Neurocrine Biosciences, Inc.

Hello and welcome everyone joining today's Neurocrin Biosciences fourth quarter and fiscal year 2025 earnings call. At this time all participants are in a listen-only mode. Later you will have the opportunity to ask questions during the question and answer session. To register to ask a question at any time please press star 1 on your telephone keypad. Please note this call is being recorded and We are standing by if you should need any assistance. 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 Nurocrine Biosciences' fourth quarter and 2025 year-end earnings call. With me today are Kyle Gano, Chief Executive Officer, Matt Abernathy, Chief Financial Officer, Eric Benevich, Chief Commercial Officer, Sanjay Kaswani, Chief Medical Officer, and for the first time, we are very pleased to be joined by Samir Sedanti, 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 balance diversification, Neurocrine has entered a new era of meaningful growth led by our first and best-in-class commercial brands. Aggressive performance continues to impress. Strategic investments in access and Salesforce expansion drove a record year for both new and total prescriptions. This momentum carries us into 2026, where despite nine years post-launch, we expect double-digit volume-driven growth supported by continued demand from the roughly 9 out of 10 TD or HD Korea patients not currently taking a VMAT2 inhibitor. Like Ingressa, Chronicity'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 congenital 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 Kernesti will become Neurocrin'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, chronicity is rapidly becoming the standard of care for patients with classic CH. This profile mirrors the attributes that supported the success of Ingreza and underscores our confidence in chronicity's impact for patients and neurocrime moving forward. Turning to research and development, at our December R&D day, we outlined three strategic pillars. First, we aim to lead the VMAT2 category by leveraging our deep INGREZA experience and advancing next-generation VMAT2 inhibitors. By way of background, INGREZA was the first approved treatment for tardive dyskinesia, and Neurocrine paved the path for the development of new medicines in this space. Our nearly 20-year history provides a durable foundation for category leadership. This starts with MBI-890, which recently entered into Phase II in tardive dyskinesia, and with MBI-675, which is following close behind. Both of these products have the potential for long-acting injectable formulations. Second, we are delivering on the promise of CRF through a two-pronged approach, advancing next-generation CRF1 antagonists, such as MBI-P1435 and CH, and expanding the platform with CRF2 agonists starting with NBIP2118 into adjacent areas, including metabolic diseases such as obesity. For more than 30 years, Neurocrine has been a pioneer in CRF biology, and this experience uniquely positions us to evolve and expand what CRF-based therapies can deliver. Third, we are maximizing evolving the pipeline, which is stronger than ever. This is led by our late-stage, industry-leading neuropsychiatry portfolio, including two Phase III programs, Osevanpator and Major Depressive Disorder, and Direct Leading in Schizophrenia. Like Ingresa and Chronicity before them, both represent potential first- and best-in-class medicines. We expect top-line data from the Osevanpator studies and the first of two Direct Leading studies in 2027, which is shaping up to be the most data-rich year in Neurocrine's history. In 2025, we achieved our phase one through phase three objectives for the first time, making it the most productive clinical year in our history. We also have a clear line of sight to repeating this level of performance in 2026, accelerating us towards our goal of delivering one new medicine every two years at steady state. As I said from the outset, we entered 2026 with the strongest foundation in NeuroCon's history. It is incumbent upon me, our leadership team, and the entire organization to continue executing and delivering for patients and shareholders. We appreciate your support, and with that, I'll turn the call over to Matt.

