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

Good day, everyone, and welcome to today's Neurocrine Biosciences conference call. [Operator Instructions] Please note today's call will be recorded, and I will be standing by if you should need any assistance. It is now my pleasure to turn the conference over to Todd Tushla. Please go ahead.

Thank you. Good morning, and welcome to today's conference call to discuss the top line results for crinecerfont in the Phase III CAHtalyst pediatric and the Phase III CAHtalyst adult studies. First, a few housekeeping items to address. Our agenda will begin with opening remarks from Kevin Gorman, our Chief Executive Officer; and from Eiry Roberts, our Chief Medical Officer. We will then turn the call over to our guest speaker, Dr. Richard Auchus, who will provide additional information and expert perspective on these Phase III trial results. During Dr. Auchus' comments, you can refer to the supplemental materials, which were posted on the Neurocrine Investor Relations website earlier today. For those unfamiliar with Dr. Auchus, he is a worldwide thought leader in congenital adrenal hyperplasia. Dr. Auchus is currently a Professor of Internal Medicine in the Division of Metabolism, Endocrinology and Diabetes at the University of Michigan and serves as Chief of the Endocrinology and Metabolism section at the Ann Arbor VA Medical Center. Thank you for joining us, Dr. Auchus. Following Dr. Auchus' comments, we will move to Q&A where additional members of the Neurocrine management team will be available, including Jean Chan, Vice President of Clinical Development, Endocrinology and Clinical team lead for Crinecerfont; Bob Farber, Vice President of Clinical Development and Crinecerfont Program Lead; and Eric Benevich, our Chief Commercial Officer. Finally, 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. With that, I am happy to turn the call over to Kevin Gorman.

Thank you very much, Todd. Good morning, everyone. I really appreciate Dr. Auchus joining us this morning. We're quite privileged to be able to have him here and for him to give his views and answer any questions that you might have. I don't think I could overstate just what a terrific day it is for children and their parents who suffer from CAH. This data, once again, in the pediatric population was just as outstanding as the data that we reported last month for the adult population. And it is also -- I think I can't say enough for the work that Jean and Bob and their teams have done over the past several years on this program. But I'm not going to take up any more time here because we have a lot to get to. We really want to get to Eiry and to Dr. Auchus and then to your questions. So Eiry, please.

Thank you, Kevin, and a very good morning to everyone. It's really an extremely exciting time here at Neurocrine given the breadth and depth of our pipeline. But today, our focus is on crinecerfont and the very impressive top line data from the CAHtalyst Phase III pediatric and adult studies. I'm incredibly proud of the results generated from these studies given the high unmet need that exists for children, adolescents and adults living with congenital adrenal hyperplasia. And the many challenges and collective efforts it took to design and advance the CAHtalyst program, the largest global interventional studies ever conducted in this patient population. Firstly, I want to take a moment to thank all the patients, families, clinicians and team members who participated in and continue to participate in the CAHtalyst program for their tremendous commitment and collaboration. In the CAHtalyst study, treatment with crinecerfont led to a highly statistically significant and clinically meaningful reduction in androgen levels when compared to placebo for CAH patients, with the magnitude of effect that was consistent across children, adolescents and adult subjects. Patients treated with crinecerfont also achieved a highly statistically significant and clinically relevant reduction in their glucocorticoid dose, while maintaining androgen control when compared to placebo-treated patients. In fact, a substantial proportion of both adult and pediatric patients treated with crinecerfont, we're able to achieve a physiologic glucocorticoid dose while still maintaining control of androgen levels. From a safety perspective, treatment with crinecerfont was generally very well tolerated with few treatment discontinuations. The quality of overall trial conduct was also outstanding, leading to a very high completion rate for patients of over 95% in the adult study and over 95% in the pediatric study during the 6-month placebo-controlled period. Crinecerfont's mechanism of action as a selective CRF1 receptor antagonist brings the hope of a novel and effective way of controlling androgen levels in patients living with congenital adrenal hyperplasia. This hope was substantially confirmed by the results of both CAHtalyst studies, demonstrating that the androgen control achieved by treatment with crinecerfont, allowed patients to reduce their glucocorticoid dosage by a clinically meaningful amount without negatively impacting control of androgens. The results of the CAHtalyst program show that crinecerfont, if approved, could fundamentally change the way in which clinicians manage the androgen excess experienced by patients with CAH potentially resulting in important improvements in clinical outcomes for children, adolescents and adults living with CAH. The concurrent reduction in glucocorticoids to more physiologic doses could also result in meaningful improvement in the significant metabolic bone and other comorbidities experienced by individuals with CAH due to their lifelong exposure to the supraphysiologic steroid dosage currently required to control the disease. I'm delighted to now hand the call over to Dr. Auchus, a renowned clinician in the field of CAH, who has dedicated much of his research career to understanding CAH and discovering ways to improve the care and outcome for patients living with CAH. We have had the privilege of working closely with Dr. Auchus for many years on crinecerfont and Neurocrine's previous CAH program, and his leadership has been instrumental to the success of the CAHtalyst program. Dr. Auchus will provide more insight into the baseline characteristics of the patient population included in these trials and context around the potential importance of these results provided today for patients living with CAH and the clinicians who care for them. Rich?

