Hi. Good afternoon, everybody. Thanks for joining us. I'm Marc Goodman, one of the biopharma analysts here at SVB Securities. Thanks for joining us at our conference. Very lucky to have the team from Neurocrine joining us here. Kevin Gorman, the CEO, Matt Abernethy, the CFO. Everybody knows these guys. Thank you so much for joining us. Obviously one of the leaders in the CNS space. You know, if you went back years ago, it was like, well, how big is this part of tardive dyskinesia drug gonna be? I think we probably started out, oh, is this even a $500 million drug? Today, you know, the over-under has probably moved above $2 billion and, you know, it could even be $2.5 billion right now. It's probably, you know, kind of the number that everybody's talking about. I think also the discussion is, okay, they've done just an amazing job with the first drug. We'd love to see a second drug. You know what I mean? Like, that's kinda like what we keep hearing, and I know y'all hear it too all the time. Kevin, maybe I'll give you a chance to make some opening comments, but in that opening comment, maybe you could just talk about your philosophy, the real philosophy around how you're building out the pipeline, how you think about it, you know, what you're focused on. Sure, Marc. Thank you very much to you and to SVB for making it possible to speak here today. Before I start, we will be making forward-looking statements. I'd like to direct everyone to our recent SEC filings. Very briefly, for those of you who are new to the Neurocrine story, we're a neuroscience company. What neuroscience means to us is three areas now, which is neurology, neuropsychiatry, neuroendocrinology, and poised to go into neuroimmunology in the future. Actually, neuroscience is quite a broad field, and that's why we stick to our knitting. We've always been a neuroscience company, and I see us as being a neuroscience company for a very long time. We've been around about nearly 30 years, as you said. We have a very good product on the market that we market ourselves in North America, discovered and fully developed here at Neurocrine. We also have another product that our partner, AbbVie, is selling that was discovered, developed through phase II clinical trials, partnered with AbbVie, worked together on the phase III. They filed the NDAs. It's in women's health, so neuroendocrinology, ORILISSA and ORIAHNN, for endometriosis and uterine fibroids. When you look at Neurocrine, as you said, we have this tremendous product that physicians and patients and their families have embraced, which is for a disease state that when we launched about 5 and a half nearly 6 years ago now, I don't think anyone had ever heard the term tardive dyskinesia. It is a debilitating movement disorder, largely irreversible. It is caused by taking antipsychotics, very important drugs. There's probably about 80 million prescriptions of antipsychotics each year in the United States. Small percentage of patients develop tardive dyskinesia, and even if they never touch an antipsychotic again, this is a disease that, once kicked off, continues and continues to progress and will be there their entire life. It's characterized by extreme movements in the entire facial area, the eyes, the mouth, the tongue, the jaws, but it also is in the hands, the arms, the trunk, and the legs and feet. INGREZZA has been an amazing drug, extremely well-tolerated and helps the vast majority of these patients relieve, if not all, but the majority of their symptoms. It is a drug that we've invested in heavily because these are generally patients that have severe psychiatric conditions. It takes a large investment to be able to touch these patients, to educate them, their caregivers, the HCPs, on a disease that, frankly, physicians were trained to ignore because there was nothing they could ever do for these patients. The disease had been around since the very first typical antipsychotics, the first generation, but even the second generation causes that. When we launched 6 years ago, maybe 2% of TD patients had been diagnosed. Now we're up to maybe 25%-30% diagnosis. That still means 7 out of 10 patients aren't diagnosed. Still a lot of work for us to do and a lot of opportunity out there. Even stepping back where we've made that first step in being able to get 30% of the patients diagnosed, only half those patients are is. That means that the size of the patient population that can be treated, even if nobody else is diagnosed, is double where we are today. As the guidance that we gave just a couple of weeks ago, we gave guidance that this year we'll be selling between $1.67 billion-$1.77 billion with INGREZZA. That's better than a 20% growth rate over last year. Yeah, around $300 million year-over-year increase. I think, Marc, as you said in the opening remarks, many people, you know, had expected this maybe to only be a half a billion, as Kevin said, a lot of opportunity still ahead. Going to the second part, obviously we there's a tremendous amount of runway and growth that we see with INGREZZA throughout this decade. Beyond. Right from the moment that shortly after we launched INGREZZA, we said, "Okay, someday, way off in the future, we're gonna have a loss of exclusivity here." At that time, we had our composition to matter was expiring in 2029. We've been extended the 2-year Hatch-Waxman extension to 2031. We've now been talking, given clearance by our our patent counsels internally and externally, that the 20 Orange Book patents that we have will take us out at least until the mid-2030s. When we launched and we started to build up Nerfin, not only to take advantage of bringing INGREZZA to as many patients as possible, we also realized that we have the opportunity now here to really spread Nerfin into all of the areas of neuroscience that we want to. We started working heavily towards that goal of that in a decade or more, more than a decade from now, we wanna be a very different-looking company than we are today. We have 13 compounds in the pipeline, 12 of which are phase II and beyond. 