Hello, and welcome, everyone, joining today's Neurocrine Biosciences Fourth Quarter and Fiscal Year 2025 Earnings Call. [Operator Instructions] Please note, this call is being recorded. [Operator Instructions] And it is now my pleasure to turn the meeting over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

Happy Wednesday to everyone, and welcome to Neurocrine Biosciences Fourth Quarter and 2025 Year-end Earnings Call. With me today are Kyle Gano, Chief Executive Officer; Matt Abernethy, Chief Financial Officer; Eric Benevich, Chief Commercial Officer; Sanjay Keswani, Chief Medical Officer; and for the first time, we are very pleased to be joined by Samir Siddhanti, Vice President of Strategy and Corporate Development. During today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. After prepared remarks, we'll be happy to address any questions. With that, Kyle, take it away.

Thanks, Todd. Good afternoon, everyone. A hallmark of a healthy company is the strength of the foundation beneath it. As Neurocrine enters 2026, our foundation is stronger than at any point in our more than 30-year history and it continues to strengthen, with growing enterprise-wide momentum and strategic and balanced diversification, Neurocrine has entered a new era of meaningful growth led by our first and best-in-class commercial brands. INGREZZA performance continues to impress, strategic investments in access and sales force expansion drove a record year for both new and total prescriptions. This momentum carries us into 2026, where despite 9 years post launch, we expect double-digit volume-driven growth supported by continued demand from the roughly 9 out of 10 TD or HD chorea patients not currently taking a VMAT2 inhibitor. Like INGREZZA, CRENESSITY's launch has also been exceptionally strong. By the end of the fourth quarter, our first full commercial year after its approval in December 2024, prescriptions covered over 10% of the classic and general adrenal hyperplasia patient population, underscoring the tremendous unmet need. What a great start, and I'd like to thank our team for making this all possible. This strong early adoption across patients, caregivers and prescribers reinforces our conviction that CRENESSITY will become Neurocrine's second blockbuster product. With an FDA-approved label supporting uncompromised efficacy, including an efficacious first dose with no requirement for titration, multiple formulations for pediatric and adult populations and a favorable safety and tolerability profile, CRENESSITY is rapidly becoming the standard of care for patients with classic CAH. This profile mirrors the attributes that supported the success of INGREZZA and underscores our confidence in CRENESSITY's impact for patients and Neurocrine moving forward. Turning to research and development. At our December R&D Day, we outlined three strategic pillars. First, we aim to lead the…

Thank you, Kyle, and good afternoon, everyone. 2025 was a noteworthy year for Neurocrine as total product sales grew to more than $2.8 billion, representing 22% year-over-year growth. This performance reflects continued strength and durability from INGREZZA and the successful initial launch of CRENESSITY. Together, these products form the foundation of our growth and generate durable cash flows that support long-term shareholder value creation. INGREZZA generated just over $2.5 billion in revenue, up 9% year-over-year, driven by double-digit volume growth, partially offset by pricing concessions associated with formulary access investments to support long-term growth. Fourth quarter performance was in line with expectations outlined on our Q3 call. New prescriptions remain near record levels achieved in Q3, a strong result given the ongoing sales force expansion. Looking ahead, we are guiding to INGREZZA sales in the range of $2.7 billion to $2.8 billion in 2026, representing approximately 10% growth. This outlook reflects continued double-digit volume growth, including contributions from the expanded sales force in the second half of the year partially offset by price declines tied to formulary access improvements implemented in 2025. Overall, we expect net pricing in 2026 to be relatively consistent with levels exiting 2025. INGREZZA enters the year with strong NRx momentum, broad access and an expanded commercial team ready to execute. For CRENESSITY, we exited 2025 with over $300 million in net product sales and approximately 10% of addressable patients being prescribed CRENESSITY. As a first-in-disease launch, quarter-to-quarter enrollment form activity can be variable, but what gives us confidence is the number of patients on therapy, refill behavior and the speed of reimbursement. Feedback remains extremely positive and our first year on the market exceeded both internal and external expectations. Given that CRENESSITY is the first product approved for classic CAH in more than 70 years,…

