in October compared to the pre full approval, it has increased by 11 fold. Therefore, this is also exceeding well above the plan, which was formulated at the time of full approval.

And on October 13, the amyloid beta PET NCD was lifted. And after that, the number of patients who are able to receive amyloid beta test is increasing in an accelerated manner. So I said 10x, do you think that it was exaggerated? Regarding the number of PET it's being increased by about tenfold and kind of some mentioned it can be challenging. But is it correct? Yes, that is correct. According to our simulation, we simulated 10x increase.

Let me explain this later. According to the external data, up until August, now as you can see here, PET CSF and blood biomarkers are conducted in these numbers. So when it comes to private insurance claim as the CMS claims, both are included in these numbers. Therefore, this is according to PoPoLabs. Therefore, this is not exhaustive. With that in your mind and then according to the level of June, about 800, out of which half is CSF test. And it's been increased by ten fold, not CSF, but PET is increasing.

As CEO mentioned earlier, regarding PET, this is based upon the shipment of the trade from the PET manufacturer, which is increasing dramatically currently. And PET amyloid centers or sites, the number of such sites is increasing by several fold. Therefore, the number of patients who are eligible for the amyloid beta test is increasing rapidly. But amyloid beta positive is found and then decided to receive the treatment by this Leqembi. And before administration, ApoE4 test needs to be explained to patients with their consent, then referred to infusion center and then slots will be secured. And therefore, in that sense, there is about 2 months' time lag.

So our members are trying to shorten that period. But currently, that time lag is about 2 months. Therefore, the revenue growth as well as the increase in the number of patients so will become more visible from around December. That is our expectation.

So based upon these and also in addition to these, as has been explained today, at CTAD, the OLE data and also sub-SOC data, which have drawn a lot of attention at CTAD the other day, our members are very highly motivated because we are dealing with the new and first in the world therapy to be established together with health care providers. In the market that is making a surge of momentum in the market at various hospitals, such as those in the IDN policy and SOPs are being developed in order to be ready for starting the treatment for patients. And actually, treatment has been started at many hospitals. And according to the media report, you may have heard a very famous large hospital in the United States leqembi administration had started. So this is happening here and there. As we explained, there are 3 momentum.

In addition to that, towards the achievement of 10,000 patients and also achieving ¥10 billion in revenue, we have a very strong confidence now in achieving this. I'm sorry about lengthy response. If I may continue a little bit, it's a great opportunity because you are here, so I would like to explain further.

Regarding the further expansion of access by patients to therapy, as we have been trying, we needed to simplify patient journey, simplifying your shortening patient journey. That is what we have been trying to achieve. As we have mentioned, the various policies as well as test to be prepared, it is going to be very complicated and a complex situation. But simplifying these market readiness will be enhanced. We are seeing such market readiness enhancement. But even with us, when patients with AD visits the medical institution for the first time and until they start administration of this leqembi several months or at the longest, the 1 year will be necessary before starting the actual administration.

In order to shorten this period, we needed to achieve the operational maturity in that worth. People in the field needed to get used to operation and the proficiency in operation must be enhanced so that they can have even more smooth operation or flow of patients. Still patients are waiting for the treatment. The physicians are trying to receive or accept patients gradually. So we are very sorry for this situation, but there are many patients who are waiting. We would like to improve the smoothness of the flow of patients. Of course, standardization will be necessary.

In addition, the important role is played as we said earlier, by BBBM, blood-based biomarkers. Currently, this is considered to be triage or like in the screening, it has started to be used. Even at that stage, amyloid beta positivity, can be identified, so that the burden of going through PET CSF will be reduced. And this is expected to be used as confirmatory diagnosis. And if that is achieved, and this will replace PET CSF and BBBM will be used more widely that will simplify the diagnosis and also access to the Leqembi will be much easier.

And at PCP, if BBBM can be available at primary care physicians and then there is a limit or stringent capacity of neurologists, this burden the capacity of neurologists can be mitigated. So therefore, it will make the patient journey much smoother. Currently, we are trying to simplify patient journey so that as soon as possible and for as many patients as possible, we would like to deliver Leqembi administration.

