Thanks for taking your time. [Foreign language] We would now like to begin. [Foreign language] Oral presentation of highlight of E2086 from World Sleep 2025 oral presentation. This is a virtual session; please check our website for presentation material. In Singapore this week, World Sleep 2025 was held. E2086 phase I study results were presented in oral presentation. The highlight of the presentation will be given today, and questions will also be taken to deepen understanding of the audience of E2086. Presentation will be given by Dr. Katsutoshi Ido, Chief Scientific Officer. Dr. Ido, please. [Foreign language] Good morning, everyone. I am Ido. I assume the role of Chief Scientific Officer in Eisai. Thank you very much for joining us today. [Foreign language] Since I joined the company in 2003, I have worked as a biologist in the Research Institute at Cambridge, Massachusetts, focusing on neurology drug discovery. While in Cambridge, I also served as the head of the Biotech Investment Division for three years, and I was appointed as CSO this spring. E2086, I will introduce today, is a compound we developed while I was serving as a group head at the Tsukuba Research Laboratories, and I am deeply attached to this compound. We recently presented findings on its wakefulness-promoting effects in patients with narcolepsy type 1 at World Sleep 2025, and I will now explain those results. Next, please. [Foreign language] Before introducing the clinical trial results, I would like to explain our company's approach to orexin drug discovery. [Foreign language] The compound E2086, introduced today, acts on the orexin system in the brain. This peptide, orexin, is a neurotransmitter that activates the arousal center. It serves as a key regulator of wakefulness, with high levels during the day and low levels at night during sleep. The relationship between sleep and wakefulness is sometimes compared to a seesaw, as shown in the diagram below. In the brain, there is the sleep center, which is shown as a blue circle, that maintains sleep, and the arousal center, shown as the yellow circle on the right, that maintains wakefulness. During sleep, the sleep center becomes more active, while the arousal center's activity weakens, and the opposite occurs when awake. To bring about the wakefulness by tilting the seesaw. Thus, the arousal and sleep centers mutually inhibit each other, tilting the seesaw toward one state or the other. Orexin plays a role in tilting the seesaw towards the arousal side. Therefore, if orexin tone becomes too strong when we are about to sleep, it tilts the balance toward wakefulness, leading to insomnia. Conversely, if orexin levels are deficient during the day, the seesaw tilts toward sleep, causing daytime sleepiness. [Foreign language] Our company has conducted over 20 years of research on this orexin system. Our first successful development was a receptor antagonist, DAYVIGO, as you see in the middle. Its generic name, lemborexant, which weakens the orexin tone at night to induce sleep, and it was launched in 2020. It currently holds the largest share in the market in Japan, with understanding by Japanese physicians of this mechanism of DAYVIGO, and it continues to expand further. Through the development of DAYVIGO, we established platforms including EEG recording system, orexin neuron-deficient animal models, and cell-based assay, etc. [Foreign language] Now. We initiated the E2086 project, exploring the flip side of the coin, developing an agonist that stimulates orexin receptors. Unlike DAYVIGO, this compound directly acts on the underlying cause of narcolepsy, where reduced daytime orexin tone leads to sudden, intense sleepiness. It is a concept where highly potent effects can be expected. However, searching for this agonist is far more difficult than searching for an inhibitor or antagonist. There was a major question of whether we could mimic orexin, a large molecular-weight peptide. We began the searching using multiple approaches, including high-throughput screening from a library we constructed specifically for this project, using our own compounds. After screening at the time, 250,000 compounds, only one compound reached the final stage. Moreover, well, usually we have several compounds reaching the final stage, but at that time, there was only one compound that hit the final stage in this project. Moreover, this hit compound. [Foreign language] I was engaged in another project to create compounds that are created, and I saw that it was a serendipity-type encounter of such old compounds we discovered in the past. But this hit compound possessed a complex structure, a cage-like framework, with stereochemically rich two carbon-rich rings. So it was a very complex synthesis. So featuring three or four chiral carbons, its stereospecific recognition requirements demanded an exceptionally intricate synthetic approach. We questioned whether it was truly feasible multiple times. Yet this structure ignited our passion of Eisai's medicinal chemists. Within a year, they achieved over a 10,000-fold increase in