Hello, and welcome everyone joining today's Neurocrine Biosciences Third Quarter 2026 earnings call. At this time, all participants are in a listen-only mode. Later, you will have the opportunity to ask questions during the question and answer session. To register to ask a question at any time, please press star one on your telephone keypad. We ask that please limit yourself to one question. Please note this call is being recorded, and we are standing by if you should need any assistance. It is now my pleasure to turn the meeting over to Todd Tushla, Vice President of Investor Relations. Please go ahead.
Thank you, and happy Monday wherever it is that you may be. Welcome to Neurocrine Biosciences Third Quarter 2026 earnings call. Joining me on today's call are Kyle Gano, Chief Executive Officer, Matt Abernethy, Chief Financial Officer, Eric Benevich, Chief Commercial Officer, Eiry Roberts, Chief Medical Officer, and Samir Siddhanti, Chief Business Officer. During today's call, we will be making forward-looking statements. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to review the risk factors discussed in our latest SEC filings. In addition, some of the information discussed today includes non-GAAP financial measures that have not been calculated in accordance with U.S. GAAP.
Reconciliations of these non-GAAP financial measures to the most directly comparable GAAP financial measures are presented in the tables at the end of our earnings release issued earlier today, which has been posted on the Investor Relations page of the company's website. Following prepared remarks, we'll be happy to take your questions. With that, I'll hand the call off to Kyle.
Good afternoon, everyone. Nearly two years ago, on my first earnings call as CEO, I shared my optimism about Neurocrine's future and the significant opportunities ahead. Today, that confidence has only grown stronger as I remain deeply confident in our ability to drive sustained growth and create long-term value for our shareholders. Our strategy to build a leading biopharmaceutical company is grounded in execution and delivering meaningful results. In the third quarter, we generated record net product sales of more than $1.1 billion and record profitability. These results underscore the strength of our diversified portfolio of three first-in-class medicines and our growing ability to reach and serve more patients than ever before. This momentum positions us well to drive continued growth across INGREZZA, CRENESSITY, and VYKAT XR in 2027 and beyond.
The strength of our growing commercial business and financial position also enables us to continue investing in our industry-leading pipeline. With several important clinical milestones anticipated in 2027, including phase III data readouts for osavampator in major depressive disorder and direclidine in schizophrenia, we believe Neurocrine Biosciences is approaching a potentially transformative period, one that could further expand our pipeline, strengthen our long-term growth prospects, and extend our impact on patients. Overall, Neurocrine Biosciences third quarter performance exemplifies the strength of our strategy, the discipline of our execution, and the significant opportunity ahead to create long-term value. As we close out the year, we look forward to hosting our 2026 R&D Day in New York City on December 15.
The event will feature a VYKAT XR panel discussion with Dr. Jennifer Miller, Professor of Pediatric Endocrinology and Director of the Prader-Willi Syndrome Program at the University of Florida College of Medicine, as well as an update on our pipeline. I look forward to sharing our progress, engaging with the investment community, and discussing the opportunities ahead as we enter what promises to be a catalyst-rich 2027. With that, I'll turn the call over to Matt.
Thank you, Kyle, and good afternoon, everyone. The third quarter reflects Neurocrine's continued evolution into a diversified, highly profitable biopharmaceutical company. As Kyle mentioned, we delivered record net product sales exceeding $1.1 billion, up more than 40% year-over-year, alongside record operating profitability. Our three commercial products provide a growing foundation to invest in innovation and prepare for a data-rich 2027. Starting with INGREZZA, third quarter sales were $801 million, up 17% year-over-year, driven by continued volume growth with record new and total prescriptions. Underlying INGREZZA performance continues to exceed our own internal expectations, leading to another full-year INGREZZA guidance increase to $2.9 billion-$2.925 billion. Third quarter sales included a $20 million benefit from customer order timing, which we expect to reverse in the fourth quarter and is reflected in our full-year guidance.
Overall, 2026 is turning out to be a remarkable year for INGREZZA, with prescription growth expected to be in the high teens, underscoring the strength and durability of the INGREZZA franchise in the tardive dyskinesia market. Looking ahead to 2027, we expect continued double-digit INGREZZA volume growth to more than offset anticipated mid- to high single digit net pricing headwinds, supporting another year of revenue growth. As customary, we will provide formal 2027 sales guidance in February. CRENESSITY delivered $211 million in third quarter sales, supported by steady patient additions, strong persistency, and favorable reimbursement. Over 15% of the estimated diagnosed classic CAH population has now been prescribed CRENESSITY, highlighting the opportunity that we still have ahead. For VYKAT XR, we delivered $107 million in third quarter sales, reflecting sequential growth driven by new patient demand.
We remain focused on our efforts to support appropriate patient identification, physician and caregiver education, and patient support. We believe VYKAT XR offers a meaningful opportunity for long-term growth to help many patients with this devastating condition. Turning to the financials, record revenue drove non-GAAP earnings above $3 per share. This reflects significant operating leverage while continuing to invest in commercial growth and our R&D pipeline. We ended the quarter with approximately $800 million in cash, generating $400 million in operating cash flow and deploying approximately $100 million to repurchase shares and offset dilution from our share-based compensation. Our capital allocation priorities remain driving commercial growth, advancing high-value pipeline programs, and pursuing disciplined business development. Overall, with three growing commercial products, expanding profitability, and a broad pipeline, Neurocrine Biosciences is well-positioned for durable growth and important clinical catalysts in 2027.
