Alrighty, let's go ahead and get started. Welcome, everybody, to the JP Morgan Healthcare Conference. My name is Anupam Rama. I'm one of the senior biotech analysts here at JP Morgan. I'm joined by my squad: Malcolm Kuno, Priyank Grover, and Ratih Pinhey. Our next presenting company is Neurocrine, and presenting on behalf of the company, we have CEO Kyle Gano. Kyle.
Thanks, Anupam, and thanks, everyone, for joining here at this early hour on day one of JP Morgan. A couple of quick housekeeping items, and I know the first one you're all looking forward to. I will be making forward-looking statements, so I'd like to direct you to our latest SEC filings for the risk factors of the business. The second one: this is not my first JP Morgan. It's not the first time I've represented Neurocrine at a healthcare conference, but it is the first time I've presented here on behalf of Neurocrine on the podium at JP Morgan. So I would like to take a moment and thank Gary Lyons, our Founding CEO, Kevin Gorman, our founder, and my predecessor. A couple of quick fun facts and a little bit of light humor here today. I'm only the third executive to ever present here at Neurocrine.
We have a lot of longstanding executives that have presented here, so the pressure's on me, starting here today. The other piece is, I think it's a reflection of how much fun and how much enjoyment we have working with our leadership teams at Neurocrine. And many of my leadership team are here today, and we look forward to taking your questions at the end of my presentation. I also enjoy, and we all have enjoyed over the years working with our employees to discover and develop innovative medicines for patients. So with that, when I stepped into the CEO role last October, I inherited a company, the responsibility for a company that's strong, stable, and growing. We've got a dynamic culture at Neurocrine, and as I've mentioned or alluded to, we've got the best leadership team in the business, and I truly believe that.
Opportunities like this don't come along very often, and I'm really grateful to have this opportunity here at Neurocrine. So today, our purpose is to relieve suffering for people with great needs, and we've largely fulfilled that purpose over time. If I look at our focus in neurology, neuroendocrinology, and neuropsychiatry, we've combined that with our expertise and experience and converted that into a competitive advantage. And with a strategy that's founded with that approach, we come here today in a humbling and enviable place. We treat thousands of patients each year with tardive dyskinesia and Huntington's disease chorea. And just as of a few weeks ago, we're bringing, for the first time in over 70 years, a new patient, a new medicine for patients with congenital adrenal hyperplasia.
So it's an incredibly exciting time here at Neurocrine, and I'm looking forward to share with you some of these things that make Neurocrine unique today, as well as why I'm energized for all the good things that are in store for us in 2025. It is going to be a year of both execution and evolution that's going to be required of us for success. On the side of execution, what I'm really talking about here is driving forward those things that are in process that will deliver near to mid-term value for our investors, as well as the patients that we serve today.
On the evolution side of things, I'd like to bring into focus the Neurocrine of tomorrow, where we have a supercharged R&D engine that's going to drive us into new therapeutic areas, new modalities, and have the opportunity to increase productivity above and beyond what you're used to seeing from Neurocrine. So let's talk about where we are today. We're on the cusp of exciting opportunities that, up to this point, are based off our past achievements. You know, if I think about the company and telling people about what we have here at Neurocrine, we start with, we're fully integrated. We have capabilities across research, development, and commercialization. And over the past few years, we've gotten, through discovery and development, four FDA-approved medicines over the finish line. When each of these medicines were approved, they were each first in class.
I'd like to talk about two of the medicines that we commercialize here in the U.S. The first one's Ingrezza. Ingrezza is our medicine that was initially approved for tardive dyskinesia in 2017. It's a VMAT2 inhibitor. It's our growing blockbuster. It's changed the standard of care for patients with tardive dyskinesia. Subsequent to our approval in TD, tardive dyskinesia, we received approval in the Huntington's disease associated, or the chorea associated with Huntington's disease. It's a very nice medicine for us, but it's not the only one. You heard me allude to another medicine in my opening remarks. crinecerfont was approved last month as a CRFR1 antagonist for congenital adrenal hyperplasia. CRF and CRF1 antagonism represents founding technology of the company from over 30 years of research and development. For our employees, for our company, to say that the approval is rewarding is an understatement.
