Good morning and welcome to the Theravance Biopharma KOL event. At this time, all attendees are in a listen-only mode. A question-and-answer session will follow the formal presentations. As a reminder, this call is being recorded and a replay will be made available on the Theravance website following the conclusion of the event. I'd now like to turn the call over to Rick Winningham, Chief Executive Officer at Theravance Biopharma. Please go ahead, Rick. Good morning, and thank you for joining us. We're excited to host this KOL event focused on ampreloxetine, a medicine with an orphan drug designation targeted to treat a rare neurologic disease, neurogenic orthostatic hypotension in patients with multiple system atrophy. ampreloxetine is finishing a pivotal phase III study called Cypress. We'll refer to it during the course of the call, with data expected in the first quarter of 2026. Today's call is to describe the significant unmet need in symptomatic neurogenic orthostatic hypotension, or NOH, and again, patients with multiple system atrophy, or MSA, and to show why we believe ampreloxetine has the potential to change the treatment landscape as it once daily oral medicine with a durable treatment effect, creating value for patients and shareholders. I can get the next slide, please. Before we begin, let me note that we'll be making forward-looking statements today involving risks and uncertainties related to our development pipeline, the expected benefits of our product candidate, and anticipated timing of clinical trials and regulatory filings and our expected financial results. You can find further information concerning the factors that could cause results to differ materially from these forward-looking statements in our filings with the SEC. Next slide, please. Now, turning to today's agenda, I'll begin with a brief overview of the company and highlight ampreloxetine and the exciting opportunity we see for this medicine to make a meaningful difference in a disease with a clear unmet medical need currently treated, treatment concentrated in centers of excellence and specialized neurology groups. After my opening remarks, we'll move to Dr. Horacio Kaufmann, a highly distinguished leader in movement disorders, who will discuss the substantial unmet need in NOH and MSA patients and review clinical evidence supporting the potential of ampreloxetine. I want to thank Dr. Kaufmann for not only joining us today, but for his many contributions in the field of dysautonomia over the years. After Dr. Kaufmann, Áine Miller, our Head of Development, will walk through the details of our nearly complete phase III Cypress study, and then we'll conclude with Rhonda Farnum, our Chief Business Officer, who will outline the commercial opportunity we see ahead for ampreloxetine. Before I hand the presentation over to Dr. Kaufmann, I'd like to take a moment to level set for those who are newer to the Theravance story. Next slide, please. Theravance today is a commercial stage biotech focused on respiratory and neurological disease. Our value drivers begin with the core fundamentals of the company, where we're operating from a position of financial strength. We ended last quarter with $333 million in cash, no debt, and achieved cash flow break-even in the third quarter. In addition, we have $175 million in high-probability near-term milestones from both Trelegy and Yupelri that we expect to be received over the next 14 months. Complementing the strong financial profile is Yupelri, our approved product for COPD, which we co-promote with Viatris in the United States. The brand continues to deliver solid growth, including 15% net sales growth in the most recent quarter, and importantly, durable cash flow generation supported by patent protection in the U.S. into 2039. The strong base, a robust balance sheet, high-probability milestones, and a cash-generating commercial asset creates a foundation for the company. And on top of this foundation, we're developing ampreloxetine, which you'll hear much more about today. We believe ampreloxetine has the potential to make a transformative impact for the 40,000 MSA patients with NOH in the United States and many more outside the U.S., a community with high unmet medical need. And it's with that context I'm pleased to introduce Dr. Horacio Kaufmann, one of the world's leading experts in movement disorders, who will walk us through the disease and the unmet need in NOH and MSA patients. Dr. Kaufmann. Hi, Rick. Thank you very much and good morning, everybody. My name is Horacio Kaufmann, and I'm a professor of neurology and medicine at New York University, and I direct the Dysautonomia Center. So for the last 40-something years, I've been seeing many of these patients with severe orthostatic hypotension, so we want to switch a little bit the focus, and I will try to tell you a little bit about the physiology of this problem. My focus is, as I told you, on the autonomic nervous system and the neurological disorders that affect it, so I want to remind you, I want to start with a comment, remind you that millions of years of evolution made humans stand in two feet in the bipedal position vertically and while that is very good to see at the distance, it created a big challenge because the brain is above the heart. So with the brain above the heart, getting the blood supply to the brain from the heart has to operate against gravity. So this is a difficult problem. And in order to get the blood to the brain, humans require a very quick and sophisticated mechanism through the sympathetic nervous system that constricts the blood vessels, increases the pressure, and is able to send the blood to the brain. When that doesn't work, we have a terrible problem. What we have is neurogenic, that means the nerves are not working. Orthostatic means vertical, hypotension, low blood pressure. Let me have the first slide. So can I have the next slide because I cannot control them here? Thank you. So neurogenic orthostatic hypotension is a sustained fall in blood pressure upon standing up. It's a chronic and disabling condition. It's not just a little bit of dizziness. It's a big problem that affects life and essentially doesn't allow people to stand up. Now, this terrible problem is present in a number of neurological conditions, conditions that either affect the central autonomic nerves or the peripheral autonomic nerves, autonomic or sympathetic nerves, and we'll get back to you with that in a minute, and it's very common, very prevalent in the synucleinopathies. This synucleinopathy is a big word to define a number of neurological diseases that share the accumulation of the protein synuclein. The most common is Parkinson's disease, and in Parkinson's, these, what you see on the right in the slide, are numbers from the U.S. Now, around 800,000 people in the U.S. with Parkinson's disease have NOH. NOH is the abbreviation of neurogenic orthostatic hypotension. Dementia with Lewy bodies and other very common, around 600,000 with NOH. And then multiple system atrophy, the one you're going to hear about today, with around 40,000 people in the U.S. and, of course, many more in the world. Can you go to the next slide, please? Next slide, please. Okay. So let me next, let me show you, I will show you that mechanism I was referring to. Upon standing up, when you go from a lying to a standing position, gravity pulls blood to, you know, everything goes down, so pulls blood to the lower part of the body. So there's a quick, can I have the next? There's a quick reflex, there's a quick mechanism that activates these neurons, the ones you see there in yellow, those are like cables, neurons. It first activates neurons in the brain, and those neurons continue the stimuli all the way to the blood vessel. Can I have the next slide, please? Okay. Here you see central and peripheral. Next slide, please. Next. So when that activity occurs, when that stimulation occurs, there's release of norepinephrine. That's the neurotransmitter of the nerves. Next. Next slide, please. And those transmitters bind directly to the blood vessel, constrict the blood vessel, and increase the blood pressure. Next slide, please. Okay. So by constricting the blood vessels, imagine this is the same as a hose. If you compress a hose, the pressure inside the hose increases, and the water can go further. By constricting the blood vessels, the pressure