Thanks, Matt. I'm very proud of our team's performance last year across both CRENESSITY and INGREZZA, and I'm equally enthusiastic about the significant opportunity ahead for both brands. Matt covered the financial highlights, so I'll add additional color and highlight key focus areas to drive continued growth for both brands. For the CRENESSITY launch, you've heard us say so far, so great, and 2025 certainly lived up to that mantra with over $300 million of net sales in the first full year on the market. Throughout 2025, we saw strong demand across pediatric and adult patients and across both genders with prescriptions now trending towards a majority of pediatric patients in female patients on therapy. Importantly, while new patient starts may vary from week-to-week and quarter-to-quarter, once the patient initiates treatment with CRENESSITY, they tend to stay on CRENESSITY. This real-world experience is consistent with our experience in the open-label extension studies. As we've said from the outset, as a first-in-disease medicine, CRENESSITY is a learning launch, very much aligned with our experience with INGREZZA in TD. In fact, the parallels between the two launches are remarkably similar. Both INGREZZA and CRENESSITY are first in disease therapies for conditions that previously lacked specifically FDA-approved treatment options and both achieved approximately $300 million in sales in their first 12 months. Being a first in disease launch, we still have much to learn about the patient population, the prescriber base and potential seasonal dynamics. And similar to INGREZZA, while we're not providing specific annual guidance in year 2, we remain highly confident that CRENESSITY will be Neurocrine's second blockbuster medicine as we establish it together with replacement of glucocorticoids as the standard of care treatment for patients with classic congenital adrenal hyperplasia. As we enter CRENESSITY's second full year on the market,…

Thanks, Eric, and good afternoon, everyone. In keeping with this year's focus on momentum and strategic diversification, our clinical organization will enroll and advance more studies than at any point in Neurocrine's history. While most of my future earnings remarks will center on enrollment progress and study initiations. Today, I'll highlight recently disclosed data for our 2 commercial assets, INGREZZA and CRENESSITY. An optimal way to compare therapies is through head-to-head studies. With that in mind, we recently published first of its kind head-to-head data comparing INGREZZA and AUSTEDO XR at the 64th Annual Meeting of the American College of Neuropharmacology. PET imaging results confirmed what we've long believed, not all VMAT2 inhibitors are equal. In this study, INGREZZA demonstrated a nearly twofold higher VMAT2 target occupancy compared with therapeutic doses of AUSTEDO XR, an important finding that indicates INGREZZA's superior efficacy in treating tardive dyskinesia. Turning to CRENESSITY. We recently shared data from our open-label extension study. While multiple analyses are still underway and will be presented at upcoming endocrinology meetings, including ENDO 2026, the main takeaway is clear. Across both adult and pediatric CAH patients, CRENESSITY continues to show robust sustained clinically meaningful benefits through 2 years of treatment. We see durable reductions in excess ACTH and androgens directly addressing the underlying pathophysiology of CAH and maintaining control over time. In pediatrics, CRENESSITY delivered sustained ACTH suppression while preserving normal physiological signaling, including the immune stress response. Hence, rates of adrenal insufficiency remained very low, 0 in the pediatric double-blind study and 1.6% in adults, identical between active and placebo patients. In a prepubertal subset, we also observed slowing of bone age advancement, translating to a predicted adult height increase of over 2 inches. In adults, approximately 70% of patients were brought into the physiological steroid range while maintaining androgen control and about 40% of overweight or obese patients achieved at least 5% weight loss over 2 years, reflecting CRENESSITY's beneficial cardiometabolic effects. Safety and tolerability remain excellent with approximately 80% retention at 2 years, no new safety signals and over 35,000 patient weeks of exposure. Overall, these data reinforce CRENESSITY's strong differentiation across efficacy, safety and tolerability and support our conviction that it will continue to be the standard of care treatment for patients with classical congenital adrenal hyperplasia. Regarding our industry-leading neuropsychiatry programs, the late-stage Phase III studies for osavampator in major depressive disorder and direclidine in schizophrenia are enrolling well. And just last month, we initiated a Phase II study of NBI-'890, our next-generation VMAT2 inhibitor for the treatment of tardive dyskinesia. All other studies in our portfolio are advancing as expected, and we look forward to keeping you apprised of our progress. With that, I will hand the call back to Kyle.

Thanks, I think we can go ahead and take questions now.

[Operator Instructions] Our first question comes from Paul Matteis with Stifel.

Congrats. I appreciate that you're not guiding on CRENESSITY, but I was wondering if you could maybe give us either a window into the first 6 weeks of 2026 or just more broadly, the number on the revenue side, obviously way above consensus in 4Q. But as we look at start forms, there's a slight decline from 2Q to 3Q and 3Q to 4Q. Curious in your perspective on what you're seeing now and where you think this kind of patient add rate might plateau in, say, the near to midterm?