activity, and a biology team also developed an AI-based automatic EEG analysis system, enabling highly efficient screening of compounds, exhibiting the ideal profile for agonists with potent efficacy and sufficient safety. As a result, we identified a development candidate with Eisai's unique chemical structure that demonstrated strong efficacy and sufficient safety in preclinical studies. As a unique company developing both agonists and antagonists, we aim to contribute broadly to patients with sleep disorders. I believe that there is none such company which are developing both. Next slide, please. Now, I will introduce a trial result for the selective orexin receptor two agonist, E2086, in patients with narcolepsy type 1, which we presented at World Sleep 2025 on Monday this week. Next, here is that introduction. There are several approved compounds to treat patients with narcolepsy type 1, but all of them are symptomatic treatments and do not directly address orexin deficiency, which is the underlying cause of NT1. E2086 that we discovered is a highly selective orexin 2 receptor agonist. In preclinical in vivo studies, it demonstrated a dose-dependent promotion of wakefulness. Additionally, patients with narcolepsy type 1 experience cataplexy, where sudden temporary loss of muscle tone occurs following intense excitement of emotions, so it damages the patient's QOL a lot. Preclinical models confirmed that E2086 also mitigates cataplexy-like symptoms in a dose-dependent manner. Based upon these results, E2086 is expected to improve symptoms caused by orexin deficiency in patients with NT1 by promoting wakefulness via the orexin neuronal pathway. Next, please. The objective of this Study 101 was to evaluate the efficacy, safety, and tolerability of E2086 compared to placebo and the existing drug modafinil in adult patients with narcolepsy type 1. This was the first clinical trial in patients or participants with NT1 for E2086, looking at the efficacy based upon the single dosing, and next, study design. This was a multicenter randomized double-blind five-period crossover phase I-B clinical trial. The group composition consisted of five groups: placebo, three doses of E2086, this time five, 10, 25 mg were tested, and modafinil. I can see in the diagram below, which specifically shows how participants in the study received the investigational drugs. For example, for patient one, at the first visit in period one, a single dose of placebo will be conducted, and then MWT will be conducted. After a three-day washout period from the following day, a single dose of E2086 five mg will be administered in period two. Another washout followed by modafinil in period three after MWT and E2086 10 mg in period four and E2086 25 mg in period five to complete the study. Thus, the study is designed to evaluate the effects of a single dose of all five investigational drugs for each patient separated by washout periods. Ten different treatment sequences were prepared, and each patient was randomly assigned to one of those sequences. In each period, after undergoing an overnight polysomnogram for a comprehensive sleep assessment, the investigational drug was administered within 45 minutes after lights on the following morning, followed by a Maintenance of Wakefulness Test. [Foreign language] Adult males and females above the age of 18 with NT1 diagnosis are the subjects. As for other inclusion criteria, please refer to the left side of the slide. On the right side, assessment of efficacy is shown. Most frequently used method in narcolepsy study, MWT 40-minute test is used. MWT is short for Maintenance of Wakefulness Test. This tests maintenance of wakefulness. In this test, patients will be sitting on the bed in a sleepiness-inducing environment, which is dark and quiet. Patients are instructed to remain awake and be seated quietly on the bed. But with narcolepsy, patients, because of strong sleeplessness, in five-10 minutes, they fall asleep. But how long wakefulness is maintained will be observed for up to 40 minutes. It starts from two hours after wake-up in the morning, and a 40-minute session will be conducted four times at a 2-hour interval. Polysomnography and EEG will be used comprehensively to make assessment of wakefulness. So this is an objective test of wakefulness. Another criteria is KSS Karolinska Sleepiness Scale. This is a subjective scoring of sleepiness of patients. This is measured at the end of MWT at each time. Statistics used a mixed model. E2086 at each dose, placebo, or each dose of E2086 and modafinil were compared. Modafinil was used this time, and the purpose is to compare modafinil and placebo to confirm the sensitivity of the assay. Adverse events data were collected throughout the whole period. This is the demographics. This is the demographic statistical characteristics and baseline characteristics of groups subject to safety analysis. 22 were randomized, and 19 completed the tests. 21 underwent safety assessments. 42.9% were female. 