Thank you, Eiry. It's great to be here. Thank you all for attending. My hat's off to Neurocrine for sponsoring this program, to my colleagues in pediatric and adult endocrinology throughout the world who have worked tirelessly over the last several years to do this and to the patients and their families who participated. I want to call your attention to the supplemental materials just to Page 3 to begin with, to just remind you what the problem is that we're dealing with here. In simple adrenal insufficiency, the adrenals don't make anything. And all you have to do is replace the cortisol and aldosterone deficiency. And we know pretty well how to do that. Most endocrinologists can do that pretty well. The problem with congenital adrenal hyperplasia is that there's a defect in one of the enzymes to make cortisol. So all that steroid flux make a lot of cortisol, is diverted to androgens. So not only do we have to replace the cortisol deficiency, but we have to shut off the spigot. And in order to do that, we have to reduce ACTH production from the pituitary. The way we've been doing that for 60 years now is by giving more than a physiologic dose of glucocorticoids to provide negative feedback on pituitary. And we know what that does. It takes about 0.4 milligrams of dexamethasone to suppress the pituitary, it's about 32 milligrams of hydrocortisone or 8 milligrams of prednisone. Now I don't know anybody that wants to be on 8 milligrams prednisone for the rest of their life. And I know a lot of drugs that have been developed to take patients with rheumatoid arthritis and other diseases off that 8 milligrams of prednisone by putting them on a safer drug. So what we have is a tight rope that for a Sophie's choice, if you will, that we can't currently with our armamentarium that we have, both replace the cortisol deficiency adequately and physiologically and lower the androgens. So we have to make a choice. We either give people too much glucocorticoids, and we know what that does in the long-term, cardiovascular disease, metabolic disease, bone disease, hypertension, psychological effects or we give them a physiologic dosing, let their androgens rise, which causes infertility, tumor development, short stature and other problems. So the mechanism of action of crinecerfont is directly on this pathophysiology to reduce ACTH production without giving people excess glucocorticoids. So the trial designs are on Slides 4 and 5. And so then on Slide 6 is the baseline characteristics. Now the Endocrine Society clinical practice guidelines for pediatrics recommends using hydrocortisone no more than 16 milligrams per meter square per day. And that is distributed throughout the day, usually in 3 doses or sometimes more in order to keep the androstenedione at the normal level. And that's the biomarker that we use to tell that the adrenal androgens are well controlled. We also use 17-hydroxyprogesterone and other things. But as you can see, this patient population was already at maximum dose and they're still on control. And we have a lot of patients with this problem. I think it was a majority of those patients who actually had the time and ability to participate in the study. So for every 1 patient that you see in this trial, there's probably 5 to 10 more who could have been in the trial, could have benefited from this, but just didn't have the time and the ability to participate. And then if you look at the adult patients, they're on a pretty comparable dose of glucocorticoids and their androgens are a little higher. So we tend to allow the adults to be in a little poor control so that we don't give them even more glucocorticoid. So I think that's a pretty typical scenario that you see that the adults tend to be in a little poor control to avoid the long-term glucocorticoids because in the adults, it's the long-term goal. In the children, we really try to keep things normal. And we will use more glucocorticoids, but we try to keep it under 17 milligrams per meter square per day. So these people are not in very good control. Slide 7 shows that the primary endpoint was met with no question, the p-values are all very, very small. I have not been involved in many studies where the p-values were this small. And on Slide 6 -- 8, the way the trial was designed, we added crinecerfont and then in the adult study, we had a protocolized glucocorticoid reduction down to a goal of a physiologic dose, like we would in someone with garden-variety adrenal insufficiency. So the primary endpoint in the adult study reaching less than 11 milligrams per meter square per day and androgen control, that's the holy grail. That's pretty much normal. We are not able to do that now. You can see in the placebo group, there is a small number who probably were overtreated. Okay. So maybe there's about 15% to 20% of people who we can control with the physiologic dose of glucocorticoid, at least for 6 months, we don't know about longer than that. But 63% of the people who had crinecerfont added were able to maintain their androstenedione controlled at 6 months after starting crinecerfont. So that's quite impressive. That's something we cannot do currently with anything in our toolkit. Now in the pediatric study, again, these children are already doing the best they can. And that's reflected by the fact that nobody in the placebo group could reduce their glucocorticoid. Okay. So when Mercury Morris talks about the '72 Dolphins and he talks about the 17 and 0 season. He says it's not about the 17, it's about the 0. And I think that this is really about the 0 in the placebo group that these people were already maxed out on everything they can and still not controlled. That's why they're in the trial. And the 30% that you see is the 30% who not only were in control, but who also were able to reduce their glucocorticoids to physiologic. We don't report the data how many people got close to that or achieved one of those 2 endpoints. So this is something, again, that with our current armamentarium, we cannot do. So the other thing that's truly impressive is the fact that 95% of people in both trials stayed through it. Very few dropouts, very well tolerated. People are motivated and looking for something better. So I'm just delighted to be a part of this study, and we're all -- all of our investigators throughout the world are delighted to see the results.

