All right. Let's go ahead and get started. Thanks everyone for coming. This is the 41st annual JP Morgan Healthcare Conference. My name's Anupam Rama. I'm one of the senior biotech analysts here at J.P. Morgan. I'm joined by my colleagues Malcolm Kuno and Priyanka Grover from the team. Our next presenting company is Neurocrine. Presenting on behalf of the company, we have CEO Kevin Gorman. Kevin.
Thank you, Anupam, and thank you everyone for being here today. I almost feel like I need to be running back and forth on here. Before I get started, I put up our safe harbor statement. I will be making forward-looking statements. What I want to accomplish this morning is to tell you about Neurocrine. What we look like today, what our philosophy is, what our strategy has been that's got us here, and where we see that strategy taking us throughout the rest of this decade. If you look at what Neurocrine fundamentally is, we're a neuroscience company. That's what we call it. How do we define neuroscience? Because it's much broader than just CNS diseases. Neurology is only one aspect of us being a neuroscience company.
There's neuroendocrinology and neuropsychiatry, and one day I hope that we will be definitely doing drug development in neuroimmunology, but it's a little early for that. That is fundamentally who we have been for 30 years, and the way we will remain going forward. We've been a commercial company for five years. We've been a very fortunate company that if you look up at these drugs, Ingrezza, ORILISSA, and ORIAHNN, these are drugs that were discovered at Neurocrine. They were developed, at Neurocrine through late-stage development. Ingrezza, all the way through development and Ingrezza is commercialized by Neurocrine. ORILISSA and ORIAHNN, with our partner AbbVie. We also look on the outside for opportunities, and so you can see ONGENTYS and now more recently, ALKINDI, as being other drugs that we've added to our commercial platform.
We've been very successful internally developing some life-changing drugs, but we also look on the outside, and we're very active on that. While we talk about how active we've been on the outside, this is a snapshot of our Business Development activities probably over the last four to five years that we have here. We have, as with many CNS companies to date, symptomatic treatments of various diseases. We have now stepped into what is the next generation beyond that, which is precision medicine. Genetically identified disease states, targets, and then using very focused resources and drugs towards them. The step into the future, which is where neuroscience is going to be. You're always gonna have symptomatic treatments, small molecule, orally active compounds, but neuroscience is evolving rapidly.
The way we've seen, immuno-oncology and the outstanding progress that it's made over the last 15 years, that's what you're going to see in neuroscience over the next 7-10 years, which m eans we're going to be tackling diseases that are going to be curative. In order to do that, we make those investments now, one of which was announced this morning. I think what that brings us to is the ability here. We have probably one of the deepest portfolios in CNS gene therapy that exists out there. These take a while. Gene therapy is not something that happens overnight as we know. It's been evolving. We've been in it several years now. I think that we're now one of the leaders with our partner, Voyager, in here. What allows us to do this?
What allows us to do this is an outstanding medicine, Ingrezza, which as I said, we discovered, fully developed, and commercialized in the United States. We've given guidance for 2022 that we'll sell between $1.4 billion and $1.425 billion. This is our fifth full year on the market. The drug has been so successful because of the tremendous benefit that it brings to patients. There's no denying that it has been life-changing for tardive dyskinesia patients. We're going to talk about how we continue to invest in this medicine in order to bring it to all the patients that are suffering today.
We have a robust pipeline at Neurocrine, and I'm going to speak more about that, but that is what we've built and what is the philosophy and how have we built that to date, and then how are we going forward. Last but not least, we have a very strong financial position. We've been very careful in the deals that we do. We have plenty of firepower as we stand here today to do deals that can be licenses or can be much larger deals, and we have plenty of that firepower. None of that has changed to date. Neuroscience means automatically you're tackling some of the most difficult and devastating diseases that exist. It's not easy, but we've been successful to date, and I think we're gonna be very successful in the future. Not everything is gonna work. Absolutely not.