5 of them are registrational studies that we have going on. We have within our research and preclinical development, a vast array of targets that we're progressing forward, and different than where we were several years ago. These aren't all orally active small molecules that we have earlier on that are following up. These are peptides, proteins, antibodies, and also, gene therapies that we're going to be introducing into the clinic over the coming years and have as products by the end of the decade. Where we are working from now with a robust pipeline is a highly differentiated portfolio of products that not all of them are gonna make it to market, but several of them probably will. That is going to be again, in neuropsychiatry and neurology and neuroendocrinology. Then following with those, and they're all symptomatic treatments. Following with those, what we're working on today, we look by the end of the decade introducing products that are going to be disease modifying or even curative in neurology. I'm gonna stop there, and I put a lot on the table for us to talk about. Yeah, yeah. Well, let me ask you this, like, you know, you have multiple approaches to schizophrenia, right? Did you decide we wanna play in schizophrenia, we're gonna diversify that risk, within schizophrenia? You know, is that? You know, it's also interesting, like if you look at the muscarinics, you know, we've got people developing M1s, M4s, M1M4s. You're doing them all. You know what I mean? Like, I'm just trying to understand how your philosophy behind it all. Yeah. The philosophy is, you're right on. We know that neuroscience as a whole is one of the most risky areas of drug development. How do you mitigate that risk? We are 100% dedicated to neuroscience. The way we do that is twofold. When we find a mechanism that we think has a tremendous amount of potential, we like mechanisms that we can drug that mechanism, get a molecule for it, and that mechanism is involved in multiple neurologic diseases. We can explore it in multiple diseases. That's number one. You've invested in a mechanism, in a compound in that mechanism, and you have multiple diseases to go to. We also, as you point out, there are disease states that we're highly dedicated to: schizophrenia, major depression, and epilepsies. Let's stick with the psychiatric ones, highest risk. If you look at schizophrenia, if you're just gonna use one mechanism to go after schizophrenia, boy, oh boy, that's risky to do that. We take multiple mechanisms into a disease state. Now what you're overlaying is mechanisms that have multiple diseases they can go into, and we have multiple mechanisms going into single disease states. That kind of overlay that we put on it gives us a higher probabilities of success. The obvious thing is that what we try to do here is we either try to kill early or show success early. That's what we do. We'll go into an area, design a trial that's going to tell us, is this going to be fruitful or not? We follow the science. Whatever the data comes out, those programs that have great data, they get more investment. Those that don't, we put on the side. We're not lacking really interesting targets, interesting and highly unsatisfactorily treated diseases to go into. Yeah. I mean, it's just so interesting with the muscarinics, right? I mean, you know, obviously Karuna has demonstrated some good data with a couple of studies with an M1M4, so everybody's like, "Okay, well, the M1M4 works," but who's to say that an M1 or an M4, you know, alone would be a better product than the combo, right? I think your approach is, we're not sure, we'll figure this out, and that's the one we're gonna move forward. Exactly right. I think that, especially in psychiatry, animal models are getting better, but I'm not gonna stand up here and defend psychiatric animal models. You need to get into humans in order to understand what you have in psychiatric diseases. Fortunately, we now have phase II studies that can be predictive of success in phase three. It wasn't that long ago that psychiatry didn't have that at all. phase II is certainly just kind of dose-finding, and then you hope for the best in phase three. That's not the situation the field is in anymore. phase I and phase II, we don't have biomarkers per se, but we have non-invasive surrogates that I think are more highly dependable. Like you say, the muscarinic is something that we didn't just get into it when we did the deal with Sosei Heptares. We've been doing muscarinic