Hello everyone, and welcome to this investor call to discuss Oveporexton Phase III Data and Commercial Readiness. My name is Christopher O'Reilly, Head of Investor Relations at Takeda . Today's presentation will take place in English with simultaneous Japanese translation. During the Q&A, we may take questions in either English or Japanese. Therefore, please confirm the language settings in your Zoom window. Please click on the globe symbol at the bottom of your screen and select English if you wish to hear the call entirely in English, select Japanese if you wish to hear Japanese translation, or select off if you would like to hear the live audio in both languages. I'd like to remind everyone that in this call we will be discussing forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those discussed today.
The factors that could cause our actual results to differ materially are discussed in our most recent Form 20-F and in our other SEC filings. Please also refer to the important notice on page two of the presentation regarding forward-looking statements. With that, we would like to begin the presentation. First, I'd like to hand over to our President of R&D, Dr. Andrew Plump.
Thank you very much, Chris. Good morning, afternoon, or evening to everyone on today's call. Thank you for your interest in our orexin franchise and groundbreaking Oveporexton phase III clinical data. We are delighted to be here in Singapore at the World Sleep conference, where we just shared our impressive phase III study results of Oveporexton in narcolepsy type 1. By the end of this presentation, you will appreciate Oveporexton's potential to establish a new era of care for patients with NT1. These results have never before been seen in a phase III narcolepsy study. This is a very exciting time for our orexin franchise as we approach commercialization. This is just the beginning as we expand into additional indications with programs like TAK-360, currently in accelerated phase II studies for type 2 narcolepsy and idiopathic hypersomnia, and bring new orexins to the clinic intended to treat more common diseases.
Across Takeda, we are laser-focused on maximizing the value of our orexin franchise. Now, let me introduce our speakers for today. First, we have Dr. Sarah Sheikh, Head of our Neuroscience Therapeutic Area Unit and Global Development Organization. She will review the results of our phase III clinical trials in which the majority of patients normalized across a range of symptoms and remarkably had high statistical significance on all 14 primary and secondary endpoints across both trials, setting a new standard for the treatment of NT1. Next, Heather Dean, Head of our Neuroscience U.S. Business Unit, will highlight the unmet medical need, market opportunity, and our commercialization readiness efforts. We are leveraging our deep neuroscience and rare disease expertise to swiftly launch the first orexin agonist to treat the root cause of NT1.
Finally, we'll have closing comments from Julie Kim, our President of the U.S. Business Unit, Head of the Global Portfolio Division, and incoming CEO effective in June 2026. Following our prepared remarks, we'll have a question and answer session. Before I hand it over to Sarah, let me remind you that we are now two for two in 2025 with positive phase III results for Rusfertide and Oveporexton. Later this year, we'll have top-line data for zasocitinib in psoriasis. Thank you very much, and now let's hear from Sarah.
Thank you, Andy. Good morning and good evening. Heather and I are thrilled to share our orexin phase III results and commercial outlook with you today. Let me start by saying that we are enormously proud of what we have accomplished so far and excited about what lies ahead. It is rare to bring a molecule from the bench to successful phase III trials in a completely new field that is orexin science, and we did just that. Within roughly four years from first in human to phase III results, we developed a potentially transformative new therapy for narcolepsy type 1, or NT1, and will now work with regulatory authorities to bring it to patients as quickly as possible. As drug developers, this is what we aspire to: to change the trajectory of a disease and to try to give patients back a meaningful life.
This is what I believe we will be able to achieve with the first orexin 2 receptor agonist, Oveporexton, once it is available to patients. Next slide. Since the R&D day in December, we have made great progress. If approved, Oveporexton is well positioned to be the first orexin therapy to address the underlying pathophysiology of NT1. Our phase III results that some of you may have seen earlier today demonstrate positive and statistically significant results across all doses and both trials on all endpoints with the potential to normalize how NT1 patients feel and function, offering the opportunity to set a new standard of care for NT1. Filings are anticipated in the U.S. and additional geographies in fiscal year 2025. The commercial potential is substantial in the range of $2 billion- $3+ billion globally. Next slide, please.
Now let me provide a brief reminder of what it is like to live with this chronic, debilitating disease that is NT1. The ability to both stay awake during the day and experience restorative sleep at night is critical for us to live healthy and productive lives. When sleep intrudes into wakefulness and wakefulness dominates sleep, our ability to function is significantly impaired. NT1 cannot be defined by a single symptom, but rather by multiple symptoms that patients experience during the day and night. Starting from left to right, excessive daytime sleepiness, one of the most commonly recognized symptoms, manifests as falling asleep in the most inopportune situations, like in class or while driving, often with serious consequences to patients' grades, professional performance, or worse, their life.
Moving on to the right, cataplexy is a hallmark symptom of NT1 and describes the sudden loss of muscle tone upon an emotional stimulus. Manifestations can be subtle, such as a facial droop, to quite dramatic, with actually falling to the ground while fully awake but unable to move. A truly terrifying experience, which of course is not only socially stigmatizing but can also result in injury. As a consequence, and out of fear of bringing on a cataplectic event, patients will very quickly guard their emotions or avoid social interactions altogether and can become isolated and depressed. Cognitive impairment is another distinct symptom of NT1 affecting, for example, memory and sustained attention, with profound effects on the ability to function at work or school, in social interactions, or at home. Even at night, there is no respite, with sleep disrupted by an increased number of awakenings and terrifying nightmares.
At the peripheries of sleep, that is, falling asleep and waking up, patients experience sleep paralysis and hallucinations, impacting the quality of sleep. With this constellation of symptoms, it is not surprising to learn that patients are often misdiagnosed and misjudged by their own families and the healthcare system, with devastating socioeconomic consequences. As you all know, today there are no approved treatments that address the underlying cause of the disease, and most patients have to take multiple medicines, dosed multiple times a day or night for different symptoms, and despite that, are not living up to their full potential, limiting themselves in everything they do. As we showed at the conference earlier today, this may very well change. Next slide. What causes NT1, and how do we address the broad spectrum of symptoms to help patients live normal and fulfilling lives?