47.6% were Caucasians. Next, turning to the results of the study, this is a very busy chart, but the next page will show easier-to-understand graphical presentation. The lower part of the chart in pink box shows individual sleep latency measured four times in a day. Sleep latency is the time it takes before a patient falls asleep, and the top pale blue box is the average from four trials. This is a busy chart, and please look at the next slide, but regarding this slide, one point about modafinil. In modafinil, sleep latency is significantly longer in comparison to placebo, confirming the sensitivity of this test. Next, this is a graphical representation of the previous chart, and this is the most important slide in the oral presentation this time. There are four measurements of MWT, as I've described in the methods. After administration of the drug, MWT tests were measured four times. The vertical axis is sleep latency, the time until a patient falls asleep. In a sleep-conducive environment, participants are trying not to fall asleep, and efficacy is measured by how long sleep latency can be extended, so the taller the bars, the better the results that we expect to see, and in placebo, oftentimes in five to six minutes, patients fall asleep. In comparison to that, the black bar showing white bar showing placebo, and pale blue, pink, and green are E2086 five, 10, and 25 mg in all three doses. In comparison to placebo and in comparison to even modafinil, we were able to confirm that sleep latency is significantly longer than in all four trials. E2086 starting from five mg showed significant extension of MWT in comparison to placebo. At the full trial, it means that even after seven hours after administration, efficacy is maintained. At 10 and 25 mg, the MWT is extended more significantly than modafinil. The vertical axis is sleep latency. As I mentioned earlier, competitors' graphs often have lines at 20 minutes. When healthy subjects go through this study, the 10th percentile have a lower limit of about 20 minutes. So 20 minutes is considered a lower limit of normal range oftentimes. In the lowest dose, five mg, in the last trial, trial four, normal range was maintained. And at 10 to 25 mg, the average level of 30 minutes in healthy subjects is exceeded even after trial four. Looking at individual tests, five, 10, 25 mg in all of the arms, and especially in comparison to a lower dose, in the mid dose, and in comparison to mid dose, in higher dose, patients stay awake even beyond 40 minutes. Strong arousal effect is observed. Patients who fall asleep in five minutes without the drug can stay awake up to the normal range of sleep latency as seen in healthy subjects. This is a similar type of chart showing KSS score, Karolinska Sleepiness Scale. Earlier, MWT showed objective assessment of wakefulness using polysomnography. In case of KSS, this is a subjective assessment of sleepiness by patients themselves. The top blue box is the average of four trials. The bottom pink box shows results from each trial. Looking at modafinil, in comparison to placebo, KSS is significantly lower. In this scale, assay sensitivity once again is confirmed. This is the graphical representation of KSS scores. The vertical axis in this study, the current sleepiness intensity is scored from one to 10 by participants. One is extremely awake, and 10 is extremely sleepy or falling asleep all the time. In between one to 10, the patients are asked to score, and the lower the number, the more wakeful the patient is, meaning the drug is more effective, and in red boxes, E2086 at five, 10, and 25 mg are increasing daytime wakefulness significantly in comparison to placebo, and 10 and 25 mg also are showing statistical significance over modafinil, looking at trial four, similar to earlier chart, at the very last trial, sustained effect is shown from subjective feeling of sleepiness of patients. This is the safety summary. E2086 was generally well tolerated. Most TEAEs or treatment-emergent adverse events were mild to moderate in severity. There was a dose-related trend, but there were no discontinuations due to TEAEs and no serious TEAEs reported. Most frequent TEAEs were increased urinary frequency, nausea, dizziness, and urinary urgency. In terms of clinical chemistries, including liver function tests, there were no items of concern, and there were no clinical trends of concern, including in blood pressure and heart rate, and no visual abnormalities were reported. So it was confirmed that E2086 was well tolerated. This is the conclusion. These data demonstrate that once daily dosing of E2086 has the potential to improve daytime wakefulness in NT1 patients. All doses tested of E2086 five, 10, 20 mg significantly reduced EDS versus placebo and modafinil as objectively measured by the MWT. All doses of E2086 significantly reduced EDS versus placebo as objectively measured by KSS. At 10 and 25 mg, KSS scores were significantly more reduced than modafinil. Dose-dependent trend was observed in TEAE incidence, but E2086 was generally well tolerated. This is the final slide, and this is the final conclusion. E2086 is an orexin receptor