Myles Minter : Hey congrats on the quarter. Thanks for the questions. First one is just clarifying. Are you going to announce the NDA filing acceptance if you do get that? And would you also use that as a forum to give us the ambulatory blood pressure monitoring data at that time. And then the second one is EMERGENT-5 has been fully enrolled since the second quarter. That’s patients that are treatment naive to KarXT in an outpatient setting. Can you just give us an update on the dropout rate and how that compares to EMERGENT-4 that’s ongoing in patients that have been experienced? Thanks very much.
Bill Meury : Great, Myles. I’ll take the first part of the question and then turn it over to Andrew to answer your second question. As it relates to the acceptance, we will announce that we expected at the end of the month. And then as it relates to the ABPM results, we expect to have those announced in the middle of the fourth quarter, which is only a couple of weeks away. Andrew?
Andrew Miller : Yeah, Myles, with respect to EMERGENT-4 and EMERGENT-5, obviously those studies continue to be ongoing, as you mentioned, it’s sort of premature to comment too specifically on any conclusions from those studies. I think we do look for those as being overall consistent with what we spoke to earlier, the pharmacology of KarXT unique being at the both M1 and M4 receptors. And our expectation is we’ll see in those long-term studies, something looks quite consistent with the data we’ve been able to release from the short-term studies. EMERGENT-1, 2 and 3, where we see predominantly an efficacy profile characterized by a robust effect, a broad effect and a safety and tolerability profile generally characterized by mild-to-moderate transient GI side effects.
We’ll, of course, look forward to releasing all of that data at the right time here in 2024 as the study is complete. But again, those studies are a great opportunity for us to further demonstrate the potentially differentiated profile of KarXT.
Bill Meury : Thanks for the questions, Miles.
Operator: Your next question is from the line of Paul Matteis with Stifel.
Paul Matteis : Hey, thanks for taking the questions. Ahead of the ABPM data, I was just curious, what’s your level of confidence right now that, that data with the FDA will not serve as a major amendment? Any more color you can provide or any analogs? And then just more broadly, how are you thinking about business development and the possibility of doing another TRPC4/5 like deal in the next year or so before the launch? Thanks.
Bill Meury : Thanks, Paul, for the questions. I’ll let Andrew tackle the first question, then I can answer the second question for you.
Andrew Miller : And I think with respect to the ABPM study, that was specifically a topic of discussion with the FDA at our pre-NDA meeting in second quarter earlier this year. And specifically, the idea that study, which again is a Phase 1b safety study, will be submitted at the day 120 safety update, which obviously, based on our submission in late September will happen in the late January time frame. And again, I think we’re highly confident that would not result in a sort of a major amendment to the NDA and NDA review process. Again, because of specifically that conversation with the agency at pre-NDA meeting, but also I think the general precedent that study, that’s a Phase 1b safety study submitted prior to midpoint review were certainly prior to day 120. We would not expect to result an extension to the PDUFA date.
Bill Meury : Great. Thanks, Andrew. And then Paul, as it relates to business development, it’s a good question. It’s a very important priority for us to build the pipeline. I would say it’s second only to the approval and launch of KarXT, which is obviously our most important priority. You mentioned the Goldfinch transaction, the TRPC4/5 inhibitor. Look, we look at new opportunities on a weekly, monthly basis. We think about them strategically, scientifically, financially. And I think that the TRPC4/5 inhibitor checked all of those boxes. We think about neuroscience fairly broadly with a focus on schizophrenia, Alzheimer’s, depression, anxiety, several other conditions. If we see something that we like, fits our balance sheet, make sense given our capabilities and our neuroscience focus, yes, we would do something.
Obviously, our number one priority right now is KarXT, but number number two is building the pipeline and new product flows for any company, the lifeblood. And so we’ll continue to look at things. And if we see something that we like, we’ll, of course, we’ll do it. Thanks for the questions.
Operator: Your next question is from the line of Ash Verma with UBS.
Ash Verma: Hi, good morning. Thanks for taking my question. So on the ABPM study, I wanted to ask, so I know we haven’t seen any impressive effect for KarXT in previous study and study of M4 molecule was pretty clean on the ABPM. But just mechanistically or theoretically for KarXT, like could the additional M1 agonism in any way impact on patients’ blood pressure? Thanks.
Bill Meury : Thanks for the question. I’ll turn it over to Andrew.
Andrew Miller : Yeah. Thanks, Ash. So specifically from a pharmacology perspective, is often challenging to separate the individual contributions. We have a molecule hitting multiple targets. That being said, I think when you look at the data that exists for some of the allosteric modulator programs, et cetera, I think you tend to see any potential pressure effect being tied to the M4 receptor. So our expectation is not that we will see any meaningful pressure effect with RXT certainly on the basis of an M1 and the M4 pharmacology. And I think as you referenced, we don’t seem to see a sustained chronic increase across the emergent program already. I think the ABPM study offers us the ability to further confirm that. And we certainly remain confident here with the final data coming quite soon, that we will be able to reject that statistical hypothesis of any sort of sustained 3-millimeter increase in systolic blood pressure.
Bill Meury : Thank you.
Operator: Your next question is from the line of Mohit Bansal with Wells Fargo.
Mohit Bansal : Great. Thank you for taking my question. And congrats on all the progress. Just wanted to ask regarding your competitor’s data on TRPC4/5 and there was this small increase — was increase in suicidal ideation. Again, the numbers are small. So just wanted to understand, is it just the law of small numbers? Or is there any theoretical reason why you will see high suicidal ideation with this mechanism. Thank you.
Bill Meury : Mohit, we had trouble hearing what you said. Would you mind just repeating the question?
Mohit Bansal : Sure. So this is regarding the TRPC4/5 and the data we saw in early October from Boehringer Ingelheim. So the trial was terminated due to slow recruitment, but there was a 15% rate of suicidal ideation in the treatment arm versus 4% in placebo. I’m just trying to understand, is this anything is it — has this anything to do with the mechanism? Or it is just a law of small numbers, these are really small numbers here. Thank you.
