At the firm, it's my pleasure to have with us our next presenting company. That would be Neurocrine Biosciences. Presenting for Neurocrine Biosciences is CEO Kyle Gano. Kyle, congratulations again for becoming CEO of the company. It's been a few months now, right? Since October. You're now a pro. Oh, yeah. All problems can be rolled back to you, I'm sure. Also on stage is Todd Tushla, our favorite IR person, of course. Oh, thank you. Thank Thank you. Why don't we talk about some macro issues? Because we've started all of our conversations so far this morning on that. Maybe with the most recent one, the executive order that was announced yesterday as it relates to Most Favored Nation. We are all still awaiting more details, but to the extent that you can comment on what kind of impact to expect on Neurocrine. Sure. I'll start there. Maybe to interject with our lawyers' view, we will be making forward-looking statements. I direct everyone to our latest SEC filings for the risk factors. In terms of the latest executive order, which we saw yesterday, I think we were all on the edge of our seat to see what it actually looked like, given some of the rhetoric that came out over the weekend, some postings on social media. At the end of the day, similar to what we've been saying about tariffs and other aspects of some policy and other executive orders that have come out in the past couple of months, it's still very early days, and we lack a lot of details on what actually is the true intent of the president here in terms of what we saw yesterday. At the end of the day, after reviewing all the information in totality, we appreciate that there is a view that we need to prevent basically foreign leveraging of our data and our medicines that we have here in their countries at a lower price. We get that. We understand that. I think we share in that same sentiment. We've also seen the setup of the president to allow the health team within the administration to set in place or in motion the terms and the communication to manufacturers on Most. Favored Nation targets. HHS then would have the ability to define rules and implement those between this team and the manufacturers that have medicines that are outside the U.S. Ultimately, if there's not significant process, again, this is kind of referring to the language in the executive order, the government could potentially import the lowest-priced medicines within this Most Favored Nation basket and bring those to the U.S. at the lower price. Not a lot of data here on how this actually gets played out and pulled through. We don't know what elements of the Medicare or Medicaid are part of this vision. Is it A, B, D? Is it Medicaid as well? What list of drugs are underneath these different categories? Is it all the medicines? What nations are part of the Most Favored Nation basket? There are a lot of things that we still see out there as needed details to really comment specifically. Like these other things that we've discussed and seen over the past few months, early days, a lot of details to be worked out. What we're going to try to focus on are those things that we can control, which is building Neurocrine into a strong, resilient business and doing best for our shareholders and our patients. We'll continue to evolve this, keep an eye on this evolving situation. Where there are things that we see impact the business, we'll be sure to let everyone know. Okay. Next macro question on tariffs. Yeah. Tariffs, kind of in the same basket where we start with executive orders. I mean, at a high level, we're really talking about here are the component parts that lead to our drug product that's available for commercial sale, not the actual commercial product itself. We have redundant supply chains across the U.S. and Western Europe for both Ingrezza and for CRENESSITY. Ultimately, when we look at the component parts here, they add up to a very low cost of goods medicine with high gross margins. We do not see tariffs playing a very significant role at all in terms of how they might affect our business. I think we're in pretty good shape there. Okay. Lastly, your interactions with FDA, to the extent that you've had recent ones, let's say over the last eight weeks or so, have you noticed anything in terms of the same people or timelines extending or any kind of data point you can share? Sure. That's a great question. I mean, there's a lot of obviously uncertainty in our industry right now with the meaning of all the executive orders that have come out, ranging from the tariffs as you've raised as well as Most Favored Nation. On the FDA, there's also changes that are going on there now. I'm extremely thankful that we have nothing in FDA review currently. CRENESSITY was approved in December, so we don't have to worry about something like that being in the hands of the FDA right now. Our most important FDA interactions just occurred over the past couple of months, in particular into phase two discussions, which outline the scope and breadth and depth of our phase three programs for osavampator and NDD, as well as our schizophrenia phase three program for INGREZZA. Those are also out of the way. Most of our interactions this year, I would say, are lighter discussions about programs coming into the clinical space, IND submissions, and things of that sort. We are very pleased where we are going through this era of change at the FDA. Ultimately, we are not seeing any timeline changes or any effects to our