Neurocrine Biosciences, Inc.

Good day, everyone, and welcome to Neurocrine Biosciences Report's first quarter 2025 results. 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. Please note, today's call will be recorded, and I will be standing by should you need any assistance. It is now my pleasure to turn the conference over to Todd Tushla. Vice President of Investor Relations. Please go ahead.

Thank you, and happy Cinco de Mayo to everyone. Welcome to Nurocrine Biosciences first quarter 2025 earnings call. With me today are Kyle Gaino, Chief Executive Officer, Matt Abernathy, Chief Financial Officer, Eric Benevich, Chief Commercial Officer, and for one last time as Chief Medical Officer, Ivory Roberts. 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. Following prepared remarks, we will strive to get to everyone's questions. Now, I will turn the call over to Kyle.

Thanks, Todd. Good afternoon, everyone. Nurocrin has never been in a stronger position as we maintain an enterprise-wide focus on execution and evolution. Even with external factors continuing to create market volatility, We remain focused on controlling what we can, executing with discipline to meaningfully deliver for both patients and shareholders. The first quarter reflected strong execution across both of our brands, with record new patient starts for Ingresa and encouraging early adoption of Chronicity. With reformed guidance for Ingresa and solid momentum heading into Q2, combined with an early but promising launch trajectory for Chronicity, We are well positioned to drive both near and long-term revenue growth as we evolve from a single blockbuster to a multiple blockbuster neuroscience company. Amazing to see the efforts from our commercial and medical teams this quarter. Well done. On the R&D front, our portfolio continues to advance meaningfully. We are encouraged by the progression of Osa Vampator and MBI 568 into Phase III registrational studies. The strong magnitude of effect demonstrated in both programs, Phase II proof-of-concept studies, gives us confidence in continued investment. We are on track for expanding our muscarinic portfolio into new Phase II studies later this year. This includes MBI-568 into bipolar mania and MBI-570, our dual M1-M4 agonist, into schizophrenia. From a leadership perspective, we are thrilled to welcome Dr. Sanjay Keswani as our incoming chief medical officer in June. Dr. Irie Roberts, our current CMO, will transition into a strategic advisory role where her expertise will continue to shape key programs. In closing and reflecting on the quarter, I'm extremely proud of our team and progress. Our growing diversified revenue base, expanding pipeline, and strong balance sheet position us well to continue building on our momentum as a leading global neuroscience company. With that, I'll turn the call over to Matt.

Thank you, Kyle, and good afternoon. We made tremendous progress throughout the first quarter, both with the reacceleration of new patient growth for Ingresa and with their successful chronicity launch. We are executing from a position of strength with these two growing commercial products, a robust clinical pipeline in CNS disorders, and a strong financial foundation that provides flexibility for continued investment to drive shareholder value. Starting with Ingresa. We posted $545 million in first quarter product sales. As anticipated, first quarter sales were impacted by one less order week, patient reauthorization processes, and gross to net dynamics. Although noisy, I do want to make a few very specific comments about the quarter and Ingresa. First, we had record new patient additions in the first quarter, which is a testament to the quality of our product, the dedication of our team, and the continued unmet medical need. Second, effective April 1, 2025, we expanded our formulary coverage in Medicare Part D, which significantly increases patient access, providing a foundation to expand our customer base in the years to come. Finally, as Kyle mentioned, we're reaffirming our 2025 sales guidance range of $2.5 billion to $2.6 billion, which factors in the expected acceleration of new patient additions, offset by gross to net impact from contracting activities. Turning to Chronicity, where we just completed our first full quarter of launch. We achieved net revenue of $15 million, which includes 413 enrollment forms, with 70% of dispenses receiving reimbursement. Although we are still early in our launch efforts, we're encouraged by this initial success. A few financial comments. Our capital allocation priorities remain intact, with our number one priority being investments to drive revenue growth. Number two priority is investments to advance our R&D pipeline. And three, investments to enable business development. And lastly, consider return of capital to our shareholders. During the first quarter, we continued to reflect these priorities to drive revenue growth with investments in our expanded and grossed sales force and chronicity launch. In addition, we continue to make investments advancing our pipeline in R&D with the initiation of two major Phase III programs. Just a reminder, R&D expense for the first quarter of 2025 includes $45 million in milestone expense, primarily for the initiation of our Osa Vampator Phase III program in MDD, and we'll recognize $15 million in milestone expense in the second quarter for the initiation of MBI 568 Phase III program in schizophrenia. In addition, we've been able to retire 3.6 million shares over the past two quarters and have retained a strong balance sheet with approximately $1.8 billion in cash to support our commercial and clinical development strategies for continued growth. With that, I will now hand the call over to Eric Benevich, our Chief Commercial Officer. Eric?