With that, I'll turn the call over to Eric Benevich, our Chief Commercial Officer. Eric?
Thanks, Matt. Our record third quarter performance reflects strong performance across all three of our first-in-class medicines: INGREZZA, CRENESSITY, and VYKAT XR. While each is at a different stage of commercialization, all three continue to address significant unmet medical needs and contribute to Neurocrine's commercial diversification and revenue growth. Starting with INGREZZA, quarterly sales surpassed $800 million for the first time, driven by strong demand with record new and total prescriptions. Remarkably, nine years into launch, INGREZZA continues to deliver double-digit prescription growth. With full-year sales guidance raised once again, 2026 is shaping up to be another outstanding year for the brand. CRENESSITY also reached a new milestone, exceeding $200 million in quarterly sales for the first time. The rate of new patient starts have remained steady throughout the year, and we estimate more than 15% of U.S. patients with classic congenital adrenal hyperplasia have now been prescribed CRENESSITY.
Just seven quarters into the launch, we're making meaningful progress towards establishing CRENESSITY together with low-dose GCs as the standard of care treatment for classic CAH. Now, turning to VYKAT XR, quarterly sales exceeded $100 million for the first time. Since the acquisition, our commercial and medical teams have focused on HCP education, including appropriate PWS patient selection, dose titration, careful monitoring, and management of potential adverse events while setting expectations for both the timing and nature of treatment response. These efforts reflect our commitment to maximizing patient safety and treatment results. As newcomers to the PWS community, we're listening to all stakeholders and gaining insights from clinicians, PWS scientific thought leaders, and the Prader-Willi syndrome patient and family community. We're confident in VYKAT XR's benefit and its longer-term potential in our rare endocrine franchise.
2026 will no doubt end up being the strongest commercial year in Neurocrine's history, and we look forward to carrying this momentum into 2027. I want to thank our entire commercial and medical organizations, including our newest VYKAT XR colleagues, for their unwavering dedication to patients and outstanding execution. With that, it's my pleasure to turn the call over to our Chief Medical Officer, Dr. Eiry Roberts.
Thanks, Eric, and good afternoon, everyone. First, I want to thank Kyle and the board of directors for the opportunity to return as Chief Medical Officer. During my previous tenure, I had the privilege of helping advance CRENESSITY through clinical development and approval, as well as generating positive phase II data and initiating the phase III programs for both osavampator and direclidine. I'm excited to build upon the team's recent progress as we advance the deepest and most diversified pipeline in Neurocrine's history. I'd like to begin today with VYKAT XR, the first and only FDA-approved treatment for hyperphagia in patients age four and older with Prader-Willi syndrome. Since Neurocrine's acquisition of this medicine in May, our clinical and medical teams have worked closely with expert clinicians, regulators, and the PWS community to support the safe and appropriate use of this important new medicine.
As real-world experience grows, we remain committed to ongoing safety monitoring, collaboration with the FDA, and timely communication of important new information. To further advance our understanding, we plan to initiate a study in 2027 evaluating VYKAT XR in people with PWS and complex health issues. Continued engagement with advocacy organizations, including FPWR and PWSA USA, remains central to our efforts also. Turning to the pipeline, we recently initiated a phase II study of NBI-'567, our M1-preferring selective muscarinic agonist, as an adjunctive treatment for cognition in Alzheimer's disease. In obesity, we initiated a phase I study of NBIP-'1968, our investigational triple G agonist. This program has the potential to complement our CRF2 agonist, NBIP-'2118, also in phase I, as we explore differentiated combinations to treat obesity.
Finally, NBIB-'223, our Friedreich's Ataxia gene therapy program in collaboration with Voyager Therapeutics, is expected to enter phase I in the coming months, with initial patient-level data anticipated in 2027. As Kyle mentioned, we will close out the year with our 2026 R&D Day in New York City on December 15. I look forward to sharing our progress and re-engaging with the investment community as we prepare for a data-rich year in 2027. With that, I'll turn it back to Todd. Todd?
Thanks, Eiry, and welcome back to the role. We are happy to have you here. Apologies for the slight delay in the distribution of today's earnings release. We appreciate your patience and look forward to your questions. Nikki, let us take the first question.
Thank you. At this time, if you would like to ask a question, please press star one on your telephone keypad. You may remove your question by pressing star two. In the interest of time, we ask you please limit yourself to one question. We will take our first question from Phil Nadeau with TD Cowen. Please go ahead. Your line is open.
Good afternoon and t hanks for taking our question, and congrats on a really strong quarter. Question on INGREZZA trends and guidance. If we back out the $20 million that you mentioned of orders this quarter, even taking that out, it does look like the top end of guidance assumes a sequentially down Q4. I guess we are curious why that would be. Was there something else that was lumpy in Q3 beyond just the $20 million, or are there other headwinds you expect in the fourth quarter for INGREZZA? Thank you.
It was a really strong third quarter across the board, and would anticipate in the fourth quarter to have similar underlying TRX growth somewhere in the mid-teens. The only other item is seasonally, there is always a gross-to-net dynamic in the fourth quarter, but overall, you take a step back.
You see we started the year at $2.7 billion in guidance, going all the way up to $2.9 billion in guidance. Feel quite good with how we're positioned, and we're in a place to have strong momentum headed into 2027.
That's helpful. Thank you.