Like Ingrezza, crinecerfont has all the hallmarks of being a blockbuster and to change the standard of care for many thousands of patients with CAH. So I'm hoping between Ingrezza and crinecerfont, you see a theme for the types of things that we like to discover and develop here at Neurocrine. And it's important to mention that because not only are they changing the standard of care, they represent growing revenue for our company and the opportunity to have a diversified revenue stream over time. So that's important when we talk about the future because I think we're well-positioned for sustained and long-term growth. It does start with Ingrezza, though. It's our medicine that we've been commercializing the longest. As you know, crinecerfont was just approved. With the 2017 approval of tardive dyskinesia, we've had the opportunity to build a market in TD.
In Q3, we saw sales of roughly $613 million in revenue. That's 25% year-to-year growth seven years into launch. It's phenomenal. We upsized our guidance the second time for the year to $2.3-$2.32 billion, which also represents 25% year-to-year growth at the midpoint. Considering 80% of patients with TD, over 800,000 patients, are still not being treated with a VMAT2 inhibitor, there's a lot of work ahead for us, a lot of opportunity, and a lot of growth still that remains between now and 2038, the end of our period of market exclusivity. So it's important to point out those key facts: financial, periods of market exclusivity, because tardive dyskinesia and Ingrezza have provided a very strong financial foundation for the company. Almost $2 billion in cash, durable cash flows, and attractive P&L.
We've built a very deep and diversified portfolio over the past couple of years, and it's built to be sustainable for the first time. And by sustainable, I mean to consistently develop and share, provide data flow from year after year after year. That's a very exciting time for us to be able to say something like that. Ingrezza has also afforded the opportunity to develop crinecerfont or crinecerfont into Crenessity . And I think that's a good segue for me to talk about all the fantastic things that we like about crinecerfont. It starts with we got an early Christmas gift in December. Our approval for crinecerfont came over two weeks prior to the PDUFA date on December 13th, and it gave us a good chance to jump-start 2025 with all of our commercial activities. But about crinecerfont, we love the label that we have.
Kudos to our development and regulatory teams for getting this over the finish line. It's the first and only medicine approved as an adjunct to glucocorticoid replacement to control androgens in adults in pediatrics age four and above with classical congenital adrenal hyperplasia. The broad label that we have is no doubt the result of the strong efficacy that we saw, as well as the good safety and tolerability in the largest ever CAH program conducted to date. This was combined, or this is combined, with two patient-friendly formulations for pediatrics and adults, so very exciting here to have this type of medicine for patients who have been waiting seven years for one that's been discovered specifically for their needs, and that's really exciting to be able to provide that to them.
About CAH, it's a very serious disease that affects about 30,000 patients in the U.S., and it's caused by mutations on the CYP21A2 gene. And this is a particular gene that's important because it encodes an enzyme, 21-hydroxylase, which is key in the synthesis of cortisol. We all know cortisol is the central regulator of the HPA axis. So what this means for CAH patients: low levels of cortisol, high and uncontrolled levels of ACTH, and high and uncontrolled levels of downstream androgens. For over 70 years, the only way to treat CAH is to use chronic and high-dose glucocorticoids like hydrocortisone. And we know the consequences of this: poor bone health and a multitude of different diseases and disorders associated with metabolic syndrome. So that's where crinecerfont enters the picture. Crinecerfont allows patients to recapture their HPA axis. So let's take a look and see how that happens.