So regarding PET, the number of the PET tests increased by ten fold with regards to the time lag. Well, I think that, that has been well come across very well. Well, I think you can finish. Thank you very much. Sorry about the time constrained. We'd like to continue the Q&A.

Kazuaki Hashiguchi

I'm Hashiguchi from Daiwa Securities. About Leqembi tau PET study interpretation. tau PET study, patient demographics, as I see the demographics. It was not included in the presentation today, but according to what was presented at CTAD, Low tau Group and intermediate High tau Group had SAD,RSP, ADAS-Cog, these cognitive function scores, which were not too different between these 2 subgroups. MCI and mild dementia AD patient proportion in active drug arm, well, intermediate High tau had more NCI patients. In Low tau, there were more AD patients.

Looking at this patient background, what can you say from the data for A-beta positives and at the same time, low tau patients. The efficacy was confirmed that interpretation is, I think, possible. But our early 80 stage efficacy was suggested. How can you make that interpretation? That question will be addressed by Dr. Lynn Kramer in the U.S.

Lynn Kramer

Yes. This is Lynn Kramer. I'm the Chief Clinical Officer of DHBL. Thank you for the question. The overall study demonstrated significant effects in all clinical endpoints, all biomarker endpoints and all quality of life endpoints. In the tau sub-study, we had specifically looked at the tau levels in addition to amyloid levels. The tau levels, which are located only in low-tau patients in the internal cortex, which means they're very localized, showed a very large responses as shown in Slide 15. However, we showed evidence also in the intermediate tau population of a very positive effect as well as was seen in the overall population. I think that answers your question. Thank you.

Fumiyoshi Sakai

My name is Sakai, I'm from UBS Securities. Regarding the domestic market. Immediately after approval, you are planning to launch the product here. And according to the reports in the media, leqembi drug price in Japan will be determined based upon the usual rules applied to other drugs. As CEO mentioned, this is regarded of innovative drugs, innovation, how innovation will be evaluated. I think this is going to be a very crucial point. So for you at Eisai, whatever price will be assigned, are you going to prioritize launching at the timing? Or do you think that there will be another round of negotiation with the regulatory authorities, not only limited to the drug price for the can be alone, but also your future pricing strategy going forward. Could you please elaborate on that? Akana is going to respond.

Masatomi Akana

My name is Akana, I am in charge of the policies. We have been saying that regarding the economy of value needs to be assessed or evaluated. Value-based pricing is advocated globally now. As you know, in the United States, this value is being evaluated on the concept that 60% of the value will be returned to the public. And annual value is calculated at 37,600 and annual price for initial administration was set at $26,500.

We do not think that there are any debate regarding this price saying that this is too high. But I believe that this value-based pricing concept is well received in the United States. Turning to Japan. In May this year in the peer reviewed paper recanemab value was published.

As for the characteristics of Recanemab and the social impact such as it is that it is likely to significantly reduce burden on the public long-term care service and the family in addition to the medical and clinical benefit based on good clinical effect, such social impact was well evaluated in the paper published. So this social impact is evaluated based upon the concept of value-based pricing. Regarding this concept, we are discussing with various stakeholders, including regulatory authorities. Now at the Chico or Central Medical Council where the discussions are ongoing. Now recanemab, at the Chico is being discussed based upon the concept of the high-priced pharmaceutical category, so-called peak sales, annual sales exceeding ¥150 billion. So that is the criteria for falling under in this high-priced pharmaceutical. But now discussions are ongoing, how to include the long-term care costs in the drug price calculation.

In Japan, after approval within 60 days or at latest 90 days after approval, the NHI price listing needs to be done. So within that time frame, how the long-term care cost needs to be valued, it is very difficult to reach conclusion within 90 days. So as you asked in your question, the first initial pricing will be done under the current rules. However, regarding the long-term care costs, there will be more sufficient discussion, which is currently ongoing at Chico based upon, including the reviewing of the cost of benefit valuation. Regarding the specific drug, such a discussion regarding how to handle the social value, I think that, that discussion is taking place for the first time at the Chico because of our efforts that we have been making in consultation with various stakeholders, I think that has been evaluated to some extent. And there has been certain progress. And the Prime Minister, Chida has mentioned this therapy several times.

