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Good day, everyone and welcome to Neurocrine Biosciences’ reports Third Quarter Results. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question-and-answer period. [Operator Instructions] Please note that this call will be recorded and I will be standing by should you need any assistance. It is now my pleasure to turn today’s call over to Todd Tushla, Vice President of Investor Relations. Please go ahead.

Thank you, and happy Halloween eve. Welcome to Neurocrine Biosciences’ third quarter 2024 earnings call. With me are Kyle Gano, our Chief Executive Officer; and Matt Abernethy, Chief Financial Officer; Eric Benevich, Chief Commercial Officer; and Eiry Roberts, Chief Medical Officer. Note that today, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. With that, for the first time, I hand it over to Kyle.

Thank you, Todd. Before we dive in, I'd like to acknowledge that this is my first earnings call as Neurocrine’s CEO. I'm excited to share my enthusiasm for our future, so my opening remarks may run a bit longer than usual. First, I want to express my deep gratitude to our Board of Directors for their confidence in my leadership as we embark on this next chapter of growth. Thanks to the exceptional guidance of our past CEOs, Gary Lyons and Kevin Gorman, Neurocrine is in a strong position to become a true leader in neuroscience. I extend my heartfelt thanks to both Gary and Kevin for their invaluable contributions to the company's success. Given our company's growing multibillion-dollar franchise in INGRE

Thank you, Kyle. Our INGRE

Thanks, Matt. We again delivered a strong quarter for INGRE

Thank you, Eric, and good morning, everyone. I'll begin today's clinical update with Crinecerfont. We continue to have constructive interactions with the FDA and remain on track for the December 29th and 30th PDUFA dates. Given the calendar and end-of-the-year timing, it would not be surprising to potentially receive approval for both formulations on December the 30th, which falls on a Monday. Turning to the mid-stage pipeline, last month we disclosed that the ERUDITE study of luvadaxistat as a potential treatment for cognitive impairment associated with schizophrenia failed to meet its primary endpoint and thus did not replicate the positive findings on cognition previously reported in the INTERACT study. The results from the ERUDITE were confounded by variability in cognition measures across the population studied and the potential imbalance in baseline characteristics for enrolled subjects. As Kyle mentioned, we're therefore discontinuing this program together with the NBI-104 T-type calcium channel antagonist program in CSWS and focusing resources on advancing NBI-’845 and NBI-’568 into Phase III studies. Both NBI-’845, our AMPA positive allosteric modulator for the treatment of major depressive disorder, and NBI-’568, the selective M4 orthosteric agonist for the treatment of schizophrenia, continue to make good progress towards our end-of-Phase II interactions with the FDA, which we anticipate will occur over the next few months to enable the start of registrational studies for each of these programs in the first half of 2025. We will provide more insight into study specifics over the coming months, together with our plans to publish key Phase II information from each of these programs in the latter part of 2025 once these registration studies are up and running. Shifting to NBI-’770, our NMDA NR2B NAM negative allosteric modulator for the treatment of major depressive disorder, the Phase II program for this molecule continues to enroll well with top-line data anticipated in 2025. The remainder of the pipeline is also progressing well, including the four muscarinic programs currently in Phase I development. With that, I'll hand the call back to Kyle. Kyle?

Thanks, Eiry. We're ready to take questions.

Certainly. [Operator Instructions] We'll take our first question from Chris Shibutani with Goldman Sachs. Please go ahead.

Thank you very much. Good morning. Congratulations on a clearly strong quarter commercially. I wanted to ask about going forward thinking about the pipeline, people as well as strategy. Eiry, we appreciate your comments. I think you have announced previously that you're looking to step away. Kyle, have you given thought to the point people who will be running the role that Eiry has been involved with as well as your previous role, which was really managing the business development leadership there, since I noticed quite a bit of focus on capital allocation. And secondly, can you just give us an update on the NextGen VMAT2 inhibitor? I know we started Phase I at the start of this year. But some visibility into when we could learn more would be great. Thank you.

Thanks, Chris. This is Kyle. I'll start, and then I'll have Eiry and the team, add anything that I missed here. For our VMAT2 follow-on compound, this is NBI-’890. What we're looking here to do is to have a more potent compound that would be amenable to all the same indications that we see advantages for INGRE

Yeah.