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 Ingresa and the successful initial launch of Crinesity. Together, these products form the foundation of our growth and generate durable cash flows that support long-term shareholder value creation. Ingresa 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 Salesforce expansion. Looking ahead, we are guiding to aggressive sales in the range of $2.7 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. Ingresa enters the year with strong inter-ex momentum, broad access, and an expanded commercial team ready to execute. For chronicity, we exited 2025 with over $300 million in net product sales and approximately 10% of addressable patients being prescribed chronicity. 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 her first year on the market exceeded both internal and external expectations. Given that Chronicity is the first product approved for classic CAH in more than 70 years, with much still to learn around market dynamics, we are not providing specific sales guidance for 2026. Later in the call, Eric will discuss the initiatives underway to continue developing this attractive market. Turning to the financials. Our cash position increased by approximately $700 million from $1.8 billion at the end of 2024 to $2.5 billion at the end of 2025, reflecting strong operating performance and a healthy balance sheet. While maximizing near-term profitability is not our primary objective, we remain highly profitable, delivering approximately 30% non-GAAP operating margin or roughly $850 million of non-GAAP operating income for 2025, including $83 million of R&D milestones and IP R&D expense. In 2026, we expect another strong year of non-GAAP operating income driven by increased product sales partially offset by investments across SG&A and R&D. These investments align with our top capital allocation priorities of driving revenue growth and advancing our pipeline. SG&A growth year-over-year primarily reflects investments related to our 2026 Salesforce expansion, which we expect to be completed by the end of the first quarter. At the midpoint of our guidance range, GAAP SG&A is expected to be in the low 40% of sales for 2026. R&D expense growth reflects a full year of investment in our phase three programs for Osevanpitor and Durecladine, with data expected in 2027, as well as the initiation of multiple phase two and phase one programs, including obesity. Overall, we expect GAAP R&D expense, excluding approximately $25 million in milestones, to be in the mid-30% of sales range consistent with our prior commentary. Overall, 2026 is shaping up to be another important year for Nurocrin as we continue to grow Ingresa and Crenessity while advancing our pipeline. We enter the year with strong momentum and are well positioned for continued growth. With that, I'll turn the call over to Eric Benevich, our Chief Commercial Officer. Eric.

Thanks, Matt. I'm very proud of our team's performance last year across both Crenessity and Ingresa. 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 and female patients on therapy. Importantly, while new patient starts may vary from week to week and quarter to quarter, once a patient initiates treatment with chronicity, they tend to stay on chronicity. 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, chronicity is a learning launch, very much aligned with our experience with Ingresa and TD. In fact, the parallels between the two launches are remarkably similar. Both Ingresa and chronicity 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 Ingresa, while we're not providing specific annual guidance in year two, we remain highly confident that chronicity will be Neurocrin's second blockbuster medicine as we establish it, together with replacement glucocorticoids, as the standard of care treatment for patients with classic congenital adrenal hyperplasia. As we enter chronicity's second full year on the market, the natural question is, so what's next? As I noted this time last year, long-term success chronicity will be driven by our ability to reach, educate, and activate the CH community on this breakthrough medicine. More than 1,000 prescribers have written a prescription for chronicity, yet roughly two-thirds have treated only one patient so far, underscoring both the progress we've made and the opportunity ahead. To support continued growth, we're focused on several key priorities in 2026. As previously announced, we're expanding the chronicity sales force with new representatives hitting the field in April. This is a rare disease team, so the overall FTE numbers are still small. However, this expansion will allow us to go deeper within the existing endocrinology HCP base and allow us to expand our reach into additional potential prescribers. While endocrinologists remain central, we've learned some classic CH patients are managed outside of endocrinology by primary care providers or OBGYNs. We're excited to leverage AI and other technology tools to help identify and engage providers likely to be caring for classic CAH patients. We're also continuing to invest in medical education to improve the community's understanding of CAH, the limitations of GC monotherapy, and reinforce Chronicity's compelling product profile. It remains the first and only new CAH-specific treatment in 70 years. As a potent and selective CRF1 antagonist, chronicity targets the source of dysregulation in CAH and directly prevents the surge of excess ACTH from the pituitary to restore downstream androgen control and enable physiologic steroid dosing. Furthermore, chronicity has the largest data set in adults and children with classic CAH. which includes greater than 450 patient years of clinical trial exposure and greater than 550 patient years of real-world exposure. With a favorable long-term safety profile, robust efficacy, and broad labeling, it's clear why uptake has been so strong after only one year on the market. In fact, we estimate that we've gotten approximately 10% of the classic CAH population on therapy in the first year of availability. This is an important milestone for us. We believe as the word continues to spread in the CH community, as the endocrinology prescriber base expands, and as they share their real-world clinical experiences, we'll see a continued peer-to-peer effect that will deepen disease understanding and drive broader adoption. Now, turning to Ingresa, we had a record number of new patient starts and a record number of total patients on therapy in 2025. Today, we estimate only about 10% of the prevalent TD population is currently taking a VMAT2 inhibitor. Even nine years since our launch, there remains a substantial opportunity to grow the class, grow our market share, and help more patients start and stay on therapy. With double-digit growth momentum, strong formulary access, and an expanded and reorganized sales force set to hit the field in Q2, a class-leading and differentiated product profile, and 12 more years of remaining exclusivity, Ingresa is well-poised to help many, many more TD and HC patients. So with that, I'll turn the call over to my colleague, Dr. Sanjay Keswani, to share our pipeline progress.