Thanks, Matt. We're celebrating two significant milestones for Ingresa. First, a couple weeks ago was the eighth anniversary of FDA approval. Remarkably, eight years into the launch, our commercial and medical teams achieved record new patient starts in the first quarter, despite a challenging payer environment. I want to take a moment and thank our teams for their exceptional dedication and performance. This second week of May also marks Tardive Dyskinesia Awareness Week. Currently, we estimate that just over 40% of patients with TD have been given a diagnosis to explain their abnormal movements, and less than 10% are currently receiving standard of care treatment with a VMAT2 inhibitor, such as Ingresa. So there remains a significant opportunity for growth of the VMAT2 class and Ingresa as the VMAT2 class leader. As part of our support for TD Awareness Week, Neurocrin continues to collaborate with the Movement Disorders Policy Coalition, mental health advocacy organizations, healthcare providers, and policymakers nationwide to increase awareness, reduce stigma, and drive diagnosis so that TD sufferers can access available treatment options. Matt provided a nice summary of Ingresa and chronicity performance in his opening remarks, and I'd like to provide additional color. First, we're pleased to have expanded formulary coverage from less than half to approximately two-thirds of Medicare TD, and HD beneficiaries. While this affects our growth to net, access will be improved for our HCP customers and the patients they care for. We view these as important investments to ensure patient access today and into the future. Second, as noted in our last call, we believe the Inflation Reduction Act, or IRA, has notably influenced payer behavior and reimbursement dynamics, particularly for specialty medicines like Ingresa. In the second half of last year, we saw an impact on the prior authorization process for new patients. In Q1, we saw the impact on the reauthorization process for continuing patients, which was a bit more challenging versus prior years. Regardless, our field sales and field reimbursement teams were persistent in their efforts to help healthcare providers and patients manage through evolving payer requirements. Great job, teams. Third, we reaffirmed our 2025 INGREZA guidance. Looking forward, our growth strategy encompasses our recently expanded sales force, investments in improved formulary access, and enhanced marketing initiatives that will strengthen INGREZA's market-leading position as the only VMAT2 inhibitor that is highly effective, uniquely selective, with therapeutic dosing from day one, and proven across the widest range of patients. With continued significant unmet need across the tardive dyskinesia and Huntington's chorea patient communities, we anticipate sales to accelerate in Q2 and through the second half of 2025. And this momentum should position us well heading into 2026 and beyond. For chronicity, while we're still in the very early stages, I'm pleased to say that the launch is exceeding our expectations. As Matt noted, in Q1, we received 413 treatment forms, which serve as a new prescription, and we reported 15 million in net sales. We're observing strong uptake across both pediatric and adult CEH patient populations, with slightly higher initial adoption rates in pediatric and adolescent segments. The prescriber response has been particularly encouraging, with good initial trial across all endocrinologist segments. including centers of excellence, pediatric endocrinologists, and community adult endocrinologists. While it's too early to comment on longer-term outcomes, we're pleased with the warm reception of chronicity from the medical and patient communities. On the payer front, we noted that 70% of the dispenses in the quarter were reimbursed. Coverage requirements have generally aligned with our approved labeling, including diagnosis of classic CH, patient age of four years or older, and concurrent glucocorticoid therapy. As we move forward through the balance of the year, we expect more health plans to conduct formulary reviews and publish their coverage criteria. However, some plans may choose not to formally review chronicity and continue to review prescription claims via their exceptions process. Overall, initial metrics are trending in the right direction across all key performance indicators. But I do want to remind everyone that one quarter is too soon to define a trend for either adoption or reimbursement. We're going to learn a lot over the coming quarters specific to persistency, compliance rates, and overall rate of adoption. If chronicity ultimately delivers significant benefit in the real world as it did in clinical trials, we fully believe it can become the new standard of care together with cortisol replacement for CEH patients. Once more, I'd like to congratulate our commercial and medical teams for getting chronicity off to such a great start. So with that, I'll turn the call over to my colleague, Dr. Irie Roberts, our Chief Medical Officer.

Thanks, Eric, and good afternoon to everyone. We continue to make substantial progress advancing neurocrines early to mid-stage clinical pipeline, particularly across our muscarinic portfolio, next-generation VMAT2 inhibitors, and epilepsy programs. Today, I'll focus specifically on our late-stage registrational assets and key 2025 data milestones. I'll start with Osovampertor, our AMPA positive allosteric modulator. I'm pleased to announce the initiation of all three randomized double-blind placebo-controlled studies evaluating its efficacy and safety as an adjunctive treatment for major depressive disorder. These studies will measure the change in total madras from baseline to day 56 as their primary endpoint, with top line data expected throughout 2027. Turning to our selective M4 agonist, NBI568, just last week, we announced the initiation of the first of three phase three registrational studies to evaluate the efficacy, safety, and tolerability of NBI-568 as a potential treatment for schizophrenia. We anticipate initiating the two additional studies in the coming months. All three studies will be double-blind placebo-controlled trials comparing the 20 milligram dose of NBI-568 versus placebo with reduction from baseline in the positive and negative syndrome scale or PANS at week five as the primary endpoint. We expect top-line data from these studies in the 2027-2028 timeframe. This year, we will report top-line data from two Phase III studies of valbenazine, the first in adjunctive treatment of schizophrenia, which serves as a proof-of-concept study for VMAT2 inhibition in this disease state. While these results will guide the development of our next generation VMAT2 inhibitors, including NBI 890 and 675, we do not plan to expand the valbenazine label for this indication. The second readout, expected later this year, will evaluate valbenazine's efficacy in treating dyskinetic cerebral palsy. With no currently approved treatments, For the 75 to 100,000 patients in the U.S. living with DCP, successful results could lead to a label expansion for this indication. For NBI 770, our NMDA NR2B subreceptor negative allosteric modulator, the phase two dose finding study in major depressive disorder remains on track for top line data in the second half of 2025. This study's primary outcome measure focuses on the madras change from baseline to day 5, potentially demonstrating more rapid onset compared to Osovampator's phase 3, day 56 endpoint. As this marks my final earnings call as Neurocrin's chief medical officer, I'd like to share some closing observations. Neurocrin stands stronger than ever, making this an optimal time for the transition. Our industry-leading pipeline continues to grow, fueled by Jude Onyer's excellent progress establishing a sustainable internal innovation engine. My seven-plus years at Neurocrine have been marked by remarkable evolution, and I'm confident in Sanjay Kiswani's capability to lead as the next chief medical officer. I look forward to maintaining an active advisory role, supporting both Sanjay and our late-stage program teams. Finally, I extend my gratitude to the board, Kevin, Kyle, my Neurocrin colleagues, and all our external partners, including the investment community. Neurocrin is well positioned to help countless future patients, and I'm proud to have contributed to this journey. With that, I'll hand the call back to Kyle. Kyle?