In this particular slide here, we show a healthy individual on the left, depicted by having colored lines here for both cortisol and ACTH. In a normal individual, cortisol regulates ACTH production at the pituitary and produces the right amount of ACTH and downstream androgens. In contrast, in patients with CAH, they have low levels of cortisol, as depicted here by the broken dashed black line, and what this means for patients, as enlarged on the right, you're not able to control the production of ACTH. You see it be uncontrolled and high, and that affects downstream androgens accordingly. Where crinecerfont fits into the picture then is it antagonizes the CRFR1 receptor at the pituitary. And by that, patients are able to block for the first time, put a brake on the production of ACTH, allows them to control that, capture it, as well as the downstream androgens.
So what are the benefits? For the first time, patients are able to decrease excessive ACTH stimulation in target tissues and organs. And here I use the plural, tissues and organs, because I think it's important that we all appreciate the ACTH receptor is in other organs and tissues besides the adrenal gland. So controlling ACTH is very important globally in the body. And then the next piece that comes from that, patients are able to normalize their androgens, or at least bring them back to the normal range. And equally important, patients are able to reduce their reliance on excessive exogenous glucocorticoids like hydrocortisone. In fact, what we're able to show from our own pivotal program is a good portion of patients are able to use a physiological level replacement of glucocorticoids. So a very exciting day for patients.
No longer do they have to deal with a choice between the consequences of high-dose glucocorticoids and high ACTH and downstream androgens. So it's a super good day for patients to have this medicine. A lot of work ahead for us to maximize access for crinecerfont in patients with CAH, but we're up to the challenge. Now, if our commercial medicines, Ingrezza and crinecerfont, wasn't enough, as I mentioned, we do have a deep and diversified portfolio. As we stand here in January, we've got 12 programs ranging from phase one to phase three clinical development. I'm going to highlight just two areas today for the sake of time. First, new entrants to the clinic in January of 2025.
We have a selective sodium channel blocker 1.2, 1.6 that we're moving forward for seizure disorders, and an additional VMAT2 inhibitor that will be targeting like NBI-1065890 and with valbenazine for movement disorders and other CNS indications broadly. This is NBI-675. I'm going to spend the majority of my time talking about our industry-leading muscarinic portfolio that has five programs. Four on the muscarinic side of the equation and on the other side, an M4 antagonist that we're pursuing for movement disorders, Parkinson's disease, tremor, as well as dystonia. That's NBI-986. But in terms of the muscarinic portfolio, given the volume here on the agonist side, I'd like to spend a little bit more time here talking about what we're doing. So we have a number of programs that range from selectivity of M1 to M4. On the M1 side of things, the molecule in development is NBI-1117567.
On the M4 selective side, it's NBI-1117568. It's also our most mature asset in this portfolio, having achieved proof of concept in Q3 of last year in schizophrenia. We also have different versions of M1 and M4 behind these two molecules. In particular, we have a dual M1, M4 agonist, which is NBI-1117570. And then rounding out the portfolio, a molecule that has the majority of pharmacology at M4, but with some M1 pharmacology as well, and that's NBI-1117569. So it's interesting. The muscarinics have been around for over 30 years, but there has been little work, but it's been little work being done to actually tease out what are the benefits of M1 specifically and M4, and also different flavors of M1 and M4 in the same molecule.
We have the luxury of doing that here in our portfolio, and we're spending the time in phase one to understand what the different pharmacologies could offer patients ranging in diseases of cognition to psychosis. So stay tuned on that. These are programs that will continue running this year. But I'd like to switch gears here a little bit and talk about NBI-1117568. I'd mentioned proof of concept in Q3 of 2024. This is our schizophrenia program. We saw excellent data coming out of our proof of concept trial. Recall, this was 200 subjects in our phase two, four doses of NBI-1117568 versus placebo. All doses worked, with one dose performing better than all others. That was our 20-milligram dose. The efficacy there on the primary endpoint of the PANSS was impressive. A placebo-corrected score of 7.5-point improvement. Total PANS S improvement of 18.1 with an effect size of 0.61.