And in the extraordinary session of the DIAD in October, he made his policy speech, he declared that considering the advent of a new era with the approach the approval of lecanemab, there needs to be the infrastructure to be promoted, including a necessity for the early detection and the testing and medical services and also the comprehensive economic measures, which were announced last week, these measures were included. Therefore, the economy is expected to play a very important role in the measures related to the dementia.

And under the basic policy economic and fiscal management 2023, in order to enhance further develop the innovative pharmaceutical products in order to strengthen the innovative capabilities in drug discovery, the further drug price meter shall be promoted, including the appropriate valuation of the innovation. So that is mentioned. So innovation reginal in Japan and the first in the world, should be appropriately evaluated.

Miki Sogi

Miki Sogi is my name. Preclinical AD, I have a question on that. AHEAD study is ongoing and I believe our primary completion is expected in November 2027. Before that, prior to that is there going to be preclinical data that will be published similar to the recently published Low tau Group data? And I think preclinical stage will be very important for treatment as well as for prevention. And business-wise, do you expect the business to grow after 2027, I believe that, that is your expectation. And if that is the case, the timing of LOE of leqembi or through a life cycle strategy, we have other products. What is the strategy of Eisai? Dr. Lynn Kramer will address that question.

Lynn Kramer

Yes. Thank you. Firstly, let me try and answer your first question about the AHEAD3-45 study. This study has about 1,400 patients expected. It has an interim analysis that could be used for accelerated approval after the first 400 patients have received 2 years of therapy. This is based on biomarkers, and we would have the ability to discuss that data with the FDA and consider an application at that time. Then we have the full examination of data, as you discussed after a 4-year completion of the 1,400 patients.

We do have other approaches to this in our pipeline, including some -- I think we have slide trying to find that slide right now. It's our Slide 17. We do have other programs that are in development that would take our Leqembi molecule and take those learnings and help develop other products that would slow down the progression of Alzheimer's disease. Does that answer your question? You had several different questions in there.

Operator

Yes. Thank you very much. We have passed the time to end the conference, but we have seen several other hands rates. Therefore, we'd like to continue. The person in the third row from the front. Please have the floor.

Unidentified Analyst

My name is Simoa. I'm a nonfiction author, Nobelist. I have 2 questions, and I think that Executive Officer earlier mentioned. Before starting administration, it takes 1 year. Accelerated approval was obtained in January. So now we are in November. So after accelerated approval and a patient who wish to receive the treatment, then what hampers this process? So why aren't they able to receive the treatment?

Yasunobu Kai

Yes, one year necessary for starting the administration, but rather, it takes several months to get appointments at the neurologists and then the administration will be started. So particularly in local areas where the sparse distribution of the hospitals, and then it may take 1 year.

Unidentified Analyst

In the United States, go-to-market enhanced structure is being enhanced. I understood that very well. But regarding the current status in Japan, in Japan approval is already given. Therefore, sales and marketing activities can be initiated. I believe you have started those activities. And similarly, my friend from my high school days is in NASH district, and they are working -- he is working for a hospital, and he wrote to me that he appreciates Eisai's efforts to develop such a new curing treatment. And those patients who are receiving care at local hospitals are in the moderate stage of disease. Those health care providers as well as the care providers in the field are not still seeing the actual patients eligible for leqembi. So those patients are not visible to health care providers. So changing the gear here, there is a significance of delaying the progression of the patients with AD. So I discussed this in Eisai's MR or sales reps and other people are struggling in raising awareness because of the car helps book was cited in Asahi or Nikkei newspaper, I think that because of the inappropriate media coverage in Japan, I think there is a misleading information spreading. Please do not criticize other media outlets.

Satoru Yasuda

I am in charge of commercial operation in Japan. My name is Yasuda. Thank you very much for your question. As you pointed out, on 25th of September, the MAH was granted in Japan as well as well. As you said, in principle, 60 days after approval, at the latest 90 days after approval, NHI price listing will be done. So by the end of year, this year, we believe that the decision will be made regarding the price testing for NHI. And we have the specialist MR or Biogen's MRs as well in the dementia area. So centering on them, we have started the information provision activities.

