Neurocrine Biosciences, Inc. (NBIX) Earnings Call Transcript & Summary

Okay. I'm not sure if I'm supposed to read any kind of disclosures, but I'm going to go ahead and introduce myself. I'm Tazeen Ahmad. I'm one of the med biotech analysts here at Bank of America. It's my pleasure this afternoon to introduce our next presenting company, Neurocrine. Speaking for Neurocrine this afternoon is CEO, Kevin Gorman; and Kyle Gano, who is Chief Business Development and Strategy Officer. Kevin and Kyle, good afternoon. Thanks for joining us.

Good afternoon, Tazeen. Thanks for having us.

So I think everyone that's joined us on this particular call is pretty familiar with Neurocrine already. So, Kevin, I won't ask you to do the 2-minute elevator pitch that we follow on this webcast. But I did want to get a sense, an update, if you will, on where you guys are currently as it relates to COVID. Where are you in terms of reopening, work from home, et cetera? Are there any new changes that have happened since the last time we all got caught up. I guess that was about a month ago on our last webcast.

Yes. Thanks, Tazeen. By the way, just to start out with, we don't have a safe harbor statement to put up there on slides. But I would caution everyone, we will be making forward-looking statements and to look at our most recent regulatory filings with the SEC. So with your -- a lot has changed actually in the last month. And as we find that I think all of us have found, it's much easier to transition to work from home than it is to transition back into the offices or the field. It takes a lot more work. So where we are at this point is, I would say, the vast majority of our field force, that would include our sales reps, our PALs teams, our national account executives, our medical scientists, liaisons, they're all back in the field now. That's not to say that they're back 5 days a week, all day long each day. It means that a portion of their time now is back in the field, and then a portion of their time is still connecting with their customers electronically. And that stepping back into the field was not on 1 day, everyone went back in. It's been discontinuous openings as their state governments have opened up and their local governments had opened up. But really, what our field folks are most concerned with is, how are their customers, are their doctors' offices, are they prepared to have them back in and have in-person discussions with them. And so that's what we rely completely on the rep who's there in their territory. They know what's best. They know where to go to. And there can still be parts of territories that as we see more recently, there are some states, some areas that are having some uptick in cases. So we leave it up to the reps as to where they feel comfortable in going back into. When it comes to the home office here in San Diego. So we have about 350 people who are usually on-site on our campus. And we have got -- I would say, we're running it at about 150-plus right now. So that's basically all of our research groups are in the labs. And that not only is the basic research, chemistry and biology. But that is also all of our pharmaceutical development work. So CMC and all the preclinical toxin ADME. They're all back in the labs right now. We work them on having them coming on shifts, and we've reoriented the labs somewhat so that we're able to keep good distancing, not have any -- too much high density and obviously taking all of the CDC guidelines that we follow here. As far as the rest of the company, those who can work from home, we are still in California under a work from home, if you can. Although what we've been doing as teams want to be able to get together, we have several huge auditorium facilities. That we're using as conference room sites now. So the distancing can be quite enormous in there. And so those are what we're doing in order to allow better facilitations of particularly teams to be able to come in, work together and then go back home and continue. As you can imagine, and as you, I think, can relate to, we're all having a little bit of Zoom fatigue, and it's good to see people face-to-face and be able to interact that way. So I think that that's where we are. We're putting -- we've put in place a number of things in order to bring back our employees who are non-lab employees back into the offices at the appropriate time. We have set up everything here to do weekly testing of all of our on-site employees. And then we are going to be rolling out very shortly weekly testing of all of our field employees for COVID. And then what we're in the midst of is redesigning our office spaces so that we can have beyond the 6-foot spacings. So that the ultimate goal here is that we can bring people back into the office space. And should someone be infected with COVID outside of Neurocrine that we picked that up rapidly, and that we're able to track and trace. And we also have sufficient safety margins within the company such that we don't have to shut the company down for what I would say is over the long-term here. The inevitability that you would get an employee or 2 positive.