Paul, so we're going to start giving weekly sales information out on the web. Just kidding. I mean it's been a tremendous year -- it's been a tremendous year for CRENESSITY over $300 million in the first year. Congratulations to the team. And we really look forward to year 2 being another strong, exciting year. We do anticipate meaningful steady new patient additions every single quarter that's going to lead to a very nice growth year. We still, of course, have a whole lot to learn associated with this launch. As you remember, with INGREZZA it took us about 4 years to get to a guide, but we will be providing insight every quarter as it relates to net sales, demand and overall reimbursement dynamics. I'd say looking around the table, we couldn't be more proud of the team and what's been accomplished this year and really feel good with how we're positioned for the years ahead.

We'll take our next question from Cory Kasimov with Evercore ISI.

I wanted to ask about that receptor occupancy poster from late January regarding INGREZZA versus AUSTEDO. Curious how you might use this information? And what are the potential implications here with regard to your next-gen VMAT2 inhibitors?

Yes. So we're quite excited by the data we showed, which is essentially a head-to-head PET study between AUSTEDO XR and INGREZZA. And as we articulated in our recent press release, we saw nearly double the target occupancy for INGREZZA after 1 dose versus AUSTEDO XR. And even when we measured at steady-state concentrations, we still had a markedly superior advantage in terms of VMAT2 target engagement. We think this underlines the efficacy that we see in INGREZZA in the community of patients with tardive dyskinesia as our belief is that the higher the rate of VMAT2 target occupancy, the greater the efficacy in terms of control of tardive dyskinesia. In terms of the second part of your question, we clearly have a lot of experience in terms of matching receptor occupancy with clinically efficacious doses. And we're utilizing that relationship with our 2 VMAT2 follow-ons. Indeed, we started a Phase II study of our first follow-on in tardive dyskinesia quite recently.

We'll take our next question from Phil Nadeau with TD Cowen.

Congratulations on a productive year. I just want to follow up on Paul's question on patient dynamics with CRENESSITY. I think in your prepared remarks, you mentioned the possibility of seasonality in patient demand. And I think investors were all debating whether there could have been an early launch bolus to patient initiations. Appreciating that you still have a lot to learn, what have you learned about those 2 factors and patient dynamics, one in early launch bolus and two, whether there's any seasonality as you go through the year?

Yes. Thanks, Phil. This is Kyle. Good question here on that. I think it's important to keep in mind that the similarities that Eric called out in his opening remarks here are quite true and accurate across the Board. In terms of the first year of launch, we've gone through our first Q1 through Q4. As we've learned in most orphan diseases and launches, whether it was INGREZZA or looking at others, there's always ebbs and flows in enrollment forms. And in particular, early in launch, it's typically a function of frequency of office visits when patients initially hear about the opportunity for a new medicine and physicians getting the word out. So I think it's too early to call whether or not there's any seasonality component. It takes a couple of quarters to draw those conclusions across multiple years. And it took us a while to get to that level of confidence with INGREZZA. So I think it's prudent right now to collect that information and make a more sound decision about guidance, enrollment forms, things of that sort as we get a little bit further in the launch. But rest assured, great feedback out there across all the stakeholders, prescribers, physicians and even payers out there. So nothing out there is saying that we're anywhere but moving towards changing the standard of care and achieving blockbuster status like we've done with INGREZZA.

We'll take our next question from Brian Abrahams with RBC Capital Markets.

My congrats as well on a very productive year. Question on the expense side. It seems like you're expecting a little bit of an uptick in R&D expenses for this year relative to 2025. Can you talk a little bit more about the components of that? How much of that is some of the earlier-stage programs like obesity? And how quickly could some of those costs potentially roll off in 2027 once the Phase IIIs readout?

Yes. Thank you for the question. The cost increase is really on the heels of the Phase III trials and pushing those forward for a full year this year in 2026. The obesity investment is actually quite minimal for 2026, but of course, is a really important program for us to be able to drive shareholder value creation, which we would expect some level of data in '27. But from an expense, when do expenses roll off, we would anticipate for the major Phase III programs. Those will carry on through 2027 with a big chunk falling off in 2028.

We'll move next to Tazeen Ahmad with Bank of America.