increases, and the blood can go all the way to the brain. Can we have the next? Next slide. So when this mechanism does not occur, this response fails and the blood pressure falls. Next. Next slide, please. Okay. So this problem, this inability to adjust blood pressure to changes in posture results in hypoperfusions of vital organs, incapacitating symptoms, persistent dizziness, inability to stand, walk, perform activities of daily living, and can also result in loss of consciousness, falls, and is one of the major reasons for patients not being mobile. So it is crucial to recognize the symptom in order to treat it and be able to decrease symptoms. Can I have the next? Next slide, please. Next. Okay. So what I'm going to show you here, what you see on the left side of the slide is a, you have two tracings, right? On the lower part is the blood pressure, the continuous blood pressure over time. And in the upper part, each of those boxes are the velocity of blood in the brain. That velocity is the equivalent of the blood flow. So you see on the left with a little figure with a person flat or in bed, the blood pressure is normal, 120 over 85, and the blood supply to the brain is around 55 centimeters per second, the velocity. When the patient stands up, the pressure falls quite dramatically. You see from 120, 85 drops to 68, 55, and the blood supply to the brain halves from 55 velocity to 28. The patient feels very dizzy, lightheaded, and is almost ready to lose consciousness, quickly sits down, and when sitting down, gravity decreases, blood supply increases, and symptoms go down, although he still has them. Can I have the next slide, please? Okay. So Parkinson's disease, a disease that you, I'm sure you've heard about that is so common, is very similar to multiple system atrophy. They share a number of features. The fact that it occurs in adults, that is neurodegenerative, and that the same protein, which is alpha-synuclein, deposits. That is the main similarity, but there are also marked and dramatic differences. Next slide. And if you see, I have the next slide, please. If you see here on the right side, multiple system atrophy is a rare disease as opposed to Parkinson's with 40,000. The survival is much lower. It's a rapidly progressive disease. Frequently, almost from the beginning, 80% or higher of patients with MSA will have severe fall in blood pressure. It starts earlier than Parkinson's disease at a younger age, and it has a much more severe clinical motor features. Patients are wheelchair-bound in a few years. The main difference, a crucial difference that I want to call your attention to, and that's what I'm going to show you in the next slide, is that the autonomic pathology, the neurons that are affected in Parkinson's versus MSA in that pathway that I showed you before are not the same. That is very important. I will show you why. Can I have the next slide? Okay. These were those three neurons that I will show you, right? One is central on the left here, one that goes from the central, from the spinal cord to the periphery, and this is the peripheral one. Next slide. In Parkinson's disease, it is that peripheral neuron, the one that dies, the ones that degenerate, because the main accumulation of the toxic synuclein occurs there, what is shown here in blue or gray. Now, in multiple system atrophy, next slide, please. In multiple system atrophy, can I have the next slide, please? Next slide, please. Okay. Next. Next slide. Okay. Next. Okay. In multiple system atrophy, can you keep going further? One more. One more. Okay. Here. In multiple system atrophy, it is the central neurons that are affected. The peripheral neuron, the one that connects directly to the blood vessel, is spared, is still working properly. So if you focus again here, the central is the affected, and the peripheral, the one that releases norepinephrine, is spared. Now, this is very important. I will tell you in a minute why. Can I have the next slide? Next slide, please. Okay. Next. Keep going. Next slide. Next. Next. Next. Okay. This is, okay. Here, it's what I wanted to, you know, I mentioned to you before is that 80% of those patients with MSA develop NOH. This produces big disability and early death. And despite all the available treatments, there are two approved drugs, almost 70% of patients remain symptomatic. Can I have the next slide, please? Okay. This is the current landscape. And as you see, both fludrocortisone and midodrine and droxidopa, those are the three drugs used. Fludrocortisone is not approved, is off-label, and is not effective. Midodrine and droxidopa are pressor agents. They require dosing three times a day. They produce supine hypertension, meaning the blood pressure increases when they are supine. And the efficacy beyond two weeks has not been proven. Next slide, please. Next slide, please. Next. Okay. So what I want to show you now is how ampreloxetine works. This drug that we believe that not only is effective for MSA is thought and designed and based on an effect on multiple system atrophy. So what you see, this is the slide I want you to remember. What you see on the upper left corner are those three neurons I was mentioning before in yellow. At the center of the slide, you see amplify the connection between the neuron and the blood vessel, that peripheral neuron. Can I have the next slide? Next. When it's activated, when this mechanism is activated, as you remember, there is release of norepinephrine, the transmitter by the last neuron. That norepinephrine, can I have the next? Next slide. That norepinephrine binds to a receptor directly in the vessel wall. When it binds to the receptor, it produces vasoconstriction. It reduces the caliber of the blood vessel. Now, the effect of norepinephrine, next slide. Next. The effect of norepinephrine is ended by a mechanism that takes the norepinephrine back to the neuron that releases it. And it does it through a transporter, like a car, that takes the norepinephrine inside the neuron. Can I have next slide, please? So the norepinephrine that was used goes back inside the neuron and is reprocessed. That's how it ends the activity. Next slide. Next. And is degraded. Next. If we block, if you see that red thing on the transporter, that is what ampreloxetine does. It blocks the reuptake of norepinephrine. Next slide. Next. So by blocking it, next. Next. By blocking it, it increases the amount of n orepinephrine in that synaptic cleft and produces more vasoconstriction. It maintains the action. Next. So by enhancing the vasoconstriction, because it doesn't allow it to leave, next slide. Next. Next slide. What, I'm sorry, the previous one. Can you go back? Yes, so as you see, this is uniquely suited for MSA because there is sparing of these peripheral neurons as opposed to other diseases. So this is directly designed for a disease that has the peripheral neurons spared. Next slide. Next, so I'm going to show you very briefly because you hear lately. I'm going to show you the phase III, the initial phase III program evaluating ampreloxetine. This has the Sequoia and Redwood. The Sequoia was a randomized control trial, parallel design, ampreloxetine or placebo. After that, patients rolled over to an open-label period, the Redwood, for 16 weeks where everybody received ampreloxetine. After that, they entered in a randomized withdrawal, what you see here, that lasted six weeks. This randomized withdrawal made half the patients continue taking ampreloxetine and the other half to placebo in a one-on-one randomization. What we were looking at, this is only multiple system atrophy patients. What we were looking at was worsening, meaning if patients had improved during the open-label, during the randomized withdrawal, the ones on placebo should worsen if ampreloxetine is effective. Can we have the next slide? Next. Okay. What we used was a questionnaire that defined symptoms. Next, can you move to the next slides? Okay. As I mentioned to you, there are a number of symptoms on standing, like fainting, visual changes, trouble concentrating, fatigue, difficulty walking. All those symptoms and activities are rated with a questionnaire called the Orthostatic Hypotension Questionnaire. Each question is answered by the patient with he has no symptoms, zero, worst possible, 10. And it answers about symptoms and also about activities of daily living, like ability to walk. The