Starting with the top panel, healthy individuals have about 50,000 - 80,000 neurons located in a part of the brain called the hypothalamus that produce the neuropeptide orexin. The function of orexin is to couple the demands of the external world with the internal state as the master regulator of the sleep-wake cycle, respiration, and metabolism. The middle panel illustrates the cause of NT1. Based on the discoveries of Professors Yanagisawa and Mignot, who were recently awarded the Breakthrough Prize in Life Sciences, we know that the cause of NT1 is due to the loss of orexin neurons. We also know that while neurons are lost, the orexin receptor remains intact, affording a unique opportunity for a pharmacological intervention.
The bottom panel illustrates that stimulating the receptor with a selective orexin agonist allows for the ability to modulate downstream neurotransmitter activity and restore signaling, with the potential to improve symptoms across all domains, allowing restoration of patient function and improved quality of life, as we have shown for the first time with Oveporexton. Next slide, please. We believe twice daily or BID dosing with Oveporexton is advantageous in NT1, and here's why. The left panel shows orexin tone in a non-human primate, and what you see is that it gradually increases during the day, probably to fight the mounting sleep pressure, and then abruptly falls at night. What you also see is that there is a small amount of tonic activity present even in the night.
If you now look at the right-hand panel, what you see is an illustration of how Oveporexton is able to mimic the natural orexin tone, making this uniquely suited to the treatment of NT1. In addition, this approach gives patients and providers optionality and flexibility regarding dosing and dosing needs. Next slide. With a treatment like Oveporexton that targets the root cause of the disease and mimics this natural orexin tone, we have an opportunity to address the symptoms that matter most to NT1 patients. Accordingly, we designed our phase III trials, informed, of course, by our phase II experience, to investigate the full spectrum of NT1 symptoms and the impact on how patients feel and function through the day and at night with 14 alpha-controlled primary and secondary and additional exploratory endpoints.
You see here regulatory endpoints that assess excessive daytime sleepiness, for example, the maintenance of wakefulness test or MWT, or the patient-reported Epworth Sleepiness Scale or ESS, or Karolinska Sleepiness Scale, KSS. You see measures to evaluate cataplexy, like the weekly cataplexy rate or WCR. We also included a range of additional endpoints assessing cognition, quality of sleep, patient-reported outcomes, and quality of life. Next. Now, I have the immense pleasure of taking you through many highlights and many firsts. This is the first time anyone is in a position to show phase III results with an orexin therapy in NT1 patients. This is the first time that such comprehensive and highly successful phase III results have been generated for an orexin therapy that will provide the basis of our filing.
This is the first time that I have ever seen this level of magnitude and consistency across doses, endpoints, and trials as in these Oveporexton phase III studies. I've been in drug development for many years. It's one of these rare occasions where you don't need to see the p-value to tell you that this drug actually works. Next slide, please. We conducted two global placebo-controlled studies that randomized 273 patients between them. After 12 weeks, eligible patients could roll over into an open-label extension study, and more than 95% did so. In the first study, we evaluated two active doses versus placebo, with a randomization scheme of three to three to two. In the second study, we had a single dose versus placebo, and patients were randomized two to one.
The baseline characteristics were actually well balanced across arms and similar in the two studies, and reflective of a pretty severe NT1 population with mean sleep latencies on the MWT of around four to five minutes and a median 21 to 29 cataplexy events per week, or around three to four events every day. Today, I will focus on the top-line results with the endpoints listed on the right, which will give you a good first impression. We're working hard to analyze all our additional data, so there will be many, many more exciting results to share in due course. Next slide, please. What I will show you now, going in order anti-clockwise around this wheel, is the profound impact across measures that define NT1, including excessive daytime sleepiness, cataplexy, symptom severity, nighttime symptoms, cognition, quality of life measures, and safety and tolerability.
What you will see is that patients derive significant and meaningful benefits, catalyzing a potential new era of treatment for NT1 patients. As we go through the results, a few themes emerge. One, you will see every endpoint at every dose showing statistically significant and clinically meaningful improvements, and for the majority of patients, achieving normative ranges across symptoms. Two, you will also appreciate consistency with our phase two results, which were shared before. Three, based on the ongoing phase two long-term extension study, most recent data cut we observed maintenance of efficacy over one year. Next slide, please. Here is the primary endpoint, the MWT, which is an important regulatory endpoint, though rarely used in the clinical setting. As I tell you about the test, you will understand why this is the case.
The test is a mean of four assessments and evaluates wakefulness by asking patients to stay awake for up to 40 minutes in a dark and quiet room doing absolutely nothing. Not really reflecting everyday life, but a rather artificial setting. To orient you, on all the data slides, you will see gray bars representing placebo, bright red, the 1 mg, and dark red, the 2 mg dose, with time points indicating baseline and week 12. NT1 patients without treatment managed to stay awake for about three to five minutes on this test, and the patients on placebo performed exactly as expected. On current standard of care, patients achieved three and rarely up to 10 minutes on this test, as indicated in the gray horizontal box at the bottom of the slide.
At the top of the slide, you see that healthy individuals are able to stay awake for 20 minutes or longer with a significant amount of inter-individual variability. At 12 weeks, patients on Oveporexton achieved statistically significant and clinically meaningful results on the MWT, as you can see, putting the majority of patients into the normative range of healthy individuals at 20 minutes or above. Next slide, please. Now let's turn to the Epworth Sleepiness Scale, or ESS, an important patient-reported endpoint that evaluates excessive daytime sleepiness and is actually often used in the clinic, where we see normalization in the majority of patients, consistent with the MWT. What the ESS is, is a short self-assessment to identify how likely one is to fall asleep during the daytime in eight different hypothetical situations, like watching TV, being a passenger in a car, and so forth.