Thank you. We'll go next to Paul Matteis with Stifel. Please go ahead.

Thanks so much for taking my question. Kyle, congrats on moving to the CEO seat. I want to ask you a question just about BD and philosophically where you stand. You guys in your public commentary over the years have kind of ebbed and flowed to the degree to which you've talked about prioritizing smaller deals versus something larger in the $3 billion to $4 billion range. How do you think about capacity now, and strategically, do you feel like this is the right time for Neurocrine over the next year, year and a half to do something that's more meaningful and bolder for a later stage asset? Or do you still like this kind of smaller BD, spread the best strategy that you've employed so far? Thanks so much.

Thanks, Paul. Appreciate the question. You know, in terms of our BD activities, the team that we have here continues to work with a high degree of urgency. Fortunately, we don't feel like we have to do something right now, either large or small. We've got a very deep and diversified portfolio with a number of investments that we're making that are late stage next year. And we've talked about some of those already with NBI-’845 and major depressive disorder and NBI-’568, our program in development with schizophrenia. And behind that, we have a very rich early to mid-stage pipeline that's developing. So right now, my mind is learning about the landscape and figuring out what areas that we want to invest in moving forward, which assets are in those areas, but really focused on executing and what we have in the pipeline right now, making sure that we're doing whatever we can there to put those programs in the best possible situation for success. And if something comes out down the road that is a program, a technology that is something that we could utilize and takes advantage of our expertise and infrastructure, we'll look at that seriously. But right now, we feel like we're in a very enviable position.

Yeah, fortunately, our financial flexibility is very strong at the moment. A lot of cash, continued cash flow generation, a very clean balance sheet as we started our convertible debt earlier this year, as you're aware. So we do have financial flexibility into the future if we did decide that was something for us to do. And as Kyle said, a very enviable position to be in.

Okay. Thanks, guys.

Thank you. We'll take our next question from David Ansellem with Piper Sandler. Please go ahead. Hey, thanks.

So looking into ’25 and beyond, how are you thinking about the potential that you might need to compete more on price to hold INGRE

And so, David, we're going to handle the first chunk of your questions. And just out of respect for others in queue, we'll leave the muscarinic question to others. But Eric can comment on price. The only real specifics we're going to give as it relates to 2025 on price is we do, sitting here today, expect our net revenue per script to be very similar to what we've seen in 2024, so no significant change that we can see at this time for 2025. But, Eric?

Yeah. So what I'll say is that every year we continue to assess our contracting strategies. And we invest in contracts where we think it makes sense. And in some cases, we have contracted access where we think that it's favorable. In other cases, we look at the contract and make decisions to pull back. And so as a result, the coverage landscape changes from year to year. But overall, our access has and continues to remain excellent with over 80% of lives covered and the majority of patients paying $10 or less. And we expect that to continue into the future. The other thing that I'll say is that we're going to learn from the first few waves of drugs that go through the negotiation process in terms of what their access looks like vis-a-vis non-negotiated drugs. So stay tuned. But ultimately, our goal is to make sure that patients that need access to INGRE

Understood. Thank you.

Thank you. We'll take our next question from Akash Tewari with Jeffrey. Go ahead.

Hi. Thank you for taking your question. This is Phoebe on for Akash. On your M1/M4 asset, can you talk about why you feel confident that you don't have to dose with Tropium like [CAH] datas? And then additionally, what should we expect to learn from initial Phase I human data next year for the muscarinic? Thank you.

Good morning. Thanks for the question. On NBI-’570, it's a very interesting molecule in the sense that it's one of a basket of small molecules that we have in development that range from M1 to M4 selectivity across the muscarinics. And 570 has equal potency on M1 and M4. One of the things that's exciting about this molecule, as well as the suite of molecules, is that it relies on explicit selectivity of just M1 and M4 across the muscarinics, which we know are the subtypes M1 through M5. So we've got that going for us out of the gate. But the other piece that Sosei Heptares, now Nxera our partner, has done is what many companies in the early stages of drug discovery do when they're interested in a CNS molecule. They dial in the selectivity they desire, and then subsequent to that, they actually make the molecule be penetrant to the CNS more versus the periphery. And in doing so, when you think about 570, that's how we're able to move forward on the M1/M4 agonists without the need to add back something that blocks peripheral effects because 570 preferentially gets into the CNS. In terms of the ongoing program with 570 and the muscarinics, they're all in Phase I right now. They'll be reading out data during the course of 2025, and with that, we'll be able to look at the totality of the data coming from the different molecules and learn a lot from the pharmacology across M1 and M4, and with that, we'll be able to determine next steps in terms of moving the patient population.