higher the score, the worse the patient feels. The lower the score, the best the patient feels. Can I have the next? Next slide. Okay. This is a forest plot. What I'm showing you here are everything that is to the left of the least squares mean difference favors ampreloxetine. To the right favors placebo. This shows those scales I was mentioning to you, the OHQ, the Orthostatic Hypotension Questionnaire with composite scores that are all the dizziness, vision, weakness, fatigue, trouble concentrating. The addition of that gives you the composite score, and the activities gives you the orthostatic hypotension daily activity scores. I want you to, as you see, the three scores favored ampreloxetine, OHSA, and OHQ being significant. Then each of the OHSA items, as you see with little, only one crosses the midline, and they all favor ampreloxetine, similar with OHDAS, with the exception of walking for a long time. So as you see, the greatest difference was in the six items of symptoms, the composite score, and most individual items also favor ampreloxetine over placebo. Next, please. Next slide. Okay. So I only have maybe two or three more slides. Let me show you. This is the composite score over time. So as you see from week zero to 16, the open label, there is a progressive improvement. If you see my arrow there, there's a progressing improvement of symptoms in the open label. Here is the randomized withdrawal. What you see in gray is placebo. What you see in blue is ampreloxetine. As you can see, the patients on placebo, there were 20 patients, worsened. Their OHSA worsened markedly. Can I have the next slide? Okay. That was for the composite score. Then this is the same story with the ability to stand for a short time. As you see, during the open label, it improves. That improvement is maintained, even slightly improved during the randomized withdrawal, and there is marked worsening in patients taking placebo. Can I have the next, please? As you see, self-score shows symptomatic benefit with improvement in standing that was lost after the ampreloxetine was withdrawn. Next. Next slide, please. Okay. Let me also show you the results of blood pressure because I showed you symptoms and ability to stay standing. This is also quite interesting. As you see, there is a mild increase in blood pressure during the standing where we are showing blood pressure standing. This is the systolic blood pressure. In open label, it goes to a level that makes symptoms disappear above the level of autoregulation. But then here, when the drug is withdrawn, what you see in gray is the blood pressure dropping in standing in patients that received placebo. So can I have the next slide, please? Okay. So this is my last slide, and I want to summarize what I told you, right? So on the left, you have norepinephrine in blood. As you see, and as expected here in blue, is that after four weeks of taking ampreloxetine, circulating norepinephrine increased, whereas in those on placebo, it was either the same or even decreased. Systolic blood pressure standing and diastolic standing increase and increase significantly in those taking ampreloxetine. On the other hand, and this is a very, very important finding because no other drugs, none of the other two drugs that we use for NOH, not only they don't work on MSA, they increase blood pressure supine. And as you see here, the blood pressure supine here, 10 minutes supine, systolic and diastolic was not different from placebo. So norepinephrine goes up, systolic blood pressure standing and diastolic standing increases, blood pressure supine does not increase. And then this is the forest plot with the symptoms that I showed you before, showing improvement of symptoms in patients taking ampreloxetine. So in summary, can I have the next slide? Next slide. So in conclusion, this pre-specified subgroup analysis only in patients with MSA showed that ampreloxetine improves symptoms and blood pressure standing and quality of life. As you are aware, we are conducting a trial only in patients with MSA that is nearing completion where we are convinced if this trial is positive and the drug is approved, ampreloxetine will be the first example of a tailored treatment for NOH in these rare and fatal diseases, multiple system atrophy. Thank you very much, and I'll be glad to answer any questions. Thank you. And thank you, Dr. Kaufmann. Áine, I forgot that I was with the slides. The next speaker is Áine, and I'm glad to introduce her. Áine, take it away. Thank you, Dr. Kaufmann, for an excellent presentation. My name is Áine Miller, and I'm the Head of Development at Theravance Biopharma. I'm going to start today with a brief look back at the development history of ampreloxetine. And as Dr. Kaufmann just mentioned, ampreloxetine is a highly selective inhibitor of the norepinephrine transporter, or NET, which is located on the presynaptic nerves at the neurovascular junction. At Theravance, we designed ampreloxetine for strong NET selectivity, high potency, and with a long half-life that would enable once-daily dosing. As you've already heard, NOH is caused by impaired norepinephrine release when a patient stands, and in MSA, the deficits result from neurodegeneration within the central autonomic pathways. Recognizing this unique pathology, our team realized we may have a molecule capable of achieving the level of NET engagement necessary to boost norepinephrine levels, support blood pressure and vascular perfusion, and ultimately improve symptoms of NOH in these patients. Following results from an early phase II study, we advanced into an initial phase III program that included patients with Parkinson's disease, pure autonomic failure, and MSA. While the overall results across this broad population did not meet the primary endpoint in the Redwood study, the pre-specified analysis in MSA subjects just reviewed by Dr. Kaufmann was very compelling. It was these findings that guided the design and initiation of our pivotal phase III Cypress study. Next, I'm going to talk a little bit more about Cypress and explain the rationale behind the study design and how the insights from Redwood shaped our approach and why we believe the program is significantly de-risked from a clinical perspective. Then finally, I'll go on to cover some of our regulatory preparations, including some of the key interactions that we've had with FDA and how we're planning for an expedited NDA submission should Cypress deliver positive results. Next slide. Now, let's walk through the key design features of the Cypress study and how they were informed by the benefit that we observed in the previous Redwood study in MSA patients. So firstly, we retained the same randomized withdrawal design used in Redwood, and this framework allows us to look directly at the effect of withdrawing treatment after patients have demonstrated a response, which is particularly powerful in a rare disease space like MSA. And in the Redwood study, most patients reached the maximal symptomatic benefit from ampreloxetine around week 12. So with this in mind, we optimized Cypress by shortening the open label period and shifting the enrichment criteria to week eight while maintaining the same enrichment criteria as previously used in Redwood. This allows us to efficiently identify responders while reducing patient burden and study duration. We also extended the randomized withdrawal period by an additional two weeks. The goal here is to maximize the potential treatment difference between ampreloxetine and placebo. And in Redwood, we observed a growing separation over time, and we believe extending the withdrawal phase may give us a better opportunity to capture divergence. And then finally, and most importantly, we selected the OHSA composite score as the primary endpoint. And this composite score reflects the full spectrum of NOH symptoms. And as you've seen in Redwood, it was the measure that showed the most compelling benefit in patients with MSA. And we believe it's the most clinically meaningful and most sensitive endpoint for detecting treatment effects in this population. And finally, the trial was designed based on the assumptions from our previous program to achieve approximately 90% power to detect a clinically meaningful treatment difference. Next slide. So as we discussed on the last slide, Cypress was very intentionally designed to replicate and build upon