Thanks, Rich. We really appreciate that, and thank you for really bringing some very important additional context there. Just one word on the -- kind of next step for us with this program right now, and then we'll open it up to your questions. So we obviously have the open-label treatment period for the CAHtalyst pediatrics and adult studies ongoing. We're working very hard, that we -- what we shared with you today is probably about less than 10% of the data that will be generated ultimately from these trials and we are looking forward to really having a much deeper and greater understanding of the overall value that crinecerfont can bring for patients as we delve into the -- deeper into the data over the next weeks and months. As we do that, we'll obviously be moving towards submission of regulatory dossiers in both the U.S. and Europe for crinecerfont. And equally importantly, working on for publication, we hope in top-tier journals and presentation of the data to enable, obviously, more in-depth discussion of where crinecerfont can add value for children, adults and pediatrics living with CAH currently. We will be sharing some additional information regarding the results as well, from these studies at an Analyst Day that we'll be putting together in December, and we look forward to discussions at that point in time as well. With that, let me open it up to your questions, and we look forward to delving into some of these topics.

[Operator Instructions] We'll go first to Paul Matteis with Stifel.

This is James on for Paul. Congrats on the data. Just wondering if there's any more granularity you can provide around some of the efficacy data. Specifically, we're curious what percentage of patients achieved androgen control. And then maybe just kind of second, as we think about translating these data, I'm thinking about these data in the real world, why did you defined a normal steroid range of 11 mg per meter squared and I guess, as we look across these measures of androgen control and steroid control, what kind of responder rate do you think would be considered clinically meaningful in the real world?