Thank you. We will move next with Paul Matteis with Stifel. Please go ahead. Your line is open.
Hey. Great. Thank you so much, and congrats on the quarter. I wanted to ask a question about VYKAT XR. Obviously, it's been discussed in the media and the press related to its safety profile. I was curious from your perspective, are you comfortable that going forward in the next set of quarters that VYKAT XR will continue to be a resilient grower? Maybe just as a sub-question to that, is there any thought that at some point there could be engagement with regulators around some of the post-marketing safety reports? Maybe you could just give a little color there. Thank you.
Yeah. Hey, Paul, it's Eric . We know that in orphan diseases, launches aren't always linear. I think we're about, what, 2.5 quarters now post-acquisition, so we're still getting our arms around the VYKAT XR business, and we're still in the thick of the integration. However, given the recent external events, we do anticipate a return to growth, but it might be a little bit more delayed. Ultimately, we still have very strong conviction in the benefit of VYKAT XR, and we're working through making sure that everyone understands both the benefits and how to safely use it. Anything to add?
Yeah. Thanks, Paul. I mean, patient safety is key at Neurocrine Biosciences, so we take every adverse event and every outcome very seriously, and we continuously monitor safety in the post-marketing environment. That said, we're very confident in the benefit-risk profile that we have for VYKAT XR, and we believe that the current label describes very effectively how to use the medicine safely and effectively in the relevant patient population. Obviously, we continue to collect ongoing information, and in particular note, I'd draw your attention to what we mentioned in that at the end of this year in our R&D Day, we will have a focus on understanding PWS, and particularly hyperphagia, more for the community by engaging with Dr. Jennifer Miller and several patients from the community. I think that will be helpful in that regard.
In addition, we are planning to initiate a study starting next year in patients with Prader-Willi syndrome who also have significant other comorbidities and other conditions that make them obviously at higher risk generally in terms of their disease to understand how to safely and effectively use VYKAT XR in that population.
Great. Thanks, Eiry. Good to talk to you.
Thank you. We will move next with Tazeen Ahmad with Bank of America. Please go ahead.
Hi. Good afternoon. Thanks for taking my question. Just wanted to get any color on 2027 INGREZZA contracting, particularly whether access and net price impact are tracking with what you would have expected. Any color would be great. Thanks.
Thanks, Tazeen. This is Kyle. It's hard to not talk about 2027 pricing without starting with access, because they are linked. For this year, as you know, we have about 70% of Medicare lives covered under the contracting that we executed on in 2025, and that gave us great momentum here throughout the course of this year, and we think that will continue to be the case as we close out Q4 into 2027. When we think about 2027, we do expect that underlying momentum to lead to, again, double-digit volume growth for 2027, and that reinforces really the durability of INGREZZA as a product in TD, as well as continued revenue growth. When it comes to contracting now for 2027, we're nearly at the end of our discussions with payers.
We do have pretty good visibility in terms of our formulary status for 2027, and what we see is a really strong year in terms of coverage and access of lives, at least as good as this year. So we're looking forward to a really strong access year for 2027. In terms of the net price, we'll get into the details of that as we move into the new year, but roughly speaking, we're looking at a mid to high single-digit price concession for 2027, but that will be more than offset by our double-digit revenue growth for next year. This will be playing out in our assessment of performance as we move through Q4 into the new year when we talk about guidance at our February meeting. But overall, really strong year ahead for 2027.
Thank you. We will move next with Brian Abrahams with RBC Capital Markets. Please go ahead.
Hi, team. This is Kevin on for Brian. Thank you for taking our questions. Maybe just back on VYKAT XR. Considering some of the on-the-ground dynamics that you're seeing this quarter, being the first full quarter with VYKAT XR, just maybe can you share your latest thoughts on how the potential opportunity, the peak opportunity in PWS may be, whether your thoughts now are a bit more refined on what that opportunity could look like and the timelines around that. Thank you.
Sure. Hi, this is Eric. Taking a step back, thinking about the Prader-Willi syndrome population, we estimate that there's roughly 10,000-12,000 patients in the U.S. The majority of them have hyperphagia. Not everyone, though. Obviously, patients that are very young typically don't experience hyperphagia until they get to be four or five or six years old. And certainly, there are some patients that would not be considered appropriate for treatment based on, as Eiry said, significant comorbidities. Ultimately, though, we feel that the majority of patients with hyperphagia secondary to PWS are candidates for treatment. And this is a medication that's still relatively early in its launch. It's only been out there a little over a year and a half. And there's a lot of providers in the community that we're still reaching and educating, and also within the patient and family community.
I don't know that we've really altered our thinking around the opportunity. We still have really strong conviction in the potential for this medication. As you know, it's the first and only approved treatment for hyperphagia in PWS. But we do recognize that we do have a lot of work ahead of us in terms of educating and continuing to generate data to understand how to best use this medication.
Thank you. We will move next with Brian Skorney with Baird. Please go ahead.
Hey, good afternoon, guys. Thanks for taking my question, and congrats on a great quarter. Maybe on VYKAT XR, you mentioned growth coming from new patient starts, but wanted to hear anything you could say about discontinuations. I know there was sort of this bolus effect in new patient starts at the launch, running into maybe a headwind in terms of discontinuations from that initial bolus once they reached therapy. Do you think we're through that at this point, and are you expecting more of a normal number of patients discontinuing per quarter because that roll-off is no longer coming from the initial bolus? I just want to get an idea of how to think about the balance between starts and discontinuations at this point. Thanks.