business, even with some of these other interactions that we anticipate having over the course of the year. So far, so good. Again, we do have a team that follows this news in Washington DC. If there is something there that we see changing in this view, we will let everyone know. Okay. Perfect. Now on to Neurocrine. Very good. All right. I actually want to start off with CRENESSITY, CRENESSITY Font. You're off to a strong start in the early innings, very early innings of the launch. Last quarter, you recognized $14.5 million in sales, north of 400 new patient start forms. That came in above, I think, what even the most bullish people were thinking would be the case. Also, an impressive number was, I think, 70% reimbursement rate, close to it. Based on how you were guiding us, has anything changed? Should we still be thinking about the launch in the way you described it when the drug was initially approved? I'll start a little bit, and then I'll ask my colleague here, Todd, to add anything that I missed that goes across the board here on our discussion. In terms of the launch, what we like to say out there is so far, so great. It really has been a nice early start to the launch. We don't feel that our messaging has changed at all in terms of how we view this launch in and of itself. We do feel that measured is still the appropriate word to describe what we'll see over time. The reason for this is that there have been no medicines approved for CAH in over 70 years. That first medicine 70 years ago, and only medicine, was hydrocortisone. There is a certain level of education that's required in this space to effectively move a medicine into the armamentarium of the physician, as well as adding that onto the patient's care on a daily basis. That education is directly related to the in-office interactions that these patients are having with their physicians. We know that all patients aren't created equal, not only in terms of their symptoms and what's important to them, but also how frequently they're visiting the physicians. You've got pediatrics in the adolescent patient population, which could be a mix of boys and girls, are obviously cared for by their parents. They tend to be the most frequently visiting their offices, the physician offices, two to three times per year. Then we move slowly to adult women and then to men, and the number of office visits drops off pretty significantly from there. We might see one to two office visits per adult woman and maybe one for the men. When you're trying to change that standard of care and change that education, you really have to get through those first visits and maybe another visit before you get the physician and patient on board for trying a medicine that they did not know was available this time last year. We do see that playing out, and that is part of the measured launch that we're working with here. We also are in a state where we're not on any of the formularies out there. Patients that want to get a prescription, they have to work through that insurance process, and that can also take time as they go through prior authorizations and things of that sort. Coming out of the gate, we like what we see in Q1, but we have this goal of changing the standard of care that's going to take time and also working through the insurance reimbursement landscape. That will play out over the course of the coming year and years. Right now, we're off to a good start. I'll just add one additional point. It comes up in questions with investors. We do have an open label extension study where greater than 90% of the patients in the adult and pediatric registration study enrolled into. I reannounced on the Q1 earnings call that the U.S. adult portion of that study is going to roll off over the coming months. That's about 50 or so U.S. adults that will eventually become paying customers. That's not going to happen all at one time. You won't have this bolus of 50 patients that's going to occur over weeks and months. Okay. Thanks for that color, Todd. Just sticking to this launch. I think you said that in terms of the age distribution, was it 50% adults? Early. Early it was about between adults and pediatrics. Early balance. That's right. But then it started to trend a little bit more towards peds at the end. In terms of that little bolus of adults at the beginning, and I say that because, as you've talked about, adults tend to see their physicians with less frequency. Where were they coming from, do you think? We think that there are, just like in any disease state, there are patients that are really on top of their care. It could be as simple as that. The early adopters that you see in certain medicines, certain classes in terms of how they approach their care, those are maybe that's the simplest explanation. It could be also the time point at the beginning of the year when they see their physician just happened to correspond with the launch of the medicine. We'll see how this all shakes out over time. I do think that we will see the pediatric and adolescent patient population be at least in the near to midterm, the patient group that is starting CRENESSITY first because of the drive in patients or the parents to get their kids on the medicine. Because the longer or earlier you start, the longer that you're on the medicine, the greater benefit that you'll see. Yeah. On the point of the 70% reimbursement rate, you talked at the beginning about needing potentially several weeks to low months for. Iron