Thanks, Irie. And just to pause here a moment before we move into questions, I do want to take a moment to recognize Irie for many contributions over the years. Irie's played a vital role in shaping Nurocrin into what it is today and really helped many thousands of patients along the way. If I think about the future here with Irie, she will continually be a player and help us along the way. But as she mentioned just a moment ago, this will be her final earnings call as an executive of the company. So, Irie, once again, thank you for your dedication, your leadership, and your support over the years. With that, let's open it up to questions.

At this time, if you would like to ask a question, please press the star and 1 on your telephone keypad. You may withdraw yourself from the queue at any time by pressing star 2. Again, that is star and 1. We'll move first to Paul Matias with Stiefel. Your line is open.

Hey, thanks for taking my questions, and Irie, congrats. Always good to work with you. Two quick ones. As it relates to INGREZA, Sounds like the quarter was not as challenging as some feared. I was wondering if you could comment on what you're seeing into 2Q and if you feel like, you know, getting back to the prior growth rate at some point is attainable. And then just on chronicity, congrats on the progress. Should we be looking at this 400 number as a bolus and then it can attenuate from here or do you feel like it's just the beginning? Thank you.

Paul, this is Kyle. Maybe I'll start here and then I'll ask Eric or Matt to chime in. On Ingresa, I think when we look at Q1, you've probably heard us talking about the challenges of the quarter over the past couple of months. I think it played out exactly as we expected it. We had that low momentum coming in to the year, the difficulties of reauthorization, the one less selling week, the hits on gross net. All those were factors that came into play. But just to round out the quarter, we saw that one element that gives us great confidence going into the remainder of the year. And that is the momentum that you get from having that growth in new patient starts. And I think it goes without saying that the growth in new patient starts was the record that we've seen of all time in terms of a quarter. And it came in the most challenging quarter. So I think there's a lot to be said there from momentum going into Q2. the remainder of the year and really just an amazing job by the team out there in the field. So I think that we have that momentum going into the remainder of the year. We have a number of elements that we put in place late last year that will play a factor for us positively this year. We mentioned the Salesforce expansion, the expanded access that we have now and other marketing initiatives that will be kicking off here very shortly. All these things will help us to continue the recovery of growth in Q2 and then acceleration the second half of the year. In terms of chronicity, maybe I'll let Eric speak to that, and we can go from there.

Yeah, no, Paul, I think your question is in terms of, you know, should we expect this number of treatment forms or new patient NRX referrals going forward? You know, as I mentioned in my prepared remarks, We only have one quarter of experience with this launch. Obviously, we're really pleased with the adoption that we're seeing. But ultimately, we need a little bit more time to understand what that pattern is going to look like. And so, you know, as we go forward, we'll continue to share, you know, what the treatment form or referral rate is. And obviously, you know, provide additional metrics like we did in this particular quarter. But I think it's too soon to tell. But I will reiterate. We're off to a great start and certainly to succeed our expectations at this phase.

Thanks, guys.

We'll take our next question from Akash Tiwari with Jefferies. Your line is open.

Hi, this is Phoebe on for Akash. Thank you for taking our question. Similarly to what was just asked, could you provide any color on chronicities sort of pair dynamics moving forward, 70% is higher than we had anticipated. So just wondering how you expect it to move forward from here. Thank you.

Yeah, just like with the adoption, the reimbursement, I think, exceeded our expectations as well. As I mentioned earlier, 70% of the fills in the quarter were reimbursed. And, you know, certainly that's very, you know, favorable for one quarter in. But I would like to caution everyone and remind them that this is still a product that, for the most part, hasn't gone through formulary reviews. And so, for the most part, we're talking about reimbursement via the exceptions process. And so, as we move through the year, you know, we do expect that some of the plans, maybe most of the plans, will be doing formal reviews of chronicity and determining what their coverage criteria look like. But at this stage, it's still formulary exceptions, and we're off to a great start in terms of securing reimbursement.

Yeah, this is Matt. Just a big shout out to the market access team. Kudos to them for educating all the payers in terms of the disease burden and also the benefits that chronicity could potentially provide. This is a high-value medicine helping a lot of patients, and it's been fantastic. fairly seamless between prescription written and ultimately getting filled. And so, I do want to give that kudos to the team that has been working hard on that.

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

Your line is open.