Yeah, I would start by saying we're still learning about the dynamics here. As I mentioned, this product's only been on the market for a little over a year and a half. Certainly, there was a bolus of starts in the first quarter or two when VYKAT XR was launched last year. Then, we did see sort of an increase in discontinuations from that bolus of early starting patients. Since then, we've seen pretty consistent and steady starts. It's hard to say whether Q3 was any different from a discontinuation standpoint, because numerically, it was similar to prior quarters. So, I would say stay tuned.
Thank you. We will move next with Anupam Rama with JP Morgan. Please go ahead.
Hey, guys. Thanks so much for taking the question, and congrats on the quarter. Look, it was a nice beat on INGREZZA, and even if you back out that $20 million one-timer, it was still going to beat consensus. Do you see any outsized growth in the various segments, psychiatry, neurology, long-term care, that you'd want to highlight. Thanks so much.
Yeah, thanks for the question. I think we see growth potential across all the prescriber segments. As we've said before, the majority of patients out there with tardive dyskinesia have yet to be. Now we're actually approaching a point where about half of the patients out there have been diagnosed, and the other half have yet to be diagnosed. There's still substantial opportunity to drive diagnosis, recognition, and treatment. In addition, only about 10% of the total TD prevalent population is currently on either of the two VMAT2 inhibitors. So, lots of headroom from a growth potential perspective. Obviously, we see the psychiatry segment as the main growth driver. Within psychiatry, in particular, advanced practice providers are really important in terms of recognizing and treating TD with INGREZZA. So, I think that reflects the deployment of our sales team.
The biggest team is focused on psychiatry. We've also seen really strong and consistent growth in long-term care. So, we're excited about the opportunity. As Kyle said earlier, we're going to carry the momentum into 2027, but we expect to see continued strong volume growth across all the segments, psychiatry, neurology, and long-term care.
Thank you. We will move next with Cory Kasimov with Evercore ISI. Please go ahead.
Hey, this is Josh on for Corey. Thanks for taking our question. On CRENESSITY, growth has been really steady here. Wondering if you can comment on where growth is coming from. Is it new prescribers? Is it returning prescribers? Any color you can give? Thanks.
Yeah. CRENESSITY has been remarkably consistent. Ever since the early days of the launch, we have seen a real steady pace of patient adds. We have also seen favorable reimbursement. Lastly, and critically important, really strong persistence. I think all those elements combined have led to what has been a really strong launch in the first. We are a year and three quarters now into the CRENESSITY launch, so it is still early in its commercial ramp. Ultimately, at the very beginning of the launch, most of the growth was driven by new prescribers. To this day, there are still the majority of prescribers have only one or two patients that are on treatment. However, we are seeing increased depth of prescribing.
As we go forward, those practices that have more than a handful of patients, we are continuing to drive adoption of the majority of their patients within those practices. We have done a really great job, I think, in the pediatric endocrinology segment, and that does represent the majority of patient starts. However, as of late, we have continued to see growth and adoption within the adult endo practices, and now we are at a point where roughly half the patients out there on CRENESSITY are adult patients. We are going to continue to do our work. We are going to drive education, and we have got a lot of remaining opportunity. As we said in the prepared remarks, over 15% of the population with classic CAH has now been offered treatment and are on medicine.
Great. Thanks.
Thank you. We will move next with Jay Olson with Oppenheimer. Please go ahead.
Oh, hey. Congrats on the quarter, and welcome back, Eiry. Looking forward to seeing you all in December. We had a question about NBI-'567. Can you just talk about, now that you have the phase II study initiated, what would be a clinically meaningful result on the 12-week neuropsychological test battery? Thank you.
Jay, it's great to be back. On NBI-'567, that's our M1-preferring muscarinic agonist, and as you mentioned, that study will be a study of phase II just started in around 135 adults, age 50- 85, with mild to moderate Alzheimer's disease, who are receiving stable treatment with acetylcholinesterase inhibitors, but still have evidence of cognitive decline. We're actually looking at a range of different endpoints in the context of the study and looking at a change from baseline for that adjunctive treatment at week 12. The primary endpoint we're looking at is a neuropsychological test battery composite score, and the goal will be to compare the two treatment groups within the study to placebo and look for any clinically significant trend, or statistical significance in difference, on that endpoint to placebo.
In addition, however, we're going to be looking at the totality of the data that we generate in that study, including ADAS-Cog measurements and clinical dementia ratings, coupled with, obviously, tolerability, given that in this patient population for acetylcholinesterase use, tolerability is one of the most significant issues that impacts use of that medication currently. We haven't talked specifically about bars or barriers in terms of the endpoints, but obviously, we'll be looking holistically at the data that we generate.
Great. Thank you.
Thank you. We will move next with Akash Tewari with Jefferies. Please go ahead.
Hi, this is Phoebe on for Akash. We had a question on the announcement of a 5x higher dose of emraclidine in the phase II schizophrenia study. I guess, number one, what is your take on this, given there is kind of an unclear dose response in emraclidine and in NBI-'568 data? Also, can you provide kind of thoughts on where you think the comparable M4 inhibition levels of emraclidine at this dose compared to your 20 mg dose? Finally, your overall confidence going into the schizophrenia readout next year.