the successes we observed in the Redwood study, but in a larger population of patients with MSA. We incorporated key learnings from Redwood while maintaining alignment across all key clinical criteria previously we used, and then taken together, these elements significantly strengthen our confidence in the probability of success for Cypress. Equally important was our focus on strong execution, and we've partnered with leading MSA centers of excellence and top academic institutions with deep expertise in managing patients with MSA. Our goal has been to ensure the right patients are enrolled at the right sites and that each patient receives the level of support needed to navigate the study. Consistent with Redwood, we're again using an external enrollment committee composed of the same experts. This committee has reviewed every single patient enrolled in Cypress. Their continued involvement ensures rigorous application of the enrollment criteria while maintaining the same high standards as Redwood. Then finally, because we're managing the study directly, we can also provide real-time operational oversight, and we've been able to maintain very close engagement with all of our sites. We've also invested in targeted site training, and we've been particularly focused on topics such as patient retention, minimizing variability, and supporting high-quality study conduct throughout the study. Next slide. Now, I'd like to walk you through some of the key regulatory interactions we've had with FDA on Cypress and also the broader ampreloxetine program. Over the years, our relationship with the agency has been highly collaborative, and that very much continues to be the case. Back in mid-2022, we had a Type C meeting with senior leadership in the Cardiorenal Division to discuss our Redwood results and the proposed development plan in MSA. The agency noted at the time that the pre-specified analysis in MSA patients from Redwood could serve as supportive evidence for a full NDA, provided we confirmed ampreloxetine's benefit in one additional phase III trial using the randomized withdrawal design. Importantly, FDA also aligned with us in the use of the OHSA composite score as the primary endpoint for this confirmatory study. As part of this interaction and subsequent interactions, the agency also emphasized the importance of establishing the clinically meaningfulness of the OH symptom assessment, and in response, we conducted a full anchor analysis across data from Sequoia and Redwood to determine how changes in the OHSA composite relate to patients' own impressions of severity of change. These analyses confirmed that the OHSA composite is an appropriate measure of clinical status and identified that around a one-point change, either improvement or worsening, is clinically meaningful in patients, and these findings compare favorably to the 1.6 benefit we observed in the MSA cohort of Redwood. If we think about beyond the Cypress design, we also engaged extensively with FDA across other components of the ampreloxetine registrational package. We believe we've aligned with the agency on the full scope of requirements for a complete NDA, and importantly, the vast majority of that work is already complete, and that includes non-clinical pharmacology and toxicology, clinical pharmacology, and CMC activities. Next slide, so now I'm going to move on to briefly comment on the clinical safety and tolerability information that we've collected just thus far. In completed studies to date, we've dosed over 800 individuals with ampreloxetine from phase I through to the end of our initial phase III program. Importantly, we've had over 200 patients with NOH exposed to ampreloxetine, over 100 exposed for greater than six months, and 60 for a year or more. Throughout its development, ampreloxetine has demonstrated an acceptable safety and tolerability profile with low side effect burden, no obvious on- or off targets, and importantly, no signal for worsening of supine hypertension. And of course, the safety data from Cypress will further supplement this safety database. Next slide. Now, as we look ahead to the Cypress top-line readout in the first quarter of next year, I want to provide an outline of the data that will be included. First, for the study population, we'll report patient disposition through both the open label and randomized withdrawal phases, along with baseline demographics, clinical characteristics, and OHQ scores. Second, with regard to efficacy, the top line will include the primary endpoint, the OHSA composite score, along with the secondary OHDAS measures and exploratory blood pressure data. We'll also share a forest plot of that OHQ domain and the longitudinal analysis over the duration of the study. The safety data will include adverse events and serious adverse events from both phases of the study. And then finally, with respect to clinical meaningfulness, we'll highlight the meaningful change thresholds for the OHSA composite score to help interpret the magnitude of effect. So overall, the Cypress top line will be a comprehensive data package and will replicate critical elements that supported the benefit seen in MSA patients in the Redwood study. Next slide, please. So now that enrollment in the open label period of Cypress is complete, our focus has shifted to managing the remaining patients through the randomized withdrawal phase, data cleaning, and then preparing for the planned analysis in quarter one of next year. In parallel, we've already proactively advanced drafting the NDA for ampreloxetine. We're leveraging Theravance's experience from the successful Yupelri NDA filing and approval, as well as my own regulatory background. Throughout this year, we've been working diligently to order the majority of sections supported by completed work so that once Cypress results are available, we can efficiently integrate data and then move quickly towards submission. And assuming the results are supportive, we'll also intend to request a priority review. With that, I'm pleased to hand over to Rhonda, who's going to walk you through the exciting commercial opportunity ahead for ampreloxetine. Over to you, Rhonda. Thanks, Áine. I'm Rhonda Farnum. I lead the Commercial and Medical Affairs Groups at Theravance Biopharma. And I'd like to finish today's presentations by outlining why ampreloxetine is a highly differentiated opportunity in rare neurology. Next slide. Specifically, I will review the size of our addressable patient population, the high adoption potential, and the anticipated pricing dynamics for bringing ampreloxetine to the market. We are targeting an orphan neurology population as there are roughly 40,000 patients in the U.S. Care for MSA patients is concentrated among a few hundred autonomic and movement disorder specialists. This makes commercial reach possible with a lean, efficient infrastructure and that a large field force is unnecessary. As we heard described earlier, patients today are underdiagnosed, undertreated, and are living with a severe daily burden. In our research and discussions with MSA specialists, they consistently indicate that the current treatment options do not deliver durable benefit. If data from Cypress are positive, they view ampreloxetine as a potential breakthrough that could address this long-standing clinical gap. Ampreloxetine is FDA approved. It stands to be the first and only therapy to meaningfully improve symptoms of NOH and MSA beyond three to four weeks. Since on average, recent orphan therapies command rare disease pricing, we believe a premium value opportunity in line with other rare neurology launches is possible. In short, this is a classic rare disease model: a focused patient population, a clear unmet need, and a compelling market opportunity. When you combine that with rare disease pricing dynamics, the potential becomes very attractive. Let me further elaborate on each of these points and how they support this opportunity potential. Next slide. Starting with the current treatment landscape. Despite the profound burden of NOH and MSA, there is no approved durable disease-specific therapy today. Existing treatment options, including midodrine or droxidopa, may be used for transient symptom relief. Their effects are short-lived and not validated in MSA. They are not designed to address the underlying autonomic dysfunction that drives NOH in this disease. What