agonist that was discovered and is being developed by leveraging the strengths of Eisai's orexin platform, particularly the experience and knowledge gained from the discovery research of the orexin receptor inhibitor, DAYVIGO. This compound, E2086, was shown to significantly reduce excessive daytime sleepiness compared to placebo and existing medication, modafinil, when administered once daily in patients with narcolepsy type 1. In particular, as shown earlier, strong potency of sleep latency of more than 40 minutes were observed in many patients, and effect was shown to be sustained, and we believe that this is a very promising profile. And at the same time, at the doses showing efficacy, good tolerability and safety were demonstrated, and no liver function disorder or visual abnormalities were observed. As for development plan going forward, not only narcolepsy type 1, but including narcolepsy type 2, we plan to start phase II study within the fiscal year. As for submission filing, we are targeting to file submission in Fiscal 2028. We would like to apply good ideas to the protocol to accelerate this time schedule. Thank you very much. Can you hear me? Yes, I'm sorry. you hear me? Yes, I'm sorry. [Foreign language] This is Yamaguchi of Citigroup. My first question This is Yamaguchi of Citigroup. My first question [Foreign language] 21 participants were included, and we start by delivering data demonstrating very high efficacy, effectiveness. And you said that the five, 10, 25 mg doses were utilized, and there were no side effects seriously once. So do you think that there will be further doses to be utilized in phase II? One One word, but do you think that one of these three will be selected? [Foreign language] Currently, the plan for phase II trial is now being finalized, but we are not able to give you any details. But moderate anti-stimulation will be utilized, inclusive of a higher dosage for this particular compound. So we would like to provide appropriate dose setting for type one and type two patients. So we would like to design studies as such. [Foreign language] Thank you very much. My brief question regarding the adverse event, I thought that the incidence of insomnia was low. So it's the flip side of the coin. So I thought that after listening to your explanation and other companies' compounds, I believe that there will be a higher incidence of insomnia. So could you please explain why it was the case in these results? [Foreign language] Thank you for your question. We evaluate the efficacy up until the seven hours after the start of administration. For about seven hours, efficacy continues. Whether or not the insomnia occurred or not, it should be evaluated looking at the test results during the night. According to PK, the efficacy will discontinue or the binding may be considered. We assume that there will be a discontinuation of the efficacy. Lemborexant and we were very careful about the PK when we conducted development of the sleeping drug. I think that this is the most important point. This result, I believe, is leading to the ideal profile that we are trying to achieve. The drug was taken in the morning, and then the efficacy will continue. Then when they go back at night, the efficacy discontinues. Thank you. [Foreign language] Mr. Wakao from JP Morgan Securities, please. [Foreign language] Thank you. This is Wakao from JP Morgan. Can you hear me? [Foreign language] Yes, we can. [Foreign language] Good morning. First question is about the adverse events. [Foreign language] Increased urinary frequency and urinary urgency in orexin agonist. These are on-target adverse events. I understand that very well. These are characteristic adverse events of orexin agonist. But unique to this compound, dizziness and nausea are adverse events not seen in other drugs. And what are your views? Do you think that these are manageable? And if these are not on-target, is this due to this specific compound? [Foreign language] Thank you, Mr. Wakao, for your question. As for adverse events observed in this study, and as shown here, these are mild to moderate in severity in the majority of the cases, and these are not at all severe. That is one point. On-target or not, in the phase II study, we would like to closely look at that. As for the studies of competitors' drugs, there are some signs such as lack of balance in developing CNS drugs, lack of balance, and nausea depending on how patients feel. These are signs that are often exhibited, inclusive of these. We would like to closely examine in phase II study. But in any case, these are transient and disappear. So we do not believe that these are serious. [Foreign langauage] I see, I understand. [Foreign language] Looking at dizziness and nausea, it is lower in incidence in 10, but higher in incidence in 25. And it looks like 10 mg is the optimal dose. But there were earlier answers that you might consider increasing the dose. So these adverse events are not so serious. That is our view. [Foreign language] And one more thing. Oh, and the second question. Takeda is ahead in