We hope that many will work. How do you increase your odds of success now that you've made the fundamental decision, our strategy is to be a neuroscience company? Well, what you want to do is you want to invest in mechanisms, and we can say compounds that can have multiple different indications. One mechanism that can be applied to different indications. Let's take our blockbuster drug, Ingrezza. It is approved in tardive dyskinesia. We have it submitted to the FDA for the chorea associated with Huntington's disease. We have two late stage programs going on here for the adjunctive treatment of schizophrenia and for the dyskinetic cerebral palsy. There's where a single mechanism can be broadly applicable. It's not the only compound that's like that.
We have another compound, which is a sodium channel blocker, which we're utilizing and exploring in a very orphan seizure disorder that's genetically defined, so very much precision medicine, and then in a much larger focal onset seizures. We also have the other drug that we had identified, which is a small molecule, GnRH antagonist, ORILISSA and ORIAHNN, same active moiety, two different large indications that are being pursued by AbbVie. Down at the bottom, you see that we have NBI-1117568 in schizophrenia currently. This is our muscarinic agonist, and you are going to see more muscarinics coming into the clinic very shortly by us that will expand that franchise, that mechanism of the muscarinics. Now, that is a very powerful way to increase your probability of success. We don't stop there.
We overlay that now in that several of the diseases, especially the psychiatric diseases that we go after, they're tough. Don't bet on a single mechanism that's going to get you success. What you want to do is you want to bring several mechanisms against those diseases, take several different mechanisms against major depressive disorder, several different mechanisms against schizophrenia. That is our philosophy. That's how we've built this pipeline that we have today, and we're not done by any stretch of the imagination. I told you, where neuroscience means neurology, endocrinology, and neuropsychiatry to us, and now you see how the pipeline fits into all of that. It is not an early-stage pipeline. We have seven phase II studies going on here. We have four registrational programs that are going on here. We have a later stage. Some of these are much lower relative risk.
Some of these are higher risk. The way we deal with that is we try to get into those phase II programs, get to data as rapidly as possible, as low cost as you can, and then cut the ones that don't work, take the ones that do work, and invest heavily and rapidly in them. That's what you've seen as we've moved over into these programs that are in registration. I'd like to talk a little bit about the milestones that we have set up for 2023. There's a number of them that we have here. I'm gonna go in a little detail in just a moment. 2024, early on, we have even more. Over the next 18 to 24 months, there's quite a bit of data that is going to be flowing from Neurocrine.
Let's look at some of those one by one here that are coming this year. Valbenazine, that is the name, the generic name for our tardive dyskinesia drug, Ingrezza. As I said, we have submitted the NDA to the FDA for chorea associated with Huntington's disease. Last year, we reported out outstanding phase three data, with this medicine. It is proving as efficacious in Huntington's as it has in tardive dyskinesia. The PDUFA date is in August of this year. We look forward to continuing to work with the FDA throughout this year, all the way until, hopefully, an ultimate approval. Crinecerfont. This is undoubtedly the next most exciting drug that we have that is in two registrational studies. Crinecerfont is for a very small genetic disease, neuroendocrine disease called congenital adrenal hyperplasia.
There hasn't been a drug developed in here since the early 1960s. Much like we were the very first company to ever develop a drug in tardive dyskinesia, we are the first company, basically, that in the last 60 years is developing a drug in the CAH. We don't go after the easy things. We go after the hard things where patients have had little to no drug development going on. What is congenital adrenal hyperplasia? Prior to the 1960s, it was deadly for all the children that were born with this. They can't make cortisol, and so you die. Hydrocortisone was discovered and developed and commercialized in the early 1960s, mainly for inflammation. The endocrinologists who were seeing these CAH patients realized, "You know what?
What we can do is try to use hydrocortisone, and then later on prednisone in very high doses to save these patients." Every day, high doses of this, because without it, they don't make cortisol. Low doses, they are making massive amounts of androgens. Each one of these situations, extremely high androgen levels or extremely high hydrocortisone levels are deleterious to human health and shorten lifespan. So it's a constant balancing act, that's all there's ever been for these patients. Crinecerfont phase II data showed we can recapture the underlying disease. It's not a steroid. It basically blocks the action of a neuropeptide, and it brings back into regulation those high androgen levels. Hopefully, and what the phase III program is designed for, and intellectually it makes a lot of sense.