I wanted to go back to CRENESSITY for a second. So I know it took, what is it, 3 or 4 years before you guys started giving guidance on INGREZZA. What kind of metrics did you need to collect in order to get confident in providing guidance? And do you have a sense of whether or not it would take that length of time before you get confident with CRENESSITY and providing sales guidance for that as well?

Tazeen, maybe I'll tackle the second question first. It may not take as long to get to a point where we feel comfortable giving guidance with CRENESSITY as it did with INGREZZA. This is a rare disease. INGREZZA is not a rare disease, but it was at the time, a rarely diagnosed disease. We have a single -- essentially a single prescriber base in endocrinology versus multiple different specialties and different sites of care and so on, which made getting a handle on INGREZZA a little bit more challenging early on. As I mentioned in my prepared remarks, both are first-in-disease therapies, both are breakthrough medicines. But as Kyle stated, we've gone through one cycle so far with CRENESSITY in classic CAH and it has been a learning launch for us. There's a few factors that have been a little bit different than what we expected, but different in the positive. The adoption rate was greater than what we had expected coming into this launch, which is awesome. Certainly, the reimbursement has been favorable, and we've been very pleased with the persistency that we've seen when patients start treatment, they tend to stay on it. So as we get more experience in this community in the CAH community and as we learn more about how we're able to reach sort of beyond that first 10% of the population that I talked about, then I think we'll get to a point down the road where we feel more comfortable providing specific guidance.

Let's not confuse not providing guidance with not expecting significant growth this year. Everything that we see from steady enrollments of new patients along with patients staying on therapy, everything points to there continuing to be strong growth. It's just a company decision that we made to not provide a guide here.

We'll move next to Corinne Johnson with Goldman Sachs.

I guess beyond the pricing discussion with respect to INGREZZA and AUSTEDO, which I guess is now better understood, how are you thinking about volume impact to INGREZZA next year with AUSTEDO becoming a negotiated product? And how do you think formularies are going to handle here in products in the context of maybe more like relatively competitive pricing than we could have expected?

Yes. I mean, obviously, we've been thinking and preparing for the 2027 formulary year and the impact of deuterated tetrabenazine having an MFP negotiated price. But certainly, we're very focused on 2026 as we kind of prepare to go into that next phase. We're in a position now, and Kyle talked about it with his prepared remarks of carrying a lot of momentum into 2026 in terms of our volume growth and new patient starts, having favorable coverage, especially in the Medicare formularies and being able to leverage all of that as we enter into the formulary negotiations for 2027. So we feel good about our strategy for 2027. We believe we'll be able to maintain formulary coverage to enable continued growth. And this is a market that has been growing at a double-digit clip for the last several years, which is pretty amazing, especially for a category that's coming into year 9, year 10. So we feel good about 2026, expect to have another really strong year for INGREZZA, and we feel good about our strategy for maintaining that growth in 2027 and beyond.

And the only thing I would add to that, this is Kyle, by the way, is that on the 2026, we have our contracting done that we pulled through in 2025. So we expect that to be stable this year, no midyear adds like we saw in 2025. So entering '26, we expect the net revenue per prescription to be roughly similar throughout the course of the year. So revenue growth should also track nicely volume growth this year. That's our expectation. So a strong year here like in 2025, we expect good double-digit volume growth and to increase our market share throughout the course of the year.

We'll take our next question from Jay Olson with Oppenheimer.

Congrats on all the progress. We're curious about the 569 study in Alzheimer's psychosis and any potential lessons learned from the ADEPT-2 study of Cobenfy, especially in terms of managing trial conduct across the study sites and any strategies you can use to mitigate operational risks for that study?

Yes. We are watching the progress of Cobenfy in AD psychosis quite carefully. But just as an aside, psychiatry studies deserve specific attention. And we are fortunate to have a very experienced team who've successfully executed psychiatry studies. So for both our Phase III studies, we spent a lot of time carefully selecting sites and ensuring that the patients enrolled in our studies are real patients rather than professional patients who may inflate a placebo response. And indeed, with respect to placebo mitigation, we have a multifold strategy with respect to design of the study, 1:1 randomization, keeping the study sites relatively small. So for example, we only have 20 sites per Phase III study for direclidine in our schizophrenia studies. And also a great deal of hands-on monitoring of sites and site investigators by our internal team. So I think the BMS data were invited some caution with respect to ensuring that we adequately monitor these sites, but we feel in a pretty good position in terms of doing that already.

We'll take our next question from Anupam Rama with JPMorgan.