development. Their dosing is twice daily. They say that the benefit of twice daily dosing is that they can mimic the circadian rhythm of orexin. Regarding this concept, what do you think? If that is ideal, then your once daily dosing potential can mimic the circadian change. [Foreign language] Thank you for your question. As for once daily potential of our compound, in order to improve patients' QOL, we believe that this is a more suitable profile in our view. As you rightly pointed out, orexin has a circadian change or diurnal change, and it will be higher in daytime. If we cannot mimic this diurnal rhythm, is there any QOL that cannot be achieved? To To the extent that I know, there's not much during the sleep. If a sleep is forced, a sleep rhythm may be out of sync. But in the questionnaire, we do not detect any discomfort. So once a patient becomes fully awake in the morning and engages in activities during the day and the effect wears off at night, this means that a patient will have good drug adherence or compliance. So I believe a benefit is strong. [Foreign language] You will be the third or fourth to introduce a drug in this indication. How much differentiation you can make from the existing drugs will be quite important. What are the points of differentiation? As far as I've listened today, it seems that safety and efficacy. So I think you will simply be pursuing best in class. [Foreign language] Thank you for your question. As you pointed out, I believe there are mainly three things. First is, as you mentioned in the question, once daily dosing. Narcolepsy patients, in terms of attentiveness, attention, oftentimes their scores tend to be lower, and they may forget to take a drug. So once daily to keep awake, wakefulness can be a huge benefit. And another point you've also mentioned, which is safety. Many patients are able to stay awake beyond 40 minutes, and this is a single dosing study, so we cannot make a simple comparison. But what we have come to understand is that in comparison to competitors, we can be hopeful that adverse events are fewer. So in a broad range of doses, we hope that the drug can be used by both type one and type two patients. And the third is efficacy. At five mg, even at five mg, beyond 20 minutes, patients stay awake. So wakefulness of healthy subjects can be achieved, and we believe that this can become a best-in-class compound. Thank you. [Foreign language] Next is UBS Securities, Mr. Sakai, please. [Foreign language] This is Sakai speaking from UBS Securities. Thank you very much. [Foreign language] This is a very basic question. There may be some data showing on the slide that the serum concentration Tmax or half-life. [Foreign language] Could you please comment on these, how much they are? [Foreign language] Thank you for your question. [Foreign language] I think at the previous last sleep conference, I think data was presented. I think that the active compound will disappear in half a day. I mean, half a day during the day. So that is the profile of PK. [Foreign language] Half a day during the daytime. So that means six hours. [Foreign language] Roughly speaking, yes, that is the ballpark. [Foreign language] And then once daily dosing. [Foreign language] And efficacy can be maintained. Is this the message you would like to deliver? [Foreign language] Understood. Thank you very much. [Foreign language] So it's a basic question. [Foreign language] For patients with narcolepsy, orexin-based drug will continue to be taken. And then, do you think that the activity of orexin will be enhanced? I mean, withdrawal can be possible in the future. Are you going to, how are you going to verify and examine that? [Foreign language] Well, thank you very much. It's a very interesting question. [Foreign language] Going forward, inclusive of the long-term, the multiple dosing studies and narcolepsy disease, the neurons which are emitting the orexin are disappearing. Therefore, in this disease, there is no site for emitting the orexin anymore. So in principle, the patients have to continue to take this drug. [Foreign language] Understood. [Forein language] Right, long-term study will be done from the time phase II study will be started. The long-term study will be also initiated at the same time. [Foreign language] Well. At the same time with the phase II study. [Foreign language] So after completion of phase II, and then if patients are going to enroll into the long-term stability study. [Foreign language] Yes, inclusive of that point, we are now working on the protocol and a plan for the future study so that we will be able to file as soon as possible for approval. We'd like to disclose that information as soon as that gets available. Thank you very much. [Foreign language] Mr. Muraoka from Morgan Stanley, please. [Foreign language] Good day. This is Muraoka from Morgan Stanley. Thank you for taking questions. I'm not able to digest fully various data. This drug, E2086. [Foreign language] As for drug interaction or CYP, with other drugs in combination use, is there anything that we should be concerned