It reflects retrospectively on the previous week. Each question can receive between zero to three points, with higher scores reflecting more sleepiness, with a total range of zero to 24 points. On this score, lower scores are better, and scores from zero to 10 reflect normal levels of daytime sleepiness, as indicated in the gray box. Scores over 10 are considered to reflect excessive daytime sleepiness. The current standard of care is only partially able to improve patient ESS scores to around the mid-teens. At week 12, we again see statistically significant and clinically meaningful improvements on the ESS scores. In fact, approximately 85% of patients were within the normative range of less or equal to 10 with a 2 mg dose. Now let me add an additional dimension to assessing the quality of wakefulness.
In addition to the ESS, which reflects on excessive daytime sleepiness over the previous week, we also measured the Karolinska Sleepiness Scale, or KSS, which looks at sleepiness in the moment at a point in time and assess that to evaluate the quality of wakefulness at different times in the day. Results across both studies show substantial improvements for treated patients at both one and seven hours post the first dose versus placebo. The results also show consistent levels of feeling alert between the morning and the afternoon assessments. What this means is that patients were rating themselves with pretty much equivalent scores indicating feeling alert or rather alert throughout the day. In summary, across objective and subjective measures of excessive daytime sleepiness, the majority of patients normalize and feel alert through the course of the day. Next slide, please.
I'll show you two slides on cataplexy, which is a defining clinical characteristic of NT1. As you know, cataplexy describes the sudden loss of muscle tone, and here we see statistically significant and clinically meaningful reductions in the WCR versus placebo with both doses and trials. In order to calculate the weekly cataplexy rate, patients actually record cataplexy episodes using a daily diary. Our phase III statistical methodology is the same as in phase II, a negative binomial approach. Another very interesting way to look at these data is to look at freedom from cataplexy. This increases from no cataplexy-free days at baseline to up to five days without a single cataplexy event for treated patients at week 12. Next slide, please. This is a different view into cataplexy, essentially showing you a time course over the study duration. Now look at the red lines.
Cataplexy rates close to zero are seen early and maintained during the 12 weeks of the study for treated patients. We know from the ongoing phase two long-term extension that they are maintained for an additional 12 months. In summary, we see statistically significant changes compared to placebo for all doses, median reductions of 80 to 90% from baseline, the majority of the days in the week without any cataplexy events for most patients, and early onset with reductions in cataplexy maintained over time. What this could mean for patients is that they are now more fully able to engage with life and the outside world again, to experience emotions, to laugh, to cry without collapsing. With this magnitude of impact on cataplexy, we are very excited about these results. Next slide, please.
In our trials, we assessed symptoms and their impact on function in a number of different ways, including severity scales, impact on function, and quality of life measures. There are way too many to discuss all here. This is just a teaser of the generally consistent and positive result that we have seen across all of these subjective measures. Here, I want to show you the impact on the Narcolepsy Severity Scales for Clinical Trials, or the NSSCT. This is one of the very few scales that assesses the full spectrum of narcolepsy symptoms with domains for sleepiness, cataplexy, sleep paralysis, hallucinations, and disrupted nocturnal sleep, looking back at the previous month. It is a validated, self-administered 15-item scale evaluating severity, frequency, and importantly, impact of symptoms.
Higher scores indicate worse and more frequent symptoms, with the scale ranging from zero, or absolutely no symptoms, to 57 at the very top end of severity. Scores are categorized into four severity levels from mild to very severe. Scores of around 30 are typical for untreated NT1 patients, whereas NT1 patients treated with current standard of care have scores of around 24 points. Oveporexton resulted in statistically significant and clinically meaningful reductions in the NSSCT compared with placebo, with 70%- 80% of patients reaching the lowest severity score. This again is a first. The results also correlated to additional physician and patient-reported global assessments, PGI and CGI. Next slide. Now let's turn to symptoms experienced at night. As discussed, nighttime symptoms lead to non-restorative sleep despite the overwhelming tiredness experienced during the day.
We assess nighttime symptoms through various different measures, including a sleep diary, polysomnography, and severity scales included in the NSSCT. As mentioned, the NSSCT also covers domains of nighttime symptoms. Looking at these symptoms specifically, you can see that Oveporexton has a significant impact on these domains, pretty much eliminating disturbing hallucinations and sleep paralysis, as shown in the red bars, and with 2/3 of patients improving their disturbed nighttime sleep. Additionally, exploratory polysomnography evaluations corroborate these improvements. Even on nighttime symptoms, the majority of patients derive significant benefit. Next slide, please. Let me again show you the impressive ability of an orexin therapy to improve cognition. Here is the Psychomotor Vigilance Test, or PVT, which measures sustained attention. The PVT is a widely used reaction performance task of 10 minutes duration. The subject is asked to press a button when a signal appears on the screen.
The signal appears randomly every few seconds, and the main measure of the test is to count the number of mistakes or lapses in attention. The test is validated in the real world and routinely used in situations where sustained attention is critical to performance, for example, for astronauts in space or jet pilots, and where consequences of lapses in attention can be catastrophic. Like in phase two, we again show normalization measured as less or equal to six lapses of sustained attention in most patients at two time points, at one hour and seven hours post the first dose, throughout the day. We show you here one study. We saw very similar results in the second study.
These results, importantly, are consistent with how patients feel throughout the day with their level of alertness that we discussed with the Karolinska Sleepiness Scale, which was also measured at one and seven hours post the first dose. Now, let's turn to a high-level summary of health-related quality of life. This is the first time anyone has been able to show this level of impact on general health scales that were not specifically designed for narcolepsy type 1, but serve to compare treatments across diseases.
Every single assessment, whether it be the SF-36 and its domains, or the EQ-5D, or patient or physician-reported quality of life measures such as mood and fatigue and others, showed not only clinically meaningful and statistically significant improvements, but even on these non-narcolepsy type 1 specific general scales, many patients reached normative ranges, indicating again that Oveporexton may provide patients the potential to engage in life more fully again. Next slide, please. Moving next to safety and tolerability. The results are consistent with the safety profile of the program to date. There were no surprises. At this point in time, we actually have many patients treated for more than two years who are continuing to benefit on therapy. The table on the right provides a more detailed view for each study and treatment arm, highlighting the adverse event severity as well as the most common adverse events.