we hear from treating physicians and see in our market data is consistent. Current therapies provide inconsistent benefit, and only a third of MSA patients are actually receiving therapy. For the majority of patients treated, about half received midodrine, a third received fludrocortisone, and about 10% received droxidopa, in addition to some off-label therapy use. Finally, many patients become refractory or intolerant over time. As you heard referenced by Dr. Kaufmann, data indicate about 70% of MSA patients remain symptomatic even after receiving these therapies. Contrasting the current landscape with ampreloxetine's potential target product profile, which you see depicted here on the left-hand side of the slide, one can appreciate that ampreloxetine could provide not only a meaningful durability benefit, but also broad symptom relief, require only once-a-day single pill dosing, and offer a potentially reduced risk of worsening supine hypertension. We see ampreloxetine as addressing an unmet need, not as competing in a crowded therapeutic space. Next slide. Having examined today's treatment gaps, let's consider how physicians view the potential of a therapy with ampreloxetine's target product profile for their patients. We've conducted market research with 200 board-certified specialists, all actively treating MSA patients with symptomatic NOH, and asking two key questions. First, how strongly do you agree that there is a significant unmet need for better NOH treatments in MSA? And second, assuming a product with ampreloxetine's target product profile was fully approved with coverage similar to current therapies, how likely would you be to prescribe it? 71% of neurologists and 62% of cardiologists strongly agree that there's a significant unmet need for better treatment options. And when asked about the likelihood of prescribing, the majority of physicians had a favorable view of ampreloxetine's blinded target product profile, with 90% of neurologists and 80% of cardiologists indicating they are likely to prescribe such a product if available. Physicians are already signaling readiness to adopt a new option. This tells us that the clinical problem is well recognized and the demand for a new solution is already there. When we further explore what drives that prescribing intention, three consistent themes emerge, starting with durability of effect. Physicians are looking for sustained benefit over time, not short-acting symptom relief, followed by ease of use. Once-daily oral dosing would fit seamlessly into clinical practice and into patients' and caregivers' lives. And equally important, safety and tolerability. A therapy that improves symptoms without adding risk of supine hypertension is highly valued. So while physician enthusiasm is essential for early uptake, successful adoption also depends on the perspective of another critical stakeholder, the payers. Next slide. As part of our launch preparation, we have conducted blinded interviews with both national and regional payers, including commercial and, importantly, Medicare organizations, which are expected to represent the majority of our payer mix. During our early payer research, after seeing the ampreloxetine target product profile and reviewing a brief backgrounder on the disease state, we asked payers to rank their perceptions across three key dimensions: disease burden, unmet need, and economic impact, in which we saw consistent scores on the upper end of a seven-point scale for all three. Given the impact on quality of life and risk of complications, payers recognized the high disease burden in NOH due to MSA. These payers also consider NOH due to MSA a high-cost condition that results in falls, hospitalizations, and a loss of independence, and they express interest in a novel symptomatic agent that can reduce these events and disability, associated cost, and improve outcomes. So with both physicians and payers aligned on need and value, let's focus on the size of the opportunity and how efficiently we believe we can reach it. Next slide. As I highlighted earlier, in the U.S., approximately 40,000 patients are living with MSA and symptomatic NOH. This figure is supported by detailed claim analyses across multiple data sources and are validated by external coding experts and leading academic institutions such as UCSD and the NIH. We have also gleaned from our data that MSA care is managed primarily within a distinct number of autonomic and movement disorder centers, large neurology practices, and academic hospitals. This concentration will allow us to reach the vast majority of treatable patients and their care teams through a highly focused, lean commercial footprint, making this a high-impact, capital-efficient opportunity to execute. Next slide. To outline our launch strategy, our plan is focused, efficient, and aiming to rapidly establish ampreloxetine as the new standard of care if approved. To enable the path to early launch success, we've also studied successful rare disease launches closely to incorporate their learnings and insights into our plan, particularly those in chronic neurology. The playbook is quite consistent. First, centers of excellence, or COEs, are the epicenter of adoption. The experience of multidisciplinary teams within these institutions will play a critical role in educating the broader group of MSA treaters. From experience, we know that peer-to-peer influence accelerates uptake. When respected clinicians see meaningful patient outcomes and share those experiences, practice patterns can change quickly. That's why our strategy is to invest early in opinion leader engagement and peer-to-peer education, ensuring that the physicians within the COEs and who have participated in our ampreloxetine clinical development program become early adopters and advocates for ampreloxetine. As shown earlier, we have already initiated permitted dialogue with payers because we know that early engagement will aid in preventing access friction, and by engaging earlier, we aim to minimize time to coverage post-approval, and finally, as in many therapeutic areas, patient advocacy drives awareness and education and serves as a trusted educational hub for both patients and clinicians. We know that patients and caregivers, particularly in rare disease communities, are highly connected, informed, and engaged, and they need dedicated support, which can include financial assistance programs, nursing support, and disease education. Our ongoing collaboration with MSA advocacy groups will ensure that these patients and caregivers are aware of diagnosis pathways, trial outcomes, and availability following launch. From these insights, we've built ampreloxetine's launch strategy centering on three strategic priorities, reflecting on what works in successful rare disease launches, starting with driving urgency among specialists to improve outcomes in NOH due to MSA. Second, establishing the value of ampreloxetine as the only therapy studied and explicitly approved for this indication, and equally important, creating a seamless and positive customer experience from diagnosis to access to adherence, which will include high-touch patient support programs. Next slide. Turning to launch execution, our approach is designed for precision and influence rather than scale. Let me start with the map you see here. This illustrates the geographic concentration of care for MSA-related NOH. Through our claims data evaluation, we've identified 550 high-volume neurology accounts across the U.S. Within them, about 90 prescribers, a relatively small number of specialists, primarily autonomic and movement disorder specialists, who treat the majority of MSA patients. Many of these physicians are located at the 40 COEs recognized by the leading MSA advocacy groups. We plan to build on the strong relationships within our 26 U.S. clinical trial sites within these COEs, which already have an established foundation through the Cypress study network and ongoing investigator interactions. What this tells us is that the prescribing universe is highly concentrated and influence-driven. We will plan to target these high-volume accounts with a lean, specialized field team, individuals who understand complex neurology, patient support, and payer dynamics, all of which will be supported by investment in targeted digital engagement. Initially, for launch, this isn't about scale. It's