This is Joyce on for Anupam. Could you discuss the feedback you've been getting from KOLs about your 2-year CRENESSITY data, specifically as it relates to durability of benefit and just how you see this data continuing to support and drive strong persistence of patients on drug?

Yes. So we've been getting a lot of positive support from clinicians who have been prescribing CRENESSITY, as you say, for some time now. And we recently showed that 2-year data and again, listed a lot of positive feedback. I think what's important for these patients and often their parents is showing that androgens are reduced in a chronic fashion. And by doing so, reducing doses of glucocorticoids to physiological levels. And that's a huge deal for this patient population who are essentially plagued by the side effects of chronic glucocorticoid use. So in our 2-year data set, we saw reductions in weight for those individuals who are obese, improved insulin tolerance. And with respect to androgen suppression, we also saw attenuation of bone age advancement and that's a big deal for these patients. And again, their parents because often these individuals have precocious puberty and don't attain the potential with respect to adult height. So really pleased to see that data and also the positive impact on the community. Lastly, I'll say that the drug is actually really well tolerated, very important, particularly in a pediatric population. So no surprises at all despite collecting over 35,000 patient weeks of exposure. Of note, we do preserve the vasopressin-induced ACTH stimulus. I mentioned that because adrenal insufficiency is always a worry, particularly as you reduce glucocorticoids. And we're very happy with that adrenal insufficiency data. Indeed, no cases in the pediatric population and an active versus placebo rate that was equivalent in the adult population. So hopefully, that addressed your question.

Yes. This is Kyle. Maybe just to add 2 quick comments on there. I think the pieces that are really important is if you think about safety and tolerability, the open-label extension, 90% of subjects rolled over and then 80% out to 2 years. Just an amazing safety and tolerability profile. In CAH, although you could say this about many disease states more so than ever for CAH, efficacy gets your foot in the door, but safety and tolerability wins the day. I think the other piece is on the efficacy that we see at 2 years, it really describes the benefits of long-term treatment. You can really bend the course of the disease in terms of progression. The earlier you treat, the younger you are and the longer you stay on treatment. So all good things to think about when we continue to accumulate this longer-term data.

We'll move next to Mohit Bansal with Wells Fargo.

So one is regarding the expenses on the SG&A side. It seems like the sales and marketing increase is more than what we have seen last year. Can you just help us understand is it more towards CRENESSITY or INGREZZA? And then I would also love to understand how you're thinking about INGREZZA given that you are guiding for a 10% growth, which is higher than last year. So do you expect volumes to continue to grow at the rate of last year? Or it's just like you're not seeing price decline this year. So that's probably what is driving it?

So SG&A expense is really the sales force expansion that we mentioned on the last call is a significant part of that. And we also have other ancillary initiatives surrounding CRENESSITY as well as INGREZZA to ultimately drive sales. But this coming year, we do expect double -- or this year, we expect double-digit growth, as we've said. That's partially offset by price, call it, negative 4% based upon the pricing that we -- the contracting that we had entered into in the first half of last year. So you're talking about volume growth at the midpoint of our guidance range for INGREZZA to be in the mid-teens. So we feel really good with where the team is positioned. And of course, with the sales force expansion going to be in place at the end of Q1, we'd expect to see more benefit in the second half of the year.

We'll take our next question from Myles Minter with William Blair.

I just had a question on the number of Tuesdays in each quarter. I'm actually going to ask about the sales force expansion for CRENESSITY onboard in April. Is that required to keep this steady new patient flow in for the product? Or would you expect sometime in the second half of the year maybe that, that sales force expansion helps inflect the product?

Yes. The way I would characterize it is that we're investing in growth. We're very optimistic about the opportunity with CRENESSITY in classic CAH. And we made our sales force size and structure decisions prior to the launch without the sort of, I'll call it, the Monday morning quarterback opportunity of having more data to work with. So obviously, we have been executing this expansion on a relative basis. It's not a large number of FTEs that we're adding into the CRENESSITY team, but we do think it will allow us to do a couple of things. One is to go deeper within the existing prescriber base. And in my prepared remarks, I talked about how we now have over 1,000 doctors that have prescribed CRENESSITY and yet 2/3 of them have only treated one patient thus far. So we know that there's more patients in those practices. And given the very large territory sizes, this will allow us to get in and follow up with the existing prescribers a little bit more frequently. Secondly, we also recognize that there are some patients out there that we haven't been able to reach through the existing sales team. So we can go deeper into endocrinology, and we recognize that some patients are not cared for by an endocrinologist. They might be seeing an internal medicine or a family medicine physician or even an OB/GYN. So we have the opportunity now to explore that a little bit with the expanded sales team. Last thing I'll say is that we're excited about the reputation that we've created within the endocrinology community. We're able to attract some really high potential and I think people with great track records onto the team. We've actually completed the expansion of that group. They're going through training now and we'll be ready to deploy into the new organizational structure at the beginning of Q2. So full steam ahead with the expansion and certainly very excited about the additional bandwidth that we'll have created as we execute against it.