Hi, Phoebe. This is Samir. Thanks so much for the question. We have our M4 selective orthosteric agonist, direclidine, which we anticipate top-line data from the first short-term study next year. Timelines are on track there. Really excited about that data. In relation to what's out there with the competitive landscape, we believe that this could offer potential benefit for patients without some of the side effects that those are experiencing with the existing commercial product, Cobenfy. With regards to your questions on other competitors like AbbVie with emraclidine, certainly watching the landscape there and wish them the best, but for right now, we're focused on our program. Thank you.
Thank you. We will move next with Mohit Bansal with Wells Fargo Securities. Please go ahead.
Hi, this is Susan on for Mohit. Thanks for taking our question. On INGREZZA this quarter, you guys had commented that trends were similar, but you definitely did better than expectations. Can you just talk a little bit about maybe where some of the upside came from? Is it pricing, inventory, net adds?
Yeah, I mean, the way I would characterize it is we exited the quarter with more patients on treatment than we started, so it is net adds, not pricing.
Great. Thank you. I am sorry, since I was really short, if I may. What is the rationale for this additional study in Prader-Willi syndrome with comorbidities? Is it more for medical education and just answering some of the questions there, or is there an opportunity for label expansion?
We think the current label really accurately reflects the benefit and risk of VYKAT XR in the population that was studied. We do believe that there is room still for education, particularly when it comes to selection of the appropriate patients to treat with VYKAT XR with hyperphagia in Prader-Willi syndrome. Also, guidance on safe and effective dose titration, and also understanding how to monitor more closely for adverse events that may occur during the course of treatment and manage those effectively from the outset. It's also really important to note that not very much is known about hyperphagia in Prader-Willi syndrome, and so there's a lot of education that we need to do around understanding hyperphagia, understanding the impact that hyperphagia has on both the patient and their family.
It's very much a behavioral disorder, and as such, I think we have to set expectations around what sort of behavioral changes can we expect to be seeing in patients when this medicine is improving the hyperphagia symptoms for them. For all of those reasons, I think we're interested in continuing to expand the knowledge base of patients treated with VYKAT XR, including those who have other complex conditions such as obesity, respiratory disorders, et cetera.
Thank you. We will move next with David Amsellem with Piper Sandler. Please go ahead.
Thanks. How would you articulate your top business development/M&A priorities as we move through 2027? I think, Kyle, earlier this year, you talked about being over-indexed in psychiatry. Post-Soleno, do you still think the case, and what therapeutic areas within your core focus areas are you prioritizing? Thanks.
Thanks, David. Appreciate the question. Maybe I'll have Samir share his thoughts here.
Hi, this is Samir. What I'd say on the BD focus is that we really want to remain focused and disciplined on future opportunities. What we're looking for are opportunities with differentiated innovative science and strong IP within our areas of expertise. So, what we term that right now are neurology, psychiatry, endocrinology, and soon to be immunology here. Transactions that we're looking at must create value for our shareholders. So, we remain engaged and prepared to act if something opportunistic comes up. We've got a lot of financial flexibility. We don't feel like we have to do a deal right now.
Thank you. We will move next with Marc Goodman with Leerink Partners. Please go ahead.
Hi, everyone. This is Alyssa on for Marc. Thank you for taking our questions. On CRENESSITY, could you talk about the discontinuation rates in the third quarter relative to prior quarters, and how are you thinking about persistency trends looking forward? On VYKAT XR, could you comment on the current dose distribution in which maintenance doses are most commonly used? Thank you.
I will comment on the persistency trend. What I had mentioned earlier was that CRENESSITY has been a remarkably consistent medication in terms of persistency, and certainly above average when you look at other rare disease drugs. In fact, that is one of the important drivers of growth. We have had consistent patient adds, we have had favorable reimbursement, and we have had really strong persistency, and it was no different in Q3 versus prior quarters. Obviously, we hope to see that continue into the future, though we are still early in the commercial ramp for CRENESSITY. But I have no reason to believe that it is going to be any different going forward. On VYKAT XR, I would just guide you to around 250 mg is what we are seeing on average per patient at this point.
I think that that is a good proxy that gets you to a WAC of around $550,000 per year.
Very helpful. Thank you.
Thank you. We will move next with Ash Verma with UBS. Please go ahead.
Hi. This is [Lian] on for Ash. Thank you for taking our question. For VYKAT XR, what is the best way to identify the frequency of side effects reported for the drug in the real world? In the FAERS database, we see that the total AEs and serious AEs are both up for 2026 compared to 2025. Can you share if this is because of the drug use is increasing, or is the absolute frequency of AEs higher in 2026 versus how much it was in 2025? Also, if we can also get your latest thoughts on VYKAT XR IP. How confident are you on the IP runway here? It seems like the 895 patent post-grant review for a generic challenging this patent was instituted recently, and it is now likely to go into a PTAB trial. What do you expect as the outcome here? Thank you.
Thanks for the questions. Lots of questions in there, so I will try and I think I may share the stage with my colleagues on the IP front. Let me start with some of the questions you asked around adverse events. Going back to the safety is our primary focus with respect to patient safety, our medicines. In the post-marketing setting, I think in terms of VYKAT XR, we have the benefit of having a single specialized pharmacy that is engaged in supplying this medicine and provides a lot of support mechanism around that, including the support provided by our own commercial and medical team.