So that's rare air. If you put all those pieces together, it's a medicine that's once a day, no titration, really good safety and tolerability, and no food effect. And that's why we're really excited about the data that we have and why we'll be moving this program forward this year in schizophrenia. So we like the data, and we also like the competitive positioning of 568 relative to other muscarinic programs today. And just to level set everyone, there are five muscarinic subtypes, M1 through M5. The important ones here to talk about are M1 through M3 and M4. M5 actually is expressed in very low levels in the brain. It's not expected to contribute to efficacy or safety and tolerability. So it really is a story of M1 through M4.
What we know about M1 through M3 is that these receptors are also found in the GI tract, and a source of safety and tolerability concerns and mechanism that agonize these particular subtypes. With the selectivity that we have with 568, over 100-fold on these subtypes, we don't see this problem in our phase one or phase two trials thus far. The other piece that's interesting to note, because of that selectivity, we don't require an add-back medicine to block these peripheral effects. We have seen this with other molecules that bind to and agonize all the different muscarinic subtypes. I didn't mention upfront, but because we are a selective and direct M4 agonist, we do not require cooperativity of the endogenous ligand of M4 to drive efficacy.
So we don't have to worry about adding back anything or worrying about or leaning on something else to help drive efficacy. NBI-1117568 is the only molecule in development that works just fine by itself. And that's why we're excited about our competitive positioning here relative to other programs in this space. The other thing that I wanted to mention as a company that spent the better part of the past two decades developing a medicine for tardive dyskinesia is if we're developing a medicine for psychosis for patients with schizophrenia and bipolar, we'd like to have one that has an improved TD profile. If we can eliminate it altogether, even better. The NBI-1117568 doesn't bind to dopamine D2, that particular receptor, which we know is common to the antipsychotics that are commercially available in the source of TD today.
So very excited about, for a number of reasons, the data, the competitive positioning, and the potential profile relative to other antipsychotics today with NBI-1117568. So we talked about our commercial products. We talked about the pipeline. What about our R&D transformation that's ongoing right now? This is the evolution part of the company, and I'm really excited to share with you what we have going on here. We start with this concept of moving away from our reliance on external innovation for a lot of our pipeline to our internal discovery engine and efforts. And then it expands to moving away from small to multimodality molecules, from unvalidated to validated targets, and then from symptomatic disease modification and curative therapies.
If you follow us down that path, where we've seen it take us to is a point where we're matching the right modality or approach to a given target and disease state. And when you do that, we're seeing it afford a number of benefits here at Neurocrine. One of them is increasing our probability of success moving from one phase to the next. It's improving our cycle timelines, development timelines across different phases of development. And importantly, it's maximizing the value of our investments on a given program. And then this manifests itself in something that's tangible for us all to appreciate. It's increasing the number of programs that we see in our pipeline. And you'll get a feel for that as I conclude here today.
But it really means for us that on average, we think we can deliver four new phase one starts per year, at least two new phase two starts per year, and at steady state, at least three phase three programs. But we're in the business of making medicines for patients. So what does that mean in that metric? Well, if we continue this thought process and we see our productivity here, we believe we have the real opportunity to bring forward a new medicine on average every two years. So that's very exciting in and of itself. We've never achieved any of these metrics across phase one, phase two, and phase three here at Neurocrine. So to hit one of these is incredible. To hit them all is amazing. And it's something that I see us being able to do here in a very short period of time.
So let's conclude and talk about where we are here with 2025. Remember, I said upfront it's a year of execution. Well, the execution starts with those things that are in process today, and it all goes back to Ingrezza. We need to continue doing what we've been doing from a commercial perspective, driving diagnosis of patients with TD and ensuring that we have maximized access for patients that want to have the opportunity to be treated with a VMAT2 inhibitor. Number two, while it's early days for Crenessity , we believe we have a strong foundation to have a successful launch and lead us down that path of changing the standard of care for patients. But that does take time. On the R&D side of things, we've completed our end-of-phase two meetings for NBI-1065845. The generic name now is osivampator and NBI-1117568 for schizophrenia.