There were no serious treatment-related adverse events. Overall, more adverse events were reported by patients treated with Oveporexton; however, they were mostly expected on-target adverse events, such as reports of insomnia and urinary events. Most AEs were mild or moderate in severity and did not require any medical intervention. Furthermore, most adverse events occurred at the beginning of treatment and were transient and self-limiting, resolving without intervention within the first few days of treatment. For example, insomnia events tend to start within the first two days of treatment and resolve within the first week or so for almost 80% of those patients who experienced insomnia in the first month. Given the interest in visual disturbances, we looked across the whole Oveporexton program and are not concerned. We did see visual disturbances, but with similar incidence, actually as single events in placebo and active doses.
They were without any significant clinical impact, and we do not deem them clinically relevant or important. Lastly, there were no cases of hepatotoxicity across the whole Oveporexton program. Overall, this drug is looking generally well tolerated with a consistent safety profile. Next slide, please. In summary, this is the most comprehensive data set of an orexin agonist to date across two independent global placebo-controlled phase III trials that recapitulate the phase II experience. We have seen transformative improvements across the broad spectrum of symptoms affecting patients with NT1 with a consistent safety profile. Specifically, we have seen statistically significant and clinically meaningful effects on all endpoints we assessed across both 1 mg and 2 mg twice daily doses and across both trials, whether it is in assessments of excessive daytime sleepiness or cataplexy, cognition or quality of life scales, with many patients reaching normative ranges.
For example, the majority reached normal ranges for excessive daytime sleepiness symptoms, and the cataplexy rate is approaching zero for most patients. All of this was achieved with twice daily doses, mimicking the natural orexin tone, which would also allow patients and physician dosing flexibility to optimize patient outcomes. Oveporexton was generally well tolerated with expected on-target pharmacological effects, which are self-limiting. More than 95% of patients enrolled into the long-term extension study. Oveporexton, an orexin 2 receptor agonist designed to treat the root cause of the disease, has declared a transformative benefit-risk profile in these placebo-controlled phase three trials. Oveporexton is on track to become a first-in-class therapy for NT1, and we're working with regulatory authority to bring Oveporexton to patients as quickly as possible, starting our first submissions this fiscal year. Next slide. As Andy said, this is just the beginning.
We have a whole stable of molecules and indications behind this as we explore what's possible with orexin therapeutics. Heather will touch upon this in her remarks as well. Heather, over to you.
Thank you so much, Sarah. I'd like to start by echoing Sarah's enthusiasm about our Oveporexton program. The entire team at Takeda is tremendously proud of what we have accomplished so far, and we are incredibly excited about what lies ahead. It is a commercial team's dream to contemplate how best to launch a product like Oveporexton, an orexin therapy that has the potential to offer an optimized profile which balances efficacy and safety for patients with NT1. Now, as you heard, patients with NT1 often experience relentless symptoms 24 hours a day, leaving no time or energy for what matters most, coping through most aspects of life. Excessive daytime sleepiness and cataplexy are really just the tip of the iceberg. The impact of NT1 often extends to many aspects of patient life, making meaningful activities like work, family care, or exercise often difficult and at times impossible.
These challenges, in combination with a lack of recognition and appreciation from the people around them, can lead to devastating impacts on patient well-being. Next slide, please. In addition to deeply listening to the narcolepsy community to understand the true burden of disease on patients, Takeda has also spent several years investing in foundational understanding of the NT1 patient journey to better appreciate the patient experience today. The long, exhausting NT1 patient journey is fraught with roadblocks, with accurate diagnosis taking an average of 10 to 15 years, often followed by a lifetime of treatment trade-offs. Now, with symptom onset, patients often feel isolated, confused, and ashamed because they struggle to explain constant tiredness. Many of the symptoms patients present with overlap with other diseases, making differential diagnosis challenging.
After eventual referral to a sleep specialist for testing, patients experience long wait times, and without adequate HCP suspicion, they may be tested with methods that are unable to accurately diagnose NT1. Accurate NT1 diagnosis requires overnight polysomnography testing, but navigating sleep center wait times, testing, and insurance systems has become progressively more difficult. In fact, up to 40% of patients who receive testing in the U.S. still do not receive the correct diagnosis. All told, this contributes to further frustration for patients and leads to an NT1 diagnosis rate of around 50% in the U.S., meaning that about half of the NT1 patients still do not have a diagnosis that can explain their symptoms. Once patients are finally accurately diagnosed and after an initial sense of relief, many report feeling disillusioned by treatment options.
Current treatments manage symptoms and do not address the underlying orexin deficiency in NT1, resulting in potentially burdensome treatment plans involving a combination of multiple standards of care. We've heard from patient communities that many patients have given up expecting more from their treatment and have adapted their lives to coping with narcolepsy. Next slide, please. There are treatments available today for patients with NT1, but I do want to zoom in on the current treatment standard of care in the U.S. to understand the challenges that patients face today. To be clear, the current standard of care does not address the underlying cause of NT1, which is orexin deficiency, instead focusing on symptoms. We know that about 75% of U.S. patients receive at least one treatment, which addresses only some of the symptoms of NT1.
The U.S. market today is broad and dominated largely by generics, with about a 60/40 split between generics and advanced treatments. However, with treatments that do not address the underlying cause of the disease, patients often need to make trade-offs with their daily living choices. 50% of U.S. patients receive polypharmacy or have to adjust their regimens due to comorbid conditions and side effects, leading to high rates of treatment switching and discontinuation, especially early on. Even after employing coping mechanisms, over 80% of patients still report experiencing residual symptoms, pointing to vast unmet need. Next slide. As we unpack these unmet needs, we see that despite treatment, many patients continue to experience symptoms and need to cope with the continued impact of NT1 on many aspects of their lives.