Okay.

Thank you. We'll take our next question from Tazeen Ahmad with Bank of America. Please go ahead.

Hi, guys. Good morning. Thanks for taking my question. On INGRE

Yeah. I think when you look at historical sequential growth in dollars, we fall right into that historical range of somewhere between $10 and $20 million sequentially, so I do think our guidance takes that into consideration. Just a few comments for Q4. We do have our new field sales team that's in place and actively calling on customers and that handoff process is occurring, but as Eric said in the preparatory months, that does take a few quarters to start kicking in. And then the last piece is something that we've had in historical years, a sequential increase in gross net discount that's associated with channel inventory. It's going to be a little bit less than what it has been historically because of some of the IRA dynamics, but nonetheless, a higher gross net discount in the fourth quarter. Thank you.

Thank you. We'll take our next question from Jay Olson with Oppenheimer. Please go ahead.

Oh, hey. Thanks for taking the question. Congrats on all the progress. We're curious about your level of interest in epilepsy since it's still an area of super high unmet need and it's also proven to be a difficult area to conduct clinical trials, so we're just curious how committed is Neurocrine to epilepsy and do you plan to replace the Idorsia molecule with another asset? Thank you.

Thanks, Jay. This is Kyle. I'll take the question here. We still have a very strong commitment to the area of epilepsy. We have a number of programs that are moving through various stages of preclinical development, and while I don't expect us moving forward with another T-type calcium channel blocker, we do have a mixed NaV1.2, NaV1.6 inhibitor that we're looking forward to bring up into the clinic next year, so stay tuned on that. Obviously, a lot of the molecules that are required to move forward have a significant body of data around them for GLP Tox, 90 enabling studies. We need to get through those and then see where we land on the other side for advancing that particular asset, but still committed to epilepsy. There's still a high degree of unmet need in that space, and we hope to be a player as we move along here.

That's great. Thank you.

We'll take our next question from Ash Verma with UBS. Please go ahead.

Hi. Thanks for taking my question. Just on 568, now that we've had some time to digest the results in Phase II, just what are you learning? Do you think this orthosteric agonism was the issue in this case, and how should we think about the rest of the muscarinic pipeline based on what you've learned? Thank you.

Thanks. I hope I answered your question properly, Ash. I think it was that now that we have the site in Phase II data, how are we thinking about the orthosteric agonism with respect to next steps in the context of the broader muscarinic pipeline? Just to address that.

Yeah.

So, thank you. So just to address that, so we are moving forward rapidly with our 568 molecule on the back of the encouraging Phase II data that we saw in schizophrenia. We're planning to enter, in the first half of next year, a Phase III registration program for the treatment of schizophrenia. The first step on that journey will be our interaction at the end of Phase II with the FDA, and we're preparing for that in the next couple of months. So in that regard, we think there is a significant opportunity to add on to the current success that there's been in the muscarinic area. We were very pleased to see the first medication approved with this mechanism in covalent earlier this quarter. But I think in terms of the selectivity for M4 and the potential benefit-risk profile and improvement in that associated with the selective agent, we believe there's a lot more room in this space to add value for patients. And so we're excited and encouraged with our Phase III planning in that regard. As Kyle mentioned, we do have a suite of muscarinic agonists behind 568, which have, again, high selectivity for either M1 or M4 as orthosteric agonists. And those are currently in Phase I development, and we're exploring how to understand the potential areas of investigation beyond Phase I as we generate data next year, which could range all the way from disorders where improvement in cognition is important, all the way through to psychosis, bipolar disorder, and other indications.