research here for about 7 or 8 years, both on agonists and on antagonists. What you see us in, as you said, we've got the M4 agonist that's in the clinic and we're enrolling really well in schizophrenia right now. That's the lead. We have an M1, M4 mixed agonist that's going to be going into the clinic this year. We have a M1 agonist that's in the final stages of preclinical. Let's see how that comes through so that hopefully it can be nominated into the clinic this year. Then we even have an M1 antagonist that we're bringing up. We're going to be able to, and I think we're the only company who can do this. Yeah. Is fully interrogate this. Our goal here with this highly relevant mechanism and receptor systems is to be able to pick the right compound, the right pathway for the right disease. Why go back to Voyager and do another deal with them? That is a question that I've gotten from investors quite a bit over the past 3 or so weeks. The bottom line is that, as I said, back when we first did the first Voyager deal several years ago, that by the end of the 2020s, prior to going into 2030, there will be curative medicines in the neuroscience space. We've already seen a couple of those that have come up early on. We are, as I said, dedicated to be a neuroscience company, have been all these, all these years. We have a goal of being a preeminent neuroscience company. In order to do that, you have to plan that you're going to actually cure and modify neurological diseases. Gene therapy holds the greatest promise of that. I've been in the business long enough to see that new therapeutic modalities go through a torturous road to get to that. I watched and was in the industry when IDEC got the first monoclonal antibody that was ever commercialized. If you recall way back then, monoclonal antibodies were so out of favor. They just weren't working. They went through a huge excitement phase, they lulled back down. Looks a lot like gene therapy today with the fits and starts. We compress those cycles now with technologies. You go through the cycles quicker. We needed to get into gene therapy several years ago. Voyager appeared to be a company that had some interesting technology to get into gene therapy, where you're still delivering the vectors centrally, but you can deliver into the brain. We got into it there. We learned a lot. We built a lot of internal capabilities that people just don't see in that. Ultimately, those first generation capsids and second generation capsids, they weren't sufficient to be able to do peripheral administration, cross the blood-brain barrier in a targeted fashion, and be able to reach the regions that you want to. In those intervening years, Voyager's undergone a number of changes, and they are now top 2 in the world with technology that has just that, the best capsids and the way of developing those capsids, discovering and developing those capsids using non-human primates as the, as the selection, as the sieve. Not just one species, but multiple species of non-human primates. In order to have capsids delivery vehicles that can be given peripherally, preferentially in a, in a markedly preferential way to get into the brain, and to then be able to deliver the genetic payload into the brain. If you're not gonna be a part of that now, you're not gonna have an opportunity in the future to be a part of it. Compared to the rest of our investments, it's a relatively, I'm not gonna discount the upfront payment, but it's relatively modest compared to what we can do in business development. We did that deal. Now I would argue that between the first deal, which we're now applying the newest generation capsids too, and the targets there. This second deal bringing in even more targets into that. We probably have the largest pipeline of neurological gene therapies of any company that exists. Voyager did a lot of advancements, basically, is what you're saying. Exactly right. Past couple of years. Yes. I think, Marc, the questions are really coming in from investors because you started off this conversation in really what's next for Neurocrine beyond INGREZZA. A deal like that that's going to evolve over the next 5 to 10 years is something that, you know, I think doesn't satisfy, you know, investor appetite right now, but we do believe in the science. I think if you reflect on where we're at, we have a great medicine, we have a long dated patent life, as Kevin talked about. From a financial perspective, we have plenty of flexibility left. I would say, even though we know we have time from an IP perspective, that doesn't mean we don't have a sense of urgency to continue to develop and evolve our company. We have a lot of important data readouts coming up. One in particular we haven't touched on yet, which is the crinecerfont data that will be out later this year, which could be, if data is good, a blockbuster medicine. As Kevin said, earlier, a lot coming out over the muscarinics over the next several years. How this unfolds, how our story unfolds, you know, we're very excited about it over the next 3-5 years. Yeah. Just to put a final note on this, and we can get into individual programs, if you'd like. The current pipeline that we have offers us multiple products, important products over the next 5 years. Voyager deals, all