Now you can just give replacement levels of hydrocortisone and not have to have the serious problems that come with the high levels. We've taken care of the underlying disease. Both of those phase III studies, one in pediatric population, the other one in adults, will both read out later this year. We've hit all our enrollment targets. We're right on track, and we're looking very forward to that. I mentioned the NBI 352 as we use it for shorthand. This is a very selective sodium channel blocker. We have it as a precision medicine in a rare pediatric epilepsy called SCN8A. We also recognize that there's a lot of evidence that sodium channels are involved in a very large epilepsy population called focal onset seizures, the largest numbers.
What we embarked on is immediately a quick proof of concept study so that we will see a little later this year, will this very selective sodium channel blocker, highly potent, be one that can change the standard of care in focal onset seizures? Finally, one of our major depression drugs, which is NBI-1065846. We're taking a part of the depressive rainbow, if you will, anhedonia, the inability to feel pleasure because this drug hits those regions of the brain. The target is in the regions of the brain that have to do with motivation and pleasure to see if we can have an effect here. Here is something where you see what the numbers say, 16 million patients. That's because anhedonia goes across the spectrum of severe mental health problems. It's major depression, it's bipolar, it's schizophrenia, it's substance abuse.
We've got a very focused program here to see if we can, for the first time, have a drug that can address anhedonia. Again, one of a number of mechanisms that we're utilizing against major depressive disorder. Where we are fortunate, and very fortunate as a company, is that we have an outstanding medicine in Ingrezza and what it has brought to the tardive dyskinesia population. We're talking about a population that is major depressive disorder, bipolar, schizoaffective disorder, schizophrenia. To give you an idea of how important these patients, their caregivers, their loved ones feel this medicine is, this is a patient population that on average is highly non-compliant with every other medication they take, whether it be their psychiatric meds or their metabolic meds, their cardiovascular meds that they're taking. They're woefully compliant. Not with Ingrezza.
With Ingrezza, when they get on this drug, they stay on this drug. They do not go off this drug. The changes it makes in their involuntary movements throughout their face, their mouth, their hands, arms, trunk, legs is palpable. They understand it. It changes their lives. Ingrezza, we continue to invest in, as you see. We wanna bring it to as many of the patients who need this drug as possible. Right now, when we started, when we launched this drug five years ago, since there was never a drug developed for TD, only 2%-5% of the patients in the U.S. who had TD were diagnosed with it. It was something that psychiatrists and other physicians stayed away from. Don't see, don't talk. Five years of hard work, 30% of TD patients we estimate have now received a diagnosis. That's tremendous progress.
It means seven out of 10 still have not. A huge number of patients that we still have to go. We make strides every day in that. Another aspect, of those 30% that have received the diagnosis, APA guidelines say first-line treatment is a VMAT2 antagonist, Ingrezza. However, only half of those 30% are prescribed a VMAT2 antagonist. Old habits die hard with physicians. We can double the amount of patients that are on drug just by taking even those that are already diagnosed, the hard work that it takes to get to the diagnosis and just flipping that over to the optimum and correct treatment of these patients without even thinking about the other 70%. We're doing both. That's where our investment comes from.
We're taking this outstanding drug, as I showed, immediately into Huntington's disease. Our commercial folk out there whose lives are basically dedicated to Ingrezza, they know that that's not just what they're working on. That's the drug that they, that they educate healthcare professionals on. That's not all that it does. This drug has patent protection that'll take it out to the mid-2030s. Lots of room to invest, both in this medicine, but as I've shown you others. That drug, the efforts of that commercial organization of ours with this drug, they know that we're treating children, we're treating people in the prime of their life. We're able to treat the elderly with devastating diseases, thanks to Ingrezza. The sales from Ingrezza, we plow right back into this company.
Our goal may be audacious, but we think it's highly attainable, is to be the world's leading neuroscience company by the end of this decade. That is with symptomatic treatment of devastating diseases. That's with having precision medicine, and that is ultimately by the end of the decade, having drugs that can change the course of a disease and be curative. I'd like to thank you very much and ready for your questions. I'd like to bring up the rest of the Neurocrine team here so that you'll have representations from clinical, regulatory, commercial, Business Development, and finance. I'll sit here.