On a daily basis, patients often face difficult trade-off decisions regarding which element of their life to sacrifice, which add up to major life consequences. The vast majority of patients with NT1 say that their daily living activities are affected, which can include the ability to complete household tasks, drive, or even care for their children. In fact, patients with NT1 are about half as likely as controls to have children. Depending on the severity and scope of a patient's NT1 symptoms, this can also limit their academic and professional aspirations, as 82% of patients feel restricted in the jobs that they can pursue. For patients, particularly young adults in crucial periods of social development, social well-being is affected regardless of treatment. Patients often feel isolated and rejected in social situations and struggle to remain close in their relationships.
The combined burden on top of these social limitations leads patients with NT1 to be 3.5x more likely to be clinically depressed as opposed to healthy controls. These core human experiences, relationships, vocation, well-being, can be profoundly impacted in patients with NT1. Next slide. As we've just discussed, current treatments for NT1 may address components of what a person with narcolepsy encounters, but they are not designed to address the totality of the disease burden on patients. Takeda is pioneering a potential paradigm shift with a development program designed to demonstrate the transformative efficacy of an orexin therapy through a deep commitment to our longstanding in-house orexin science expertise and intentional investment in understanding the patient journey. We heard the patient voice from patient listening sessions and translated that into the robust clinical development plan you heard Sarah talk about.
This holistic evidence package you see here positions Oveporexton as the transformative therapy that targets the underlying cause of the disease, with the potential to redefine treatment outcomes that matter most to patients. Next slide. Now, to help you understand just how impactful these outcomes are for patients, I want to return to our North Star, the patient voice, and highlight what these endpoints actually mean for patients. Exit interviews from our phase II studies have exemplified how transformative these holistic outcomes can be for patients. Anecdotes from these conversations may help contextualize the potential impact for this treatment. For some patients, the outcomes driven by Oveporexton in the studies have informed their experience of feeling and renewed aspects of life that were taken away by the condition.
As one patient notes, being able to laugh and be sad freely, I feel like I've become a normal person and gained confidence. The functional improvements experienced by patients during the Oveporexton trials gave one of them the ability to re-engage with the things that they had to make trade-offs with previously, with the patient expressing that, quote, "You recover the life you want. You also make up for lost time." "You start doing the things you couldn't do for years." Those are pretty powerful quotes, I think. Next slide, please. With Oveporexton, if approved, Takeda has an opportunity to introduce a transformative orexin therapy with the potential to redefine treatment outcomes, truly changing the way that patients with NT1 live, building a new category of treatment, and aspiring to deliver a new era of care.
As an orexin 2 receptor agonist that helps restore the orexin signaling lost in NT1, if approved, Oveporexton will be the first and only treatment to address the underlying cause of the disease. This mechanism gives Oveporexton the potential to offer holistic disease control beyond core symptoms, giving patients the ability to experience a new level of efficacy that may translate to functional improvements and day-to-day quality of life impact that is maintained over time. Next slide. We at Takeda have the experience, capabilities, and commitment necessary to bring Oveporexton to the patients who need it worldwide. Our global rare disease and neuroscience experience and history of success serves as a strong foundation to build upon. Our global commercial capabilities equip us with flexibility and breadth to grow our impact.
While the prevalence of NT1 categorizes it as a rare disease, we recognize the impact that Oveporexton can have on patients with NT1 and are investing our full resources to deliberately execute on every component of the Oveporexton launch once approved. To aspire towards a new era of care in NT1, we will work to accomplish three key things. First, expand our disease state and orexin education to equip physicians, patients, and payers with the knowledge to understand orexin deficiency as the underlying cause of NT1 and the true burden on patients, empowering them to search for new options. We've conducted the largest real-world studies and generated the most comprehensive evidence to date, capturing the burden and unmet needs of NT1, and continue to push the frontier of orexin science.
Second, if approved, we will work to ensure Oveporexton is recognized for the profound outcomes that it may drive for patients globally, as demonstrated by the phase III results, prioritizing access and developing innovative ways to communicate the benefits and safety profile realized by addressing the underlying cause of NT1. We believe patients and physicians will be motivated to make a change. We've taken a deliberate approach to delivering our access strategy and have proactively engaged with payers to ensure we are best positioned for success. We have developed novel patient-relevant endpoints and captured the health economic impacts of NT1 to support value-based pricing, and will continue to generate evidence supportive of Oveporexton's potential value to patients through continued outcome monitoring as we work to bring it to patients who need it.
Third, we are expanding our efforts beyond treatment to streamline the NT1 patient journey through targeted industry-leading solutions to support early and accurate diagnosis of NT1, both internally driven and developed in partnership with academic and commercial innovators in the field of sleep medicine, including one recent collaboration that you may have heard of with EnsoData and others in the final contracting stage. We are advancing novel biomarkers, developing innovative wearable and home test solutions, and leveraging AI algorithms to potentially increase accuracy of diagnosis. As we've highlighted, we are deeply committed to leveraging our orexin biology and neuroscience expertise, along with our global commercial footprint, to bring a transformative therapy with the potential to redefine outcomes for patients with NT1.
We already have MSLs engaging in the field with KOLs, and just last week, I am thrilled to announce that we launched our HCP and patient disease education campaign in the U.S., which highlights, quote, "what it takes for patients with NT1 to simply make it through critical parts of their day." We will continue these disease education efforts in the U.S. next year. Post-approval, subject to regulatory review and approval, the sales team will share the final approved label and Oveporexton patient support resources with HCPs. U.S. patients will be able to find the full complement of Oveporexton information and support resources in numerous destinations online, where the NT1 patient community is actively engaged today. Next slide. Our aspiration to unlock a new era of care in NT1 translates to a significant commercial opportunity for Takeda through Oveporexton.