In fact, we have very close contact with patients and their prescribers as they are starting this medicine, so we are able to provide the education that helps and is necessary to ensure appropriate patient selection, that the dose titration is done in a safe and effective way, and the label itself provides the guidance that is needed around side effects such as the hyperglycemia and fluid retention, which are known to be associated with diazoxide use. I think we have a well-controlled environment to enable patient support and the support of their families and clinicians as well as we go through that process.
On the IP front, this is Kyle. I think it is probably too early to talk about any of the challenges on existing patents, but in terms of our overall view on exclusivity, we have commented that we feel good about that going out to the mid-2040s on patents to be published and issued, and I think we are confident with what we have there.
I see. Thank you so much.
Thank you. We will move next with Myles Minter with William Blair. Please go ahead.
Thanks for taking the question. Congrats on the quarter. Just curious about the terminology about a collaboration with the FDA when you are talking about VYKAT XR. Was the study in PWS and complex health issues a result of those collaborative talks and they wanted you to do it, or is this something that you are proposing that will definitely help use of VYKAT XR in this high unmet need patient population? Thanks very much.
This was our proposal in collaboration with the several key opinion leaders in the field, and I think it reflects the fact that, given that this is the first and only approved medicine to treat hyperphagia in Prader-Willi syndrome, there was a desire to understand the breadth of the population that could be served effectively by this medicine beyond those individuals who are included in the clinical trial program that led to registration.
So, we are finalizing the design of that study in collaboration with these KOLs, including Dr. Jennifer Miller, and we are also very pleased that Dr. Miller has already taken the step in terms of publishing an article that gives guidance around the use of VYKAT XR in a broader patient population in the real-world setting already, and that is already something that we are using in support of the community as we educate out there in the field.
Awesome. Thanks very much, Eiry. Congrats.
Thank you. We will move next with Sean Laaman with Morgan Stanley. Please go ahead. Sean, your line is open. Sean Laaman, your line is open. Please check.
Let's go to the next question.
We will move next with Sumant Kulkarni with Canaccord Genuity. Please go ahead.
Good afternoon. Thanks for taking our question. Samir alluded to some aspects of this, but given the somewhat muted launch for Cobenfy in schizophrenia, does this change your market outlook for direclidine in schizophrenia at all, and what would you most like to see in phase III that could make you excited about the product's competitive profile in the schizophrenia market?
Thanks, Sumant. This is Samir. Let me start with the, excuse me, the bar for the phase III study here. Really what we're looking for is a positive study. What we've seen in psychiatry is that medicines that make it across the finish line tend to have strong and high uptake, particularly if they have a novel mechanism of action, which we believe our M4 selective orthosteric agonist does. Really, where we're going to win here is on safety and tolerability. We've got a drug that's administered once daily, no titration. If you look at the phase II data, we saw limited GI side effects relative to placebo. We think that this is going to be a best-in-class, very convenient, easy-to-use medicine for patients with schizophrenia that will offer a novel mechanism in a patient population that hasn't had many new treatments for several years here.
Very excited about the first study data to come next year. Eiry, anything you want to add there?
No, the only thing I'll add is that we continue to be doing very well in terms of the progress of the phase III program. With reference to what Samir said about the importance of safety and tolerability here, I will comment that in the context of that program, we've had several DMC meetings to look at safety and tolerability of the program, and we've not had to make any changes to the program as a result of those. Also, if you look at discontinuation, which we know is an issue for Cobenfy in the context of some of the tolerability issues that are seen there, we have a low discontinuation rate of 3% or less in our current program. We are very confident about the profile that we're seeing there.
Thank you. We will move next with Yigal Nochomovitz with Citigroup. Please go ahead.
Yeah, hi. Thank you for taking the questions. I just wanted to return to a topic that was first introduced back at your R&D Day in San Diego last year, and that's your early obesity program. I'm just wondering if you could comment on the two programs, the CRF2 and the triple G. How are you thinking about those in terms of development? Is it sort of a bake-off between the two? Are they going to serve different patient populations, and what would you want to see in the early phase I data to determine how to take one or both of those programs forward? Thank you.
No, I appreciate the question. This is Kyle. So our leading CRF2 agonist is NBIP-'2118. This is a subcutaneous, at least a once-weekly injectable peptide that we're developing for obesity. It has a lot of redeeming qualities that we see from preclinical studies. Obviously, we need to replicate that in the human condition, which is really our focus in the near term, is getting this study in healthy volunteers that are obese and see if we can replicate a similar profile from the preclinical studies. But what we're trying to look at here is comparable weight loss to the incretins, but with quality weight loss, with the loss of weight coming from fat, not muscle, so muscle mass preserving. We've seen also preclinically additional benefits in the cardiac and renal areas as well that could offer some differentiating properties.
But certainly not going through the GLP pathway, we're also looking for a more favorable safety and tolerability profile. So there's a lot to like about the mechanism, and obviously, we know a lot about CRF1 and CRF2 as a company and want to be able to leverage that moving forward. Where our triple G program, which is NBIP-'1968, comes into play, is a mix-and-match type of strategy. We know that mechanisms are used in combination in the real world, and that's probably where this space will go over time. So having our own triple Gs is something that's important for our program. We have that as a standalone medicine that can be paired with NBIP-'2118, and we've also combined the two in a bivalent molecule that could be a single medicine that could be taken forward as well.
We are excited with what we have, but right now, it is all about getting into the obese population and seeing if we can replicate that earlier profile. We are really excited what we have, and being at this particular stage of the program is exciting.