So Myles, I'll be holding a webinar about the calendar and how it lays out the rest of the year. Just kidding, but I did want to go back to a question that Phil had regarding CRENESSITY seasonality, and I think Kyle and Eric addressed it nicely in terms of not having enough experience with CRENESSITY demand side. I meant to mention there is a gross to net impact in the first quarter. It's about 5%, and it's associated with the commercial co-pay reset. So that's one thing I wanted to make sure as you're developing your models and expectations for Q1 for CRENESSITY, that would be something that you take into consideration.

We'll move next to Yigal Nochomovitz with Citigroup.

Congrats on all the progress. I just wanted to probe a little further on the 10% share in CAH. Is it correct that that's all endos? Are you seeing any early share from some of the other categories you mentioned like PCPs and OB/GYN. And I'm wondering to what extent at this point you can use some of the AI database inferencing to sort of tease out which PCPs and OB/GYNs may be the best candidates for CRENESSITY?

Yes. So yes, I just want to clarify when -- in my prepared remarks, I talked about the fact that we estimate that we've reached and gotten on board treatment of approximately 10% of the prevalent CAH population. So taking a step back, in the U.S., we estimate it's around 20,000 people with classic CAH. And obviously, in year 1 to get to about 10% of them and get them on treatment is a really important milestone for us. Virtually all of those new patient starts have been originated within endocrinology. And we recognize that for us to be able to continue to expand the use of CRENESSITY and get broader within that patient population, we're going to have to be able to reach patients beyond the prescriber base that we've reached thus far. And you mentioned patient finding. I talked about that a little bit in my prepared remarks. So we are leveraging different technology platforms and different data sets that will allow us to identify where are patients that look similar, at least in the data to the patients that we've already gotten on treatment and then allow our field sales organization to follow up and to confirm whether those patients exist at this or that practice. Using that information and feeding it back makes the system smarter and allows us to improve our targeting. So this is a rare disease, and there isn't a specific diagnosis code for classic CAH. And so for us to continue to grow and to have that steady growth that we expect, we have to leverage technology, and we also have to leverage the team.

We'll move next to David Amsellem with Piper Sandler.

Maybe I'll ask another CRENESSITY question, but a different way. As you think about furthering penetration, are you getting any kind of pushback from endocrinologists? Or maybe I'll ask differently, what -- are there any barriers to further adoption that you're seeing? And also, as you think about the competitor that's in development, the ACTH antagonist, do you have a sense that doctors are waiting out the availability of that drug to put patients on that modality as opposed to CRENESSITY. Maybe you can talk about that dynamic as well.

Yes. Maybe I'll tackle the second question first. The answer is no. I don't think that community endocrinologists are for the most part, aware of an investigational drug or are warehousing or holding back treatment of patients for a drug that may or may not be available several years down the road. In terms of what's the biggest barrier, I would say it's lack of knowledge. And the reason I say that is that, yes, there are some endocrinologists that are quite familiar with and skilled in managing these patients. But the vast majority of community endocrinologists have little experience with classic CAH. And if they have CAH patients in their practice, they might have a couple of them. And so a big part of our educational effort, I mentioned this in my prepared remarks, is really continuing to educate around classic CAH, the inadequacies of high-dose glucocorticoid treatments, the consequences of patients being either over or undertreated and then tying that back to the clinical profile that's emerged for CRENESSITY, especially the very strong safety and tolerability that we've seen both in the trials and in the real-world experience. So it's really getting physicians past this sort of, I'll call it, pre-CRENESSITY belief that they're treating their patients with these steroids. They think they're doing fine. But when they look closer, they realize that they're having a lot of comorbidities and a lot of complications from either their disease or from their GCs. And as we continue to make that education more broad, certainly, we're seeing that doctors are realizing that, hey, CRENESSITY is a whole new way of treating CAH. It's a paradigm shift. And I think that, that's been borne out in the adoption. The other thing that I'll say is that we've been working really closely with the patient advocacy group, the CARES Foundation. They've been a wonderful partner in terms of educating their membership. And certainly, coming into this launch, we recognize that a lot of patients with CAH or families with CAH didn't fully understand the consequences of either uncontrolled androgens and/or excess glucocorticoid exposure. And so we continue to direct our educational efforts, not just towards HCPs, but also towards the patient community, and I think it's really a benefit to both groups.