The next steps here with these programs is to figure out those activities needed for us to work through the initiation of the registration program, and that's something that's on track now. We can't keep our eye off the pipeline. We have to remain focused. We have a number of data readouts this year as well that are going to be important. For valbenazine, two phase three data readouts, one in the adjunct of treatment of schizophrenia and the other in the dyskinesia associated with cerebral palsy. We also have a proof of concept study that we'll read out with our NR2B NAM and MDD. This is NBI-770 that will occur later this year as well. And then I spent some time talking about the muscarinic portfolio.
Our phase ones are ongoing, but we'll look to wind these down this year and continue to execute on all those learnings that we have to pick one molecule or more to move forward in a variety of different diseases of cognition to psychosis, so the new starts this year go back to where I began in the R&D update. We're going to take the successful end-of-phase two meetings that we had with the agency recently and pivot those into the initiation of the registration programs for osivampator and MDD, as well as NBI-1117568 and schizophrenia. Now, some new starts in phase two. We spent a lot of time talking about the muscarinics. We spent a lot of time internally looking at the data that we've collected today across all of our molecules, including the phase two data in schizophrenia.
We like what we see, and we'll be expanding the indication of 568 into bipolar mania. The same learnings have been helpful for us to understand the opportunity with our M1, M4 dual agonist, and that will be moving into phase two for schizophrenia this year as well, both second half starts. On the phase one side of the equation, you saw the programs entering the clinic in January this month. In our earlier pipeline slide, we'll execute the phase ones there this quarter. Then that takes us really to the stronger evolution part of our thesis. We see a clear line of sight to four new programs entering the clinic this year that will advance from preclinical to clinical development. It starts by leveraging our history on CRF in our leadership position in CAH.
We'll be moving forward a peptide in this space, NBI-1432, that will start this year. We've also been working for quite a long time on a novel neuroendocrine target that will be addressing diseases within the metabolic space. That's a program that will start this year as well, and then returning to a familiar therapeutic area, neuroimmunology, we have an antibody in this space that will be advanced for the area of CNS and immunological disorders, and of course, we're on track. We've spoken about our gene therapy programs in the past. We're on track for these programs to enter the clinic this year for Friedreich's ataxia and GBA1-related Parkinson's and Gaucher's disease, so a lot going on this year in terms of new starts, new programs, the evolution of the pipeline and the new therapeutic areas and modalities. Too much to go through here.
We will be hosting an R&D day this year to go through a lot of the data that is underpinning some of these new starts, and we look forward to those discussions when we next get together. Now, they often say a picture's worth a thousand words, and I believe in that. You saw our pipeline slide that starts here today at JP Morgan. We see significant growth going from today to the end of the year, from 12 to 18 programs. That's 50% growth. Four in phase three, three in phase two, or sorry, four in phase three, three in phase two, 11 in phase one. That productivity exceeds the productivity I shared just a moment ago that we're hoping to achieve at study state. So we're making good progress along this R&D transformation. The key is we need to do this year in year and year after year.
The last piece to point out here is that diversification of our approach is important, and you can see from the slide here that 30% of our pipeline comes from modalities outside of small molecules, so I think we're about on time. I'd like to thank everyone for taking the opportunity to listen to me here this morning. We look forward to your questions now and throughout the course of t he week and giving you an update on our R&D transformation as the year goes along. Thanks so much so our team, if I could have you all come up here and have a seat.
All right. I just want to remind folks that there are three ways to ask a question, right? So you can raise your hand and do it like the old school way. You can email me your question, or you can put it in the question portal, and it'll be right here.
Hey, Anupam. Should we do a quick introduction?
Yeah.
Who's here?
Yeah. Go ahead.
So I'm Matt Abernethy, CFO of the company. I've been with the company eight years. And as Kyle said, I feel quite fortunate to be in the spot where we're at today, launching Crenessity . It is a dream come true for the company and then also for a lot of patients out there. And so really encouraging. Would also just say big shout out to Kyle doing JP Morgan like that his first time through. Well done. And I think he covered 10 times more ground than Kevin Gorman if you're listening. Start from the beginning.