Okay. That's a lot of color. Yes, a lot has changed since we last spoke. So thanks for that, Kevin. We're now approaching the end of the quarter. And so I know, obviously, you can't give granular details, but to the extent that you can comment directionally on how you're -- how the continued uptake of INGREZZA has been -- this would be the quarter that everybody looks to for most impacts, at least so far from COVID, but kind of navigating around that and also us trying to take into account as analysts, traditionally, your 2Q has a very strong bounce back after 1Q. How are you just sort of thinking about all those variables right now?

Yes. And as you said, we don't give intra-quarter color. Although we kind of did is why we held off the Q1 earnings call, so that we were well into April when we had that call. And as we said then, what was really encouraging through April was the fact that your -- the refills of INGREZZA continually hold up quite well, they have since launch. As you've told me several times, I kept talking about the fact that while refills are going to go back down, are going to eventually go down to where all the other meds, this patient population is on, which is around 50% or 60% our refill rate, and we've consistently stayed well higher than that. And even in the face of COVID, we have stayed well beyond that. So it is a drug that is appreciated by the patients and the prescribers that once on the drug, they do not want to have any interruption of treatment. So that's been very good. We were concerned about what NRxs would look like, new prescription fills with office visits down, patients' visits during April were down well over 70%. We were thinking, okay, is that what we're going to see in NRxs. And no, it wasn't by any stretch of the imagination. So we're really gratified to see that. And so all those things bode well. In addition, I would say that Q1, which was other than the last 2 weeks, was relatively unaffected by COVID. That is usually our toughest quarter because of all the prior-auths that come in, all the reauthorizations that have to happen. And we had planned for that and worked to put in a lot of initiatives in order so that we wouldn't get hit. Well, we get hit as hard, but we could get that paperwork through quickly, and we did. So the downdraft of Q1 wasn't near what it could have been had we not put all those in. We're a victim of the success of INGREZZA that we keep doubling basically every year the number of patients that we have, and that really comes into play in Q1. This Q1, our sales team, our PALs, our national account executives, they all did just an excellent job. So Q1 was really a very nice quarter for us.

Yes. Indeed. So I guess, as we look to 2Q, should we, just in general, be thinking that this may not be the same type of 2Q that we would normally expect, just given the dynamics of office visits being impacted. And to the extent that new patients could be added, is that a challenging environment for new patients to be added?

Well, I think that the sales team has done a terrific job in transitioning to this electronic form of reaching out to the docs and their staff. I think the docs, as you well know, the psychiatrists are about 80% of our calls, they were the largest users of telemedicine prior to COVID, and they have really turned to telemedicine during COVID. So they didn't -- it wasn't like their practice was closed like other practices are closed and the doctors then went into the hospitals to work with COVID patients, the psychiatric community had a whole other pandemic on their hands during COVID. And that was the mental health pandemic that's been going on. So their practices were open, but they were doing it via telemedicine. And we have worked with them closely while they're doing this in order to help them be able to diagnose TD via telemedicine. It's kind of a double-edged sword with TD and telemedicine. On the one hand, the psychiatrists are really looking at the patient now. It is right upfront when they have them on video. There's a lot of face-to-face contact. And approximately 80% of all TD patients have TD in the orofacial buccal area. So it becomes maybe even much more evident to the psychiatrists than it was when they were seeing them in their office, which the psychs head was mainly down into their computer, it was a med check, and they were spending just a very few minutes. It turns out that the doctor is spending much more time in a telemedicine with the patients. The other positive aspect of it is that we've heard is that the no-shows are much less when it's telemedicine than when it is an in-office visit. So they're having actually not only more time with patients via telemedicine, but they're actually getting -- they're having a higher hit rate with their patients on this, showing up to their appointments. On the next, like I said, double-edged, though, on the other side of it, not all of the patients have access to video. So there's still a good proportion of patients that the psychiatrist is just speaking with on the phone. Obviously, diagnosing TD without any visual cues is very difficult, not impossible, but very difficult. And then within the video calls, it is more difficult for the doctor to be able to see all the different presentations of TD unless there is somebody else in the room, who can hold the computer or the smartphone up so that the doctor can see other parts of the patient's body, their arms, their trunk, their feet and legs, watch them walk, do some of the activation exercises that they can do to really see that. So good and challenging, all at the same time.