Hi, good afternoon. Thanks for taking my questions. First diary, great job on everything and good luck in your next chapter. I did want to ask about the shared split between what you're seeing now on Ingresa versus TAVA for new to treatment TD patients. I don't know if you could share any color on that. And then on chronicity, can you give us a split of what percent of patients, and I'm sorry if I missed it, are PEDs versus adults in the early innings of usage? Thanks.

Yeah, so we haven't...

provide a historically share split exactly, because if you look at the syndicated prescription data, it underreports in BREZA. And so we've always cautioned to not look at the numbers as exact measures. But overall, you know, what we have said is that we have had the majority of prescriptions in TD, and we continue to have the majority of prescriptions. That's for both TRX and for NRX. And so we'll leave it at that. The other thing you were asking about in terms of the split or the demographics of the patient population, very early on, you know, what we were seeing was sort of equal distribution of pediatric and adult patients and pretty equal distribution of females versus males. But as we've gotten more treatment forms in and the launch continues to mature, We have seen that it's starting to trend in the direction that we expected prior to the approval, which is more pediatric and adolescent patients than adult and more female versus male. Once again, we've got a long way to go in terms of understanding the launch dynamics. And, you know, one quarter does not make a trend. But ultimately, you know, it is essentially trending in the direction that we expected it to prior to the launch.

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

Your line is open.

Good afternoon. Thanks for taking our questions and let us add our congratulations to Irie on a great career at Nurikrin. Two from us as well. First on Ingresa trends. Ingresa grew 15% from Q1 to Q2 in 2024. Can you give us some sense of what's likely to happen in Q2 of 2025? It seems like with one additional Tuesday, at least 8% growth is reasonable, but how are some of the factors that impacted Q1 transitioning into Q2, and what should that do to sales? And then second, just a follow-up, brief follow-up question on chronicity. You mentioned that chronicity was relatively seamless from script to fill. Can you give us some sense of the time, the average time it takes from a prescription being written or an enrollment start being received to when the patient actually gets drug in hand? Thanks.

Thanks. Thanks, Phil, for the questions, as always. Yeah, from a Q1 to Q2 dynamic, you would expect a nice step up. You do gain back one order week in the quarter. That does provide a sequential benefit. You also have the record numbers of new patients that we mentioned earlier, and then the natural recovery of refill rate per patient. The one aspect that you will want to contemplate that's different than previous years, as mentioned, We did enter into some contracting during the quarter and as a result of that we do, we will have a sequential hit in gross net. I call it slightly down from Q1 to Q2 that will push down the growth profile just a little bit. But overall, you would expect a nice step up for Q2 and it positions us well for the second half of the year. As it relates to time, I would just say that it's time to ultimately get a fill or get the reimbursement for chronicity. It's still too early in the cycle to give any specific number. As you have heard us say before, patients, once they have an enrollment form written, it's typically a five- to seven-day process where the pharmacy is trying to get reimbursement. And whether the patient has had reimbursement granted or not, a patient will ultimately get a fill. And as we alluded to in the percentages we provided, you know, 30% did get free goods during the quarter. But overall, team performed very well. And I think the feedback on our pharmacy channel has gone great so far.

That's very helpful. Thank you.

We'll move next to Brian Abrams with RBC Capital Markets. Your line is open.

Hey, guys. Thanks very much for taking my questions. Congrats to Irie on a great career at Nurocrin, and congrats on the strong chronicity start. Maybe just two quick ones from me on chronicity. Can you provide any more specifics on the proportions of patients being treated at centers of excellence versus community centers and how these doctors are managing the glucocorticoid down titration, whether that differs at all? And then on Ingresa, as you continue to invest in formulary access, can you give us any more specifics on how to think about contracting cadence going forward and what the pricing trends might look like beyond second quarter of this year? Thanks.

Yeah, so let me take a crack at the second question first and then tackle the chronicity question. Irie might want to chime in as well. Contracting cadence. So we've always said that, you know, our priority is to maximize access for patients. And historically, you know, we have contracted, but we've been, you know, fairly prudent in terms of selecting where we want to contract and where we think it can make a difference in terms of improving access. In the prepared remarks, we talked about increasing coverage in the Medicare segment for the TD market and the HD market from less than half to approximately two-thirds with the most recent rebate agreement. And we're going to continue to monitor the environment. I don't think there's anything immediate that could happen, certainly nothing that we're anticipating in terms of additional rebate agreements, but certainly if anything does happen, if we enter into any additional rebate agreements, we would flag that going forward. But ultimately, you know, the benefit of improving access certainly accrues starting this year, but carries into 2026 as well. So I think it sets us up well for the future. With regards to your question about, I'll call it sources of business, volume of treatment forms coming in from centers of excellence versus the community. Right now, what we're seeing is that it's really across the board. We have seen adoption and referrals coming in from those centers of excellence, but keep in mind, there's not very many of them. There's only nine accredited centers of excellence accredited by the CARES Foundation, a similar number that have most of those services, but they're not accredited. So we are seeing adoption and referrals also from community pediatric endocrinologists as well as pediatric adult endocrinologists. And it kind of ties back to the comments that we made earlier about really seeing that chronicity is being embraced by the broader endocrinology community. Anything to add, Irene?