Yeah. Yeah. Good job, Kyle.
Maybe I'll just do a quick introduction. I know we have a lot of time for questions. Ingrid Delaet is here, our Chief Regulatory Officer. Samir Siddhanti, to her right, is my lieutenant. Now in business development, he heads up our group there. So anything BD-related, please direct that to Samir. He's also the leader of the muscarinic portfolio that I just shared. So he's wearing multiple hats at Neurocrine. Eric Benevich, our Chief Commercial Officer. Eiry Roberts, our Chief Medical Officer. Jude Onyia, our Chief Scientific Officer. So you got 15 minutes, Anupam. Fire away.
Yeah. I'll start out with a couple of questions. Realize it's only a couple of weeks into the CRENESSITY launch. But any sort of anecdotal things that you would highlight that you've heard from the marketplace in the early innings here, very early innings?
Yeah. I'll start us off. We're super excited about the opportunity to bring Crenessity to the CAH community. We were very pleased with the clinical data that emerged from our registrational studies. And a tip of the hat to Ingrid and her team for the clean label and broad label that we were able to secure. And as Kyle noted, we got approved four weeks ago today, so a few weeks early ahead of our PDUFA date. So far, we're off to a great start. The receptivity from the endocrinology community has been very strong, and even more so from the patients and the families. It's very early. We're just a few weeks into this launch. So we're not reporting any metrics yet. But ultimately, the word is getting out, and the response has been very favorable. Eiry, do you want to?
Yeah. I mean, I think to build on what Eric was saying, I mean, we were very pleased with the clinical data from the phase three program, which was, as Kyle mentioned, the largest phase three program that had been conducted in pediatric and adult patients with CAH. I think it did afford us the opportunity to understand that, and we hear this also from the external environment, that up to 80% of the population of pediatric and adult patients with CAH, we think, have the opportunity to benefit from crinecerfont. And so it's clearly, though, going to be a need to change the paradigm in terms of how these patients are treated. There hasn't been a new medicine for over 70 years in this space.
And so there's an enormous amount of education that needs to happen both at a clinician level and at a patient and community level to understand where this medicine fits into the treatment paradigm. We started that educational process many years ago, but I think it's accelerated really over the last six months as we got ready for the approval and launch. And so we're now really excited to be able to engage fully with the community and understand how to serve them.
Just, Kyle, maybe a clarification point. I think one of the slides said that you'll have one new medicine every two years. Is that right?
That's the plan. I mean, obviously, it starts with the go-to-market. The substrate, we like to use that word here at Neurocrine, really begins by emerging from efforts from research into clinical, and there we think that you can even see from our pipeline advancement this year, four new phase one starts per year, two new phase starts per year, and that gives us a nice steady-state portfolio of about three programs in phase three, and if you look at those and you look at your normal progression from there, that gives you that opportunity. Of course, these are all averages, but it does require productivity that we haven't seen at Neurocrine over time. Now, we're not just talking about productivity here. We're talking about quality assets that we're investing in. I think that over the past six months, we've made some tough decisions in the portfolio.
Some programs have been discontinued, and we've been investing in other programs that we thought could benefit more patients, and we'll continue to make those difficult decisions on programs to make sure that we're making the right ones to advance into the clinic and certainly to support the late-stage development and bring forward the patients.
It's amazing when you look back just five years ago. We probably had one to two programs in the clinic, and to see the evolution of the company to now have 18 programs is really a testament to a lot of the efforts both on the in-licensing front, but now you're starting to see the fruits of Jude's organization and everything that we've in-licensed that was very early stage, so we find ourselves quite fortunate to be able to invest the way that we are right now in a pretty balanced way from phase one through phase three.