Okay. That's fair. We'll come back to INGREZZA in a few minutes, but maybe we could spend a couple of minutes on talking about your latest update, your -- announcement of your Takeda collaboration and maybe a couple of questions for Kyle. Can you just talk if at the top level about the molecules that you chose to want to opt-in to from the library that Takeda has? As it relates to 831, what about this particular molecule that you find interesting? It's an indication that, obviously, others are pursuing. But what makes you confident that, number one, this will work? And number two, it would be competitive with the things that are potentially going to be out there at the same time?

Right. No, I appreciate the question. And first, just let me start by saying that we're really excited to work with the Takeda team and on these programs starting this year once we are on the side of close of HSR. It's very rare that especially for me here at Neurocrine, where we can drop in 3 clinical programs into our pipeline, where overnight, we increased the number of these programs by 40% to 50%. That's a huge add to the pipeline. And they all represent potential first-in-class opportunities. So we're really pleased with what we were able to accomplish here with the Takeda team and look forward to starting development. As it relates to 831, I think our excitement stems from, like a lot of things here in Neurocrine, from learnings from our past failures. And you think about psychiatry, oftentimes, you have a hypothesis about a target, a biological mechanism, but you may not have a lot of data of the relevance of that mechanism in the human condition. And the best that you can shoot for or hope for is showing efficacy in an animal model of disease. And we all know the risk of putting too much weight on those animal studies, especially in psychiatry. So when it comes to TAK-831, for example, this is the potential first-in-class D-Amino Acid Oxidase inhibitor. There are 2 fundamental aspects that once you appreciate you have some real-world examples that pull the hypothesis all the way through and gives you a really good reason to believe. And the 2 aspects that are worth mentioning here is that there is hypofunction of the glutamatergic signaling that has been directly implicated into the pathophysiology of schizophrenia. So that's 1 piece. And the other one out there is a well-established linkage between NMDA hypofunction in schizophrenia. Now the examples when you set that foundation are clear in NMDA antagonist like PCP or ketamine mimic positive, negative and cognitive symptoms of schizophrenia. And what DAAO inhibition does is it increases levels of D-serine, which is an NMDA receptor coagonist. So what we have on the other side of the coin that is agonist and their study in schizophrenia, we have D-serine studies in sodium benzoate, which is a weak DAAO inhibitor, both linking to increasing levels of D-serine in the CNS. Both of those particular agents or approaches have improved both the PANSS, the positive and negative symptoms in patients with schizophrenia. So what we have here is a very potent DAAO inhibitor, much better than sodium benzoate, which has been shown to increase D-serine levels quite significantly in preclinical studies. And now what we're trying to do is show what others have done with suboptimal approaches trying to increase our D-serine in the CNS. So that takes us to where we are today. We have a Phase II study that's ongoing in the U.S. and in Europe. And we're looking on completing that study with Takeda that will read out sometimes next year. So that's the excitement is the mechanism that we've been able to link to the human condition, which is really what's been a challenge for a lot of psychiatric-based programs in development thus far.

Okay. And when the study does read out next year, what should we be looking for to feel like this is good clinically validating data?

Well, we'll be using the standard scale, as we're looking at both the positive and negative symptoms within schizophrenia. But obviously, we're going to be drilling down on the negative symptom scale for the subjects that are in that study. It's a well-run study. It's everything that you would expect from a large pharmaceutical company in terms of having all the positive attributes of a larger well-run study. And so we're really comfortable and confident that the type of outcome that we'll get from the study will really help inform a Phase III program.