We'll move next to Brian Skorney with Baird.

This is Luke on for Brian. So on CRENESSITY, with regard to the remaining estimated 90% untreated prevalent market, can you remind us what proportion is managed at an endocrinologist compared to primary care or other settings?

Yes. I think we're learning that. And so it's difficult to give you an exact proportion of what proportion are under the care of an endo versus a PCP. And one of the things that we've seen at least in the cohort of patients that have been started already on CRENESSITY is that some of them appear to be co-managed by endocrinologists and primary care. And it may be that they see their endocrinologists once a year, but they may be seeing their primary care physician more frequently in the questions who's managing their CAH and refilling their prescriptions and so on. So as we go forward, teasing that out of the data, I think, is really important. And I think that, as I mentioned earlier, being able to identify those primary care or OB practices that appear to have multiple CAH patients and having our sales team go in there and follow up, that creates the mechanism or the feedback loop that allows us to understand where these patients are and the best way to educate, motivate and activate these patients.

We'll take our next question from Marc Goodman with Leerink Partners.

Matt, just a clarification. You mentioned negative 4% price thoughts for 2026. Is that off the $5,500 that was, I think, previously guided for the full year of '25? And then I just actually have another follow-on on the conversation about ACTH antagonist and just how you guys view that drug to be used eventually if it ever comes out with everyone hopefully on CRENESSITY by then? Like is it an add-on? Do you think it will be a competitive product? Or how do you even view it at that point?

We haven't disclosed what the net price was for 2025, but you can think about the 4% being year-on-year, more heavily concentrated year-on-year in the first half of this year based upon the timing of when we entered into contracting. But importantly, and Kyle mentioned this earlier, is that exiting 2025, our net revenue per script is going to be very similar throughout all of 2026. So we did take a bit of price through 2025, but do expect a lot of stability on the net price side as well as and most importantly, on the access side to continue to allow us to build this market.

And then Marc, on your competitor question, I've learned a lot over the course of my first full year as CEO, and one of them is how to talk about competition. When it comes to CRENESSITY, we're really talking about 2 different programs, 2 different medicines at 2 different states. CRENESSITY is an approved medicine. It's had a great launch, and we have a multiple year head start. I think we've got a medicine that's changing the standard of care across the efficacy, the safety, tolerability, the formulations, and we're generating a lot of data over time. I think it leaves us in a really good position. And I think that you all listening on the phone, certainly, I've been doing that here, looking at orphan drug launches, I'm really hard-pressed to see any medicine that delivers on the profile of CRENESSITY and is displaced at all by any future medicine. So I'm really excited about what we have with CRENESSITY. It's a 2 variable positive year for us. We've got a great medicine and a great team that's out there doing great things with prescribers and patients that are there, and we're going to focus on building this brand into a great medicine for patients in the company.

We'll move next to Akash Tewari with Jefferies.

This Phoebe on for Akash. My question is on CRENESSITY as well, but more so on the pipeline. We saw that there's a Phase II study being initiated for patients under 4 years old, which we know is not currently on the label. Can you talk about kind of the importance of the study and when we should expect an update here? And could we expect this to be sort of a growth opportunity when and if on market for this population?

Yes. So as indicated, we are soon initiating 2032, which is a pediatric study. These are individuals less than 4 years of age, the youngest age being 3 months. And the intent is to expand our label, which currently is 4 years and above. So again, we're excited about this opportunity. We should have some data next year on that study.

We'll move next to Sumant Kulkarni with Canaccord.

Bigger picture one here. It looks like you sold your U.K. and European rare commercial business recently. What does this mean for your plans to develop crinecerfont in U.K. and the rest of Europe? And does that decision mean Neurocrine is going to remain U.S. focused? And how much did the potential enforcement of most favored nations pricing have to do that decision?