On Jude's organization, just wondering, we've talked previously about just maybe diversifying away from small molecules, right? Big biologics, maybe even gene therapy. How do we think about you outlined the 18 months, right? How do we think about, let's call it the 36, 72-month timeframe when we might see a little bit more from different modalities?
Yeah. Jude Onyia, Chief Scientific Officer for Neurocrine. Excellent question. I think if you go back, I think a year and a half ago, we laid out a strategy of transformation, R&D transformation strategy that allows us to begin to think about scale, competitiveness, and sustainability. The key elements of that strategy was for us to really recruit the expertise needed to do that, one, build the platforms, and then point that engine to being able to deliver the ambitious pipeline that Kyle spoke to. And three years into it, I can say that we've done all three above and beyond. I'm frankly surprised at this pace at which we've been able to do what we've done, but it speaks to the quality of the men and women, the platforms we've built. As it relates to the multi-modality, we have strengthened our small molecule capabilities. That's first and foremost.
We have also built a competitive, more than competitive peptide team. We've built a more than competitive antibody engineering and protein engineering team, as well as we're continuing to advance in gene therapy, and in gene therapy, we've done it through partnership, through internal build, and a partnership with one of the leaders in the BBB penetrant capsid space, Voyager, and these efforts, consistent with our expectations, have delivered three years in a row way above what we had planned. I think we laid out a plan of about 20 candidates over five years. We're ahead of that, and that really spreads the modality. We have multiple candidates of peptide, multiple candidates of antibodies, multiple candidates on gene therapy, and multiple candidates on small molecules.
And so you're going to see that payout for modality in the next. I think by the end of the year, we share some of that data, start beginning to share some of that data. You're also going to see it across the therapeutic areas, neuroimmunology, neuroendocrinology, neurology, psychiatry. And you're also going to see the flavor of more validated high-value spaces that we believe we can be competitive, as well as also from symptomatics to disease-modifying opportunities across these spaces.
One of the questions we get is, how are we going to afford this?
What I'd say is Ingrezza and CRENESSITY obviously give us a platform for investment. But as Kyle said, it really comes down to the quality of the substrate that we have. And I think that the team has been able to really deliver well on that. Just to remind folks of the guide that I've given previously is that we would expect for 2025 to invest between low 30% to mid-30% of our revenue back into R&D. We truly believe that long-term shareholder value is going to be driven by revenue growth and advancing pipeline, not in the focus of maximizing profitability in the short term when we do have quality assets to invest behind.
And Matt, maybe just on the expense side, you just talked about low to mid-30s on R&D. Maybe a little bit of color on SG&A. You had the sales force expansion last year. So how do we think about that? But you are launching a product, clearly.
Yeah. We've shown tremendous leverage over the last three years. We've gone from 53% of SG&A as a percentage of sales being invested down to it should be around 42%-43% this year. So over 1,000 basis points of leverage. 2025 is going to be a year of investment. We did make the decision to expand significantly the sales force for tardive dyskinesia because of the opportunity there, as well as fully funding Eric's team for the CRENESSITY launch. And so that, I've given a guide, would be a sequential increase of spend of, call it around $125 million. So 2025 is a year of investment in launching Crenessity and getting these two major phase 3 programs stood up. Really a lot of things going on, as Kyle said, focusing on executing in 2025.
Maybe just to add to that, Anupam, the sales force expansion is a good reminder for me. We have two large phase three programs that are kicking off this year, one for osivampator or AMPA PAM and NBI-1117568 and schizophrenia. We all have an idea of what recruitment and time to topline data is, but assuming that we have good phase three outcomes there, those are products and medicines that are going to be available to patients this decade and be able to leverage the sales organization that we developed for Ingrezza almost completely, so very exciting to be able to leverage that moving forward as well.
Questions from the audience? We've got a couple of email questions here. Ingrezza one. So the question basically says, is the battle on awareness for TD, where are you on that? And how do you see market penetration getting deeper?