Thank you. We'll take our next question from Phil Nadeau with TD Cowan. Please go ahead.

Hi, this is Alex on for Phil. I'm for Phil. Congrats on the quarter, and thanks for taking my question. On 568, just curious if the upcoming emraclidine data on your pivotal trial plans in any way? And also, could you maybe just walk us through your broader strategy for 568's pivotal, including regulatory conversations and trial design? Thanks.

Yeah. So we actually haven't talked very much about the Phase III trial design yet, and I think we want to clear our way through the end of Phase II meetings before we do that. But certainly, as we start to post the trials that will be included in that registration program in the first half of next year, we'll be able to get into much more detail around that. With respect to the impact of emraclidine, or even [covalency] information on our planning and thinking, I think we're very encouraged by the fact that M4 cell activity appears to be sufficient to produce a psychotic effect in schizophrenia. And I think from that point of view, the fact that our model is an orthosteric agonist, that's the approach we've chosen, and that's the approach that we are confident in on the back of our Phase II data that we generated earlier this year. And so we're very much more focused on our own program in terms of understanding the emerging benefit risk from our Phase II data, and ensuring that we're incorporating all of that learning into our Phase III trial designs and into our Phase III program. And we'll be happy to talk more about that as we see it through the end of Phase II interaction with the FDA.

And maybe just to add to that, the excitement that we have around our own program stems from the fact that we're the only approach that can selectively and directly activate M4 and deliver on the promise that we've seen from the muscarinics thus far without any need to rely on any other aspect of an add-back therapy or some sort of endogenous ligand for either efficacy or safety or tolerability. We think at the end of the day, physicians are going to be feeling a lot more confident about our approach being able to be used than the wider population of the patients.

Thank you.

Thank you. We'll take our next question from Anupam Rama with J.P. Morgan. Please go ahead.

Hey, guys. Thanks so much for taking the question. I'm going to ask the same question I've asked for the last 10 years on third-quarter earnings. So any chance of an INGRESA pre-announce and guidance at a Smart Healthcare Conference in January? Or is this more of a fourth-quarter earnings report scenario in February?

Yeah. Anupam, I can pick up a trend without you even acknowledging it. So always good to hear your questions. We're obviously looking forward to J.P. Morgan this year. Kyle has an ambitious plan for 2025 with full detail. But as consistent with the last, I believe, two years, this will be the third year where we do not pre-announce our revenue at the J.P. Morgan conference. And we'll save commentary for both Q4 results and then for your sales guidance for 2025 until our February earnings call. But always glad to see you in January to kick off the New Year.

Thank you. We'll move next to Evan Seigerman with BMO Capital Markets. Please go ahead.

Hi, guys. Great. Thank you so much for taking my question. So, you know, as we think about your salesforce expansion and the opportunities for treatment of Chorea associated with Huntington's disease, how should we really frame that opportunity? I know Eric’s been there. But, you know, with the investment, where do you see, I guess, INGRE

Yeah, let me take your second question first in terms of our reassessment of the prevalence of TD. And, you know, that's something that we haven't looked at for a number of years. And so, you know, I would look at that as more of just an updating our prevalence estimates, you know, using a methodology that's similar and consistent with what we had done previously. The time that we launched in 2017, our estimate was at least 500,000 people in the U.S. with TD. A couple of years later, we updated our estimate to at least 600,000. And fast forward, I think it's been four or five years since the last time we looked at it. And, you know, the numbers of people living with TD continue to grow, I think commensurate with the expanded use of antipsychotics, especially in non-psychotic conditions. And so, in our prepared remarks, we did update the number now to at least 800,000 people with TD in the U.S. And I think that that number is similar to other estimates that are out there and, frankly, maybe a little bit on the low end of the range. So, that's the prevalence story. In terms of the sales team, you know, we certainly felt like the decision to expand our salesforce was in line with the growth of the market. And certainly, as I mentioned in the prepared remarks, consistent with the growth of the prescriber base in TD. And in terms of Huntington, the only part of our commercial team that we didn't expand or change, really, was the neurology team. And the strategy of penetrating that Huntington's opportunity is primarily through our neurology salesforce. On a relative basis, the neurology opportunity is much smaller, excuse me, the Huntington's opportunity is a lot smaller than it is in Tardive Dyskenisia. And yet, there's still significant unmet need in Huntington's Chorea. You may have seen that we've recently presented some data showing the use of INGRE