Just about the steroid reduction piece of the question as well. So the first thing, just to build on what Eric was saying, we've been incredibly impressed by the engagement of the endocrine community around chronicity and the level of interest in gaining additional education on how to use the medicine effectively and safely. I think in general, as our medical team has engaged, there's a few things that we're learning. First of all, I think there is a real enthusiasm about the safety and tolerability profile that we saw with chronicity in the registration studies. And so that creates a foundation for a good opportunity to start the medicine in a patient. The second thing is the label that we achieved for the medicine which is broad in its description and doesn't require very specific or guided information on steroid reduction. And what that allows us to do is engage with clinicians as they ask questions of the medical team to provide guidance where appropriate while still ensuring that on an individualized basis the clinician and the patient can decide what's the right regimen for the patient and how to reduce the steroids effectively.

Yeah, all in all, many of these patients are just getting started on chronicity and just getting started on that journey.

So I think we'll learn more in the coming quarters.

Thanks very much.

We'll take our next question from David Amsalem with Piper Sandler. Your line is open.

Thanks. Just staying with chronicity, can you talk about the mix between starts in adults versus pediatric and adolescent patients, bearing in mind that these are early days, but can you talk to which of these patient groups, if any, you're gaining more early traction in? Thank you.

Yeah, David, I think I mentioned earlier that at the very beginning of the launch, in other words, the beginning of Q1, we were seeing, it was about even split between adults and the pediatric patient population. But as we went through the quarter, we saw that we're getting more treatment form referrals for those pediatric and adolescent patients. So we're starting to see a trend towards greater uptake in the younger population, which is what we expected to see. We'll have to see how things shake out over the next several quarters. As I said before, you know, when you've got very little data to work with, things can swing in one direction or another. But as we get more utilization, more adoption from the community, I think we'll have a better sense of how the launch is going.

We'll move next to Anupam Rama with JP Morgan. Your line is open.

Hey, guys. Thanks so much for taking the question, and best of luck, Irie, on everything you pursue going forward. On the INGREZA and the record number of patient starts, what should we attribute this to in terms of thinking about your share of voice gain relative to OsteoXR? I know you pointed to that as a headwind coming into the year. How do we think about Have you stabilized your share of voice, or were there other factors like PD market expansion or other factors we should be considering? Thanks so much.

Yeah, I mean, obviously, you know, we made an investment last year to expand our sales force, and we targeted that investment towards the areas that we thought would yield the best results, and specifically into psychiatry and into long-term care. So we're starting to see the tangible benefit of that. You know, we had cautioned that when you expand a sales team in the near term, it can be disruptive. It can negatively impact your productivity. But as the newer representatives, you know, become more productive and they start to level up to the level of their colleagues that have been in the field for some period of time, you know, then you start to see the tangible benefits. And I think that's really what we're seeing here. it manifests in terms of new patient starts so we're certainly pleased to see a record number of new patient starts in q1 but we've also mentioned you know that we've implemented some newer marketing initiatives and really the idea is to be better at helping our customers to appreciate the meaningful differences between ingressa and the tetrabenazine products that are out there so I You know, between having more people in the field calling on the right accounts and doing a better job of differentiating Groza, I think really those are the two elements that probably have the biggest impact in terms of driving those new patient starts.

Thanks so much for taking our question.

We'll move next to Josh Shimmer with Cantor. Your line is open.

Thanks so much for taking the questions. A couple of quick ones. Has your contracting for Ingresa contemplated the Stato IRA price negotiation implementation, or will you have to renegotiate as you get closer to that kicking in in 2027? And then just in terms of this, the record number of starts, just trying to align that with your comments, I guess, around last year and early into this year that you didn't really expect your redeployed Salesforce to start to contribute meaningfully until later this year. Has that contribution occurred earlier than you expected, or are you still waiting for a significant inflection from their contributions? Thank you.

Maybe I'll take on the first question on the contracting piece. I think if you look at our history on contracting in the past, It has been really, you know, the north star here is to maximize patient access, and that's always been how we viewed contracting. We've done that in years in the past. We've also walked away from contracting at certain time points when that was not the case. I think when we look at the strategy overarching is to have a parity type of situation with other products in this space to make sure patients have as many options as possible. The thing that's different moving forward is IRA does bring a complication into the story about how we view contracting and maximizing patient access. So this is a variable. Now that's part of the equation that's growing in magnitude of its significance, and that is something that we have an eye on, in particular for our competitors' IPAY moment in 2027. Obviously, contracting that we do now is really with an eye on 2026 and in some cases you can pull forward into the same year. But we do look at that as something that's important for us to continue looking at and as things change and evolve over the coming months and year, we will certainly keep the external community up to date in case any changes in our contracting approaches change. But right now we're happy where we landed. with the expanded access here starting this quarter and moving into the remainder of the year. Eric, do you have anything to add to that?

Yeah, just in general, especially in the Medicare space, you go year to year with your contracts. Several of the agreements that we have in place, however, carry us through 2025 and the entirety of 2026. And so that does provide some stability. from a planning perspective and right up to the doorstep of that I-Pay moment, as Kyle described. The second piece was really around the contribution of the expanded sales force. Was it earlier than what we expected? I would say no. It was pretty much in line with our expectations. I recall that the expanded sales team hit the field in Q4. And we had said that we need a few quarters for the team to kind of hit their stride. And we saw that really manifest with the record new patient starts, especially as we move through Q1. Keep in mind that Q1 is a quarter every year that we have to go through somewhat of a rite of passage because of the many, many patients that need reauthorization. So kind of working our way through that with our customers, with the ACPs and the pharmacies does consume a lot of our effort in Q1 every year. But we're able to do that in tandem with driving new patient starts. And I really do think it's the tangible benefit of the expanded team, not just more people, but also the new hires becoming more proficient in driving diagnosis and treatment with ingresses. So I'd say right on schedule, feeling really good about the expanded team. And, you know, as we said earlier, we do expect to see accelerated growth for the balance of the year.

as we've reiterated with our guidance. Maybe just to add to that real quickly, eight years in the launch, and to think we just had our greatest quarter in terms of new patient starts is phenomenal, and I do attribute that to the team and their ability to catch up quickly and work through a very challenging Q1.