Thanks, Eric, and good afternoon, everyone. In keeping with this year's focus on momentum and strategic diversification, our clinical organization will enroll in advance more studies than at any point in neurocrines 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 two commercial assets, Ingresa and Cranesity. 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 Ingresa and Ostido 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, Ingresa demonstrated a nearly two-fold higher VMAT2 target occupancy compared with therapeutic doses of Ostido XR, an important finding that indicates Ingresa's superior efficacy in treating tardive dyskinesia. Turning to chronicity, 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, chronicity continues to show robust sustained clinically meaningful benefits through two 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, Krenesi delivered sustained ACTH suppression while preserving normal physiological signaling including the immune stress response. Hence, rates of adrenal insufficiency remained very low. zero 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 two 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 two years, reflecting chronicity's beneficial cardiometabolic effects. Safety and tolerability remain excellent with approximately 80% retention at two years, no new safety signals, and over 35,000 patient weeks of exposure. Overall, these data reinforce chronicity's strong differentiation across efficacy safety, and tolerability, and support our conviction that it will continue to be the standard care treatment for patients with classical congenital adrenal hyperplasia. Regarding our industry-leading neuropsychiatry programs, the late-stage Phase III studies for Ossiphampertor in major depressive disorder and Directladine 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'll hand the call back to Kyle.

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

Absolutely. If you'd like to ask a question, press star 1 on your keypad. To leave the queue at any time, press star 2. Once again, that is star 1 to ask a question. Thank you. Our first question comes from Paul Matisse with Stiefel. Your line is open.

Hey, good afternoon. Congrats and thanks for taking my question. I appreciate that you're not guiding on chronicity, but I was wondering if you could maybe give us either a window into the first six weeks of 2026, or just more broadly, the number on the revenue side, obviously way above consensus in 4Q. But as we look at star 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 ad rate might plateau in, say, the near to midterm. Thank you.

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 for... Love it. It's been a tremendous year for Chronicity, over $300 million in the first year. Congratulations to the team. And we really look forward to year two 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 Ingress, it took us about four 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.

Look forward to the weeklies.

We'll take our next question from Corey Kasimov with Evercore ISI. Your line is open.

Hey, good afternoon, guys. Thanks for taking my question. Wanted to ask about that receptor occupancy poster from late January regarding ingresiverse osteto. Curious how you might use this information and what are the potential implications here with regard to your next-gen VMAT2 inhibitors?

Thank you.

Yeah, so we're quite excited by the data we showed, which is actually a head-to-head PET study between Ostida XR and Ingresa. And as we articulated in our recent press release, we saw nearly double the target occupancy for Ingresa after one dose versus Ostida 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 ENGREZA in the community of patients with tardive dysgynesia, as our belief is that the higher the rate of VMAT2 target occupancy, the greater the efficacy in terms of control of tardive dysgynesia. 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 two VMAT2 follow-ons. Indeed, we started a phase two study of our first follow-on in tardigradeskinesia quite recently.