Maybe just to put a finer point on that, we talked about the TD prevalence being around 800,000 in the US for HD Chorea, there's about 30,000 patients, about 20,000 patients have Chorea that's moderate to severe, about 5,000 patients currently on a VMAT2 inhibitor. So, the 15,000 patients that we're looking to address, that's about a 50 to 1 ratio of patients that we can serve with INGRE

Thank you. We'll take our next question from Cory Kasimov with Evercore. Please go ahead.

Hey, good morning, guys. Thanks for taking the question. I wanted to ask about Crinecerfont, and if you can talk about how many prescribers are located at the CAH Centers of Excellence and the portion of the overall patient population they serve, and are there certain segments of the CAH population they are most eager to treat upon approval? Thank you.

Yeah. So, let me take a step back and say that we're really excited about the opportunity to make a difference with the CAH community. With the PDUFA date coming up here at the end of the year, we've been preparing for a launch early in 2025. As you know, we have a salesforce that's out there. They're doing disease state education right now. They're meeting with future customers. They're profiling and learning about their practices. And so, this is all important work that will help us get off to a strong start once we, knock on wood, get approval later this year. In terms of the proportion of the patient population that's within the care of the centers, the CARES Foundation Centers of Excellence, there's only about a dozen or so of those Centers of Excellence out there. And we're still learning about what proportion of the patient population are being managed through those centers. But I would say it's in the range of 10% to 15% of patients in total. And so the majority of patients with CAH are still being cared for within community endocrinology practices and also within pediatric endocrinology practices. So obviously, we are going to be putting a lot of focus early on those two segments, the pediatric endocrinologists as well as the CARES Centers. But ultimately, for us to really make a difference in this patient population, we're going to have to make sure that we also are reaching out to those patients that are cared for in community endocrinology practices. Do you have anything else to add, Eiry?

No, I think you said it well, Eric. mean, I think there is a lot of excitement that we're hearing as we're talking with clinicians who are working with these patients given that there's been nothing new for this patient population in the last 70 years. And we do know in terms of focus that in the pediatric setting, obviously there is a very significant level of interest in a potential medication that could help with androgen reduction in that patient population where very tight management of androgen levels becomes so critical in the face of normal growth and development. And so we are seeing a lot of, a very significant interest as we continue to hopefully progress towards an approval for both pediatric and adult patients living with congenital adrenal hypoplasia by the end of this year. Eric, you had something else?

Oh, yeah, just one last thing I want to say is that our team, the receptivity that we've seen since our team has gone out into the field since this summer has been really strong. So I think there's really great interest in the endocrinology community, and certainly I think it's a testament to the unmet need in CAH.

That's helpful. Thank you.

Thank you. We will move next to Brian Skorney with Baird. Please go ahead.

Hi, this is Luke on for Brian. With the upcoming pivotal trials in psychiatry, should we expect 845 and 568 to progress largely in parallel following the end of Phase II meetings, or will you be looking to emphasize or accelerate one program over the other? Thanks.

I appreciate the question. I think given the proximity of when we reported top-line data would be commensurate with how we would look at starting the Phase III trials in 2025. We don't anticipate any need to stagger them in any particular way for any reason. It's going to be more based on when we have our end of Phase II discussions and then we can stand up the pivotal trials for both 845 and 568. So I expect them to be started nearly at a similar timeframe, but not at the exact time for both of these studies.

The other thing I'd ask there, Kyle, is that obviously from an operational perspective as well, these are focused on two different indications within the psychiatry space with 845 in major depressive disorder and 568 in schizophrenia. So we don't anticipate competitions for patients between our two programs, which I think is really important. And the internal team is extremely excited about the opportunity to potentially bring value in both of these areas with these programs, moving forward.

We will move next to Carter Gould with Barclays. Please go ahead.