Okay. I'm going to answer the second question first and then refer back to the Phase II data for a little bit about the granularity. So 11 milligrams per meter square per day, average person is about 1.7 meters square, 1.8 meter square. It's about 20 milligrams a day of hydrocortisone. That's about what we use now to treat people with garden-variety adrenal insufficiency. People who are smaller, we try to get to about 15 milligrams per day. The daily production rate is about 7 milligrams or 8 milligrams per meter square per day, but you can't really achieve that because of the pharmacokinetics of the hydrocortisone tablets. So we want to kind of give a little more, get a little higher peak to allow for a longer duration of action of the hydrocortisone. So that's, I think, quite reasonable as a goal. I mean, we can quibble whether it should be 10 milligrams or 12 milligrams but that's about right. Now if you look at the Phase II data, pretty much at 100 milligram twice a day, everybody responded. And I think that's -- so -- and if you look at the 4-week pediatric data when we -- which is similar to the Phase II trial where we left the glucocorticoid dose the same dramatic reductions in the androstenedione level when we just add crinecerfont. So we get pretty much everybody responding. I don't know if Eiry wants to say anything further.

Yes. No, I think Rich you said it very well. The one thing I'll add about the use of the 11 milligrams per meter squared, where obviously, we had a lot of discussion with experts such as Rich and other individuals involved in the program, but also with the regulators. And I think it was really important to get to a clarity of definition that was acceptable in this -- setting of this clinical trial where we were obviously trying to also balance in the first time this has been looked at in a Phase III program, the risk of adrenal insufficiency, and we did not want to put patients at risk of that. And so I think it was a fair balance in that regard, and we were absolutely delighted with how that worked out. I would definitely agree with Richard's point. We talked about the mechanism of action here being a direct mechanism on control of androgen levels. And so from that perspective, I think all the patients have the opportunity to have a response to crinecerfont. We have not seen evidence of nonresponders in that setting. Obviously, it gives clinicians then the opportunity to have more flexibility in how they manage the glucocorticoid dosing on an individual -- individualized patient basis with the ultimate goal, as Rich said, of getting to that ideal scenario of just physiologic replacement. And I think we've demonstrated in this trial that a significant proportion of population were able to achieve that even in the course of this clinical trial setting.

Yes, in the adult study, the entry criteria were 14 milligrams per meter square per day or more. That winds up being about 30 milligrams of hydrocortisone and as I showed you and, they get down to about 20 milligrams. So it's about a 30% or 10-milligram reduction. That's a pretty sizable reduction.

We'll go next to Tazeen Ahmad with Bank of America.

I just wanted to expand on the comments about quality of life endpoints. What are they? And how should we interpret them when we see them in December? And then secondarily, on the discontinuation rate, I think it was around 5%. How do you view that rate in the grand scheme of things? And was there a key reason why patients discontinued?

That's an incredibly small discontinuation rate for 1 year -- well or even a 6-month phase. Again, I don't think I've ever been involved in a study of this size that has had that small of a discontinuation rate. And most of those discontinuations were because of people moving and things like that, there were no -- there are no SAEs that were assessed as being related to crinecerfont, which speaks to the safety of the drug. The common adverse events were fatigue, headache and coronavirus infection. I think everybody gets those. And in the pediatric study it was headache, fever, vomiting and upper respiratory tract infections, which again, children get. So it was pretty safe and the people talked with their feet, they stayed in the study. So I think that was quite impressive. I'm trying to remember the other part of your question.

Yes. Let me take that. We haven't talked a great deal about the quality of life endpoints in the study. And I think obviously, as the big difference of the data and come forward there's more information, we can talk more about that. The other thing I would say about the safety and tolerability is, obviously, this program comes on the back of us already having approximately 1,000 subjects having been dosed with crinecerfont over the course of the clinical program. And we have been extremely impressed by the continued fashion in which crinecerfont has been well tolerated. And in particular, now with the results reduced -- released today, seeing that safety and tolerability profile continue into the younger pediatric age down to an age of 4 that were included in the trial.

