Eiry Roberts: Thank you. The NBI-568 molecule is a highly selective M4 agonist, and as such, I think we know now from both KarXT and the Cerevel molecule, that the M4 mechanism is implicated in the psychosis of schizophrenia and blocking–and agonizing M4 can result in benefit in terms of the improvement of the PANSS scores and psychosis symptoms. Clearly there is a difference and differentiation between the molecules in terms of the way in which they agonize M4, and so that may play out in terms of differentiated efficacy, but also may play out in terms of differentiated tolerability. I wouldn’t say that we are only interested in tolerability. We’re interested in both. This is a dose finding study, and as part of that we will be look at the efficacy in terms of the impact on psychosis scores and the tolerability in terms of overall tolerability to this molecule.
I think both are important, and it will be an integration of those data from the Phase II read-out that will be important in determining our path forward.
Ivy: Thanks.
Operator: Thank you. Our next question comes from Jay Olson with Oppenheimer. Please go ahead.
Jay Olson: Hey, congrats on all the progress, and thanks for taking the question. Just going back to crinecerfont, can you talk about how long patients need to be treated with crinecerfont before they start to experience some of the benefits on the complications of CAH, like cardiovascular or bone density, and do you think you’ll have some of that data when you file? Then separately, do you have any plans to study crinecerfont in other diseases besides CAH? Thank you.
Eiry Roberts: That’s a lot of questions there. Taking them one at a time, in terms of the effectiveness of crinecerfont and its direct benefit in terms of the androgen control, just to make a comment there, we see that very rapidly, and we’ve shown that on two occasions, first in our Phase II proof-of-concept study where within 14 days of dosing, the degree of reduction in androgen control–of androgens was pretty much maximal, because that was also how it played out in the four-week study in our Phase III data. In terms of controlling androgens, crinecerfont does that very rapidly. Obviously, that then allows clinicians to reduce the steroid dosing, and by both controlling androgens with crinecerfont and being able to reduce steroid dosing, that’s how we get to the benefit associated with the clinical longer term outcomes.
We do have measures of clinical outcome in terms of metabolic measures, bone related measures, growth and other important elements within our NDA submission. Obviously, those are based on data out to one year, essentially, and beyond that, the other impressive thing about the program to date has been the rollover rate into the open label, which is essentially greater than 95% for both the adult and pediatric trials, and so we are collecting longer term open label data on an ongoing basis, and we’ll continue to do that until we reach the market. Also, we have a registry effort going on, called catalog, which will allow us to put in context our clinical outcome data in terms of what is seen in the general population of CAH.
Jay Olson: Great, thank you, and any plans for other diseases?
Eiry Roberts: Oh, actually I think–obviously we are thinking about that on an ongoing basis. I think Jude also alluded to it at our R&D day that we have a whole effort around next-generation molecules in CAH and other indications in that space as well, and so we’ll certainly be talking more about that in due course.
Jay Olson: Great, thank you very much.
Operator: Thank you. Our next question comes from Marc Goodman with Leerink. Please go ahead.
Rudy Li : Hey, this is Rudy on the line for Marc. Thanks for taking my question. Can you talk about your IP following the recent patent litigation settlement, and just curious what are your current thoughts on impact of IRA on your pricing towards the end of this decade. Thank you.
Eric Benevich: We’re very pleased with the way that the litigation ended up. We have protection that goes out into 2038 at this point in time, so I think that that really spoke to the impressive patent efforts that we put behind all of our molecules here at Neurocrine. When it comes to the IRA, as you know, the first 10 drugs are under negotiation right now. In September of this year, we’re going to see the first time what those negotiations yielded, so I think we all look forward to seeing that before we can comment any further on what we think the IRA impacts are going to be.
Rudy Li: Got it, thank you.
Operator: Thank you. Our next question comes from Myles Minter with William Blair. Please go ahead.
Myles Minter: Hi, congrats on the progress. Thanks for the question. Just a quick one on the Phase I 570 trial, the dual M1/M4 agonist in healthy volunteers, I think that trial initiated in September. Just wondering how dosing is going for that and when we’ll hear about safety for that program. Secondly, would you ever think about running head-to-head studies against 568 or 569 in a CNS indication? Thanks.
Eiry Roberts: Thanks Myles. On the 570, that’s progressing very well. We are going through the Phase I program and at some point, obviously, we’ll come forward and talk about that more as we enter Phase II – that’s usually what we tend to do in that space, but things are progressing as expected. You know, there’s always a lot of discussion about whether to try to put more than one investigational product into a clinical trial, in order to profile them directly with one another. As you can imagine, that is something we’ve talked about in the context of the fact that we have such a broad portfolio of muscarinics. It’s very challenging to do that, though, given the fact that we want to try to accelerate each molecule as much as possible individually, and so at least in my experience over many years in this business, they don’t seem to line up perfectly for you to be able to do that.
In the absence of being able to do that, what we are doing is essentially running very, very similar Phase I programs for each of these assets, so that we can look at the same measures, look at the same outcomes, and understand how to compare those individual molecules indirectly.
Myles Minter: Fair enough, thanks Eiry.
Operator: Thank you. Our next question comes from Neena Bitritto-Garg with Deutsche Bank. Please go ahead.
Neena Bitritto-Garg: Hey guys, thanks for taking my question. I just wanted to circle back to the MR read-out later this year and Paul’s question originally about dosing. Is there anything else that you can kind of share on the dose levels that you’re testing and dosing frequency, and maybe how they may compare to some of the doses that we’ve seen for emraclidine and KarXT from an activity perspective? Thanks so much.
Eiry Roberts: We haven’t shared the doses from our Phase II dose finding study up to this point. Obviously it’s not that long before we get our data, so we’ll get to see that later this year. What I can say is that we’re confident on the dose range that we’re testing, based on an integration of our preclinical data, both efficacy and tolerability from the toxicology program, and also from our Phase I studies where obviously we explored a lot of different pharmacology to understand how to pick the right doses for Phase II.
Neena Bitritto-Garg: Got it, thank you.
Operator: Thank you. Our next question comes from Jeffrey Hung from Morgan Stanley. Please go ahead.
Michael Riad: Hi, this is Michael Riad on for Jeff Hung. Thank you for taking our questions. Could you talk a little bit more about Efmody? What are you hoping to see in the Phase II data, and how would you see this becoming part of the treatment paradigm? Is there anything to suggest maybe different uptake, depending on whether a patient is in early adolescence versus adulthood? Thank you.
Eiry Roberts: Yes, we really haven’t talked much about the Efmody strategy particularly here in the U.S. As I said, it is an approved product in Europe for CAH, and these are just very straightforward Phase II read-out studies. Once we have the data, I’m sure we’ll talk a little bit more about that and whatever our next steps might be.
Michael Riad: Thank you.
Operator: Thank you. Our next question comes from Danielle Brill with Raymond James. Please go ahead.
Danielle Brill: Good morning. Thank you so much for the questions. I guess I’d like an update on the cerebral palsy dyskinesia and schizophrenia studies of valbenazine. Should we expect data from those studies this year, and then what sort of impact to sales might we expect from the sprinkle powder formulation of Ingrezza, once it’s approved? Thanks so much.
Eiry Roberts: I can give an update on the ATS and DCP programs. Both are enrolling and we anticipate data during next year.