about the data, a depth of understanding of customer needs, and the precision of targeted efforts. Next slide. So turning to the next critical question, what kind of value can a therapy like ampreloxetine command in this market? Looking at how pricing has evolved across the rare disease landscape over the last several years, we see the average annual wholesale acquisition cost per patient per year was approximately $300,000, driven by the combination of small patient numbers, severe disease burden, and limited alternatives. Given ampreloxetine's differentiated mechanism, its potential to become the first and only durable therapy for NOH and MSA, and the high unmet clinical and economic burden we've discussed, our pricing expectations are consistent with these established precedents in rare neurology. Furthermore, as seen with recent launches, orphan drug policies have supported a higher willingness to pay threshold in small, high-severity populations. Though we are still finalizing our pricing strategy, we anticipate our pricing expectations will align squarely within current norms. Next slide. So the opportunity actually extends well beyond the U.S. With a sizable ex-U.S. opportunity, we plan to pursue through partnership. As you can see here, there is meaningful potential across Europe and Asia, driven by similar factors that make the U.S. opportunity so compelling. The market fundamentals in these regions mirror those in the U.S., a rare, high-burden condition with limited treatment options and concentrated care among a relatively small group of specialists. Taken together, these conditions create a receptive market environment and a path to early adoption once efficacy is confirmed. Importantly, our Cypress study includes European study sites, giving us established relationships with key opinion leaders, MSA COEs, and patient advocacy groups across the European market. This advocacy support will be instrumental in accelerating physician awareness and patient identification, which creates a natural bridge to future regulatory and commercial engagement. To my next and final slide, so step back to where I started. I hope that you can see that the components of this opportunity come together in a strategically differentiated way: a concentrated, accessible treatment landscape with a well-defined, urgent medical and unmet need, a focused, efficient commercial model, and a rare disease economic structure that supports innovation where it is most needed. Most importantly, if approved, ampreloxetine has the potential to provide meaningful benefits to patients living with the daily burden of NOH due to MSA. Taken together, these elements position the commercialization of ampreloxetine to potentially deliver measurable clinical impact while establishing a scalable and sustainable value creation opportunity for the healthcare system and our investors. So with that, I will turn the presentation back over to Rick to close. Rick. Thanks, Rhonda. In closing today's discussion, it reinforces why we believe ampreloxetine represents a truly compelling potential treatment for patients. We're operating in a rare disease neurology market where the commercial potential for a therapy that delivers real, durable benefit can be significant. We have a Cypress phase III program built with FDA alignment and informed directly with what we have learned in our prior phase III study. That gives us confidence heading into the Cypress's readout. And if the data are positive, we believe ampreloxetine has a clear path to becoming standard of care for symptomatic NOH and MSA patients where the unmet medical need is high and the treatment options are extremely limited. Importantly, this is a market where a lean, highly targeted commercial model can be effective, given the concentration of treating physicians and centers of excellence. And beyond the U.S., the ex-U.S. opportunity, as Rhonda noted, is meaningful with sizable patient populations across Europe and Asia. All of this comes together at a moment when our catalyst is directly ahead of us: phase III data in the first quarter of 2026. We're excited, we're prepared, and we believe ampreloxetine has the potential to transform care for a community that's gone far too long without a targeted treatment option. And with that, I'll open it up for questions. Great. Thank you, Rick. So before we go to audience questions, we'd like to ask Dr. Kaufmann one. So can you talk about the competitive landscape a little bit more and how you would intend to use ampreloxetine if the data is positive, and how many of your patients would you put on it if the study is positive? Sure. You want me to answer now, or how does? Yes, please. Yes, sure. Okay. I can tell you that, as you said, it would be a no-brainer because this is the ampreloxetine will be the only drug that is specifically targeting multiple system atrophy as opposed to, let's say, Parkinson's, dementia with Lewy body, or even pure autonomic failure. The type of pathology that MSA has indicates that ampreloxetine is targeted and almost designed for this disease. So what is the landscape? The landscape is fludrocortisone, which is not approved for this. It's still used widely. Acutely, it works. Chronically, it's a disaster because it produces supine hypertension, and then the complications of renal and cardiac fibrosis, we already know that as a chronic treatment is a problem. Droxidopa, which is a very interesting drug, was not in the analysis per disease. It was not effective in multiple system atrophy. It got approved with the effect on all of them, but on the strength in Parkinson's. In multiple system atrophy, it's not effective. And Midodrine has similar limitations, and all of them require three times a day dosing. But aside from the dosing, which is a problem, but to me, it's not such a big deal, the supine hypertension and the efficacy only for MSA, I think, makes ampreloxetine, if the trial is positive, I think, the number one drug, and that everybody will use it for MSA. Every neurologist will use it for MSA. I don't know if I answered your question. I don't see the audience, so I'm a little. Yes, that was great, Dr. Kaufmann. Yeah. So at this time, we are going to take questions from the audience. To our analysts who are joining us live, please use the raise hand feature to indicate you have a question. And to our audience that's on the webcast, please use the written Q&A text box at the bottom of the player. So please hold for a brief moment while we pull for analyst questions. So our first question comes from Mayank Mamtani at B. Riley. Please go ahead, Mayank. Yes. Good morning, team. Thanks for taking our questions and appreciate all the detail provided today. First, for Dr. Kaufmann, in Redwood, we see a 1.6-point improvement on the OHSA composite, as you highlighted, and in Cypress, there's a target one-point change. If you could maybe talk to subcomponents that you highlighted in forest plot that tend to have maybe more variability than less and perhaps less plausibility with the NET inhibition mechanism. I'm sorry. I didn't get exactly your question. You want me to. In the forest plot, in the different subcomponents that you have in the forest plot within OHSA, I was just curious, are there subcomponents that have more variability than less in general as you assess these evaluation metrics? And then with the NET inhibition mechanism specifically, is there short versus long-standing, for example, is there plausibility of certain metrics that are more related to the mechanism versus not? If you could talk to that. Okay. First, interestingly, the main improvement, as you saw in the forest plot, was with the symptoms, with the composite of the symptoms, the OHSA, meaning O rthostatic Hypotension Symptom Assessment. It was also very significant with the OHQ. The only one that wasn't as favorable as all the others was walking for a long time, which is understandable also because walking for a long time, it also involves motor problems. So walking for a short time and the lack of symptoms were clearly favored, and we see that in the open label, right? In the open label, and I can tell you what I see in my patients is that their symptoms improve. I mean, patients do not want to stop taking the drug, right? And the symptoms improve. So I'm pretty confident that the effect appears to be there. Regarding long-term effect, look, all