And also, it's worth noting, Tazeen, that this is -- almost every aspect of this collaboration, the companies, both ourselves and Takeda approached this as what works best for the patients and the molecules that are involved here. So Takeda got this program all the way to this point. They've been running this study. That didn't make any sense for them to transfer the IND over to us, for then us to take over the conduct of the study. No, Takeda is going to run this study to its conclusion. And it's past that point when Neurocrine steps in onto this study. So again, no -- a very good launching into this collaboration, going with the strengths of each company. And by far, Takeda has the greatest strength when it comes that this is a study they started. As Kyle said, an extremely well-designed study, well-executed study. So they're going to continue that all the way to the end of this study.

Okay. That's helpful. And then for 653, this is going to be studied in -- or is being studied in treatment-resistant depression. This is an area that has a lot of generic options, just a lot of difficulty historically for studies to have positive data in depression overall. So maybe Kevin and Kyle, how are you thinking about this particular molecule? How is it different from all the others that are in the market or trying to get into the market? And do you have any sense of concern about just the general difficulties in showing placebo-adjusted efficacy in these types of studies?

Yes. You've certainly drilled down to the issue here in terms of depression studies, and we continually see companies succumbing to high placebo effects and things of that sort. I think it goes back to the underlying biology and the conviction around that. I think for 653, it's an AMPA receptor potentiator, the hypothesis here is that the antidepressant effect of ketamine is mediated by the AMPA receptor activation. So it's not a stretch to see how these 2 -- this molecule and the system interact with each other here. And that's what we're trying to leverage. I think the near-term challenge that we have is one that most of the companies in the space have faced is how do you show target engagement so you can effectively get to concentrations of the study medicine that would put you in a range that would be efficacious. And for these types of molecules, companies have failed due to various safety reasons, and their margins have been cut short or their caps for dosing actually were lower than what they needed for testing the efficacy hypothesis. And what Takeda has done a really nice job of is taken their time and spent a lot of resources developing the right molecule that has the best type of profile that you could use to test the hypothesis of AMPA potentiation in depression. So we can take some of those risks off the table that other companies have had to try to address during the clinical program. And there's some recent technologies that have come out, in particular, in area of PET ligands that we'll be using to attenuate the question around target engagement and then complementing that with a dosing regimen that allows us to test the hypothesis of this mechanism and treatment-resistant depression, I think for the first time. So we're excited because we have the right molecule, we think. And we have the right technology out there now that we can put the 2 together and have success.

And also, I think it's not well understood out there with Neurocrine. But certainly, it is within Takeda that we have a lot of basic research expertise and very much clinical expertise in psychiatric trials and diseases within Neurocrine. And so that was one of the reasons why Takeda entrusted us with these assets.

Okay. When is the next data events for 653?

For 653 and 041, given they're at a similar stage, we'll be starting Phase II trials next year. This year would be all about across the board for the programs. It's hitting on the other side of HSR close and then tech transfer, regulatory ownership transfer for the remainder of this year and teeing up those study activities for 2021.

Okay. Then just lastly on 041, what is the market opportunity for anhedonia?

Well, it's interesting that you asked the question. Anhedonia is actually a symptom that's shared amongst a variety of psychiatric diseases. When you talk about depression, for example, it's the reduced motivation or inability to experience pleasure or joy, things that were once providing content for someone or an individual no longer are providing that level of satisfaction and that's what we're trying to effect here with this molecule. One of the reasons why we're so excited about this as well as all the programs in general, this is right in our wheelhouse in terms of being a G Protein-Coupled Receptor agonist. It's an agonist to an orphan receptor, which means we don't know the endogenous ligand, which complicates research and development, but Takeda has circumvented that by getting some really nice molecules to develop. In terms of the actual opportunity, when you think about just depression and anhedonia, we think there's about 2 million patients diagnosed here in the U.S. and about 1.6 million that are treatable. Now obviously, we're still early in the program in our understanding of the market and market opportunity, it's still early, but that's kind of where we are right now. And as the program matures, we'll be able to add to that granularity.

