Bill Meury : Andrew. Go ahead.
Andrew Miller : Yeah. Thanks. So you’re referring to a study where the results were recently posted on clinicaltrials.gov that was actually a remote mobile-based study that was done by BI as — really as a result of the pandemic. That study was terminated early. I think the final enrollment was like low single-digit number of subjects. I think given that in some of the considerations around MDD and more generally, studies in depression or things like schizophrenia, it’s really premature to read too much into that study — those study results. Particularly when you speak to adverse effects or things like suicidal ideation, which tend to be rare. It’s often more challenging to make any conclusions about that until you get larger numbers.
There’s also, I think, more details with respect to things like to suicidal ideation, there are specific rating scales for that. We implement that across the emergent program as well. So simply looking at TAEs is not, I would say, a thorough assessment of the potential effects. And I would further say that from our perspective, we certainly don’t see any preclinical evidence or a specific scientific rationale for why that could be an adverse effect associated with TRPC4/5. We’ll certainly obviously be carefully assessing that as anyone would and being diligent in conducting studies in expression when we push forward into [indiscernible] this year with the 2618 program.
Bill Meury : Thank you for the question.
Operator: Next question is from the line of David Amsellem with Piper Sandler.
David Amsellem : Thanks. So on ARISE, can you talk to pace of enrollment? And are you still onboarding sites? Just wanted to get a flavor for where things are on that trial? And then secondly, on ADEPT and AD psychosis more specifically, how are you thinking about it vis-a-vis AD agitation. Some companies that are looking at agitation, you guys are looking at psychosis. Do you think that agitation and psychosis is sort of a distinction without much of a difference? And I just wanted to pick your brain on that. Thank you.
Bill Meury : Thanks for the questions. David, go ahead Andrew.
Andrew Miller : Yeah. Specifically for the first question around the ARISE program, we have continued to activate sites over the course of this year, really in the second and third quarter, we initiated two new countries as part of that programmable area, so we have to cross this. There’s about 20 sites that are active at this point in time. I think as Bill maybe mentioned a little earlier, obviously, whenever we’re managing studies, it’s always a day-to-day and week-to-week basis. I do think you’re likely to see some additional site activations across the ARISE program. Again, that’s pretty typical studies like this, you also see sites that will drop off over time who aren’t actively enrolling. But I think we feel good about where we are with the ARISE program, continue to see momentum as part of that program.
But obviously, we’ll provide any additional updates going forward to the extent they are already. And then with respect to the ADEPT program and our focus on psychosis, I think if you rewind the clock 10 to 15 years, there perhaps wasn’t as much distinction among psychosis and agitation. We really look at that as a separating out of an agitation-related indication over the last five to 10 years, given, frankly, the lack of approval for anything more broadly for psychosis. Specifically agitation and aggression, I think, are potentially more, I think, affected by drugs that have somnolence or sedative based effects, fundamentally, that’s sort of a hetroparadigm. Whereas when you look at hallucinations and delusions in that sort of core psychosis, that’s really where we look at taking advantage of the non-antipsychotic effects of xanomeline and as part of KarXT.
Bill referred to this in the original or the opening of the call that is the population Alzheimer’s patients where the antipsychotic effect of xanomeline was first discovered. And when you look at that data, which is all published, you see benefits specifically on hallucinations, delusions, agitation and aggression across that program. So we really look at the opportunity with KarXT as something to capture that broad effect. But specifically starting with hallucinations and delusions as the basis for the primary endpoints in the ADEPT program.
Bill Meury : And the only other thing I’d add to, David, we know that the product has a procognitive effect, which was observed in the very same trial that Andrew just talked about. And so when we think about that Alzheimer’s population, of course, the first step would be an official indication or FDA approved indication for psychosis, but we know that there’s data on other aspects of Alzheimer’s disease, both agitation, aggression and cognition, which I think creates a compelling opportunity for us as we go into in this area. Thanks for the question.
Operator: Your next question is from the line of Jay Olson with Oppenheimer.
Jay Olson : Hey. Congrats on all the progress. Since there seems to be a lot of interest in the ABPM study, can you just remind us what blood pressure signals have you seen in the past? What’s the rationale behind running this study? And ultimately, is there a legitimate blood pressure concern for KarXT that investors should be concerned about? Or is that just a false narrative contrived by competitors? Thank you.
Bill Meury : Thanks for the question, Jay. Go ahead, Andrew.
Andrew Miller : Yeah, sure. Happy to speak to sort of what we’ve seen, how that projects and ABPM and I think maybe I’ll just start with, I think with respect to ABPM, it’s not something that we have a lot of concern about internally. Obviously, we’re running the study to provide a more definitive data point about what any blood pressure effect of KarXT could be. But when we look at the EMERGENT program, which has the same dosing also in patients living with schizophrenia fundamental at the same paradigm as the ABPM study, even in that setting where we’re measuring vital signs at Cmax of the drug two hours of the first dose. We don’t see a 3-millimeter increase even in that set, which you would describe more as kind of a fundamentally a worst-case scenario.
So we translate that data into the ABPM paradigm. That’s why we have such a high level of confidence in having a successful outcome from that study. Consistently, across the program with KarXT, we generally have not observed any meaningful pressure effect and not something that was historical consideration with this mechanism really until you’ve seen some of the M4 or selective compounds come into early-stage clinical development over the last couple of years. So from our perspective, we’re obviously greatly looking forward to be able to see the final ABPM data and get that out into the public domain, which I think will provide in our minds, the most definitive data point around any potential pressure effects. But we expect that to be consistent with what we’ve already seen in our clinical assessment in the emergent program.