Great. We'll get started. Just a quick reminder that if you want to use the ask-a-question feature, it is in the digital handbook. I'll get it here on this iPad. If you'd like to get bold and ask a question in the room, just raise your hand, and we do have microphones, and we can make that happen. I'd like to just start with the deal announced this morning in terms of if you could provide a little bit more kind of color on the strategic rationale, given it's a new modality. Yeah.
What I'll do is, Anupam, if I may, you're flanked by the two people who did the deal and championed the deal.
Let me just scoot back.
Jude Onyia, who is our Chief Scientific Officer, and Kyle Gano, our head of BB. Whichever you two of you would like to start, please.
Sure. I'll start by introducing myself. Jude Onyia, Chief Science Officer for Neurocrine. I've been at Neurocrine 13 months. Prior to Neurocrine, I spent well over 25 years of my career at Eli Lilly and Company, leading their biologics research organization. Shortly after leaving Lilly, I spent four or five months of a sabbatical as a chief science officer for a gene therapy company in Thousand Oaks, called Capsida. From there, Kevin and the leadership team here convinced me to join Neurocrine. It's been exciting 13 months. Let me tell you a little bit about the 25 years, especially the last 14 years at Lilly, leading their biologics research organization.
What my team did, it was part of a team that created well over 65 clinical candidates. Ten of those are drugs today, three are in regulatory review, and another two, three that I believe will be drugs in the next two to three years. I cite this for a couple of reasons. One is frankly, the incredible opportunity we have in this business to change patients' lives. I joined Neurocrine for that and to do more of the same and to be part of this great team. It's been an exciting 13 months. The second reason I cited, it's relevant to the deal with Voyager today.
I've spent much of my career building and advancing platforms, biotech platforms, from antibodies to proteins, peptides, antibody conjugate bispecifics, you name the combinations thereof. I wanna make a point. There are good platforms, there are bad platforms. There's no perfect platform. A good platform is one that is significantly differentiated from the current state. Okay? These are a premium. This deal with the expanded collaboration with Voyager really gives us an expanded opportunity at such a industry-leading platform. I'll talk a little bit about the platform in a minute. It's not just the platform, it's where you point the platform. This expanded opportunity gives us the opportunity to create an industry-leading pipeline and franchise in gene therapy.
We have with the GBA announced as a lead, we have the opportunity to advance well over seven clinical candidates. We hope that the first of these efforts will make it to the clinic in about maybe 2025. Okay. The pipeline is key, a diversified pipeline of gene therapy franchise. The core piece is one that as you listen to Kevin, is strategic. This is part of an intentional strategy to begin to diversify the modalities that we have. To be clear, we are a small molecule company. We will continue to strengthen our core in small molecules, but diversify into additional modalities, particularly participate in biologics to include gene therapy. What this deal does is accelerates our ability to do this.
While we have some internal programs, this gives us a significant acceleration. With these improved modalities, it gives you the chance now to pick the right modality against the right target and against the right disease and will facilitate the quality, the speed, and the value that we put in our pipelines. That's at a high level. I can let Kyle talk, or I can give you a little bit more about the technology that play what we've seen. As you know, we've had the long-standing relationship with Voyager. In this time, we've learned a lot about ourselves, about them, and our collaboration together, importantly, the evolution of the platform. Okay? This platform is clearly today, the number one industry-leading, my assessment, number one industry-leading platform for CNS delivery. Okay?
These are brain penetrant capsids that allow you to get into the brain in a way the first-generation, capsids, can. As you know, for CNS, gene delivery, that is the number one challenge. Ability to transverse the blood-brain barrier and to get the intended cargo, into, the CNS, into the neurons or astrocytes, as the case may be, to deliver the therapy that you want. Okay? If you look at the field today, all of the clinical assets and many of the preclinical focus on first-generation vectors.
The first-generation vectors have very poor brain tropism, very poor transduction when they get across the blood-brain barrier, and hence have to be given whopping doses, really whopping doses that result in the safety, exacerbation of the safety that you see with these therapies, and also limits where you can go in terms of disease indications with this. This can be obviated through protein engineering, and that is exactly what Voyager has done and done very well in creating this next generation BBB-penetrant capsids that will now allow you to do, one, less invasive IV delivery. Second, it's lower the doses. The third is to push the efficacy safety in a way that will really allow you to get what the patients need and desire.