out the payer dynamic there. Yes. At least in certain cases, it seems like it's going a little bit faster than that. Can you talk about what types of payers are more streamlined and what types might require more hand-holding? Yeah. I'd say there's a handful of payers that have already made coverage determination criteria, and it's encouraging in what they require. It's right in line with the label that you have to have a diagnosis of classic CAH. You need to be four or older, and you need to be on a glucocorticoid. That's all encouraging to see. A majority of the reimbursed scripts in Q1 were through the exceptions process that we know how to manage well via INGREZZA. We'll continue to work through the plans through the course of the balance of this year. It's something that we continue to work through. Would we be noticing any difference between now and when CRENESSITY is formally added to formulary? I think we feel pretty comfortable. It was surprising to have the reimbursement rate as high as it was in Q1 given some of the work that we had done upfront. That is just going to be an evolving number over the course of the year until we get into the next calendar year, I think. Okay. Now, in terms of finding patients, because I guess the pediatric and adolescents, let's say, see the doctors more frequently, are we right to assume that maybe the initial few quarters will be, like as you said, at the end of the quarter, was shifting more towards peds and adolescents? Do you expect that trend to continue near term? Yeah. I think it's reasonable to think about that just from the motivational factor, again, driven by the patient's parents wanting them to get on medicines as early as possible in the course of their life for the greater longer-term benefit, as well as their frequency of interactions with the physicians. That's logical to think that way. I think that will play out, but let's see what the data looks like here in a couple of quarters. How would DTC look like for CRENESSITY versus what was done for INGREZZA? I think that DTC as a tool, direct-to-consumer advertising, can work well for disease states that have higher prevalence numbers. With INGREZZA, there are 800,000 patients, and there are families and caregivers watching over those 800,000. The reach of individuals that might be affected by TD in some shape or form is quite large. In contrast, for CAH, we are talking about a disease with a prevalence of 20,000-30,000. Of course, there are family members and caregivers that go around that, but a much smaller patient pool. I think traditional direct-to-consumer advertising may not be as effective here, at least from an ROI perspective, because you just do not know where the patients are definitively to get the benefit out of your DTC advertising, if you will. I think we'll be looking at more targeted ways of accessing media, whether it's internet-based social media, things of that sort that would give us access to patients that might be using those types of tools, learn about their disease state. I think right now, where we are in the commercialization effort is trying to identify what those different media types are that patients are using. Once we have a good idea for that, what would it make sense for us to invest in to help us identify these new patients? The goal here is to do two things. One is to ensure consistent growth of the medicine over time. We want to make sure that we're accessing all the patients that need the medicine. We're also trying to do this as quickly as we can because we know we don't want to have another patient wait another day. There's no reason for that. When they've got a medicine that benefits the patient, the sooner they start on it. Both of those are top of mind. It is a goal that we identify the best tools to reach these patients and their families, and we'll be doing that over the course of this year. Okay. As you think about the evolution of this launch, obviously, Southside has its own view about where sales could peak. Just in terms of the size of the population, would it be wrong to consider this a blockbuster indication, meaning north of $1 billion in sales? We think this could be our next blockbuster, for sure. That is one of the things that we think we've always said from the get-go. We're incredibly excited about having the opportunity to have another first-in-class medicine for patients, first and foremost. I think you see a trend here over Neurocrine's history in the sense of even Orilissa, what AbbVie that they commercialized, that was a first-in-class GnRH antagonist to INGREZZA. That was a first-in-class VMAT2 inhibitor for tardive dyskinesia. Now with CRENESSITY, first-in-class CRFR1 antagonist for CAH. Being that company that develops medicines like that is a very rare air. I I think that gives you the opportunity of a blue sky opportunity to really reach patients and their families and potentially change the course of their disease. When you're talking about the patient population that we have in the absence of the medicine over decades, we also think that they're equally excited about having the opportunity to try something and benefit from it. I think it's a perfect number of variables coming together here for Neurocrine that leads to very significant upside for the medicine. Yeah. You became the first approved drug in this space, but interestingly, it's coming at a time where interest in CAH in general has increased, and that's good for patients. As you