Eisai Japan has been very strong in the neurology area. We have MR groups. And they are making utmost efforts in providing information to HCPs. And so far, as of today, we have already covered about 18,000 physicians for the first round of information provision so far. As Mr. Shimoa mentioned, those patients who are indicated for leqembi package insert information is correctly communicated. First ever treatment for MCI and mild dementia in Japan, well, specialists or the neurologists do understand those indications. However, as you pointed out, patients themselves do not understand that once they reach the moderate phase of the disease, they are not eligible or indicated for this therapy.

In order to fill the gap, more specifically, safety as well as the biomarker-related web seminars, which are being actively held and we have held such web seminars 6x already in which about as many as 3,000 physicians have viewed those seminars and this was well above our expectation. So many more physicians than expected are viewing the seminar soon. So I think that the awareness about the drug itself will be enhanced.

In addition, ARIA diagnosis and management and also, as you pointed out, appropriate eligible patients for them to start treatment earlier, particularly in hospital and in-center or interfacility collaboration is being promoted, such environmental establishment is being promoted. We are continuing to work on this.

Unidentified Analyst

If I may add my question, physicians in hospitals information is being provided right? Yes, that is correct. But for those patients in the early stages of the disease, I think only 1% of those patients are actually seeing doctors at hospitals. So there are many more patients who are in early stages, but not seeing doctors how can you bring them to seek medical treatment? Mr. Simoa has asked your question.

Satoru Yasuda

Now MCI, or 10% or less than 10% of the patients in the MCI stage are actually visiting the hospitals according to the epidemiological study and others are MCI patients, as CEO explained for achieving the inclusive society, NOUKNOW or other tools are provided and not mentioned here today, but with local governments, the brain checkups are being promoted together with local governments through such brain checkups in the horizontal networking among local government, about 600 local governments are participating in that network. And the brain checkup, it is not a medical service in Japan, but there are many people who are receiving the brain checkup. And NOUKNOW is adopted for such the brain checkup so that we can get earlier awareness raising among patients in order to bring them to seek the medical treatment.

And after launch of the product, MCI related awareness raging campaign or activities will be conducted. So by doing this, we'd like to increase the treatment ratio. So towards the inclusive society, the basic act on dementia on the municipality level for prevention of dementia and also checkup of the cognitive function, planning needs to be made on the municipality level because this is the requirement under the law.

Under the anticancer basic law, the basic diagnostics are now available based upon the public feed or public funding. So that has changed the oncology treatment very much. Therefore, we can expect the same thing may happen in the dementia area. Thank you very much.

Unidentified Analyst

Chiodo from Toyo Kezai. About a detailed issue. In Japan, similar to the U.S., will there be insurance reimbursement of genetic testing for ApoE? And 100% post the marketing survey that was required at the time of leqembi approval, is this at a level such that it will affect the profitability that you estimated? The question will be addressed by Ms. Nakahama.

Akiko Nakahama

Thank you for your question. I am Nakahama responsible for regulatory affairs in Japan. First, about insurance reimbursement of ApoE4 testing, according to the current package insert, before Leqembi administration, ApoE4 test is not required. Irrespective of ApoE genetic typing as a risk countermeasure and treatment after onset, there are no differences irrespective of ApoE genetic type. So irrespective of ApoE-type safety measures should be thoroughly taken. And we will be asking health care professionals to do so. And I do understand that some companies are planning to develop such diagnostics.

And as much as possible, we would like to collaborate in such development activities. And if physicians or patients so wish, we would like to be able to offer ApoE4 test, which is covered by insurance reimbursement. Towards that end, we would like to cooperate.

Regarding your second question of all patient survey post marketing -- was that the question? About all patient survey as CEO explained earlier, this is an innovative new drug originating from Japan. And immediately after the launch of leqembi, we would like to ensure safe use of the drug. And we would like to cultivate and nurture that leqembi together in Japan. And we believe that the best way includes 100% patient survey. And for that purpose, we will be implementing that survey.