the work that we do internally on peptides, proteins, and other and other gene therapies that we have, that's that 5 years afterwards. We're extremely active in continuing to, from a business development aspect, to be able to look at opportunities that give us late-stage opportunities that can even be products even earlier than that over the next 5 years. Let's talk about crinecerfont. I think you used the word blockbuster. I think today, blockbuster to us means a billion-dollar drug. I don't wanna put words in your mouth, is that what you think this drug could be? If it could be that, how does it get there? When you look at crinecerfont, you have something that reminds you an awful lot like tardive dyskinesia. When we launched INGREZZA five years ago, six years ago, there was never a drug developed for tardive dyskinesia. Here we have one for that population, a population that was largely ignored. If you look at patients who have congenital adrenal hyperplasia, which they can't make cortisol. Therefore, since they can't make cortisol, you have to give them a replacement dose of hydrocortisone. That's the last drug that was developed into this back in the 1960s, like 1964. That's their one and last drug that was ever developed. It was clear that you could give them very small doses of hydrocortisone to replace their lost cortisol. That kept them alive. What became clear quickly is because they can't make cortisol, all the precursors for cortisol pile up, and they get shunted into another pathway where they make massive doses of androgens. How do you control that massive amounts of androgens? If they had a normally functioning hypothalamic-pituitary-adrenal axis, the naturally occurring cortisol would go back, shut off the signal on a 24-hour basis about keeping their androgens at a normal level. The only way taking hydrocortisone daily, multiple times a day, can do that is to give them very high doses of hydrocortisone. That's the only way they can start dampening down those endogenous androgens. You have this seesaw that the endocrinologist does with these patients. Let their HPA axis go completely out of control and have these kids growing up with massive amounts of androgens. Stunts their growth, has a lot of metabolic effects in addition. give them massive doses of hydrocortisone every single day. that controls the androgens, there's the whole host of problems that come with massive doses of that. Crinecerfont recaptures. It's not a steroid. It actually recaptures that HPA axis and lowers the androgens down to normal. We've shown that in phase II, the drug works. If crinecerfont does the job to lower androgens, you should be able to take the hydrocortisone and bring it down to just replacement levels, not these massive doses that you have to give each day. That's what the phase three program is all about with this. 30,000 patients in the United States with CAH. another 30,000-40,000 in Europe. We plan on commercializing this ourself. Obviously, in the United States, we can handle that easily. Also, this is a perfect drug to do our foray to internationalize Neurocrine and to be able to market it ourselves over in Europe. You look at those 2 regions for having a drug that will completely change the face of treating CH patients from babies all the way up to now we have CH patients who are in their late 50s. That is the promise that we have for this drug. It's a game changer. It's first in, and it could be a high-priced product given those two. It's an extremely high-value drug, we believe. Knock on wood that our phase III trials show what we anticipate them showing. With that high value, we plan on pricing it appropriately. Your view globally is this could be a billion-dollar drug between. Our- The regions. Our- If the data are good and the safety profile is clean, you could see a very large percentage of CH patients benefiting from a medicine like crinecerfont. Yeah. Matt, switching gears. I think, you know, on the quarter, the incremental spend that you provided for guidance in SG&A was just a big number to people, whether it truly is a big number. I think it surprised people. Can you just help us like here are the 5 or 4 or 3 things that drive the increment and why we're spending? Yeah. Well, why we're spending is pretty clear, right? 7 out of 10 patients with tardive dyskinesia have not- Yeah. You're a believer. diagnosed, yeah. Your incremental spend last year was totally worth it, right? Yeah. The, the sales force expansion is in place for a full year now, so you do have an increment of spend there. You have the continuation of the DTC campaign. You have natural, you know, inflationary pressures that push up costs in particular, when you're trying to motivate team members. Lastly, I would highlight that we are investing with the hopes and expectations that the Huntington's indication gets added to the label this year. Our top line sales number does not include anything. The $1.67 and $1.77 does not include anything associated with Huntington's disease. It only includes tardive dyskinesia. Right. Our spending in SG&A includes what we intend to spend to support a Huntington's launch. We understand the pressure. You have to grow. You have to continue to grow, and at what cost do you have to spend to get to that growth? We