drugs have been approved only for two weeks. The duration of the ampreloxetine trial is quite longer, right? I mean, the open label gives us four months, and the effect is persistent. And I think it continues more, right? Am I answering, w as this your question, Mayank? Yes. Yes. Thank you. That durability comment was helpful. And then maybe for the company, on the Cypress execution details, to the extent you're able to share, would love to hear what proportion of patients have progressed from the initial open label to the randomized withdrawal section, whether any differences versus Redwood. And I guess a commercial question, how does the initial screening rate in Cypress provide insight into both sort of the epidemiology of MSA and OH and kind of the diagnosis trends that you're seeing that can inform commercial uptake? Thanks for taking our questions. Yeah. I'll address the first question. But, Mayank, what we're seeing by and large with Cypress is the same type of experience that we had with Redwood with regard to patients. Obviously, what we're executing here is a clinical trial over a specific duration, which is in measuring the impact of the study or the medicine at specific times within the study. So it's very different than what you'll see in the real world, and that the methods that we've used are really meant to measure the effect of ampreloxetine in this particular patient population over a specific period of time. I think back to my initial comment, and what we've seen to date in Cypress is by and large what we've seen in the Redwood study. Áine, anything to add there? No. I think you've covered it, Rick. I mean, I think we're just seeing a consistent pattern across both studies. Yeah. Remember, again, Mayank, the open label is 16 weeks, right, which is pretty long, plus the seven weeks of the withdrawal. The ones that continue on ampreloxetine maintain that effect. So here you have 20-something weeks that no other drug showed that. Yeah. So yeah, to Horacio's comment, if you look, it's 12 weeks plus 8 in the Redwood or the Cypress study. And you've got 16 weeks in the earlier study plus 6. So it's a long-duration study. And then we've had almost everyone roll over to the long-term extension study following the conclusion of the randomized withdrawal. So we've got in this study, in both studies, Redwood and Cypress, we've been able to keep patients on study for quite a long period of time. And then on the commercial question, any learnings from the trial that inform the epidemiology or diagnosis trends that might be changing? Well, I'll kick off, and then I'll turn it over to Rhonda. I think critical for us is we focused the trial on centers of excellence throughout both the United States as well as Europe, and that was so that we could have really the best treaters and the people with the most knowledge of the disease in executing the study, but also to build relationships with these centers of excellence, learn everything that we can from them about the market and what we need to address, so I think this has been very important to building a commercial knowledge at baseline. Rhonda? Yeah, so I think what's important is to appreciate that we have done considerable work to validate the 40,000-patient epi view of the NOH patient population. So really feeling quite clear on what our addressable patient pool looks like. That data are based off of multiple refreshes of claims analyses and requires a diagnosis claim of the G90.3 or the G23.2 ICD-9 codes or ICD-10 codes, and then that's followed by a treatment or drug claim, so we feel quite confident in that really substantiating the addressable pool. What we need to better understand in doing further work beyond that 40,000 is how many more patients out there perhaps are either undiagnosed or underdiagnosed, and we're currently working with opinion leaders to conduct a study to better understand what that pool looks like, but I think looking at how stringent the executive steering committee and rigor behind the study enrollment, I don't see that there's any conflict or misalignment of information of where these patients are and how many there are. Super helpful. Thank you, guys. Thanks for the questions, Mayank. Our next question comes from Debanjana Chatterjee at JonesTrading. Please go ahead, Deb. Hi. Thanks for taking my question and congrats on the excellent presentation. So I have a couple. The first one is regarding the potential for off-label use. Given the high unmet need in neurogenic orthostatic hypotension, do you see any potential for off-label use of ampreloxetine in broader population beyond MSA? Yeah. I mean, I think just I'll make a quick comment and then turn it over to Dr. Kaufmann as he runs a major group at NYU. So obviously, our promotional effort will be consistent with the label, which is MSA. I think physicians will. Those are the messages that we'll take to physicians. And Dr. Kaufmann may be better able to answer sort of how the medical community might react. Sure. Look, it's a great question, Chatterjee. I mean, I can tell you my impression. This is not a scientific answer. My impression is that, yes, yes, that with a drug that is so safe once a day and that proves efficacy in one type of disease, it's likely that it could be used off-label. But as Rick says, the only thing we can do, me as a physician and them as a company, is to focus on multiple system atrophy. Perhaps, and here I'm getting ahead of myself, perhaps a widespread off-label use would teach us that the drug may be effective on other, which is what happened. But that is sort of another issue. It's a separate discussion, right? Thanks. And do you see any potential for payers implementing step edits if ampreloxetine is approved and commercially available, given its premium price? Rhonda? Yes. Thanks, Deb, for that question. And we're very focused in that arena. I would anticipate that some payers, and I'm qualifying that, some payers may require step edits through current existing standard of care. But as standard of care changes, and as I mentioned earlier, we would anticipate ampreloxetine to become a new standard of care once approved. We would see that evolve over time. Nonetheless, we will ensure that they, being clinicians and patients, have very robust support programs to aid with any prior authorization, letters of medical necessity. A process will be in place to ensure this is not an access barrier. Sure. And the last one, what gross-to-net discount assumptions are you modeling for ampreloxetine at launch? And what factors like payer mix, Medicare drives these estimates? Yeah. I think we'll probably keep gross-to-net assumptions to a little bit closer to launch. But, Rhonda, you want to comment on anything else? Yeah. It's a little too early, Deb, to provide that guidance. As we get closer and closer to finalizing our pricing, that will be a part of the communication that we'll share at future forums. Thank you so much. Thanks for the questions, Deb. Our next question comes from Andrew Kassin at BTIG. Please go ahead, Andrew. Hi. Thanks, everyone, for this great event. Just a quick question on the OHSA composite score. Could you put the MCID for this composite score in context for us? Do you expect payers are aligned on the expectation for efficacy considering no other safe alternatives exist? I don't know if it's to me, Andrew, but yes. I think the FDA has taken the OHQ as the parameter, either the item one or the OHSA, as the main parameter for approval for the previous drugs. So rather than the blood pressure, they want these questionnaires. Yeah. And just to add to Dr. Kaufmann's comments, obviously, we've now published on the clinical meaningfulness of a one-point change in the OHSA composite score. So there's quite a bit of support for a one-point change being clinically meaningful in the treatment of the condition. Got it. And then just one more on the commercial side. I know you've discussed the centers of excellence as a focus. What percentage of patients or a proportion of patients would be treated by community neurologists that could be available? Thank you. Thank you. I would still say I want to make sure we're aligned on when we say community neurologists, there are still specialists within the neurology specialty. So taking that qualification, I would expect about 80% of our targets are in that realm, and the 20% are in the COEs