Yes. This is Kyle. I appreciate the question. I think when it comes to the EU business, the programs that we're working on over there weren't necessarily a good alignment for what we have for our own portfolio today. So we found a good place for those programs to go with the new team there. In terms of our own interest, obviously, we're focusing on the U.S. market now and making sure that we have a really good launch here with CRENESSITY and so far, so good there, and we want to keep focusing our attention there. And look at ways we can potentially bring CRENESSITY and other future medicines to Europe. Right now, we're not really looking at considerations and variables that play in most favored nation per se as much as we are focusing on the U.S. market. But it is an area that is evolving. And before we make any decisions definitively outside the U.S., we'll want to get clarity on where that's going here in terms of a policy standpoint.

We'll take our next question from Sean Laaman with Morgan Stanley.

I have a pipeline question on 890. Just going back to the recent data you showed for INGREZZA and the 80% receptor occupancy, it seems like a pretty high hurdle. So do you think you can beat that with 890? Or is it really with 890 more about just expanding the population base through that long-acting profile?

Yes. Really good question because with INGREZZA, as you mentioned, we're actually doing really well from a receptor occupancy point of view. So with respect to 890, we're expecting at least the same receptor occupancy. But to your point, the potential for long-acting injectable formulations, that's because of reduced clearance and also reduced aqueous solubility. So it's a molecule that really is designed to be both oral but administered relatively infrequently. And we think that could capture patients who are not doing so well or not so compliant on their current treatment.

Yes. Just to add to that, we've certainly looked at that potential with INGREZZA over time, and it's not a well-suited molecule for that as well as other follow-on molecules that we've had over time. So we're quite excited what we have with 890 and 675. Those are the next-generation VMAT2 inhibitors. And it's taken us a while to get a molecule that actually has a profile that we think is competitive or if not better than INGREZZA. So we're excited about getting this Phase II study up and running and looking to have data sometime towards the end of next year.

And we'll take our last question from Danielle Brill with Truist.

So I know we talked a lot about general barriers to prescribing CRENESSITY and mentioned a few times that 2/3 of your prescribers have written a single prescription. I guess I'm just trying to understand what's driving that pattern specifically. Like how many CAH patients do these physicians typically manage? What feedback are you hearing regarding barriers or hesitations to expand adoption more broadly for these specific prescribers, patient bases at this point?

Yes. I think the circumstances are going to be different from physician to physician. But generally speaking, I think the 2 biggest factors here that are guiding the pace of adoption, especially with those that have written one prescription is really just the flow of patients into the practice. As I mentioned earlier, a lot of these community endocrinologists that are treating adult patients, they may only see their patient once a year. So that is a factor. And then the second one is, and this is not unique to CRENESSITY. A lot of these physicians also when they start a patient, they want to see how it does and get some clinical experience. A few months into treatment typically is when they would be starting the GC tapering. And anecdotally, what I'm hearing is that many of them are taking it easy in terms of just slowly bringing down the GC doses. So it's not sort of a forced down titration. So I think those 2 factors together kind of get at what might be inhibiting some of these doctors from getting their second or their third patient on treatment. But like I mentioned earlier, most community, adult endocrinologists, if they have classic CAH in their practice, only have a few patients. So this is a market that is -- has a small number of what I'd call KOLs or experts and then a large number out in the community that have very few patients. And so it's an inch deep and a mile wide, so to speak. But in order for us to really optimize this opportunity, we have to reach and educate everyone, and that's what we're doing. And obviously, we're very pleased with the first year, and we expect to have a lot of success in 2026 and beyond.

That does end the Q&A session for today's call. I would now like to hand the call back to Kyle for any additional or closing remarks.

Thanks, Clay. I want to thank you all for joining today and for the constructive discussion. During the call, we shared updates on our commercial performance and development programs as well as the outlook for the business. I want to be clear, our focus remains on disciplined execution as we think about 2026, which means a couple of things: driving revenue growth and diversification with INGREZZA and CRENESSITY, advancing the pipeline and the process of delivering meaningful -- and in this process, delivering meaningful long-term value for patients and shareholders. We've got a lot of momentum that we're building this year for a data-rich 2027. That's just going to be the tip of the iceberg. The way that the pipeline is set up will deliver a constant flow of data starting from '27 and in future years. So in close, please don't hesitate to reach out on any of the topics that we discussed today. We look forward to continuing the dialogue and meeting with many of you as we progress throughout the year. So thanks again, and talk to you soon.

Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.