think about the potential for, I don't know, one or two competitors to enter over the next few years, how are you thinking about the size of the opportunity? Is it big enough to support more than one drug? If you think about ways in which Neurocrine can differentiate either in terms of the way you're launching the product or in terms of Crinege itself, what would those things be? Yeah. I think I mentioned the different medicines that we've played a role in over the years. In each of those medicines that we brought to market, we've always brought forward at least one competitor. It is a bit of a sign of pride that we can shine a light on a disease state and bring others into it. Ultimately, I think you touched on this, it benefits patients to have different options, and that is rewarding. In terms of competition in our space, I try not to talk that much about it, given that the data that we're often asked to compare is not apples to apples. It is apples and oranges. It is really hard to make any comparative remarks. I do think CAH is one of those disease states where efficacy gets your foot in the door, but safety and tolerability once a day for both approval and adoption by patients, and in this case, parents and family members as well. What we have is that in spades with Crinege. It all starts with our approach. With a CRFR1 antagonist, we work upstream at the HPA axis and it allows us to reduce and control ACTH all the way down to the androgens. All of those pieces from ACTH to the androgens themselves are important factors of how the disease progresses and the side effects of treatment. We do think we have the optimal approach here ultimately. Something like ACTH, it's something that we hear a lot about from our competitors, either a monoclonal antibody or ACTH antagonist. ACTH is something that binds to ACTH receptors throughout the body. We can't forget it's not just on the adrenal gland. It's everywhere throughout the body. Excessive ACTH stimulation is not something that's been well studied, and it's hard to view that preclinically. The consequences of long-term excessive ACTH is an unknown that our competitors have to address. We don't have that issue because we're able to reduce that and control that with Crinege. We like our approach. We've got a medicine that has great efficacy, great safety and tolerability that translated into a very nice label. We think that we'll be able to treat the vast majority of patients that are available for CAH treatments by the time another potential medicine comes to market. Yeah. I just want to punctuate on the safety and tolerability. That's supremely important, especially for the pediatric patients here. And Crinege has been studied in over 1,200 patients. In CAH specifically, there are some patients that have probably been on the drug for four years now or plus. Really pleased with the balance between efficacy and safety and tolerability that gives us a competitive edge. Yeah. Last question on CRENESSITY, and then we'll move on. You're making a lot of headway early, and it looks like it's shifting initially towards the peds population. But if I understand correctly, there's actually the adult population size-wise would be bigger over time. That's two-thirds the size of the patient population. That's right. Yeah. What are the efforts that you're making to try to find these patients? I would bifurcate the adult patient population as well from women and men. The women are more motivated than, say, the middle-aged man for a number of reasons. You can look at irregular menses, hirsutism, infertility, things of that sort that they could potentially improve by being on CRENESSITY. They are more motivated than the general male. I think that's what you'll see as time moves along. We'll have more women than men as well. On the adult men's side of the equation, really for all the patients, you're able to track their diagnosis codes and claims databases. You're able to track prescriptions of hydrocortisone in the same databases as well. You can triangulate where these patients are from a geographical standpoint and be targeted in how you look at capturing patients that might be visiting offices that are in the area. I think that's something that we look at, and there's more that goes around that. At a high level, that's a practice, a tool that many companies use to identify patients in a given disease state. Those are things that we're looking at, more traditional ones, and we'll be able to marry that with some of the media outreach that we'll be doing over time to help us bring patients into the office as well and ask about CRENESSITY. Like the disease state and changing the standard of care, identifying patients is going to evolve as well with us as we learn more about where these patients are. Okay. Maybe let's ask a few questions about pipeline because I know this was always Kevin's pet peeve. I thought you guys had no pipeline, but you've always had a pipeline. Can you just remind us of what data sets to expect this calendar year, and then we'll talk about beyond? Sure. A couple of data readouts this year. We often talk about externally, it's a year of execution evolution. The execution side of things is in a couple of areas. We talk a lot about the commercial side of the business and INGREZZA Chronicity. Obviously, we need to execute well there to treat as many patients as we can. There is execution on the pipeline, and that comes in a couple of different flavors. One is making