about? [Foreign language] No, no such concerns. [Foreign language] I see. Thank you. In today's presentation and recently, Takeda also gave a presentation looking at these overall. My impression is that Takeda is able to launch the first, so it will be able to lead even though it's twice daily. Your company's compound is well balanced in terms of safety and efficacy. So even though it's mid-comer, it looks very good. And Alkermes has blurred vision, and it seems that it is at least promising. That is my impression. Is it a similar perception that you have in terms of positioning of three drugs? [Foreign language] Thank you for your question. I'm not able to offer detailed comments on competitors' drugs. But in terms of benefits, we believe that our compounds have the benefits that I've described earlier. The main efficacy includes efficacy on cataplexy. If this is confirmed in phase II, we believe that this drug will become the most used drug in patients. And we do not have a blurred vision problem as observed today. [Foreign language] Thank you very much. NT2 will be included in phase II, as I understand. As for dose, in phase I, it was up to 25 mg. In your gut feeling, how high do you think you can go in dose? [Foreign language] Thank you for your question. It may sound repetitive, but we have a modeling simulation team, which is quite strong and capable based on the results from this study, and those are publicly available studies, and we have already confirmed that we can go higher in dose, so we believe that we can go to higher dose that can be effective in NT2, but I would like to refrain from commenting on specific dose in numerical terms. I can understand that, but in order to make it effective in NT2, do you have to go to as high as 50 mg to quite high dose? On that point, we will be conducting simulation. The point that you've raised, meaning for NT2, those may be higher. Looking at the past situation, those are twice or three times as high, starts to be effective. And in preclinical data of ours, that is what is suggested. And we believe that we can go to that level with our compound. Thank you very much. [Foreign language] From Goldman Sachs, please. [Foreign language] This is Ueda speaking. I'm from Goldman Sachs Securities. I'd like to ask about the MWT profile that you are aiming at. What is the need for that? [Foreign language] This time, five mg arm, there was extension of over 19 minutes as you spoke. So for over 20 minutes for a healthy range, am I using like this enough target? Or as you said earlier, 10, 25 mg for extension of over 30 minutes, which will be necessary? Or would you like to see the efficacy lasting until 40 minutes? And according to other companies' explanation, if you reach 20 minutes, and then if it's too efficacious, but there is no incidence of insomnia, so then 30 minutes or 40 minutes, stronger efficacy compared to other companies. Is this something that you are aiming at? Could you please give us your take? [Foreign language] Thank you very much for your question. As you summarized right now, for healthy volunteers, mean value was 30 minutes. So according to the compound profile, although we have just tested the single dose studies, but I believe that we would like to first verify that first. As you commented, if the time extension reached the 40 minutes, and then we believe that we are able to reduce the dose for this compound, so then we will be able to make adjustments by reducing the dose of the compound. In terms of the durability or sustainability, for example, when on the way back from the office home, and then during the driving, 20 or 30 minutes have to be maintained. This should be the profile that we would like to achieve by the once daily administration. Thank you very much. [Foreign language] Second question is about strategy for developing this compound going forward. In this area, there are several competitors which are ahead of you and your company. You have a strong share for DAYVIGO in Japan. Thinking about the franchise, thinking about the players outside of Japan, are you going to think about the standalone development, or are you also considering the partnership with other companies in development? [Foreign language] Thank you very much for your question. Our goal is to deliver this therapy for as many patients as possible, as early as possible. So if there are any partners who can empathize with this goal, so we like to be very open and flexible in considering the potential collaboration. Thank you very much. [Foreign language] Next, Ms. Sogi from Bernstein Securities, please. [Foreign language] Thank you very much. I have three questions. First, about MWT in phase I study. Up to seven hours, you are assessing efficacy. Based on the results so far and considering half-life, how many hours per day can the drug stay effective? Dr. Ido, you've said that a patient should be able to stay awake even when they are driving home. So with once daily dosing, how long will efficacy last? How many hours? [Foreign language] Thank you for your question. This time, seven