And in terms of quality of life, we talk about quality of life for the patients. But I want to talk about burden of disease to the family, okay? These parents have to split pills 4 times a day, some of them have to get up at 3:00 in the morning to do this. And despite that, some of the children are still not controlled and having advanced bone age. So what I think will come out over time is how the burden of disease on these families is alleviated by the sort of block and replace approach, by eliminating the concern that the androgens are going to rise, by controlling that with crinecerfont and then just replacing the cortisol deficiency as we would in someone with simple adrenal insufficiency. So I think that in the pediatric population, assuming we're [indiscernible] pediatrics, I think that's a huge impact on this. I think in the adult population, it's about being able to find an endocrinologist who can take care of you. I get people from all over the country that come to see me because many endocrinologists don't want to take care of this disease because it's hard and because you can't accomplish both ends with the tools that we have right now. And this makes it easy. Anybody can give this dose and then replace the cortisol deficiency. You know how to do that. But it's very hard to control the androgens and to split the pills and give the bedtime doses in the right amount and so on. So I think quality of life is one thing for the patients but burden of a disease is a whole another thing.

We'll go next to Brian Skorney with Baird.

Congrats on the data. Based on the comments about the results being sort of at baseline, a little worse off, I would have thought that would predict a lower rate of conversion to physiological doses. But across both studies, treatment and placebo that kind of happened can you just help us understand sort of the differences in adults versus peds patients or any parts of the trial design that sort of impact the lower rates of patient conversion to physiological levels in these 2...

Brian, would you mind repeating the question you broke up just a little bit. I think, at some key points of it.

Okay. Is there any differences in the adults versus the peds patients for the trial design, that sort of impacts the lower rates of conversion of patients going to physiological glucocorticoid doses. There's just kind of a little bit of subjectivity here bringing them down and maybe more caution about bringing the peds patients down. And just how do you kind of think about the open label experience and would this imply that there'd be a much higher rate for a longer time to get these peds patients to physiological levels?

Brian, there's quite a lot of questions in there, but let me just make sure I understand and clarify. So is your key question about, why the rate of getting patients to physiologic levels might be a little different between the adult and pediatric trials. Okay. With regard to the question around the open label, obviously, we have -- we're reporting the results of the 6 months randomized trial, we have a lot of that -- very high proportion of patients continuing in open label, and we continue to see good tolerability, but we haven't dug into those data in a fashion that I think would be able to address your question there yet. But Rich, you have [indiscernible]

Well, so there was a protocolized glucocorticoid reduction in the adults. So we sort of forced down titrated them. In the pediatric study, they also had a schedule that they -- where they were more flexible about [indiscernible] had to have normal androstenedione to go on. And we know that all these children had high androstenedione to be in the study. That's why the placebo group was 0, okay? So it was a slightly different patient population, so to speak, that in the adult study, there were some people who could have been in control, but were taking too much glucocorticoid. That's the 18% placebo responders. In the pediatric study, everybody was being treated as intensively as they could and still not in control. So nobody could improve in that trial. And saying that 30%, remember, this is 30% that got to physiologic and maintained normal androstenedione. So we're not capturing those people who got close to physiologic, got to 12 milligrams per meter square per day and [indiscernible] or who got to 11 milligrams per meter square, but we're a little bit above physiologic. So that's where we have to get more granular and that will be coming in the subsequent presentation. But that is a good question.

Sorry, Brian, just to finish off the thought on that. Sorry, I was trying to turn my microphone on. The other thing is, bear in mind that this was the first time that any study of crinecerfont had been performed in children under the age of adolescence. We had a small cohort of adolescent patients that we had dosed in Phase II. And that was the reason why we chose the sequence of end points for the pediatric study that we did with the androgen control being the primary and the steroid reduction being a key secondary, because I think we anticipated that clinicians would be more cautious and would require more flexibility in the reduction of steroids in this first study. And so your question about the open label is a very valid one. Your question about how that translates into real world experience. And now that we have such supportive data and the tolerability and safety profile being what it is, I think that we could certainly anticipate that they would look much more similar. There's no reason physiologically to believe that from a biological point of view, the response to crinecerfont would be different in the different age groups.

We'll go next to Phil Nadeau with TD Cowen.

Congratulations on the data. One question for Dr. Auchus. Dr. Auchus, can you talk about how you would use crinecerfont in clinical practice? How would you use it in adult patients and pediatric patients, which patients would be most appropriate for therapy?