sure that we start all of our phase three trials for osavampator 568. The piece that we often overlook too, because everyone's excited about what's moving into phase three, is the data readouts that we have available this year. We have a couple, just no random, just no particular order. Maybe a little bit interesting to me is the NR2B NAM, the NBI 770 program that we have. This is a program that allows us to potentially have a fast onset of action in major depressive disorder, the same type of approach that you might see with esketamine, but oral, and have a much better or improved profile as it relates to things like dissociative effects. We have that study that's ongoing now that will read out towards the end of the year, and that looks at three doses of active versus placebo. It's a small study, about 70 subjects, but it's consistent with our signal-seeking approach in early phase two development that we've employed over the years. This is looking at the MADRS as the primary endpoint, day five. That fast onset of action is what we're looking for here. What is fast in your definition? Fast? Within a week. You look at the SSRIs or even osavampator in our phase two program, and oftentimes the efficacy endpoint can be four to eight weeks. We are looking at something that's more of that faster onset that you can get with an esketamine or ketamine approach. That's NBI 770. Keeping with the second half of this year, we have a phase three study ongoing for valbenazine for the dyskinesia associated with cerebral palsy. This is a movement disorder, kind of in our wheelhouse with TD, Huntington's chorea. Cerebral palsy, as you know, is a consequence of perinatal trauma in utero or during childbirth. When this occurs, you often get damage that occurs throughout the brain. One of the consequences of this is motor fluctuations, motor disturbances, and dyskinesia is the most common one. This ultimately is in the region of the brain, the basal ganglia, which is important for the VMAT2 mechanism. We think it seems reasonable to test the biology here for these patients that suffer from dyskinesia. We also know that physicians use VMAT2 inhibitors in some of their patients and have seen success. We are looking at a study here that has about 80 subjects where the primary endpoint is the total motor chorea score, which is the subset of the UHDRS, the Huntington scale. We will be looking at the mean change between week 12 and 14 to baseline. This would be, of course, relative to placebo. That will come out towards the second half this year, depending on the strength of the data, what safety and tolerability looks like, and if it's a positive outcome, if we take that to the agency and they say it looks good as well, that could be an indication expansion opportunity for valbenazine. The last study that we have reading out this year is the adjunctive treatment of schizophrenia. This is not an indication expansion opportunity for valbenazine. It's a learning study. This looks at about 400 patients with schizophrenia that are not getting their symptoms completely resolved using an antipsychotic. This is a study that we just got the data. It's hot off the press. The past couple of days, we've gotten our hands on this. The data was as expected. We did learn a lot from the study, but we did not meet the primary endpoint of improvement of PANSS at week 10. We did see numerical separation there relative to placebo. We did see a statistically significant effect on the positive symptoms of the PANSS, but we did not see it on the total PANSS score. We did see also numerical differences, improvements, valbenazine versus placebo in all other key measures. We had the moderate factor scores in there as well, as well as some other biomarkers that are important in schizophrenia. They all favored valbenazine. We did learn a lot from the study. We did not meet the primary endpoint. It was a miss on that. We are applying back the learnings into the next-gen compounds, which are represented by NBI-890 and NBI-675. They are both in phase one right now. I think with these learnings, it really does give you insights into the possibilities of VMAT2 inhibition more broadly within psychiatry. I think that's been the goal here for the next-gen compounds. They've been specifically designed to be more potent than Ingrezza and to offer long-acting injectable opportunities to take us in these broader disease states where these attributes would be beneficial. We got what we wanted from the study, but not the ultimate positive result. The learnings are there, and we'll be able to take that and use those for the next follow-up molecules. Those are the three readouts. For this year. For this year. Okay. Looking on beyond, I wanted to spend a couple of minutes talking about muscarinics because I think, I guess, investors view it now as sort of mixed because of Corona, which is likely successful, followed by the failure of Sara Veld. You have your most advanced molecule is your M4, but you have also got other molecules that are kind of a mishmash of everything. You have got an M1, M4. You have got an M1 by itself. What are you trying to accomplish by looking at all of these different variations? That's a great question. You know, I think that at a high level, xanomeline, one of the two components that are part of Cobenfy, has been studied for 30 years. And it's a pan-muscarinic agonist. There's been very little success on getting selective muscarinic agonists in the clinic to actually tease apart what different pharmacologies could actually bring to the table, both in terms of efficacy and safety and tolerability. That has changed because Neurocrine has those different flavors in its pipeline or mishmash, as you said. I like that. We have four agonists in clinical development. We have ranging from NBI 567. I'm going to drop the NBI here for a moment. 