The last is broaden the disease spaces that you can go with this particular capsid. When we look in the space today, it's our judgment that Voyager truly leads in this particular space.
Again, I would say, and not to steal Kyle's thunder, since he worked on this for quite a long time, and I think got us to a very good spot here, is that, this is a foundational deal for us, for the technology, for the space that we want to be a player in. At the same time, it's actually just a small piece in our portfolio. At the same time, it leaves us, as I said, with plenty of firepower to do additional deals of very different sizes going forward.
We've actually got an email question that came into my inbox, which is: Since your last collaboration with Voyager, which, you know, was unsuccessful, what have you learned, and why does this deal make it so, like, you know, different, I guess? You've called this a, you know, transformational modality and platform. Like, what's changed? What have you learned?
Yeah. Kyle, why don't you start out with what we've learned, what's changed? Jude wasn't here in 2019 when we first did the deal.
Sure. That is a good question. I think that the two pieces that I would point to, is one is our first program that we had in collaboration with a program for Parkinson's that required a local delivery option through a neurosurgery. That presents itself some challenges. I think over the years, we've even seen it recently, that some of the positives and benefits of local delivery over not being able to deliver something via IV really haven't panned out either from an efficacy or a safety perspective. That's one learning. The other one is, when you think about capsid technology and evolution, you're hoping to see what you've seen, say, in a rodent or a monkey be replicated in man.
Some of the early validation work on capsids simply didn't pan out. I think the field has moved towards a much more rigorous validation of capsids across multiple species, not only rodent and non-rodent, but in multiple species of monkey, to predict what's going to happen in man. With that's led us to the point where we are here with Voyager today. I just wanted to close out this piece by saying is that our previous collaboration is still ongoing.
We have three programs at various stages of preclinical development now, and that those three that we'll be combining with the four that are part of our new collaboration, that's headlined by our GBA1 program, which we're quite excited about because it's already in preclinical itself, versus some of the new targets that we're going to add to the mix based on our ideas. It's the three plus the four or seven programs that we're really excited about because that really rounds out a very nice, robust gene therapy portfolio that I think any CNS company would be quite jealous of, in fact. We're looking at pushing a couple of these forward to have an opportunity to enter the clinic in the 2025 timeframe.
Does the collaboration, the deal today indicate anything about modality interest for future business development or even phase interest in terms of how early this deal is relative to the rest of your pipeline?
Yeah. From a modality standpoint. It's a little odd leaning in, but I'll do that. From a modality standpoint, I think as Jude puts it best, talking to everyone at Neurocrine is the key is having the right target for the right disease, and then you have small molecules, peptides, proteins, antibodies, and gene therapies. Pick the right modality that's going to actually prove successful in that. As he said, it's not the platform itself that can determine success or failure. It's where you point the platform. We have those platforms within Neurocrine. It's up to us to pick the right diseases and the right targets to treat those disease and then point the right modality to it. When it comes to is this giving a tell about, okay, so we're wanting to go into more foundational things?
No. That it doesn't change our philosophy. The deals, the numerous deals we've done over the last five or six years have spanned, preclinical, research tools, phase I, phase II, phase III, and commercial. That is going to continue going forward.
Maybe switching to one of the pipeline readouts that are coming this year, 352, the selective sodium channel blocker. Where do you think a drug like that fits into the treatment paradigm of focal onset seizures and what are the drug attributes that could lead to differentiation? You know, I love a good win scenario. What does a win look like?
Yeah. 352 is a selective Nav1.6 channel antagonist, it was specifically designed to be highly selective to that sodium channel. The reason for that is that if you take focal onset seizures as a disease state, we do know that sodium channel antagonists work in at least some patients there. One of the biggest challenges has been that the majority of sodium channel antagonists available right now are have activity across the whole range of sodium channels, and many of those then, like Nav1.5, lead to toxicity or side effects, cardiac and otherwise, GI side effects.