Thanks, Kyle.
Thank you. We will move next with Sean Laaman with Morgan Stanley. Please go ahead. Sean, your line is open. Please check your mute function.
All right, Sean, this is Todd. You can give me a call later. Let us go to the next question, please.
We will move next with Danielle Brill with Truist. Please go ahead.
Hi, this is Tyler in for Danielle. Thanks so much for the question. With the sales force expansion now a couple of quarters into deployment, how much of the recent growth reflects this investment, and is there still meaningful productivity upside ahead?
I assume that you are referring to INGREZZA?
Yeah.
I would say that, obviously, we have seen strong growth in Q2 and Q3 subsequent to the deployment of the expanded sales team. However, historically, our experience has been that it takes a few quarters to have the full impact or see the full impact of the expansion. So, I would expect that Q4 would be more impact from the sales force and really carrying that into 2027. As we said earlier in the call, we do expect to see double-digit growth next year, in part due to the sales force expansion.
Thank you.
Thank you. We will move next with Rudy Li with Wolfe Research. Please go ahead.
Thanks for taking my question. For PWS, can you provide additional color on the growth trajectory for VYKAT XR into Q4 2027, I mean, patient starts and discontinuation rates? Should we expect meaningful sequential growth from Q4 into 2027, or is it most likely into the second half of the year? Thanks.
Yeah, the way that I would characterize it is, first of all, that we do see that there is a lot of potential with this medicine, and there are a lot of untreated patients yet with hyperphagia and PWS. Given the recent external events, we do think that it is going to delay somewhat the growth trajectory that we are expecting. Ultimately, I think we are doing the right things from an educational standpoint and from a promotional standpoint to continue to drive growth with this medicine. Just feeling good about the potential of VYKAT XR in hyperphagia. We had a growth quarter this quarter, and like I said earlier, every quarter we want to see more patients on than the prior quarter.
Thanks. Congrats on the quarter.
Thank you. We will move next with Delma Caiati with Guggenheim. Please go ahead.
Hi. Thank you for taking my question, and congrats on the quarter. Maybe one on NBI-'569 in Alzheimer's psychosis. What do you need to see in phase I on both efficacy and safety to move to phase II? Since elderly patients tend to be more sensitive to muscarinic side effects, how are you thinking about the dosing and titration in this population? Thank you.
It's a little bit early days, really, to understand what we're going to see in terms of dosing, in particular whether we even need to do dose titration. That hasn't been the case for our other muscarinic agonists to date. Just answering that last piece first. We're still in phase I. A lot of phase I work, as you know, is focused on understanding safety and tolerability and helping us choose the appropriate dose for a phase II study. Right now, we're working through that. I would say that NBI-'569 has been well tolerated in the patient population to date, and we're accomplishing the dosing regimen that we need to do in terms of going into the next stage of development. Obviously, we won't know for certain until we complete that work.
Thank you. We will move next with Laura Chico with Wedbush Securities. Please go ahead.
Good afternoon. Thanks very much for taking the question. One back on the obesity franchise with NBIP-'1968 and NBIP-'2118. I apologize if I missed this, but what is the scientific rationale for pairing a CRF2 agonist with the triple G agonist? Then, I guess, kind of related to that, what is the R&D spend that you're willing to commit to for obesity, just given the other events you've got going on in psychiatry? Just curious if you can kind of elaborate there. Thank you very much.
Well, I think on CRF2 and NBIP-'2118 and NBIP-'1968, I think we appreciate at the stage of development that we are, and we still have a lot of unanswered questions in terms of how CRF2 can work as a standalone treatment or potentially better in a combination with an incretin or triple G type of approach at lower doses. These are things that we're going to learn early, and I think that's a good segue into your second question. When it comes to obesity studies and spend, the way that we look at it is that it's a nice balance of the types of programs that we invest in particular on the neurology and psychiatry side of the business. There, we have to invest all the way through phase III before we know our winners and how they look completely.
With obesity programs, what we get in early development are things like biomarkers, objective endpoints, and the ability to see the opportunity for efficacy as early as in phase I if you have patients that are healthy volunteers. So, we think there's a good opportunity here for us to identify which programs we can take into later stage phase II and phase III development, and knowing what those profiles look in comparison or in contrast to our psychiatry program. So it's a nice way to strategically diversify Neurocrine Biosciences. I use that word strategically here deliberately because we're moving into a broader foundation that we've already set with CRENESSITY and endocrinology, and we're leading into the biology that we already know in CRF.
Thanks very much.
Thank you. We will move next with Ami Fadia with Needham & Company. Please go ahead.
Hi, this is Poorna on for Ami. Thank you for taking our question, and congrats on the quarter. For CRENESSITY, what is the headroom for growth in the male adult population, and how are you targeting these patients? Also, what additional proportion of the market can you capture with the ages under four study? Thank you.
I am sorry, can you clarify? Which population were you asking about?
The ages under four.
The male. Yeah, the male.
The male adults, yes. Yeah.
Yeah. So, obviously there's a lot of headroom in the adult population, and I said earlier in response to a different question that we're now at a point where roughly half the patients on treatment are adults. Skews slightly towards females. So, there's still a lot of opportunity really across all the different patient populations. Roughly north of 15% now of the overall classic CAH populations on treatment, and we're only about seven quarters into the launch. So, there's a long way to go and a lot of headroom here. I'll let Eiry comment on the opportunity below four.