Thank you.

We'll take our first question from, or we'll take our next question from Phil Nadeau with TD Cowen. Your line is open.

Good afternoon. Thanks for taking our questions, and congratulations on a productive year. I just want to follow up on Paul's question on patient dynamics with chronicity. I think in your prepared remarks, you mentioned the possibility of seasonality in patient demand, and I think investors are all debating whether there could have been an early launch bolus to patient initiations. I'm appreciating that you still have a lot to learn. What have you learned about those two factors in patient dynamics, one, an early launch ball lesson, two, whether there's any seasonality as you go through the year. Thanks.

Yeah, 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 of 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 in Greza 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 application. 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 quarters to draw those conclusions across multiple years. And, you know, it took us a while to get to that level of confidence within GREZA. 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 and 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 Ingresa.

We'll take our next question from Brian Abrams with RBC Capital Markets. Your line is open.

Hey, guys. Thanks for taking my question, and 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 two Phase 3s read out? Thanks.

Yeah, thank you for the question. The cost increase is really on the heels of the phase three 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 2027. But from an expense, when do expenses roll off? We would anticipate for the major phase three programs, those, you know, will carry on through 2027 with a big chunk falling off in 2028.

We'll move next to Tazeen Ahmad with Bank of America. Your line is open.

Hi, guys. Thanks for taking my question. I wanted to go back to chronicity for a second. So I know it took, what is it, three or four years before you guys started giving guidance on IGREZA. 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 chronicity and providing sales guidance for that as well? Thanks.

Yeah, hi, Tuzine. 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 chronicity as it did with Ingresa. This is a rare disease. Ingresa is not a rare disease, but it was at the time a rarely diagnosed disease. You know, we have a single, essentially a single prescriber base in endocrinology versus, you know, multiple different prescribers. specialties and different sites of care and so on, which made getting a handle on Ingresa 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, you know, as Kyle stated, you know, we've gone through one cycle so far with chronicity and classic CAH, and is it, has been a learning launch for us. You know, there's a few factors that have been a little bit different than what we expected, but different in the positive. You know, the adoption rate was greater than what we had expected coming into this launch, which is awesome. Certainly the reimbursement has been favorable. And, you know, 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 industry, community and the CH community. And as we learn more about, you know, how we're able to reach sort of beyond that first 10% of the population that I talked about, then I think, you know, 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 their 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. Your line is open.

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

Yeah, I mean, obviously, you know, 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, you know, as we kind of prepare to go into that next phase. You know, 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, you know, we feel good about our strategy for 2027. We believe we'll be able to maintain formulary coverage to enable continued growth. And, you know, this is a market that has been growing at a double digit clip for the last several years, which is, you know, pretty amazing, especially for a category that's coming into year nine, year 10. So, you know, we feel good about 2026, expect to have another really strong year for Ingresa. And we feel good about our strategy for maintaining that growth in 2027 and beyond.

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 mid-year ads 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. Your line is open.

Maybe we'll ask more about that.

Oh, hey, guys. Congrats on all the progress, and thank you for taking our question. We're curious about the 569 study in Alzheimer's psychosis and any potential lessons learned from the ADEPT2 study of CoBENFI, especially in terms of managing trial conduct across the study sites and any strategies you can use to mitigate operational risks for that study. Thank you.

Yeah, we... We're watching the progress of Cabenzi and AD psychosis quite carefully. But just as an aside, you know, 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 three 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 studies, you know, one-to-one randomization, keeping the study sites relatively small. So, for example, we only have 20 sites per phase three 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 JP Morgan. Your line is open.