hours and a half up to that assessments were made. We would like to confirm details in the future studies. The trial four on this page scores are similar to the start of the administration. Looking at the half-life, we believe that the scores or wakefulness can be maintained through to the evening. [Foreign language] Thank you. Second question is a modeling simulation. Between narcolepsy type 1 and type 2, I think you are looking at different pharmacodynamics. In narcolepsy type 1, clearly, orexin level is lower. In narcolepsy type 2, orexin level, it may not be completely normal, but the profile may be quite different from narcolepsy type 1. In modeling simulation, in particular, how do you plan to simulate looking at the differences between NT1 and NT2? [Foreign language] That is a very good question. We also consider that to be a very important point. First, subjective data. In narcolepsy type 2, we have reported values of efficaciousness, and we are able to utilize that data. Another point is what we are doing on our own called QSP, looking at pharmacological study from preclinical studies based on preclinical model we will be applying in the simulation. So we can take these approaches at the same time in the simulation. I see. I understand. Basically, this drug and orexin receptor interaction will be studied, and so you will be looking at that for both NT1 and NT2. Once again, thank you for a very sharp question. Sensitivity cannot be fully explained only by bonding, and I think our strength is that we are able to incorporate that aspect as well. [Foreign language] I see. Thank you very much. This time, idiopathic hypersomnia, IH. Development plans were not mentioned today, but what is the view of the company? This IH is a different disease from NT1, NT2, but what is the view of Eisai on IH? [Foreign language] Thank you for that question. First, we would like to focus and concentrate on narcolepsy. So currently, we are looking at type 1 and type 2, but as you pointed out, given the mechanism, we believe that there is potential including IH. In addition, with the orexin platform going forward, we would like to better understand how orexin is involved in a wide range of diseases, including neurodegenerative study, and we are conducting detailed analysis of this. Once narcolepsy efficacy is demonstrated in phase II, we would like to once again consider the widening of indication. Thank you. [Foreign language] Mr. Hashiguchi from Daiwa Securities please have the floor. [Foreign language] This is Hashiguchi from Daiwa Securities. [Foreign language] First is the basic question. As you explained. Crossover design was adopted. What's the objective of adopting this design? And by having this design and compared to the studies without a crossover design, in terms of interpretation of the data, what are the points? What are the points that you have to take into account? [Foreign language] Thank you very much for your question. This time, crossover study design was adopted. The reason why we chose it is. [Foreign language] Each patient will be able to experience all five drugs or investigate drugs. There will be an effect of controlling the variation, fluctuations. The profile of the patients may vary. Therefore, within one single person, we are able to see the results. We have five arms, so it's 20 patients, and it used there should have been 100 patients, but with this study design, it could be contained to 20 patients. Within this group, we were able to show and demonstrate a significant difference. I think it was a good way to have the significant difference in an efficient manner. Regarding your concern, yes, we are looking at that. The washout period was determined as three days based upon the earlier simulation and also the PK data in advance. We confirmed that when the efficacy or the exaggeration can go back to the original baseline level. After conducting analysis on the results of the administration, there was no carryover effect from the previous dosing. In generally speaking, clinical trial, this is not something that we have done by ourselves. I believe that this is one of the study designs which are widely adopted. [Foreign language] Thank you very much. Based upon this study, I believe that there may be potentially obtaining additional data from this same study, for example, a longer follow-up period of data and also data on the other evaluation items. And the points? I believe that I think that the data to be presented for now is limited to what you have presented today. [Foreign language] Thank you for your question. This is Study 101. Broadly speaking, the datasets that we are able to present are limited to what's presented today, but we have taken the blood samples as well. So there may be, as necessary, additional studies on that, but in principle, there will be no further long-term data from this design. [Foreign language] Thank you very much. Based upon that. Regarding the partnership, what do you think will be the timing for you to consider partnership? Could you please give us your input? According