567 is an M1 agonist. We have 568, which is an M4 agonist. That's the one that's in phase three now in schizophrenia. We have 569, which has a bit of M4 and M1. 570 is the dual M1, M4, more equally weighted across those two subtypes. They do not hit anything else. They do not hit M2. They do not hit M3. They do not hit M5. Our collaborator here did a great job of finding a binding pocket that is only conserved in the two subtypes, M1, M4, and not in the other subtypes. We do not have to add back anything to block peripheral effects that might be important when it comes to GI side effects and tolerability, which are primarily attributed to M2 and M3. Our approaches are the only one that selectively and directly activates the muscarinic subtypes of interest without needing anything else for efficacy or safety and tolerability. The reason why I bring up safety and tolerability and efficacy is because the PANS that are in this space require cooperativity of the endogenous ligand acetylcholine. When you would open up an M4 receptor with the PAN, the actual work, the efficacy is delivered by the body's production of acetylcholine. Our approaches don't lean on that at all. They can directly activate these subtypes of interest. That's what we think is the winning strategy here. We think that the data plays that self out between the Cobenfy phase two and phase three data and the imracladine PAN data, which is quite noisy that we saw from AbbVie in phase three. Our approach right now, we move forward with NBI 568. We conducted a phase two trial that read out in Q3 of last year. We studied four doses of Activ versus placebo. The 20 mg dose, the lowest dose, outperformed the higher doses. It's something that we didn't anticipate, but it's not uncommon in this space. The efficacy that we saw and safety and tolerability was outstanding. The 20 mg dose showed an 18.2 improvement on total PANSS. Placebo-corrected PANSS improvement of 7.5 points. Effect size of 0.61 is once a day. There's no food effect, no titration. That's a winning profile relative to the muscarinics and relative to the antipsychotics that are out there. The goal is to replicate that finding in phase three. What we're doing now in the phase three program is much more simplified study design, one dose of Activ versus placebo, parallel design. We're going to have about 280 subjects across 20 sites, and we'll do a study here in the U.S. and another study to be started here shortly, which will be primarily in the U.S. We're excited about what we have there with 568 and schizophrenia, but we're not done yet. We'll be expanding the indication with 568 later this year with the proof of concept study in bipolar mania. When it comes to the other muscarinics, we really do want to test that hypothesis of what's the difference between a selective M4 agonist and an M1, M4 dual. We are going to bring 570 forward into a phase two schizophrenia trial. As those studies read out, we'll be able to compare what does a dual bring to the table versus a selective. We also have some other important physical chemical property differences with 570 that might afford something like a long-acting injectable. We're excited about the portfolio. We're the only one that has it. We're going to be looking at ensuring that we understand the pharmacology across all these different subtypes. Okay. If Matt were here, I would ask him, how does this plan jive with how you're thinking about expenses overall for the company? In terms of expenses, there's probably a couple of things. I mean, right now, as you can probably see across INGREZZA, CRENESSITY, late-stage pipeline, we really are investing in growth. Certainly, profitability is something that we're looking at. As a near-term strategy to maximize profitability, that's not the goal right now. On the SG&A side of things, obviously, we're investing big in both INGREZZA and now the launch of CRENESSITY itself. That takes dollars to do that. We've shown historically we can improve our leverage by 1,000 basis points. We did that over the past three years. That's something that we'll look at doing as time moves along through the CRENESSITY launch. We've also guided this year about $125 million incremental spend in SG&A. I think it takes care of that component. On the R&D side of things, we usually peg about 30% of net revenue goes into our R&D spend. Right now, we've got some big tick items with our phase threes going on. I think we would guide to kind of like a mid-30% R&D spend range. We'll continue to look at that as time moves along. Ultimately, the North Star here is the quality of the assets and the need to move those forward if they're aggressively, if they're high-quality assets. Yeah, I'm not going to do an impression of Matt since he's listening, but he would say it's a high-quality problem to have. High-class problem. High-class. Hey, Matt. Hello, Matt. We miss you. Okay. All right, guys. I think we're out of time today. Thanks for. Thank you, Tazeen. Thanks, Tazeen. We appreciate it. Thank you, Diego. Thank you, everybody, for joining us in the room. Thanks, everyone.