There are approximately 95,000- 120,000 patients in the U.S. with NT1, and the prevalence is similar globally. We believe that we can improve diagnosis by 10%- 20%, both by accelerating patient pathways to diagnosis and improving the accurate differential diagnosis of narcolepsy type 1. That means advancing from a diagnosis rate of 50% today to 60%- 70% in the future. We expect treatment adherence to improve with an orexin therapy that addresses the underlying cause of NT1. If approved as the single treatment addressing the root cause of narcolepsy for patients, we expect significant profit share in the range of 30%- 50% as patients with NT1 and their providers begin to broadly appreciate the potential impact of this orexin therapy on a broad range of symptoms observed in our trials, coupled with a consistent, safe, and tolerable product, as Sarah discussed.
Given the data you just saw, we are confident Oveporexton has the potential to be the first-in-class orexin agonist which addresses symptoms that matter most to patients. Taken together, we estimate Oveporexton's peak revenue potential at $2 billion- $3+ billion globally. Next slide. Oveporexton is the foundation of our leadership in orexin science, which represents a significant opportunity for Takeda. Within our tailored portfolio, we are already working to advance our next orexin agonist program that is designed for increased flexibility and use in orexin non-deficient populations. This will allow us to unlock potentially transformative treatment outcomes for patients with NT2 and IH who suffer from much of the same burden and unmet needs as those with NT1. Beyond these indications, we seek to unlock the full potential of orexin science through additional opportunities in sleep, wake, respiratory, metabolic, mood, and beyond.
We are continuing to lead in the exploration and translation of orexin science and transform patient outcomes across the care ecosystem. Next slide. To summarize, at Takeda, we are pioneering orexin science and catalyzing a potential new era of care for patients with NT1, with Oveporexton as our foundation. There are three things I'd like you to take from this presentation today. One, orexin deficiency is the root cause of NT1. Two, we are advancing to market the first and only treatment that addresses the underlying cause of NT1. We are deliberately and proactively working to ensure that globally, patients have access to this potentially transformative therapy once it is approved. Three, now with our well-established phase III results, we are confident in the potential for Oveporexton to achieve outcomes that matter most to patients.
At Takeda, we will further our commitment to the sleep-wake disorder space by going beyond therapeutics and continuing to invest in building innovative patient-centered solutions to optimize the arduous and draining patient journeys. Takeda aims to file Oveporexton in the U.S. in fiscal 2025, and through its potentially transformative nature in the market, it is projected to yield a global peak revenue potential of $2 billion- $3+ billion . All in all, if approved, Takeda's oral orexin 2 receptor agonist, Oveporexton, will be the first to address the orexin deficiency in NT1 and would mark the first launched orexin agonist as we continue expanding our franchise by leading and innovating in orexin biology with TAK-360 and beyond. In closing, with Oveporexton, we aspire towards a new era of care for NT1, delivering a transformative therapy from an innovative franchise that has the potential to redefine treatment outcomes for patients.
I'd like to turn things over to Julie to summarize and wrap things up.
Thank you. Thank you, Heather, Sarah, and Andy, for a fantastic presentation. Before we move to Q&A, I'd like to conclude by reiterating our excitement for Oveporexton and the opportunity to offer a new era of care for patients with NT1. Let me reiterate four key points across the entire presentation, four points that I want you to walk away with. One, Oveporexton is the first treatment that targets orexin deficiency, the root cause of NT1, and has demonstrated normalization across a broad spectrum of symptoms that patients with NT1 face, including excessive daytime sleepiness, cataplexy, nighttime symptoms, as well as cognition, functioning, and quality of life. As Sarah described, Oveporexton demonstrated the potential for transformational efficacy with our primary and all secondary endpoints, meeting statistical significance, delivering results that are clinically meaningful to patients in terms of how they function and feel.
In addition, the phase III studies showed a safe and tolerable profile consistent with our phase II studies, and these results are further substantiated by the greater than 95% of patients who chose to continue on to the long-term extension study. Two, Takeda is leveraging our neuroscience and rare disease commercial expertise to prepare for the launch of the first orexin therapy. Current treatments only address symptoms of NT1 and do not treat the root cause, which is orexin deficiency, and therefore, there is still a high amount of unmet need in the market today, as you heard from Heather. Despite available treatment, greater than 80% of patients today report residual symptoms.
Three, we remain extremely confident in our global peak sales range of $2 billion- $3+ billion because Oveporexton's anticipated launch as the first orexin therapy designed to address the root cause of narcolepsy has the potential to create a new era of care for patients with NT1 through market education, enabling access, and accelerating diagnosis. Four, this is just the beginning for our orexin franchise. We'll expand into additional indications with programs like TAK-360 and bring other new orexins to the clinic to treat more common diseases. With that said, we are happy to take any questions you may have. Chris, I'll hand it back to you to start the Q&A.
Thank you, Julie. We'd now like to open the lines for Q&A until about 8:45 P.M. Singapore time. Andy, Julie, Sarah, and Heather are all available to take your questions. To ask a question, please raise your hand in the Zoom window, and I'd like to request that each person limits to two questions each. For the first question, I'd like to call on Tony Ren from Macquarie. Tony, please unmute and ask your question.
Excuse me?
Yes, Tony.
Okay, perfect. Thank you for the opportunity. Just two quick questions from me. The first one is about the side effects. It appears that your insomnia rate appears to be a little bit higher compared to Alixorexton, which was presented at the same session this afternoon. I just wanted to see if there's any hypothesis why this might be the case. Another question that I have for you is about your disturbed nighttime sleep, DNS. You guys showed 67% of the patients showed meaningful improvement on disturbed nocturnal sleep. At the conference here, speaking to the physicians, the consensus I got is that most people think this is one area, this is one of the very few areas where oxybate still do better than the orexin 2 agonist. The scale you use, the narcolepsy severity scale for clinical trials, it's a self-administered scale.
Could this be, could your improvement be a false positive finding? Thank you.