Good morning. Thanks for taking the question. Maybe to follow up on one of the earlier questions some time ago in the queue. I guess for a long time we looked at Neurocrine’s pipeline, you guys were sort of mid-stage heavy. That's clearly evolved. And now it's a little bit more of, I guess, a barbell approach where you've clearly made those Phase III investments or about to make those Phase III investments. And the earlier stage pipeline now, at least from kind of where we sit, seems very focused on VMATs and muscarinics. So can you maybe talk about how you're looking at that early stage portfolio? I guess the breadth and diversity of those assets and should we expect sort of another replenishment either through in-licensing or homegrown assets to sort of bubble up over the course of ’25?

Yeah, thanks for the question. I think also we'd like to point out that in addition to the later stage assets and the earlier portfolio that you mentioned that spans the muscarinic agonists and VMAT2, we also have a muscarinic antagonist that we're moving forward for a variety of movement disorders and then in Phase II we have an NR2D NAM that we're moving forward with major depressive disorder. So there's a lot going on across the organization in terms of early to the late stage portfolio. And we'll have more to say about what's emerging in terms of our earlier stage portfolio and add to the clinical programs in early 2025. So stay tuned on that. There's a lot of productivity that's ongoing right now in our labs and it just takes a bit of time to move that forward into clinic and we'll start seeing that in 2025.

Understood. Thank you.

Thank you. I'll take a question from Brian Abrahams with RBC Capital Markets. Please go ahead.

Hi, this is Joe in for Brian. Thank you for taking our question. Can you elaborate more on the growth drivers you're seeing on INGRE

Yeah, in terms of the dynamics for Q3, it's primarily driven, the growth is primarily driven by demand and as I mentioned in my prepared remarks, continued strong compliance for INGRE

Got it. Thank you.

Thank you. We'll take our next question from Mohit Bansal with Wells Fargo. Please go ahead.

Great. Thank you very much for taking my question and Kyle, congrats on your first call as a CEO. Maybe, would love to understand how internally you are thinking about, the upcoming competition in CAH space. I mean, kind of we are probably putting cards before the horse here, but there is an ACTH antagonist out there as well. How do you see that as a competitor to Crinecerfont? Do you see this as a direct competitor or more like in lines of therapy where something could be first line versus second line? How do you -- how should you think about that?

Maybe I'll start that question if there's anything I'm missing, I'll ask my team to chime in here. So when we think about CAH, I think we can all agree that this is a very serious disease. You know, at the heart of the matter is the body's struggle to capture its HPA axis. And by HPA, I mean the hypothalamus-pituitary-adrenal axis. In terms of how the disease is initiated, it's caused by mutations on the CYP21A2 gene and that results in dysfunction or absence of the synthesis of cortisol, which is the key regulator of the HPA axis. So for the past 70 years, patients, physicians have used super physiological or very high doses of GC glucocorticoids to act as that regulator of the HPA axis. What we get with Crinecerfont is the ability for the patient to capture or recapture their HPA axis, allows them to control ACTH, reduce ACTH and therefore control -- reduce and control of your androgens. And at the same time we think about that, when you control ACTH, the androgens are able to remove the requirement for excessive control of your -- excessive use of glucocorticoids and we've seen it from our Phase III trials that that puts a little number of patients into using a physiological range of their GC dose. When we think about the competition then, our approach uses the angle of working upstream at the HPA axis to control the regulation of the HPA at the top and then everything below that we're able to reduce the control as well, starting with ACTH. Our competitor in this space, a company here in San Diego that we know quite well, Crinetics' is developing an ACTH antagonist called Atumelnant and it's an early stage clinical development right now with a small number of subjects. And the time will tell to see how their approach will work relative to ours because they actually work downstream of our approach. So they only look at the androgens, not the other piece of the cascade which is ACTH. But ultimately where we are right now, we're very excited about our position. We've got very strong efficacy across both children and adults. We've got excellent safety and tolerability and we have formulations that match the needs of both children and adults. So we feel like we're in a very fortunate position here and we look forward to hopefully getting approval later this year and launching this important medicine for patients which is going to change the standard of care in CAH.

Excellent. Thank you.

Thank you. We'll take our next question from Marc Goodman with Leerink Partners. Please go ahead.