Okay. So we look forward to that. So going back to INGREZZA for a few minutes again. As it relates to sort of where you are in sort of the cadence of your launch, you said before that the rate of diagnosis and the current penetration rate is low because there's still a lot of patients left to be found. And how realistic are your goals do you think? For what type of diagnosis rate is reasonable? Are you trying to get to as close to 100% as possible? Or do you think that even if, let's say, 50% of patients are diagnosed that, that represents a really meaningful dollar opportunity, and that's really what the goal would be for you guys?

Yes. I think that where we are now, we've gone from like 2% or 3% at the beginning that we believe were diagnosed, and we're probably getting close to 20% that are diagnosed. At this point, I don't see a reason why it wouldn't get to 80% or maybe even 90% in a diagnosis rate. And it's -- to actually get a formal diagnosis, it's not -- there's a whole lot of hurdles to a formal diagnosis beyond finding the patients or identifying the patients that stand between them and a formal diagnosis. There are still a lot -- and I know I sound like a broken record. But I'm going to sound like that broken record for still years to come. There's a lot of education that still needs to go on here in order to have the psychiatric community really be comfortable and confident in their abilities to recognize and diagnose TD separately from other tic or movement disorders that they see quite often in their patients. So I do think that it 80% or 90% is possible. There's other hurdles that we go through also even past the diagnosis. Let's say that we're almost a 20% diagnosis right now, only about half of those patients who receive that formal diagnosis of TD are being treated with a VMAT2 antagonist. And that is because that they -- the physicians still fall back on older unsubstantiated and not useful therapy, which we call the 3Rs, which is where they go to, okay, well, the -- what caused the disease is antipsychotic usage. So I'm going to go and try to modify antipsychotic usage to see if I can impact the disease. They'll either reduce the dose of the antipsychotic or they will replace this antipsychotic with another antipsychotic. Or if they're working with a bipolar major depressed patients, someone who is not schizophrenic, they'll remove the antipsychotic, but none of those have shown to be effective in this. So it's -- there's diagnosis rate, but immediately, the number of patients that can be helped can be doubled right now if the treating physician would just go to a VMAT2 antagonist. And INGREZZA is by far, the most preferred VMAT2 antagonist there. So this is a patient population that is still in its infancy of being treated. And so we see that there's quite a lot of runway here. And fortunately, we have quite a lot of time from an intellectual property standpoint here to really fully develop this therapy.

What do you think, Kevin, specifically has been the driver, if there is a main driver of getting these patients diagnosed? Is it advertising? Is it just simply educating the physicians? What is it? And why are you so confident that you can get to 80% or 90%?

Yes. I really do think that it is education. It is education, and it is experience on top of that. So educating the docs and them having enough experience with patients that they've treated or patients that they've not treated. To see that, the effects of treating the patient's TD goes beyond just the physical aspects of TD, that the quality of life that comes from now having better motor control really translates to them in having a much better status of their underlying psychiatric background. So I think that is one of the things that comes with this. And it's also being able to -- as we've talked about before, not just educating the physician, but educating the other health care professionals, the nurses, nurse practitioners, physicians' assistants. Because quite often, they're going to be the ones who are really going to take note of the patient's movements and bring it to the attention of the psychiatrist. And quite often, because the psychiatrist is, at times, and many times, especially now, so overwhelmed with serious mental health disorders that they're trying to keep patients stable that they do need somebody else who is able to bring up the fact that, hey, I know that this is what you're primarily occupied with this patient, but they are showing signs of what could be TD. Could you take a serious look at the TD aspect of this patient? So it's -- we're well aware that with many physicians, TD is not top of mind for them. And so it is bringing that into them as just a part of their everyday practice, and that takes a long time.