Hi, this is Joyce on for Anupam. Thanks so much for taking our question. Could you discuss the feedback you've been getting from KOLs about your two-year chronicity data, specifically as it relates to durability of benefit, and just how you see those data continuing to support and drive strong persistence of patients on drugs? Thank you.

Yeah, so we've been getting a lot of positive support from clinicians who have been prescribing Quinesti, as you say, for some time now. And we recently showed that two-year data and, again, enlisted 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, in quotes, 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 two-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 mention that because, you know, 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.

Yeah, this is Kyle. Maybe just to add two 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 two years. Just an amazing safety and tolerability profile. And CH, although you could say this about many disease states, more so than ever for CH, 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 two years, it really describes the 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. Your line is open.

Mohit Bansal, Wells Fargo, Great. Thank you very much for taking my question. 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 Clinacity or Ingresa? And then would also love to understand how you think about Ingresa, given that you are guiding for the 10% growth, which is higher than last year. So So do you expect volumes to continue to grow at the rate of last year or just like you're not getting price decline this year? So that's probably what's driving it. Thank you.

So SG&A expense is really the Salesforce expansion that we mentioned on the last call is a significant part of that. And we also have other ancillary initiatives surrounding Chronicity as well as Ingresa to ultimately drive sales. You know, 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 Engraza to be in the mid-teens. So, we feel really good with where the team is. is positioned and, of course, with the Salesforce 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.

Excellent. Thank you.

We'll take our next question from Miles Minter with William Blair. Your line is open.

Hey. Thanks, guys. I just had a question on the number of Tuesdays in each quarter. I'm actually going to ask about the Salesforce expansion for Chronicity on board 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 Salesforce expansion helps inflect the product? Thanks.

Yeah, the way I would characterize it is that we're investing in growth. You know, we're very optimistic about the opportunity with Chronicity and Classic CAH. And, you know, we made our Salesforce size and structure decisions prior to the launch without the, you know, sort of, I'll call it the Monday morning quarterback opportunity of having more data to work with. So, You know, obviously, we've been executing this expansion on a relative basis. It's not a large number of FTEs that we're adding into the chronicity team, but we do think it'll allow us to do a couple 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 and yet two-thirds 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. You know, they might be seeing an internal medicine or a family medicine physician or even a OBGYN. So, you know, 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 was created within the endocrinology community. We're able to attract some really high potential and, you know, 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 they'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 Miles, 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 chronicity seasonality, and I think Kyle and Eric addressed it nicely in terms of not having enough experience with chronicity 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 copay reset. So that's one thing I wanted to make sure as you're developing your models and expectations for Q1 for chronicity, that would be something that you take into consideration. Thanks.

We'll move next to Yugal Nokomovitz with Citigroup. Your line is open.

Hi, great. Thank you, and 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 OBGYN, 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 OBGYNs may be the best candidates for chronicity.

Yeah, so yeah, I just want to clarify when in my prepared remarks I talked about the fact that we've, you know, 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, you know, obviously in year one 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, you know, we recognize that for us to be able to continue to expand the use of chronicity and get broader within that patient population, you know, we're going to have to be able to reach patients beyond the prescriber base that we've reached thus far. And, you know, you mentioned patient finding. I talked about that a little bit in my prepared remarks. So we are, you know, 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, you know, 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, you know, this is a rare disease, and there isn't a specific diagnosis code for classic CEH. And so for us to continue to grow and, you know, to have that steady growth that we expect, You know, we have to leverage technology and we also have to leverage the team.

We'll move next to David Anselm with Piper Sandler. Your line is open.

Thanks. Maybe I'll ask another chronicity 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, 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 chronicity. Maybe you can talk about that dynamic as well. Thank you.

Yeah, 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, and 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, you know, tying that back to the clinical profile that's emerged for chronicity, 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-chronicity 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, you know, more broad, certainly, you know, we're seeing that doctors are realizing that, hey, chronicity is a whole new way of treating CH. It's a paradigm shift. And, you know, 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, you know, we recognize that a lot of patients with CH or families with CH didn't fully understand, you know, 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 Scorny with Baird. Your line is open.