or academia. Perfect. Thank you so much. Thanks for the questions, Trevor. Our next—sorry, Andrew. Our next question comes from Douglas Tsao at H.C. Wainwright. Please go ahead, Douglas. Doug, we can't hear you if you're. Yeah, you may be on mute. Hi. Can you hear me now? We can hear you. Yes. Yes. Hi. Good morning. Thanks for taking the questions. Just trying to understand, Dr. Kaufmann, obviously, ampreloxetine is aimed to treat one aspect of the disease in terms of the NOH. But obviously, these patients have been significantly impacted. Can you just talk about the potential to more broadly impact the patient's well-being and their overall sort of conditioning or sort of ability to—and overall mobility? Thank you. Yeah. Look, Douglas, it's a very important comment, the one you make. And I tell you, MSA, and these are the patients I see. And although it's a rare disease, it's not rare for me at all because we see a huge, well, not huge, but a large amount of these patients. In the first, mortality is high, and the disease is rapidly progressive. Now, the first two, three, four years, many times, most of the times, the main limitation for activities of daily living and being able to function properly is this terrible fall in blood pressure that prevents people from standing up. Now, the problem of not being able to stand up and walk is a big deal because it starts a Catch-22, a vicious cycle. People cannot stand up. They get deconditioned physically. So the orthostatic hypotension worsens even more. And then they are completely unable to stand up and move. These, in people whose parkinsonism, meaning the motor problems, are very mild, or the cerebellar problems are very mild in the first few years, so the importance of realizing that the fall in blood pressure is the main determinant of the disability and immobility and makes things worse is crucial, and by treating that, you can block that vicious cycle and give people a few years of much more functional ability. Their quality of life improves dramatically. More so, there are a number of disease-modifying treatments, and it's likely, and they may work on the motor, so still, the treatment of NOH is crucial in these patients. And just as a follow-up, when you think about the potential for some disease-modifying therapies that are in development, your perspective would be that they are likely not to address the NOH symptoms, and there would continue to likely be still a need for ampreloxetine? Exactly. Exactly. Because suppose, and again, all these are suppositions, Douglas, but suppose that one of the disease-modifying treatments actually slows motor progression, but let's say 10%, 20%. Well, there'll be a longer time in which the main limiting factor, which is the fall in blood pressure, should be treated. And if we have something effective for what prevents people from moving, we are getting a big factor out of the equation. Again, in the first few years, it's the fall in blood pressure that prevents people from doing things, affected patients from doing things. Okay. Great. That's very helpful. Thank you. Thank you, Douglas. Yes. Thank you for the questions, Doug. So our next question comes from Trevor Allred at Oppenheimer. Please go ahead, Trevor. Hey, thanks for taking my question. And thanks for this great event. My first question is for Dr. Kaufmann, and it kind of goes along the same lines as Doug's question. Can you expound a bit on how, say, a one- to two-point OHSA improvement correlates to clinical benefit? What's the change in the patient's daily experience? Rachel, I think that's directly you. It's just a sort of a correlation. It got disconnected. I'm sorry. I reconnected. You were asking me because I got startled that it got disconnected. In which way a one-point change in the OHSA correlates functionally? Was that your question? Yeah, essentially. How a one- to two-point improvement correlates to the daily patient experience? Okay. Very good. I mean, very important question, and that's what regulators want to know. To answer that is that we did this study that was referred to, and I'd be happy to send it to you, which is the anchoring of the scale. So based on all the previous studies, independent of the treatment, we correlated a change in OHSA with a change in Patient Global Impression. And there is, for each one-point little difference in the OHSA, there's an improvement in the P atient Global Impression of Severity. So in a different scale, one-point reduction in the OHSA translates in a significant patient recognition of being better. And I'll be happy, Trevor, to send you that paper that was just published. Yeah. That'd be great. Thanks very much for that, and I guess a follow-up question for maybe the broader company or Dr. Kaufmann as well. Can you discuss some of the results we've seen in studies with atomoxetine and how ampreloxetine compares to atomoxetine as well? Yeah. Happy to answer that. It's a very different drug. It's a different drug because of the pharmacokinetics are very different, and the pharmacodynamics also, the binding to the receptor is different. On the other hand, the study that was published that we did was with a pediatric dose, right? So the dose was very low, but aside from the dose being low, the drug is significantly different. I mean, they share some of the norepinephrine transporter inhibition, but the binding and the thrust are completely different. We were puzzled by that, but they were very different. Yeah. Just to add to that, and this was really work Theravance in the selection of the 10-milligram dose for NOH is that to stay away really from effect on serotonin because increasing serotonin may have a negative effect on patient symptoms, which is why 10 milligrams of ampreloxetine was chosen to really isolate the effect of the medicine on norepinephrine solely so that it wasn't potentially negatively affected by any effect on serotonin. Got it. Super helpful. Thanks for taking my questions. Great. Thanks, Trevor. So our final question comes from Ellen Horste at TD Cowen. Please go ahead, Ellen. Hi, guys. Thanks for this presentation. It's been super helpful in helping us frame expectations and understanding of the disease launch a little bit better. I guess if I could just ask a question that's a little more launch-focused. I'm wondering, assuming the trial hits, assuming approval, I understand this should be modeled kind of like a rare disease launch, but do you have any expectation that there should be a bolus of patients? Is there kind of a pent-up demand leading up to the approval based on the concentration of physicians and patients? Just wondering kind of how we can get more granular on modeling this launch. Thank you. Rhonda, do you want to take that or? Yes. Thanks, Ellen, for the question. Obviously, we're certainly very focused on understanding the patient pool. As I've outlined, we know that there are existing patients that are receiving treatment today, given those 40,000 patients are validated by both a diagnosis code and a treatment code. But then also, we know beyond those patients are patients that are not receiving treatment. As I mentioned earlier, only about a third of patients are receiving treatment. So coupling that with where we see intent to prescribe when we define and outline the example of the blinded target product profile and see those scores on likely and very likely to prescribe, the intention to prescribe and knowing that these individuals have patients, I think is quite high to ensure that there is a bolus of patients ready. Yeah. Ellen, let me just throw once a day. And in patients that are not happy with their treatment, there will be a big pent-up demand. I have no doubts on that. If the trial is effective, everybody will ask for the drug. Thank you. That's really helpful. Great. Thanks for the questions, Ellen. So this concludes our Q&A session. I'll turn it back to Rick for some quick closing remarks. Yeah. I'd like to thank all the presenters. Thank Dr. Kaufmann in particular for his time and his work in the field of dysautonomia and the contributions to healthcare in general. Thank all of you, the listeners, for joining us today. As I said, we're very excited about the upcoming Cypress data in the first quarter of 2026 and look forward to sharing it with you just as soon as we get it, and so have a great day and a good holiday season. Please take care.