Yeah, I just want to come back to that question about aggressive competition in the competitive environment. There seems to be a lot of agita going into the quarter. A lot of investors kind of felt that Teva's been the one growing faster. They're making more noise. Can you give us a sense of what's really going on out there? You know, do you feel like you're outgunned with respect to the share of voice and the noise on the media? Maybe you could just give us a sense there. I think the prescription trends have really confused people. So anything you could do to help us just think about this. Thank you.

Yeah, I mean, obviously we felt good about the quarter we just reported. As I mentioned before, the VMAT2 market is a growing market. The vast majority of TD patients remain undiagnosed and untreated. Both brands are growing and as expected with the rollout of their XR formulation of deutetrabenazine, it's helped the growth of our competitor. However, INGRE

Thank you. We will take our next question from Myles Minter with William Blair. Please go ahead.

Hey, thanks for taking the question. I think just over a week ago there was some correspondence in the New England Journal about Crinecerfont from a couple of Spanish docs and they were kind of calling in a question the definition you use for normal thresholds of daily glucocorticoid “dosing”. Just curious as to your response to that and if payers in particular in your early conversations are asking for surrogate metrics like insulin resistance and percent of total fat masses, sort of confirmatory endpoints that you are getting efficacy in this population? Thanks.

Yeah, thanks, Myles. So, first of all, I think we were really happy with the Phase III data that we have both from an efficacy perspective in terms of the androgen reduction effect of Crinecerfont and the ability to reduce steroids in the vast majority of the population treated. And that's the case in both the pediatric and the adult population. Now, in terms of the discussion in the New England Journal and I think it's important that there's a discussion around what criteria were used in a clinical trial, etc. But I want to remind you this is the first time a trial of this sort has ever been done. And so we negotiated very closely with the Agency to come to the set of definitions that were used including the definition of what constitutes physiologic levels of GC. And that was important because this is a highly heterogeneous population. And so I think our bottom line from the Crinecerfont data set that we generated is that we really believe that the vast majority of patients living with CAH, whether they be pediatric or adult patients, can gain benefits from treatment of Crinecerfont if and when it's approved. And so from that point of view, we're highly encouraged and I think it's going to be very important to understand the real world experience of patients once we start to get out into this chronic condition and once we start to see the long term benefits that can result from a treatment like Crinecerfont.

Thank you. We'll take our next question from Jeffrey Hung, Morgan Stanley. Please go ahead.

Hi. This is Michael Riad on for Jeff Hung. Thank you for taking our questions and Kyle, congrats on the strong start. For the NMDA-NR2B program, is it safe to assume that 770 is being developed as an adjunct to background antidepressants? And if so, how are you thinking about evaluating the top line? What would you want to see to gauge the competitive potential like maybe versus SPRAVATO? Thank you.

So yes, in the context of the trial that's being performed right now in Phase II, the patient population is those who have inadequate response to currently available antidepressants. That actually could in due course be both as an adjunctive treatment or potentially as a standalone monotherapy. One of the key differentiators from this obviously is a mechanism that acts in a similar fashion to ketamine but being more selective in terms of the mechanism of action, we hope could translate into a favorable benefit risk profile relative to other treatments in this phase. One key differentiator is this is an oral mechanism obviously compared to some of the other things that are out there right now.

Thank you. That's very helpful.

Thank you. We'll take our next question from Laura Chico with Wedbush Securities. Please go ahead.

Good morning. Thank you very much for taking the question. Just with respect to the 800,000 TD revision there, could you provide additional color in terms of the breakdown of severity or kind of estimates within there? I guess I'm trying to understand how does this impact or change your views on the peak INGRE

Yeah, we don't have any color in terms of severity. Overall, when you look at the literature the estimate is that about half to two-thirds of patients would be in that moderate to severe category and the balance being milder TD. So in the medical literature there's really no standard definition of what constitutes mild, moderate, or severe TD. And so ultimately the guidance that we give to the CP community is that not only do they need to look for abnormal movements and differentiate TD from other drug and movement disorders, but they really need to look at the patient and have a conversation with the patient and understand to what extent does that impact their quality of life and their functionality. And even milder abnormal movements can significantly negatively impact these patients. And so what you see in terms of people that are being treated with INGRE

Thanks very much.