to the information meeting held in March, CEO Mr. Naito mentioned that the data necessary for partnership will become available in one or two years. So that is what the company wants to do, he said. In one or two years, that timing has not come, but rather than based upon this particular dataset, that the data will be derived from the next trial phase II will be the foundation for considering the partnership. Is this something that we should think? [Foreign language] Thank you for your question. That data is something that we are able to call POC, proof of concept. So utilizing even this data, we will be able to consider such a negotiation for potential partnership as an option. [Foreign language] Thank you very much. That's all I have. [Foreign language] Mr. Wada from SMBC Nikko Securities, please. [Foreign language] This is Wada from SMBC Nikko Securities. Can you hear me? [Foreign language] Yes, we can. [Foreign language] Thank you. [Foreign language] Regarding compound, I have two questions. [Foreign language] First, this is a unique compound, including its stereo structure. Is there going to be any issue in manufacturing? For example, mass production may be difficult or cost could be higher. Is there any negative issues? As for positive points, such compound. In what way were you able to come up with such a unique compound? And with such a unique compound, can it be used for other targets? [Foreign language] Thank you for your question. So first question, we have no concerns. Looking at the past history, we have dealt with naturally derived compounds with many asymmetries. And so based on that track record, we believe that we will be able to manufacture this compound without any problems. And the second question, we believe that there is a possibility. I have explained the history of this compound in the beginning of my presentation. This was not a compound brought from outside. This was found as we were exploring other things. And from the compounds on the orexin platform, we were able to consider other compounds in addition to what initially developed. So in that sense, I think there is a potential for broad application. [Foreign language] Thank you. [Foreign language] We start receiving questions from the media. [Foreign language] Questions from the media. If you have any questions, please raise your hand. [Foreign language] I think you were raising your hand earlier, Dion Büchner. If you're still with us, please start asking your question now. Thank you very much for taking my question, and congratulations on fantastic data. This is really exciting. I just have two quick questions. The first being, I wonder if perhaps Dr. Ido can say a bit more about tolerance of the compound over time, given that it's long-term therapy. Then secondly, if you could speak a little bit about your plans. I know it's very early, but access globally has become access to payers has become an increasing issue, and especially at IH. I wonder what is the issues overseas, but also in Japan for limits to prescribing. As you know, modafinil in Japan is not prescribable by GPs, for example. I wonder if there will be any pre-authorization requirement or perhaps scheduling of the drug. In other words, a DEA schedule in the United States to be observed. Thank you very much, and congratulations again. [Foreign language] Thank you very much for your question. Regarding the tolerance. [Foreign language] Going forward, we will conduct the long-term studies, in which we would like to observe closely. And in the preclinical data, we have observed the data demonstrating the efficacy. And at the dosing, where the efficacy is confirmed, there hasn't been any issues with the tolerance. So I don't think that there will be an issue with the tolerance. But once again, if I may repeat, I would like to closely observe what will be the situation in the long-term studies going forward. And regarding the schedule, your second question, based upon the mechanism of this drug, orexin receptor [Foreign language] We do not believe that there are any big concerns about the scheduling. But of course, this is about the CNS compound. So regarding the. [Foreign language] Concern. It's going to be one of the core batteries in the study design. So we would like to demonstrate that there is no such concern in our studies going forward. So you do not consider any kind of addictive potential or any studies to assess that? [Foreign language] Currently, if there are no concerns, then we do not believe that there is a necessary new studies to be conducted. But based upon the results from the core battery, we will start consultation with the regulatory authorities. Thank you very much, and congratulations again. [Foreign language] Thank you very much for your active participation with many questions. We would now like to close the briefing session on highlights of E2086 oral presentation at World Sleep 2025. When you close the Zoom window, there will be a questionnaire. It will take only a couple of minutes. We appreciate your feedback, and thank you very much for participating.