Yeah. So we're seven years in with the launch of Ingrezza. And I still consider it to be a launch. And the reason I say that was that tardive dyskinesia was the most undeveloped market at the time that we launched in 2017, the most underdeveloped market, at least that I've seen in my time in the industry. And we currently estimate at least 800,000 people in the U.S. with tardive dyskinesia. And as Kyle said in his comments, less than 15% of them are currently being treated with a VMAT2 inhibitor. And that's really part of the rationale for the expansion of our sales team last fall. We have business segments across psychiatry, neurology, and more recently, long-term care. And the reality is that all three of those segments are still growing robustly. And so we intend to continue growing Ingrezza in all three of those segments.
And as Kyle said, we've got a great platform for the future with the two psychiatry programs that are on the way. So lots of opportunity still, a lot of room, a lot of headroom for growth. And frankly, one would think that seven years in, you wouldn't have to invest so much in terms of disease education. But even still today, especially in psychiatry and long-term care with the high turnover that we see in the provider community, we're still introducing tardive dyskinesia and drug-induced movement disorders routinely to providers and educating them on that and VMAT2 inhibitors, Ingrezza in particular.
I think the other piece to that is the antipsychotic category continues to grow. It's growing at a rate that is higher than the growth rate of the general population. So more prescriptions, more prescribers, TD continues to grow. And that's why we upsized our prevalence number last year as well from 600 to 800,000. It's a really unique situation that's set up in the movement disorder space.
Another email question is, when can we get a publication or conference presentation for NBI-1117568 where we can learn a little bit about the sort of the dose response stuff that you're seeing?
Yeah. That's a good question. We've gotten some inquiries on that in the past. I think that's something that we're still working through. We appreciate the interest in the muscarinics as well as our AMPA program. They're in slightly different positions in the sense of expectation bias that's out there. I think a lot of people already know the benefits and opportunities with muscarinics. And we're working through that right now. I think our main goal is let's get up the phase three programs as quickly as we can. We know we're in a competitive space. And then on the other side of that, let's see what makes sense to get additional data out. Maybe it's something that we share at an R&D type of day event or it's a publication. But we'll find the best venue to get additional data out there.
Really quickly, another email question just came in. How are you thinking about Crenessity pricing and payer dynamics? And can you comment on how your payer engagement and receptivity has been to the Crenessity price?
Yeah. Once again, just reinforcing it's very, very early days yet, just a few weeks into the launch. We did a fair bit of work to prep the market for the introduction of Crenessity . And as Eiry said, it involved educating providers and patients and families, but it also involved engaging with payers ahead of the approval. And so last fall, our national accounts team, our field medical teams were engaging with payers to lay out the clinical profile of, at that time, crinecerfont and preview our launch plans, help them understand the population, help them understand the burden and the inadequacies of the current standard of care and so on.
Ultimately, now that we've got approval and product is now in the channel and available, I'll reemphasize it's available, now we're starting to engage with payers on the other side of that, both in terms of following up with the plans, letting them know about the availability, but also getting prescriptions and claims approved through that process. Right now, it's not on any formularies, and it's approved through an exceptions process. The majority of these patients are commercial, and the second biggest segment is Medicaid. But so far, so good in terms of the interactions with payers. And I just want to emphasize that our primary goal from a pricing perspective was to make sure that we have really good access for these patients. And we expect the vast majority of patients will pay $12 or less per month. And so we're off to a good start.
I'd say one last comment because we get asked this quite often and want this on the record. What are we going to disclose every quarter early on in the launch? Because there's going to be a dynamic where patients are getting treatment, and there may be a good percentage of them not actually it not being a reimbursed script. So we will be providing quarterly new patient treatment forms or new patient starts that everybody can be aware of what the demand is and then, of course, revenue. But that has been a common question, so figured I'd clarify that, Anupam.
All right. We're up on time. Thanks, everyone. Thank you, Neurocrine team.
Thanks, Anupam. Thanks, JP Morgan. Thank you.