Tony, thank you so much for those two questions. Both of them I will direct to Sarah Sheikh to address, but let me just reiterate that from an overall safety profile perspective, we're very confident in what we see with Oveporexton. Sarah, the first one is about the insomnia rates appearing slightly higher, and the second one is about the disturbed nighttime sleepiness and should the oxybates need to continue to be used.
Thank you, Julie, and thanks, Tony, for the questions. The adverse events that we saw were, as expected, on-target adverse events, and that included insomnia. In fact, nobody discontinued because of insomnia. As I shared, insomnia events started early within the first one or two days, and then the majority of them disappeared essentially within the first one to two weeks. They were also mild to moderate in severity, and I don't really think we're concerned about the insomnia. You might have heard in the conference too that patients, if you will, voted with their feet in that they got more than 95% rolled over into the long-term extension.
I think it's very hard to try and compare across two very different trials with very different populations, and it's important to bring home the fact that this here is the largest, most comprehensive program of any orexin agonist, and it's shown that insomnia events are really just that, a tolerability event that is easily managed by patients and is not a concern. Now, to your second question, what about disturbed nighttime sleep? That's really a very interesting question because what is reasonable sleep at night? For that, a patient's subjective impression is absolutely critical. We have a number of results that show that sleep at night is positively impacted. You mentioned the NSSET, which has three different aspects that look at sleep symptoms, so hallucinations and paralysis, as well as specific questions about nocturnal disturbed nighttime sleep.
We also corroborated these improvements with more objective endpoints, if you will, or exploratory endpoints in the polysomnography where we see that the REM phases are shifted to normal ranges in the night. We see also on sleep diaries that patients report better nighttime sleep than before. As such, we do believe that there is quite significant improvement on nighttime symptoms, including disturbed nighttime sleep. Your question about might some patients still require additional help with nighttime sleep, I think that remains to be seen. Oveporexton addresses the underlying cause of the disease, and you would expect, as we've shown across a whole range of symptoms broadly that include excessive daytime sleepiness and cataplexy, but also nocturnal symptoms where we've shown impressive results as well as patients coming back into the normative range. Importantly, something I didn't mention yet is that a number.
Patients actually had to wash out of their standard of care to enter into our phase III studies, and a number of patients washed out of oxybates and remained within the trials for the entire duration and into the long-term extension. At this point, we have some patients in the long-term extension for more than two and a half years. I think it's probably a mix of we'll see what happens over time. What people experience as reasonable sleep once they are exposed to an orexin agonist again will probably change their expectations overnight. There's a good chance that many, many patients are going to derive significant benefit, even on the nighttime symptoms, with an orexin agonist.
Okay. Thank you, Sarah, for the answers. Do you think there might be an option to combine oxybates with Oveporexton, perhaps in a fixed dose combination?
I wouldn't want to speculate on that at this point. We've shown for the first time again such an impressive magnitude of effect with a monotherapy normalizing the vast majority of symptoms that patients with narcolepsy type 1 experience. I think that's what we should focus on for right now. This really sets a very high bar for a new standard of care. We actually had some testimonials at the conference today where some of the investigators told us that their patients remarked that after Oveporexton treatment, they felt as if they no longer had narcolepsy type 1. I think that speaks for itself.
Great. Yeah, thank you very much. Indeed, very impressive data presented today at the conference. Congratulations.
Thank you.
Okay. Thank you, Tony. Moving on to the next question, I'd like to call on Shinichiro Muraoka from Morgan Stanley. Muraoka-san, please unmute and ask your question.
[Foreign language] Thank you. [Foreign language] I would like to ask my question in Japanese. My name is Muraoka from Morgan Stanley. My question is about safety, about blurred vision. Placebo versus active drug, I understand blurred vision actually occurred in both arms. Is that the correct understanding? Can I double-check that with you, please? Also, [O'Camus] study also showed some blurred vision as well. How does it compare? Is this potentially going to be a problem going forward? That's my first question. My second question is about your future development strategy. 360 development in NT1.
[Foreign language] Based on the result of Takeda study, competitive study, 360 NT1 development potential, how do you see the potential of doing that? That's the question. Thank you.
Thank you for those questions, Muraoka-san. In terms of the blurred vision, let me just start by saying we are not concerned by what we saw in our phase III studies. Sarah can confirm some of the specifics, but it is not the same thing as the visual disturbances reported by [Alchemy]. Sarah can answer that first one. In terms of your second question for the development of our TAK-360 program in NT1, today, as you heard from the team, we're looking at both NT2 and IH for TAK-360 at this moment. With the incredible results that we saw for TAK-861 Oveporexton in NT1, that's where we're focused at the moment for NT1. Sarah, do you want to address the blurred vision question, please?
Yes, thank you, Muraoka-san, for the question. You know, for us, with Oveporexton, visual disturbances are not a concern. I can't really comment on the other company's program in that regard. For us, this is absolutely not an issue. Because there's been so much interest in visual disturbances, we actually went to our entire Oveporexton program to search for them specifically. I can tell you that not only were they equally balanced between placebo and active groups, but they were very low, around the 1% mark. Don't forget that we now have patients exposed for more than two and a half years and have really not had visual disturbances come up as anything that we need to be concerned about.
Andy, is there anything that you want to add about the broader portfolio of orexin assets that we have in our pipeline?
Yeah, no, thanks, Julie, and thanks, Muraoka-san. Just to emphasize what Julie said, we have just extraordinary data with Oveporexton in NT1. We don't feel that there's a need to push this further with the molecular 360; we certainly could. 360 has all of the potential to work across multiple indications. We think with the data that we have, with the flexibility that we have with BID dosing, we have a shot really not just being first in class, but a true best in class with Oveporexton. For 360, we are moving really quickly in phase II in IH and NT2, and we expect results early next calendar year. As we mentioned earlier, we're not stopping there. We have another molecule that will be entering the clinic later this year.
This will give us optionality to pivot and to move quickly in rare sleep disorders and then across the range of potential indications that could expand quite broadly.
[Foreign language]Thank you very much.