Thank you. We'll take our next question from Yatin Shunaya with Guggenheim. Please go ahead.

Hi this is Thelma for Yatin. Congrats on the quarter and thanks for taking our question. So on the 845 in MDD, can you guide us through your strategy for the pivotal program? How many studies are you planning to run? And can we expect to see Phase II data at any upcoming conference? Thank you.

Thanks for that. So in terms of the actual program design for Phase III, obviously we'll be following the path that's been followed by other antidepressants in registrational development but we haven't talked specifically about number of trials or designs of trials and we will do that after we have engaged in our end of Phase II interaction with the FDA and are starting those trials next year. And yes I think we alluded to in our early comments we are planning to release the information from our Phase II program in the latter part of next year.

Thank you.

Thank you. We'll take our next question from Uy Ear with Mizuho. Please go ahead.

Hey guys. Thanks for taking my question. Just going back to the Crinecerfont launch. You guys indicated there you’ll be giving our free drugs, what not? Before the insurance comes on, just maybe just help us understand a bit about the number of patients that are currently on free drugs at the moment with your extension safety extension studies, and how do you sort of maybe focus on in terms of uptakes? Would you be giving free drugs essentially to everyone that comes on or yeah, just want to get maybe a better sense of the demand at the outset? Like are you seeing a lot of excitement demand with respect to this drug? Thanks.

I’ll answer the piece about the long-term extension. But we do have long term extension programs going on, right now, globally in both pediatrics and adult patients. Two comments on that, first of all, I think its enabling us collect some longer term real word information about the patients. And that’s important. And secondly, the number of patients remaining in the program remains incredibly high, which -- with very, very dropouts. Which I think, again is indicative of the ongoing tolerability, safety, and excellent uptake with respect to Crinecerfont in this program.

Yeah, and with regards to the reimbursement dynamics, as I mentioned in my prepared remarks, the majority of the patients in the CAH community, are either commercially insured or from Medicaid. And many commercial insurance plans have policies in place that restrict reimbursement free drugs and/or have a new market blocks in place. And so the expectation is that even as we get patients started on therapy it's going to take some time to work through the reimbursement. So we are going to have a program in place that allows us to get patients started and that is really across both commercial and Medicaid. Ultimately we're confident in our ability to get patients started as indicated by our success with INGRE

Okay. Thank you.

Thank you. And we will take our final question from Ami Fadia with Needham & Company. Please go ahead.

Hi, this is Buna on for Ami. Thank you for taking our question. So on NBI-’845, how do you see it fitting into the current treatment paradigm and what are the expectations from the upcoming FDA meeting? Thank you.

So in terms of the FDA meeting, we will be getting clarity on our Phase III strategy and that will enable us to start our Phase III program in the first half of next year. In terms of the indication or the area of focus in major depressive disorder the Phase II data that we generated was in the context of inadequate response to currently available treatments and then in that setting we anticipated this could either be an adjunctive treatment to other antidepressants currently in the field or as a standalone monotherapy and we'll be exploring both the treatment forward.

Thank you for your response.

Thank you and there are no further questions. At this time I'll turn the call back to Kyle for closing remarks.

Thanks Ashley. So this morning we covered a great deal of ground. I'd like to close by reinforcing my opening message. Our exceptional leadership team and our energized organization are really positioning our kind of lead in neuroscience moving forward. I'm certainly inspired by all work that’s ahead and ever more confident in our potential. You know today we touched on a lot of different things. We talked about a bit on our strategy, our pipeline and our promising commercial opportunities. If you think about this being my first earnings call, I'm hoping you take away two things from our opening remarks and our Q&A. One is our commitment to discovery, developing and commercializing innovative medicines and I think you've seen from our discussions that this comes with risks and requires time and investment. But I'm hoping that you also see that we're committed, equally committed to delivering near and long term value for our organization and our shareholders. So with that, I think that we'll close here today by saying that busy year end ahead for us all and we're looking forward to connecting with many of you virtually and in-person for those who will be attending some of the many healthcare conferences that remain here in the next couple of months. So with that, thanks again, for the call and looking forward to speaking with you soon.