As for the impact of that expense company-wide about testing items and the number of patients who will be receiving the treatment, we are still consulting with the authorities, but this is a post marketing survey and we do not expect such a major impact on the business of the company.

By utilizing this survey, we would like to ensure safety after the launch and would also like to collect the efficacy data and make good use of that data. Thank you for your question.

Unidentified Analyst

My name is Sakata. I am from Yakuji Nippo. Regarding the launch of the leqembi into the Japanese market as has been asked by another person earlier, go-to-market structure in the United States may be replicated in Japan as well, is it correct understanding? And also the tests for diagnosis is an area of concern for many people. So what extent do you think this environment for diagnostic testing has been established? Mr. Yosi is going to respond.

Satoru Yasuda

Thank you very much for your question. This is Yusa speaking. Let me respond. In Japan as well, as you can see on the slide, we have specialist MRs and general MR sales reps and key account manager. And of course, oncology area, we are facing the aging issues in the society. So we are utilizing various channels like omnichannel in order to promote leqembi. So there is no change in that. And regarding the structure, could you please say your question again?

Unidentified Analyst

This kind of structure will be replicated in Japan? Are you going to make the similar approach?

Satoru Yasuda

Yes, there is no significant change. So we are almost completing the preparation for that. And regarding diagnostic tests, do you think how well the environment has been prepared. Regarding diagnosis, as you know, amyloid beta testing is already approved. But however, the reimbursement is not given yet. For that, we are making coordination with various companies and the regulatory authorities, but we would like to make it available for the launch of the leqembi even for the reimbursement. And also capacity itself, we started our efforts in investigation since 3 years ago. So, at least during the initial stage of our launch, we believe that there would be no problem. So at medical institutions, do you think that they have enough capacity for conducting tests. Yes, it depends on the regions. However, there are some areas where such capacity is not well established, but our specialty MRs or sales reps are discussing with the physicians in order to prepare them in place. But overall, at least in the initial phase after launch, we don't think there will be any problem.

Operator

I see the palm has been raised for a very long time from online participants. Yamauchi-san from Citi Group, please.

Hidemaru Yamaguchi

Just one question. SubCue data and submission. That is my question. In SubCue data, ARIA incidents, I think was higher in SubCue. And in terms of patient background, those who are more likely to have ARIA in terms of ApoE were smaller in number in subcutaneous study. And so this suggests a higher risk of ARIA? And is there going to be a need that you will have to do those finding once again because of this result? Dr. Lynn Kramer will respond.

Lynn Kramer

Yes. Thank you for the question. We do not believe additional dose finding will need to be done. The reason we don't believe that is we have now very good data that indicates exactly the PK and the PD for this subcutaneous formulation and can model this information along with our IV to predict area and exactly the correct dosing. We'll be discussing this with the FDA very shortly. Thank you.

Shinichiro Muraoka

This is Morgan Stanley, Muraoka speaking. Thank you very much for calling me for raising a question. Regarding the revision of the guidance, sales revenue, how should I interpret the breakdown of the revenue? I think there was a discrepancy in micro creation, ¥29 billion increase in revenue by Lenvima HALAVEN and others are subtracting these items. And at the time of May, budget included the leqembi is Americas revenue and Japan's revenue budget. And under this revised guidance, America and Japan's leqembi sales budget, which seemed to be reduced or more reduction is seen in Japan's budget or guidance for Japan Lean sales. Is this correct understanding? For your question, Mr. Shuman is going to respond.

Unidentified Company Representative

Thank you very much for your question. This is Shuman speaking. Let me respond. As we explained earlier, regarding the revenue, ¥29 billion was the upward revision to ¥741 billion. And breakdown, we rounded numbers for disclosure, but we haven't changed significantly the numbers for Lenvima please understand as such. So that means that the leqembi projections have stayed unchanged for both Japan and United States when you project published half year ago, right. That is correct. We haven't made any significant change.

Operator

With that, we would like to end the earnings presentation meeting. Thank you very much once again for taking part despite your very busy schedule. Thank you.

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Eisai Co Ltd (ESALF) Q2 2023 Earnings Call Transcript