Thank you.

We'll take our next question from Jay Olson with Oppenheimer. Your line is open.

Oh, hey. Congrats, Irie, for all the amazing achievements that she's accomplished on behalf of patients. We have a question about the journey study of valbenazine for adjunctive treatment of schizophrenia. Clinicaltrials.gov shows a March 2025 completion date, so should we expect those results any day now? And then as a follow-up, can you talk about the learnings you expect to leverage from the journey study? How will you apply those learnings to your next-gen VMAT2 inhibitors? And what, if any, are the implications from the recent failure of cobenfi in ATS? Thank you.

Yeah, thanks very much, Josh. Thanks for the kind words as well. I really appreciate that. And I think in terms of the journey study, yeah, it's a very important study for us in terms of learning for the VMAT platform. And obviously, this is a must-win area for us with biology. And so we're We're really interested in understanding what we'll learn from that trial. We will be reading out the study in the near future. I mean, we said somewhere around the middle of the year, and I think we're still on track from that, as you saw from clinicaltrials.com. as well. And I think we're going to be interested in understanding the potential efficacy as it's measured by reduction in the PANS total score. But we also have a lot of other functional endpoints and other subgroup analyses within that study, which are going to allow us to understand more about what type of patient within that population might respond best to the biology that's represented within VMAT2 inhibition. I also think just one brief comment on the recent CoBEMFI study. As you know, there are no medications approved for the adjunctive treatment of schizophrenia currently. And I think that study showed us again the difficulty in performing clinical research in this area. I mean, our take on that was it was a well-run study for a medication that has already been proven to be effective in the treatment of acute psychosis in CoBemphi. And so the inability to show an additional improvement in that setting, I think, reflects more on the nature of the clinical trials that are performed in this area and also some of the challenges there in this patient population area. Just one thing to add in that regard, because we have been asked, I know you didn't ask this, but we are asked, does that have any implication for us with respect to our 568 program? And it doesn't in any way dampen our interest and belief in the phase three program that we have for 568 in acute psychosis. I think we're very confident in the phase two data that we generated for the 20 milligram dose and very pleased to have just started the phase three program in that setting. I think I said your name wrong, Jay. I'm terribly sorry about that. But yeah, and thanks again for the question.

No worries. Thank you, Irie.

We'll move next to Corey Kasimov with Evercore. Your line is open.

Great. Good afternoon, guys. Let me add my congrats to Irie on a great run at Neurocrin. So two questions on chronicity for me. One really quick one. Was there any amount of material amount of inventory stocking in the first quarter? And then a second question, when could we expect to see longer-term chronicity data from your ongoing Phase III open-label extension, and what endpoints do you believe could be positively impacted by longer-term androgen control? Thank you.

Hey, Corey. I love inventory questions, so there was very little there was very little stocking in the quarter from an inventory perspective. I'll let Irene comment on planned upcoming data.

Yeah, and just to remind everybody, more than 90% of the patients in the randomized trials of chronicity rolled over into the open-label extensions, both on the pediatric and the adult side, and the vast majority of the patients have remained in the study ever since then, over 90%. And so we are in the process of actually shutting down the U.S. portion of the adult open label extension study, and those individuals will be rolling onto commercial product over the next few months. The pediatric study we are keeping going because it's generating additional very important data for us, and obviously we are continuing the studies outside the United States. With respect to the data from those studies, we will be releasing one-year data on both androgen control, glucocorticoid levels, and clinical endpoints such as metabolic endpoints and other reproductive hormone-related endpoints over the coming months at the endo meeting in July. And the nearest future is this month at PES.

That's very helpful. Thank you.

We'll take our next question from Brian Scorny with Baird. Your line is open.

Hey, good afternoon, everyone. Thank you for taking my question. Congratulations on your pending retirement. So maybe I'd also love to ask you a question just from your comments on the 568. Phase 3 plans, it sounds like you wouldn't necessarily write off an opportunity for 5, 6, 8 in an adjunctive therapy setting. So I'm just wondering, you know, and obviously you're doing a commercial light-up. If you had a successful Phase 3 study in that setting with Coventry failing, is there a study design that you see that would be worth pursuing for 5, 6, 8? Not sure if you think the risperidone subgroup analysis is a real effect or if there's some other unique design you would think about pursuing.