What has been challenging for many patients with focal onset seizures and the sodium channel antagonist is the ability to get to a dose that gives them efficacy via the Nav1.6 channel without getting the side effect profile that leads to discontinuation. Our approach is, with this highly selective agent, to be looking in this phase two study at the ability to control seizures in focal onset seizure patients, with a view to being able to demonstrate a beneficial benefit risk profile relative to other sodium channel antagonists.
Questions from the audience? Go ahead.
Yeah. Just it's a two-part question. One is could you quickly comment a little bit about your exposure to IRA, especially for Ingrezza, as you see that despite the good patent life? Also maybe for your pipeline compounds, comment a little bit about the commercial potential that you see beyond the U.S. market.
Yeah, sure. Just a quick one on the second part of the question, because it can be a much quicker answer, is that we are internationalizing ourselves. Clearly, we develop our drugs in phase I, II, and III studies outside of the United States throughout virtually all of Europe. We're already a development organization internationally. What will take us commercially into Europe is we've built a commercial organization in the United States. Well, what will do that is a couple of things. We bought a small U.K.-based company that is a commercial company. That kind of gives us a foothold overseas. What are the drugs that are gonna take us over there? The two that I would point to, number one primary among them is crinecerfont for CAH. Why?
Number one is because there's a tractable prescribing population over there. It's endocrinologists primarily in centers of excellence throughout Europe. That is something that a company of our size, our stage of commercial development, we can bite off on that. We plan on, knock on wood, with good data later this year and an approval from the FDA and EMA, who we designed these trials in consultation with, that we will not only commercialize this ourselves in the United States, but we will also commercialize in Europe. You can also look at the rare pediatric epilepsy that the Nav1.6 is in clinical trials with for SCN8A. Again, a highly focused patient population, genetically defined centers of excellence, we could commercialize that in Europe. Learn how to walk before you run over in Europe.
Be able to go in with very tractable patient and prescriber populations and then grow yourself from there. IRA, it is a question that comes up. What I'd like to first start out with, is there any changes we're doing with our business? Is this diversification outside of just small molecules have anything to do with IRA? No, it doesn't. This is something we started on years ago. It took a long time to recruit a person like Jude into the company. We had been building large molecule presence within Neurocrine for quite a few years now. That's not the impetus for us to do that, and there's no change we're doing to our business right now. What I would say briefly about the IRA is twofold.
The more onerous portions of it that are in the laws that exist today, which is the changes to the Medicare Part D design and to be subject to price negotiations. We fall under the small manufacturer exemption. We fall under the Small Biotech exemption. By and large, those things don't hit us until 2031. All right? In their full effect. The second thing that I would say about it is, it's early days in what IRA is going to look like. ACA is the best example in recent history, Obamacare. When that came out, and the way it's administered today, it looks vastly different than where it came out. There's no mandatory insuring that every patient had to have in the United States. There is no tax on devices.
There is no, whatever the real name was for the death committees that were in there. Basically, committees that would ration care and be beholding to no one. Those were all taken out through a give-and-take through the administrative branches of the government, working with the legislative branches of the government. We're talking about, again, between now and the next, let's say, seven eight, nine years when impacts would come onto us. That's a lifetime in Washington, D.C. I look at one of our, one of our colleagues who has spent his life in Washington, D.C. Those are at least four different elections in the House, two different elections in the, in the, in the Senate, and there's probably at least three different elections for President. There's a lot of changes that can take place to there.
I would say certainly it will look different. How? I can't predict that right now. A lot of work is being done with the internal machinations of government. Where bio and pharma can add their voices, we do, and we'll see how it all goes out. The worst thing about it is, for the next two years or so, there's gonna be a lot of uncertainty swirling around, and you're not gonna hear a lot about what happens behind the scenes there as those branches of government work with one another. It will change.
Okay. I know it's almost lunchtime, so I wanna end a couple minutes early 'cause some of us have to go to different places and whatnot. I hope everyone has a great rest of the afternoon at the conference as well.
Thanks.
Yeah. Thank you.
Thanks so much. Enjoy the rest of the conference.
You too, man.
Thank you.
All right. Appreciate it.