Hi, team. Thanks for the question. This is Luke on for Brian. So on chronicity, 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?

Yeah, 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, you know, one of the things that we've seen, at least in the cohort of patients that have been started already on chronicity, is that some of them appear to be co-managed by endocrinologists in primary care. And it may be that they see their endocrinologist once a year, but they may be seeing their primary care physician more frequently in the questions, you know, who's managing their CEH and refilling their prescriptions and so on. You know, as we go forward, teasing that out of the data, I think, is really important. And I think that, you know, 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, you know, where these patients are and the best way to educate, motivate, and activate these patients.

We'll take our next question from Mark Goodman with Lear Inc. Partners. Your line is open.

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 antagonists and just how you guys view that drug to be used eventually if it ever comes out, you know, with everyone, you know, hopefully on chronicity by then, like, is it an add on? Do you think it'd be a competitive product or how do you even view it at that point? Thanks.

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 and, 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 a 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 Mark, on your competitor question, you know, I've learned a lot over the course of my first full year as a CEO, and one of them is how to talk about competition. When it comes to chronicity, you know, we're really talking about two different programs, two different medicines at two different states. Chronicities and approved medicines 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 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 chronicity and is displaced at all by any future medicine. So I'm really excited about what we have with Chronicity. It's a two variable positive here 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 Tiwari with Jefferies. Your line is open.

Hi, this is Phoebe on for Akash. Thank you for taking our question. My question is on chronicity as well, but more so on the pipeline. We saw that there's a phase two study being initiated for patients under four 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? Thank you.

Yes, so as indicated, we are soon initiating 2032, which is a pediatric study. These are individuals less than four years of age, the youngest age being three months. And the intent is to expand our label, which currently is four 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. Your line is open.

Good afternoon. Thanks for taking our questions. Bigger picture one here. It looks like you sold your UK and European rare commercial business recently. What does this mean for your plans to develop Cronosophon in UK and the rest of Europe? And does that decision mean Neurochron is going to remain US focused? And how much did the potential enforcement of most favored nations pricing have to do that decision?

Yeah, this is Kyle. Appreciate the question. I think when it comes to the EU business, the programs that we were working on over there weren't necessarily a good alignment vote we have for our own portfolio today. So we found a good place for those programs to go with a new team there in terms of our own interests. Obviously, we're focusing on the U.S. market now, making sure that we have a really good launch here with chronicity and so far so good there. We want to keep focusing our attention there and look at ways we can potentially bring chronicity 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 Lamon with Morgan Stanley. Your line is open.

Hi Kyle and team, hope everyone's well and thanks for taking my question. I have a pipeline question on 890. You know, just going back to the recent data you showed for Ingresa 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 brace through that long acting profile?

Yeah, really good question because with Ingresa, 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.

Yeah, just to add to that, we've certainly looked at that potential with Ingreza 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, but we have with 890 and 675, those are the next generation of 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 IGREZA. 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. Your line is open.

Hi, guys. Good afternoon. Thanks so much for the question. So I know we talked a lot about general barriers to prescribing chronicity and mentioned a few times that two-thirds of your prescribers have only 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. Thank you.

Yeah, I think the, you know, the circumstances are going to be different from physician to physician, but generally speaking, you know, I think the two 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. You know, 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, you know, and this is not unique to chronicity, you know, 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 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, you know, I think those two factors together, you know, kind of get at, you know, 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 CH in their practice, only have a few patients. So this is a market that 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.

Thank you. 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, Goliath. 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 discipline execution as we think about 2026, which means a couple things. Driving revenue growth and diversification with Ingresa and Chronicity. Advancing the pipeline in the process of delivering meaningful long, 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, and that's just going to be the tip of the iceberg, the way that the pipeline setup will deliver a constant flow of data starting from 2027 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