Okay. That's helpful. So another aspect of the dynamic of the INGREZZA launch has been your relationship with payers. And so far, it seems like you've navigated negotiations with the various payers extremely well, if not perfectly. Can you talk about any trends that you might be seeing for discounting relative to when this topic had first come up, I guess, it was a year ago, maybe a little bit longer?

Yes. Access right from the very beginning has always been a critical priority. We want to make sure that when a prescription is written for INGREZZA that, that patient gets INGREZZA. And for a specialty drug, regardless of formulary position, 70% -- over 70% of written prescriptions have been filled. That is great for any specialty drug. And this is something that has worked well for us since launch. We have had good relationships with payers. We spent a lot of time prior to launch in educating them. There was never prior to our launch. There was no treatment for TD. So in many payers' minds, there was no disease, TD. So there was a big education effort there. And to this day, there's still quite a number of plans that were not on formulary. But not being on formulary does not mean not being reimbursed. We are reimbursed quite often. This is -- being a specialty drug, you always have a prior-auth, whether you're on formulary, not on formulary, not in a preferred position on a formulary, there's always a prior-auth. And when you're not preferred on a formulary, generally, a single appeal is sufficient the vast majority of times to get the patients access to INGREZZA. So we really have been quite successful in doing that. Now that there are times, as we started talking about last year, where there are some hurdles that over time certain plans would put in front of us. And what we look at it as is there's just an additional investment by engaging that plan very selectively that we can remove those hurdles and, therefore, make life easier for the doctor and for the patient. And so that's what we have done. But it's been very selective where we've entered into contracts. And it hasn't, by and large, really had a great effect on our gross to net. Now when we do -- one of the reasons why I think that's the case is that when we do enter into these discussions, we are not looking for a preferred placement on these plans. We're not looking for any exclusion of anyone else. And so, therefore, we want patients to have choice. We want the physicians to have choice. So because we're not asking for any sort of exclusions or preferred placement, I think that makes it a bit easier for us also.

Okay. So now if all goes well, you could be launching into a Huntington's indication. In that space, there's slightly some -- slightly different dynamics. One of the things that's helped you with TD is, of course, your focus on psychiatrists. Huntington's is different. It's more of an emphasis on neurologists. And so since you already have a competitor there through AUSTEDO, and it's a different call point relative to your heavy call points for TD, how are you thinking about that market? And also, what is the status of your registrational study?

Yes. So I'll start out with the very last thing you asked, the status of the registrational study. It's a single Phase III that we started in Huntington's patients. That's been temporarily paused because of COVID. And as you can imagine, these are generally elderly patients, so they're in the very much high-risk group of patients. And so those sites are being very careful with when they bring patients back in. So we continue to be paused on that, and we will advise you when we are enrolling again, in that study. You're right, our -- there are several competitors, generic and then a deuterated tetrabenazine that are on the market and available. However, the very same advantages that INGREZZA has in TD, it has those advantages for Huntington's patients. It's well tolerated. There's no black box warning here. It's a simple, noncomplicated dosing regimen that we have here. And in addition, it's a once per day -- 1 capsule, once per day. And that's important because Huntington's patients have a real problem with swallowing movements. And also their jaw movements could actually break a capsule or break a pill. And that can be a real problem when you're talking about tetrabenazine or deuterated tetrabenazine because of you would get a dangerous drug dump that would take place all at once into these patients. So I think that there's still a big opportunity that is in the Huntington's population. There's about 30,000 Huntington's patients, 90% have chorea and 70% have moderate to severe. And only about 20% of them are being treated with the VMAT2 inhibitor, whether it's deuterated or whether it's the generics. So there's really a lot of room there. As you point out, our call point -- our predominant call point in TD is with psychiatrists. But we do have, depending on the territory, 20% to 25% of our calls are into neurologists for TD. And these are the same neurologists that treat Huntington's patients. So I do think that, that -- having that indication is going to be a real lift of value added, if you will, to the calls that our sales force will be making into those offices. In addition, later this year, we plan on launching ONGENTYS for Parkinson's disease. Again, the very same neurologists that we already count on. So you can see what this can do for our sales reps access into the neurology office and the interest on the part of the neurologist office in meeting with our reps. Now that there's even more value we can bring to their practice with 2 indications in -- with INGREZZA. And then also yet a second important drug for their Parkinson's patients.