Thank you very much. Okay, moving on to the next question from TD Cowen, Mike Nedelcovych. Please unmute and ask your question.
Great. Thank you for the questions. I have two. My first is on the dose regimen. You've suggested that twice-daily dosing could translate into an improved clinical profile by mimicking endogenous orexin tone, which makes total sense theoretically. As has already been alluded to, we have some phase II data from a once-daily competitor program this morning that suggests, if anything, that perhaps that may not be the case. Can you elaborate on how twice-daily dosing might ultimately translate to a better profile and how we would know? That's the first question. My second question is a commercial one. Feel free to disagree with this statement, but it's probably reasonable to assume that the orexin 2 receptor agonists might all end up looking more similar than different. However, Takeda, of course, has the potential advantage of being first to market.
My question is, how important could that first-mover status be in the NT1 space? Thank you.
Thank you so much for those questions, Mike. In terms of the dose regimen that you saw from our two phase III studies, I'll ask Sarah to address the benefit of the BID dosing. When it comes to the commercial differentiation, of course, we do believe that our orexin agonist, Oveporexton, has demonstrated an outstanding profile. We'll have to wait and see what the competitors can demonstrate in their phase IIIs. We do have other things that we are doing in terms of the diagnosis, et cetera, that Heather had mentioned. I'll ask Heather to add some more detail in terms of why we believe we'll be differentiated and our first-mover advantage will be a benefit.
Yeah, thanks, Mike, for the question. You're right. BID dosing does mimic the natural orexin tone. In fact, in our hands, we know this is the better profile. Why do I say that? I say that because we actually tested ourselves once-daily profiles in our phase II study and elected to take a twice-daily profile into phase III. As I hope I've convinced you with showing you these impressive phase III results across the whole spectrum of efficacy endpoints, those results corroborate that impression that BID dosing with the doses that we selected are the right ones for this molecule in this population.
I think there's a really important additional advantage that BID dosing has, and that is flexibility in dosing that then allows individualized treatment decisions both for the patients but also the physicians to allow the patient to meet any demands in the day, especially later in the day, that they might have to fulfill. I actually think this is a huge advantage to have twice-daily dosing in this particular patient population for this particular disease.
Mike, I can answer your second question, which I'll dovetail off of what Sarah was just saying. I think starting first with the clinical profile, being able to have that dosing flexibility that physicians and their patients can adjust as necessary to really customize their care and mimic that underlying orexin tone, we actually think is a really important differentiator and something that very much reflects our focus on patients and customizing their care. I think beyond the clinical profile, as Julie was starting to mention, the investment that Takeda is making in this space to really change this landscape and introduce a new era of care is a tremendous opportunity for us.
Not only are we introducing this first orexin therapy that targets the underlying cause of the disease, being orexin deficiency, but we've invested so much in understanding the patient journey and investing also in recognizing how important shortening the diagnostic odyssey is and also improving diagnosis. As we look at the market today, we talked about the fact that over 80% of patients are still having breakthrough symptoms. Upon our approval and launch, we will be able to communicate to patients the benefit of being able to look at a monotherapy agent that offers dosing flexibility that for the first time ever targets the underlying cause of the disease with a full complement of support program and resources and also access support for the patients as well.
We believe it is incredibly important to have that first-mover advantage and really set a new standard of care in the treatment of narcolepsy type 1.
Great. Thank you so much.
Thank you, Mike. We're approaching the end of our allotted time. I'd like the next question to be our final question today. Hidemaru Yamaguchi from Citi, please unmute and ask your question.
Hi, can you hear me?
Yes, we can hear you.
Great, thank you. This is Yamaguchi from Citi. Thank you very much. The first question regarding the time course of NWT, because your phase II data was eight weeks and the phase III is 12 weeks and the comparison phase II are eight weeks, it's hard to compare. Can you tell me the time course is getting deteriorating in general from eight weeks to 12 weeks and you used to have 34 weeks? That's a general trend or not? Otherwise, it's hard to compare and it's easy for the competitor to say they are better in eight weeks. That's the first question. The second question is that dosing, 1 mg, 1 mg, 2 mg, 2 mg, seem to be 2 mg, 2 mg seem to be better, but not really that difference between the two.
Are you going to file 1 mg, 1 mg, and also 2 mg, 2 mg and try to use the flexibility once it's launched? Or it might be a little bit complex for the patients. How are we going to file those 1 mg, 1 mg, and 2 mg, 2 mg? That's the second question. Thank you.
Thank you for those questions, Yamaguchi-san. Of course, it's always a little bit dangerous to compare directly across clinical studies. I will ask Sarah to address your questions about the NWT and the time course, both from our phase II and phase III. From the dosing perspective and filing, again, Sarah to address our regulatory approach here for the two different doses.
Thank you very much, Yamaguchi-san, for the question. This question of loss of efficacy with time or tachyphylaxis is really important to ask for any agonist. As we showed in our phase II study, we did not see any drop in efficacy in the long-term extension. We had a data cut that we shared previously where we had an additional six months of dosing, including the MWT, where we showed maintenance of efficacy from the eight-week study up to 36 weeks, right? That is the data that I can speak to. I would not really want to compare across studies and, you know, phase II to phase III and other companies. From the data that we have in our hands, we do not see a loss of efficacy. That is not just corroborated with the MWT, but actually across all the other endpoints.
We have the ESS, you know, and the Epworth Sleepiness Scale, cataplexy, and so on and so forth. From what we know right now, there is no tachyphylaxis. Your other question was about what we are going to file. We have the privilege or the wonderful thing that every single dose across every single endpoint has such amazing results. It is an embarrassment of riches, but what that means is that patients and physicians will actually have flexibility. We believe that is a huge advantage. As we go to discuss our data with regulators, we will take both of those doses forward.
Sure, thank you.
Okay, thank you, Yamaguchi-san. With that, I would like to bring today's call to a close. Thank you, everyone, for your participation today. If you have any further questions, please reach out to the Takeda Investor Relations team. Thank you and goodbye.