Brian, this is Cobb. Maybe I'll start this question and Irene and I can tag team a bit on this. I think what we've seen from the early CoBEMPHE launch is that 70-80% of patients are taking the therapy from a monotherapy perspective. Maybe there's some overlap there as patients transition from one medicine to the next and there's some overlap of two medicines, but for the most part it seems like it's used in a monotherapy type of setting. So that'd be kind of point number one. Number two is I think what we've seen for CoBEMPHE is from BMS and others that have worked in this space. You know, we have our own data that we'll be having be available around the first half of this year. ATS trials are extremely difficult to run. I think there's still a lot of learnings there that can be applied and thought about for the future. That's why we're excited about running the study and seeing the results for valbenazine in this space so we can get a feel for that. And learnings from that will be plowed back into our next generation compounds. But when it comes to the muscarinics themselves, we think that there is a significantly large opportunity standalone with the acute studies that we have planned for the registrational program and then moving into other indications in particular later this year with 568 and the bipolar mania.

And that's our current strategy.

We'll move next to Mark Goodman with Learing Partners.

Your line is open.

Yeah, Matt, with Ingresa, you've talked about 5,800 as the ASP that we should be thinking about for this year. Obviously, that number has changed, if you could give us a sense of what the new number is. And then, Irie, definitely, we'll all miss you. Maybe just a question for you, excluding 568, can you talk about the rest of the Muscarinic portfolio and where we are? Thanks. Thanks.

Yeah, Mark, I think I've gotten away from getting into the nuances of the exact net revenue per script for, you know, a handful of quarters now. But I guess the guidance that I would give you is you typically see an improvement in gross to net going from Q1 to Q2. I would expect that to be sequentially down just slightly. And so I think that's the color that I would provide on net revenue per script, Mark. Go ahead, Irene.

Thanks. And thanks, Mark. On the remainder of the muscarinic portfolio, just to remind you, we have 570, which is a dual M1, M4 agonist, 569, which is an M4 preferring agonist, and 567, which is an M1 preferring agonist. And then our own internally discovered 986, which is an M4 antagonist as a potential treatment for dystonias and Parkinson's tremor. With respect to the agonists and actually including the M4 antagonists as well, all of those medicines are progressing currently through phase one studies. For 570, we will be completing phase one in the very near future and starting a phase two study by the end of this year in acute psychosis. And that will be the next phase two start for us from that platform. And then as 569 and 567 complete their phase one studies, we'll be talking more about that and the potential next steps there, including any potential phase two starts in the foreseeable future.

Thanks.

We'll take our next question from Sean Laman with Morgan Stanley. Your line is open.

Hey, this is Mike Riad on for Sean Laman. Thank you for taking our questions and a big congrats to IRI for all the impact you made. Thinking about Ingresa, Tevo's Osteto guidance suggests a good amount of patients can come to Osteto this year, but the data that was presented at AMCP show half of patients don't reach that therapeutic dose on Osteto or XR. So thinking about that, how do you see the Osteto drop-off market evolving and Do you think that some proportion of those drop-offs can switch to Ingresa and help the new patient starts?

Thanks.

We were very encouraged by the information that we recently released and published regarding the therapeutic dosing. And I just remind you that, obviously, with the 40 and 80 milligrams of Ingresa, we start dosing at a therapeutic dose level and continue throughout the patient's period of time on the medicine. And so from that point of view, I think, as Eric alluded to in his prepared remarks as well, I think we have a very high confidence level in the value that Ingresa can bring to patients. You know, it's, as we said, highly effective, including in the data that we recently published on long-term data in more elderly population as well, uniquely selective in terms of its VMAT2 inhibition. And we have the broader set of data that we believe in patient populations that can experience value. And so we're focused on that and continuing to educate around that.

Yeah, the only other thing that I would add The only thing I would add, just to piggyback here, is that the majority of patients that we see starting on Ingresa have been and continue to be newly diagnosed and newly treated. There isn't a lot of switching that happens in the VMAT2 market, and we haven't seen that dynamic really change that much over time. You know, we continue to make progress with diagnosis and motivating treatment, but for the most part, the patients that are starting IGREZA are getting started on the DMAT2 for the first time.

I appreciate that. Thanks.

We'll move next to Ash Varma with UBS.

Your line is open. Hi, congrats from my side as well. Just on Ingresa, maybe can you talk about any pull through on these new contracting or the Medicare Part D formulary access that you mentioned? When does that happen? Like, did that benefit 1Q or is that more of a 2Q or later in the year? And just secondly, what was the percentage increase in the Salesforce footprint, if you can remind us, and when do you expect that benefit to start to accrue? Thanks.

Yeah, I got the first part of your question in terms of the pull-through effort. Can you repeat the second part?

Yeah, like what was the percentage increase in the Salesforce footprint, and when do you expect that benefit to start to accrue?

Okay, well, I'll take on the second part first. We didn't give exact headcount numbers when we did the expansion in Q4 of last year. But, you know, it was a substantial increase of our psychiatry footprint. And as I mentioned before, we do think that it is starting to see tangible benefits here in the market, primarily manifest as the record number of new patient starts we saw in Q1. With regards to pull through, yes, you know, certainly our plan of action has always been when we have a formulary win, we attempt to pull it through. And the way that that translates is certainly through personal and non-personal promotion. Our sales teams are aware of where there's been an ad of Ingresa onto a formulary. They're aware of the HCPs that are having more patients underneath that plan. And they're sure to communicate those changes. And with regards to this most recent formulary, when that process has already started as of the beginning of April. So We're going to continue to leverage when we do have increases in formulary coverage, but the way to think about it is it really benefits new patient starts. Existing patients already on treatment under that plan, they're already covered. They have a certain number of authorized refills. It's the new patient starts where there's a little less headwinds because it's now on formulary. Thanks.