Okay. That's helpful. Maybe, like if we can just finish off talking on a couple of questions on ONGENTYS since you brought it up. What are the gating factors here to get this launch up and running since the last time we spoke?

Yes. So the -- obviously, the -- there was COVID and wanting to launch immediately into that environment. As we're just trying to get our legs underneath us in taking our field force in working at home and getting them there. The second aspect and probably more important to that was that there was an incident at one of the contract manufacturers for our partner, BIAL, who invented this drug and got it approved about 3 years ago over in Europe. And that -- we have our launch materials, but we needed to know that with that event with there -- and it's a non-COVID-related event, with one of their manufacturers. It made it unclear path to exactly when we would be getting our subsequent deliveries of drug because BIAL is 100% completely responsible for supply chain. Neurocrine has no role in supply chain. And so what we did not want to do is to put the drug on the market without having very, very clear and high -- as high probability as we have for INGREZZA about we are going to always be able to resupply, and there will never be any interruption in supply of drug. And so as I've said, that it's going to be late this month into next month, where we anticipate getting further information from BIAL as to exactly when that time line is going to be and, therefore, what is our time line -- our exact time line for launch. And we're still on that. It's still late this month, early next month that we will have that information, and then we'll be able to relay to you a firm time line as to when we'll be able to launch.

Okay. That's helpful. And then what is -- what has been your discussions with physicians on this product so far? And can you help us maybe, Kevin, frame what the market opportunity could be?

Yes. So the discussions with physicians has been quite good, but it's a little bit difficult because, again, another one of those double-edged swords. Once we licensed this from BIAL, it was up to us then to get it approved in the United States, which we were able to do. That took a lot of work. And it started out with the discussion with the FDA right from the get-go about did we need to do another pivotal study on this, meaning use North American patients since no one in North America had been treated with ONGENTYS. Very good news was that, no, they said that the current package is developed by BIAL would be sufficient for a filing. And clearly, it was. The downside of that is none of the U.S. physicians have treated a patient with ONGENTYS. Their experience with COMT inhibitors is largely with 2 very old first generation COMT inhibitors, one that was pulled from the market shortly after it was introduced because of lethal liver toxicity. And the other one which also did not satisfy the initial excitement of COMT inhibition in that it had to be given multiple times a day with every dose of levodopa. And it also had side effects, GI side effects that were very undesirable. And then it discolorated body fluids, such as tears and saliva. So there was -- it just never came anywhere close to what was hoped for a COMT inhibitor. That's all they know about COMT inhibition. That's why they put COMT inhibition at the very tail end of their treatment paradigm over the lifetime of a Parkinson's patient. So you have approximately 1 million Parkinson's patients in the United States. About 800,000 of them are on levodopa/carbidopa. And about 600,000 to 700,000 of them are on yet another adjunctive treatment. And again, as I said, COMT inhibitors are the last choice of the adjunctive treatment. So what we look at is taking the COMT market is the real low-hanging fruit. That's not success. What is success is to move COMT inhibition, move ONGENTYS all the way up to the front of the line of adjunctive therapies. And even more than that, it is that when a physician is at that point where they have got their patient on levodopa/carbidopa twice a day before they look at upping the dose of levodopa/carbidopa because the patient is not adequately treated or increasing to it 3 times a day. That what they do instead is they prescribe ONGENTYS and really optimize the gold standard, which is levodopa/carbidopa. And that's what success is, and that's what we strive for. Like TD, it's going to be a big educational effort. Like TD, it's going to be changing ingrained habits of the doctor.