expect to have 300 basis points of leverage this year, and we would expect to continue to see leverage over the years ahead. What's the biggest part of that $110 million increment? people. It's people. Yeah. I think it's people supporting people, whether it's inflation or expanding teams that surround INGREZZA to make sure that- Right ... a script written gets filled. I'd say, from a personnel perspective, that's a large chunk. The second piece, like I said, is some of the marketing activities that we expect to spend, associated with Huntington's. Getting ready for positive CH data. Yeah. Right. Right. Right. Right. We've got a couple of readouts, the anhedonia, proof of concept. What's the reason to believe that that can work? Yeah. The, the anhedonia, it's an interesting indication. It means basically an apathy and inability to feel pleasure, joy. We're studying it in major depression, where it's obviously very prevalent, but it's very prevalent across the spectrum of different neuropsychiatric diseases. The, the reason to believe here is it's going after an orphan receptor, okay? That's one thing. It is an orphan receptor, but it's in a very tiny portion of the brain. It's the only place that this receptor exists, the habenula. That is the area that is responsible for pleasure and joy. It makes a whole lot of sense. You have a unique receptor that is only in an area, and this tiny area with its projections, is known to control that. We were fortunate to have a drug that came through our Takeda relationship because they really believed in this. We took it further after doing it after doing the deal with Takeda. What we wanted to do was a relatively quick but very good study to again say, "Is this real? Is this pathway a pathway that's going to show us efficacy in this?" If it is, that is an amazing opportunity for patients, an amazing opportunity for Neurocrine. The spend- Oh, sorry. The spend on it is small, and we're getting the signal. We're gonna get this data relatively rapidly after doing that deal. You've got good target engagement. You know you're hitting where. We know we're hitting it. Yes. Yeah. you know that hitting that is helpful to anhedonia, so now it's just a matter of- We know that because of the circuitry, there's a very good chance- Yeah that it has to do. Again, animal models. Yeah. In psychiatry, I don't-. Mm-hmm. Yeah. It looks good in animal models. I don't put my faith in animal models. Let me ask you the same question for the focal onset data we're gonna get later this year. Yeah. Recent same kind of, you know. Yeah. That's a collaboration that we did with Xenon Pharmaceuticals. Where that is, that was a molecule that Xenon Pharmaceuticals did a terrific job in their technology, because they have some of the best ion channel technology that's out there. Xenon Pharmaceuticals designed this molecule to hit very specifically sodium channel Nav1.6, and that's all it hits. It doesn't hit any of the other sodium channels, none of the others that are in the heart or anywhere else. It hits just Nav1.6. They specifically targeted that and the region of Nav1.6 that is mutated in a genetically defined population, which is called in a pediatric epilepsy, SCN8A. That's what the drug was designed for, and we have that in a clinical trial, phase II, 3 in SCN8A. We know from many old antipsychotics, and that's all that exists, that sodium channels are extremely important in one of the large seizure disorders, which is focal onset seizures. What we wanted to know was, would a highly specific sodium channel blocker be as effective or more effective than the dirty ones that are out there that are far less potent, like a 1,000-fold less potent than our compound, and would not have all of the off-target toxicities, nor do you have to give it in such high doses that you have just very low tolerability. Because of the specificity and because of the potency, are we going to be able to have similar efficacy, but we don't have to pay a price, the big price on safety? That's what the hope in focal onset is. Again, I would tell you, going with let's look at this rationally designed molecule for SCN8A. Let's look at it in another indication that we know the mechanism involved, but is this the right molecule for that? We are getting that answer pretty rapidly in what could be a very large indication. Thank you. We're kinda running out of time. Any last comment, anything that we didn't cover that you wanna make sure we cover? I think that we covered a lot. Your questions, I think, gave us a lot of leeway to go places. I say what we have here is, I say, a very exciting and growing commercial base anchored with INGREZZA, where we're adding multiple indications, Huntington's being the first, adjunctive treatment in schizophrenia, dyskinesia, and cerebral palsy. All of that is adding on to this wonderful base that we have formed with INGREZZA. We have a great pipeline that's going to yield commercial products over the next five years, and we're making the continued investment for the end of this decade. Then we are probably one of the most active biotech companies out there on a business development front, and we'll continue to be that way. Thank you. Thanks, guys. Really appreciate your time. Thank you. Marc, thank you. Take care.