Yeah, we're just initiating our study in the under four year-old patient population, and I think the belief is that in order to gain control of the hypothalamic-pituitary-adrenal axis as rapidly as possible, the ability to use CRENESSITY early as possible would be beneficial. Because we know that even in those very young patients under the age of four, there's often a need for very high steroid dosing, and the impact that that has on growth, bone development, and other developmental features really from the outset can be very detrimental for patients. That's why we are very keen to get that study up and running. We're working on that now with the goal of being able to expand the label to an earlier age group.
Thank you.
Thank you. We will move next with Graig Suvannavejh with Mizuho. Please go ahead.
Great. Thank you for taking my question. Congrats on the quarter and the overall progress. A question on CRENESSITY, please, and its growth prospects. As you look out over the next several years, could you just remind us how you were thinking about the potential impact of competition, and particularly the Vertex candidate for CAH. While I realize we do not have phase III data yet for that asset, what are your thoughts around differentiation between the two assets, and what is your market research telling you about BID dosing that you have versus QD dosing. Thank you.
Yeah, this is Kyle. I appreciate the question. It is one of these rare instances where I like talking about competition because I get to bring up all the good data that we have. CRENESSITY has really set a very high bar out there, not only for competition, but our own next-generation programs in the pipeline. That is actually concerning to me because we are investing in those in our pipeline right now. But, if you look at efficacy, safety, and tolerability, we have patients out to five years now in our long-term data. We have from our two-year data, which is turning into three-year data that we will be able to publish on, 70% of patients are on a physiological dose of their GCs.
70% of patients have normal levels of androgens. We have seen sustained and control levels of ACTH and cardiometabolic improvements, as well as improvements on pediatric growth trajectory. So there is a lot to get excited about with CRENESSITY. Eiry and her team did a great job pulling those themes through a very simple and broad label that allows us to treat pediatrics, the adult patient population, and we have multiple formulations. So, I really feel good and happy about the position that we are in, regardless if it is competition or our own next-generation medicines in the portfolio. I think we really have an excellent opportunity here to change the standard of care. With the demand that we see, we have plenty of runway here to do so over the next couple years. So that is where the focus is for now.
Thank you. We will move next with Evan Seigerman with BMO Capital Markets. Please go ahead.
Hi, I am Malcolm on for Evan. Thanks for taking our question. Wanted to touch again on the muscarinics that you have in your pipeline. I saw that you had discontinued NBI-'986, the M4 antagonist for movement disorders, and I was just wondering if you could give a little bit of color. Is that due to a safety or tolerability issue, or just more of a broad strategic decision for the pipeline? Appreciate it. Thanks.
Thanks for the question. NBI-'986 was an M4 antagonist, which was focused on the potential use in movement disorders, including dystonia and potentially Parkinsonian tremor. We completed the phase I program on that medicine, and we were able to look at pharmacodynamic markers in addition to the PK and tolerability. Looking at all of those data in totality, we did not really meet the bar that we had set ourselves to be willing to go forward into a phase II study in Parkinsonian tremor. For that reason, as we were doing our portfolio prioritization, we paused and discontinued the development of that molecule at this time. There was no particular safety issue that per se stopped the program. It was basically the review of all of the data in aggregate.
Appreciate it. Thanks, guys.
Thank you. Our last question comes from David Hoang with Deutsche Bank. Please go ahead.
Hey, this is Sam on for David. Congrats on the quarter, and thanks for taking our question here. I will try to be brief. Just on CRENESSITY as use broadens, how much of the real-world challenge here is now kind of around tapering glucocorticoids appropriately, and how should we think of that dynamic as it relates to prescribing and, I guess, potentially capping penetration down the road? Appreciate it, and congrats again. Thanks.
Yeah, I don't see it as an impediment to prescribing. Actually, I think it's the promise of treatment. Certainly, the label isn't specific in terms of that process, and it's very much individualized on a patient-by-patient basis. A few months ago, we published essentially an expert opinion piece on how to down-titrate the GCs for these patients, and I certainly think that that was well-received in the community in terms of helping to provide a little bit more guidance. Ultimately, I don't see that as a deterrent at all. I think it's the promise. Frankly, we are seeing great results as reflected in the two-year data that was recently released. Anything to add, Eiry?
I think it is really encouraging to see that a significant proportion, majority of patients can reach physiologic dosing, and that's done in a safe and effective way without the risk of adrenal insufficiency, which is obviously what these patients are concerned about. We have not seen any increase or issue around adrenal insufficiency, which has been very encouraging. To Eric's point, I do think this is the promise of the treatment, rather than an impediment.
Great. Thanks so much.
Thank you. I will now turn the call back to Kyle Gano for closing comments.
Thanks, everyone, for joining our call today and for your thoughtful questions. As you heard, we continue to demonstrate strength across our commercial business and R&D pipeline. We are delivering strong commercial performance while advancing an increasingly broad and innovative pipeline of potential new medicines. In fact, we remain on track to deliver six phase I's, along with five new phase II starts this year. Never in Neurocrine's 35-year history have we achieved this level of R&D productivity in a single year. With that, thank you again for your continued interest, and I look forward to connecting with many of you at the remaining investor conferences this year, and certainly at our R&D Day next month. Thanks again.
Thank you. This brings us to the end of today's meeting. We appreciate your time and participation. You may now disconnect.