Okay. And what kind of a launch ramp do you think this will have? Would this be as steep as what we saw with INGREZZA? Or it be more of a spec-pharma traditional type of a launch if you want to call it that?

Yes. It's not going to be specialty pharma because we're not going to price this in the specialty category. Not all important drugs have high prices. This is going to be an important drug, and it's not going to be a high-priced drug. This patient population is extremely sensitive to co-pays. They're mainly on Medicare. And so, therefore, that demands that we be very, very selective about what the prices and not price it in the specialty category. And so -- but as far as going back to your direct question about what do I think the launch looks like, I think the challenge in front of us with having a very effective and a very safe drug is we have a drug that the U.S. psychs have no experience with. And so that's what they're going to have to do, is get experience with this drug. And that's going to be our main challenge there. So I would expect a slow ramp initially with this.

Okay. That's helpful. We only have a 2 or 3 minutes left, but I did want to touch on CAH for a little bit. Can you tell us what's the statuses of the Phase III trial that you were -- I guess, were waiting for details on that for the adult population.

Right. So with crinecerfont, as we announced earlier, Dr. Auchus presented the Phase IIb proof-of-concept study with crinecerfont in adult patients with classical CAH, and that was on the virtual ENDO online meeting just earlier this month, June 8. And those were the data, very powerful data, very consistent data that we took to the FDA, and that's how we came out from those FDA meetings, very positive FDA meetings with needing only a single Phase III clinical trial for this. And so we're going to be kicking that off shortly. And you will -- we haven't talked about the trial design, but you will see that trial design on clinicaltrials.gov when we post there. And then we're going to talk more about that. Simultaneously, we have the Phase II trial in the pediatric population. And it's very important that we treat these patients. The biggest effect we can have on the CAH population is the earlier in their lifetime that we can intervene. And so that's why being able to treat the pediatric population is so important. And we've completed all the developmental and pediatric talks for this compound crinecerfont, and that turned out to be clean. And so that is in the proof-of-concept phase right now. It had to be paused also. And that will be restarted also very shortly. And it is an adaptive trial, much like the Phase IIb in the adults, where there will be several cohorts, and we'll be bringing that data as it is developed to the FDA in order to be able to transition quickly and seamlessly into the registrational program in the pediatric population.

Okay. I think those are all the questions that we have time for. There was an e-mail question earlier as it relates to the competitive landscape for schizophrenia. And to the extent that you can offer an opinion, Kevin or Kyle, Concert Pharma has a molecule called CTP-692. What are your thoughts, if any? It's also a deuterated serine approach? Any thoughts on how that could be received in this market versus what advantages your program would have?

Yes. I think it's still real early days to know about the PK of that compound and to know if it's going to be a benefit to patients with the negative symptoms of schizophrenia. It's also a function of potency, which we think that we've got that advantage with 831, a molecule specifically designed to hit the enzyme here of interest. So I think that we'll see what that looks like when the data is out, and then we'll be able to talk more confidently about that. But in terms of negative symptoms in schizophrenia, there are certainly other companies out there in the space. We know, for example, recently, Minerva released some data out there that was not as positive as what they anticipated, but it looks like they are pooling data across some earlier study or studies to potentially submit a package to the agency. We know ACADIA is working on this space. And I think if there's anything that we've learned about psychiatry is that there's no one mechanism that's appropriate for all. So we think that there's plenty of room out there for everyone to have an option for patients with the negative symptoms of schizophrenia.

Okay. Great. With that, I believe we are now out of time. And so I want to say thank you to both you and Kevin for joining us this afternoon. It was a great use of our time, as always. We wish you guys the best of luck with the upcoming quarterly results, and we're going to continue to follow all your updates for your now-growing pipeline.

Thank you, Tazeen. Pleasure talking with you too. Take care.

Okay, guys. Bye-bye.

Thank you. Bye-bye.