Yes. So I think there's -- again, from the adult studies, it's about 15% to 20% who can maintain good androgen control with the physiologic dose of glucocorticoids and probably don't need this. But the other 80%, they're either on too much glucocorticoids or they're on a reasonable dose, usually still above physiologic and their androgens are a little high and they don't want to take any more and we allow that to happen because they're not planning to have children in the near future or things like that. I think I would offer it to any of those 80% of people. And I think in the pediatric population, I can see several scenarios. Again, I think if a family has a choice between taking medication twice a day and 4 or 5 times a day, I think you're going to say, twice a day. But -- and I think in the adolescent group, this is just like in type 1 diabetes. This is a situation where children tend to get into poor control, and then that mars them for the rest of their life. This is an opportunity to -- and enjoying adolescence is a time when people are concerned about their looks and their weight and things like that, that glucocorticoids do bad things to. So I think these families will welcome a way of being able to minimize the disease burden and allow the children not to be exposed to high doses of glucocorticoids.

Maybe one follow-up. This concern among investors that payers are going to push back that you're replacing largely generics, which -- with what's likely to be a branded price therapy. How would you make the case to payers that the benefits here are meaningful and deserve to be paid for over the generic glucocorticoids?

What I would just jump in here and say is that now that we have actual data in hand from the adults and from the pediatric, now you can really have meaningful conversations with payers, having conversations with payers prior to this was a little premature. We did that anyway. But we're going to have more meaningful discussions with payers as we go forward. And so I think it's a little premature to actually talk about that now.

We'll go next to Brian Abrahams with RBC Capital Markets.

Congrats on the data. I was wondering if you could talk a little bit about your expectations for real-world patient management for patients who go on crinecerfont. How much education of endocrinologists do you think will be required both around management and the risks that are associated with supraphysiologic glucocorticoids? And how would the down titration take place in the commercial setting just in terms of monitoring and doctor visits, would these be -- would you expect protocols that mirror what you had in these Phase IIIs? Or would this be more at physician discretion?

Well, so I do a lot of physician education now, and it's really hard now because of the tools that we have that don't work all that well. This actually makes it super easy. The block and replace approach, endocrinologists are used to doing that with Graves' disease, with adrenal cancer. There's lots of scenarios where we do that. And so this will make it actually quite easy. And I think what they're going to do is, like you say, pretty similar to the trial design, add the crinecerfont, watch the labs, as you see the labs improve and the clinical findings improve, you start to wean down the glucocorticoids, you don't want to go so fast that you induce withdrawal symptoms, you want to make sure that they're still replaced. You have to do a couple of other things, like, for example, we have to -- instead of just "doubling your dose", if you're only taking 2 doses a day of hydrocortisone, we now have to tell people to distribute the dose differently. We often have to raise the fludrocortisone dose as we reduce the hydrocortisone dose. So there's a few other things that we'll have to do, which is sort of similar to what we do with a patient with Cushing's disease after they're cured. So again, I think endocrinologists are more comfortable there, but that's how it would be. We add the crinecerfont, start reducing the glucocorticoids to physiologic, monitor as you go along, both laboratory and symptom-wise and then get to your end point and then just keep going.

We'll go next to Chris Shibutani with Goldman Sachs.

This is Stephen on for Chris. I have a regulatory one. Can you talk about what alignment you've gotten from FDA in terms of what they're looking for from an efficacy and safety standpoint? And is there more data that's necessary from the open-label extension to say, fulfill some sort of safety database?

Let me answer the last part first. In our discussions with the regulatory agencies both in the United States and in Europe, we reached agreement around the patient numbers and number of the patients we included in the program that would be required to address the safety question. And it's pretty consistent results required in a rare disease like crinecerfont -- like CAH. And so I think we have confidence in that moving forward. With respect to the -- the programs were discussed with regulatory authorities around the world and we did get alignment around the endpoints that would be important for consideration in both the adult and the pediatric population. And I think it's incredibly gratifying to see that we hit with such a highly statistically significant outcome on both primary and key secondary endpoints across the board, including other endpoints, obviously, that we're not disclosing it right now. So we're very confident in the data package that we have, both from an efficacy point of view and a safety and tolerability perspective. Our next steps will be to engage with regulatory authorities to -- in the kind of pre-NDA setting as it's called in the -- with the FDA in the United States. And obviously, we're moving as rapidly as possible to be able to do that.