But just to be clear on how the financials flow on this, we will take a more immediate hit to gross net starting in Q2 and the benefit from the new patient additions, as Eric mentioned, too. will accrete over time. So it typically takes, you know, two, three, four quarters to get to a place where you're ROI positive. But it's something that, as we mentioned and as Kyle mentioned, strategically important for us to continue to be a major player in this market.

Thanks. We'll take our next question from Mohit Bansal with Wells Fargo. Your line is open.

Hi, this is Serena. I'm from Mohit. Congrats on the great quarter. First, I wanted to ask a clarification question on Ingresa growth to net. I think previously you guys have said you would expect some tailwind from the lower phase-in of rebate under Part D redesign. So I was wondering if that was any bit of a factor this year. And then wanted to ask on the phase three program for 568. How are you thinking about the number of sites, any ex-US sites, and then any other changes in how the studies will be run versus the Phase II beyond the selection of just one dose? Thanks.

Yeah, from the Med-D design change on the mandatory rebates, that was a slight benefit. I'd call it like 1%. And that was a tailwind entering into this year. But that will, of course, be more than absorbed by the incremental contracting, which really is what's going to drive continued growth and value for Ingress and for the company going forward. Irie, do you want to comment on phase three?

Yeah, we'll obviously provide more information as we get the remaining studies within the program up and running, but just a couple of comments. The first study is a U.S.-only study for the phase three, and as you mentioned, it is a single-dose level of 20 milligrams, one-to-one randomization with placebo, so very simple in design. And we are taking all the learnings that we achieved from the phase two which we can talk more about once the full program is up and running. The number of sites doesn't increase substantially which I think is really important because if you remember our phase two was a study that was run over a number of sites and a relatively complex adaptive trial design. So we think the simplicity of the phase three program that we've designed and are implementing will be beneficial for us moving forward.

We'll move next to Myles Minter with William Blair.

Your line is open.

Thanks, and off of my congratulations to Ira as well for a great career there at NERC.

Just on Otovampitor, the two Phase III studies that are listed on clinicaltrials.gov, just wondering about the powering assumptions for those trials, given that 200 patients seems on the smaller end from what we've seen from peer studies that have obviously had mixed results. And secondly, I think on slide six, it says you've initiated four phase three studies. What are the other two?

Yeah, so thanks, Miles. A couple of questions there. Let me get to the number of studies, first of all. Within the registration package for Osovampato, there are three key studies, the two short-term randomized studies. placebo control studies and one longer term open label study which is obviously essential to enable us to look at longer term safety. With respect to the powering and the subject number, this is a, could be quite a long conversation but let me make it short. We, one of the things we worry most about in the context of major depressive disorder studies is placebo effect and obviously expectation bias. And there is also a large body of research that suggests that the larger the study gets beyond a number of around about 20, the increased likelihood of placebo response and therefore the increased likelihood of potentially failed studies. So while each of the phase three studies is adequately powered and appropriately powered to measure an effect size significantly smaller than that which we saw in phase two, so we're highly confident in the size of the study, we have limited the size of the studies because of our take on understanding of the research in this area about the balancing act between increased subject numbers driving increased placebo response and increased risk of failed study.

Thanks for the questions.

We'll move next to Laura Chico with Wedbush. Your line is open.

Good afternoon. I just wanted to revisit real quick on the ingress of patient numbers and congrats on the record ads here. Not sure if you could also comment a little bit more about persistency and discontinuation rates. I think, Eric, you mentioned the reauthorization was challenging, but are there differences in the duration of treatment depending on the channel from which patients are originating, say long-term care versus psych. And then separately, I'm just curious with the R&D day and the second half here, any highlights to share in terms of how we should be thinking about the potential focus of the event? Thank you.

Yeah, with regards to the question around patient persistency, generally it's been very steady from the early days of the launch through the most recent cut that we looked at. And we haven't seen any real differences in persistency across the different channels, whether the patient's being treated by a psychiatrist, a neurologist, or more recently coming in through long-term care. I did comment that this was a challenging Q1, a little bit more challenging perhaps than what we've seen in years past. Anecdotally, feedback from the customers was that the reauthorization process It was a bit more challenging from their perspective, and we saw slightly higher drop-offs in delayed refills versus prior years. All of that was counterbalanced by the record number of new patient ads. And so that's really what gives us the, you know, sort of the confidence and conviction in the acceleration of our growth, given the uptake that we saw with new patients in Q1. But overall, no, we're not seeing any real differences in patient persistency by segments.

And this does conclude the question and answer portion of our call. I would now like to turn it back to Kyle Gano for any additional or closing remarks.

Thanks, everyone. I know we didn't get to all of your questions. For those of you that missed, we'll be following up with you individually. But thanks, everyone, for joining this afternoon. As you can see, we've made meaningful progress across several critical priorities of the business when we think about Ingresa. re-accelerating new patient starts, improving access for healthcare providers and the patients they serve, successfully launching chronicity and initiating multiple phase three studies. Neurocrine has never been in a stronger position and will continue to remain focused on execution and evolution of the pipeline as we move through the remainder of the year. So looking forward to seeing all the upcoming conferences or on your latest Zoom call. So looking forward to speaking with you soon. Thanks so much.

This does conclude today's program. Thank you for your participation. You may disconnect at any time and have a wonderful rest of your day.