We'll move next to Carter Gould with Barclays.

Congrats on the data. This is Leiyang Wang on for Carter Gould. I guess, another regulatory question or just kind of kind of what's your expectations on what you have had dialogue with the FDA by the time we get to your September -- December Analyst Day, and have a better understanding of the path forward. And also for Dr. Auchus, you mentioned about one of the benefits being to [indiscernible] the frequency of glucocorticoid use in patients, now on the Analyst Day or just at a later point, should we see a greater level of granularity on kind of just measures such as this, in terms of things that could potentially drive adoption?

It was a little difficult to hear the second part of your question, I must admit and maybe we need to ask you to repeat that. With respect to the first question, the regulatory path forward, I think we have confidence in the package that we have in hand right now. And we had a lot of discussion with regulators prior to commencing this Phase III program. And actually in the way that the Phase III program played out with the highly statistically significant efficacy outcomes and the safety and tolerability that we've seen to this point, we don't really anticipate surprises in the upcoming conversation. With respect to the timing of that relative to our Investor Day, I really can't comment on that at this point, I mean we're -- as I said, we're moving as fast as we can, and we're engaging in those discussions as rapidly as we can.

Yes, I'm going to need you to repeat that last part of the second part of the question because I couldn't understand that.

Yes. I'm just curious about any other type of probably quality of life or any other type of things that you could show on the December Analyst Day, such as a reduction in the number of times the patient takes glucocorticoids while they're on crinecerfont, anything that helps on that, that can help better frame adoption or compliance for these patients?

Yes. No, I don't want to set false expectations around that. In terms of information that we'll share towards the end of this year, obviously, we will be continuing to dig into the data, but it will be more in line with what we're actually sharing today and a little bit of additional information there. And the primary reason for that is because we want to preserve the ability to publish these information in a top-tier journal in as rapidly as possible and also present the data because I think the full publication and presentation of the data is what's going to enable us to really understand the full value proposition of crinecerfont and we do not want to jeopardize that.

I would also just jump in to say, Carter (sic) [ Leiyang Wang ], that one of the things that we look at here that's so surprising and Dr. Auchus said it just a little bit earlier, 95% completion rate within those first 6 months, that's just incredibly high. Patients have to and their families have to feel that they're recognizing a benefit and staying on the drug for the entire time with such a small dropout rate.

Yes. And even where people on placebo because whether they know it or not or staying in so they can be on the drug in the open-label phase. I mean that's quite -- because people who aren't producing their glucocorticoids might feel like they're on placebo, so everybody is staying in the trial.

We'll move next to Anupam Rama with JPMorgan.

Congrats on the data. One for the company and one for the KOL on the line. For the doctor, based on what you know from the Phase II experience and kind of the top line for crinecerfont in CAH, would you have any hesitation using this product as a chronic therapy long term? And then for the company, just on Analyst Day, is it safe to assume that in conjunction with Analyst Day, we might get the anhedonia and focal onset seizures proof-of-concept data as well? Or could those come ahead of Analyst Day?

Well, as far as safety -- I mean, in safety, it's very clean. I have no hesitation about using this drug, and I'm not just saying that because I'm here and they've sponsored the study. But -- and I can tell you that the patients want to stay on the drug.

Yes. In terms of Analyst Days, we're going to cover a variety of different topics across our entire pipeline, which as you can see is evolving and has a lot of excitement around it. In terms of data, I don't want to set false expectations that we're going to have a big unveil event at Analyst Day. It really could be a dive really deep into our existing programs and to get a even deeper look into what we're doing in the preclinical space. And so you'll need to only -- and be able to get some insight there. So we'll provide more detail on what we're going to cover at our Analyst Day when we have our earnings call here in a few weeks. But stay tuned.

The only thing I'd add, Anupam, just to be clear that we don't have any delay on our FOS or anhedonia programs. We're completely on track with the commitments that we've made around sharing data in the fourth quarter around those programs.