Operator: Our next question comes from Laura Chico with Wedbush Securities.
Laura Chico : Just one quick follow-up. So with respect to the 845 program, what’s your confidence that you’ve adequately explored dose ranging sufficiently to advance the program? I guess, I’m trying to understand, as you said, coming out of these FDA regulatory discussions, do you anticipate needing additional dose-ranging studies before entering a registrational program?
Eiry Roberts : Yes, I’ll make a couple of comments and then ask Jaz to comment as well. I mean I think if you look at the preclinical data and Phase 1 data, there was a broad range of doses that were tested. And one of this is that Takeda did extremely well in the translational medicine space was look at pharmacodynamic effects using transcranial magnetic stimulation and also cognitive testing and other pharmacodynamic measures in the Phase 1 setting. And so we had a really good handle on pharmacodynamically effective doses going into the initial Phase 2 evaluation. And we completed a small safety study first in Phase 2. And then, I think we were highly confident in the dose selected for the Phase 2 study that we just read out.
We — and also, there were two doses in this study rather than just one, which is common in some Phase 2 setting. And so I think in our discussions with the agency, we — there’s a lot of information to support the selective doses to this point and how we might move forward. Jaz, I don’t know if you want to add it?
Jaz Singh: [indiscernible]
Operator: Our next question comes from Danielle Brill Bongero with Raymond James.
Danielle Brill Bongero : Just a quick one INGREZZA. I was wondering if you could share the average revenue per patient in 1Q?
Matt Abernethy : Yes. The average revenue per patient, if I heard you right. Q1 is always the most challenging quarter where patients go through reauthorization. And so as a result of that the refill rate per patient typically goes down. And so I think that’s something that we’ve talked about historically, which has caused pressure on our sequential growth from Q4 to Q1. And this is the third straight year where we’ve had sequential growth. So the team did a really great job ensuring that patient stayed on medicine and try to close that gap for the — for those — for that refill rate. Now on net revenue per script, if you’re asking on the dollar front, as I said by the call, we do expect our net revenue per script for the year for 2024 to be somewhere over 5,800 and that compares to 5,600 in 2023.
And then the last piece is we typically have seasonal pressure on gross to net in Q1 as a result of the Medicare part on the whole and commercial co-pay reset. And so you would — you do have a bit of a higher discount, a couple of points in Q1 that then recovers in Q2 and beyond. So hopefully, that gives you the components to answer your question.
Operator: Our next question comes from Yatin Suneja with Guggenheim.
Unidentified Analyst: This is [Thelma] for Yatin. So you recently initiated a Phase 1 study with the next-generation VMAT2 inhibitor. I’m just curious, what are the key differentiating properties of this agent versus INGREZZA? And what do you want to see from the Phase 1?
Eiry Roberts : Yes. So I’m not quite sure I fully heard the question, it’s breaking up. But I think it was about our next-generation VMAT2 inhibitor. We’re pretty excited about getting this module into the clinic. As you can imagine, INGREZZA valbenazine is an incredibly well performing module. So in terms of finding a next generation that can potentially be even better is about really, really high. And so — but we’re very happy with the molecule that we have in hand right now. We’re just starting to Phase 1. In that Phase 1 setting, obviously, we’ll be invested in the tolerability, PK profile and how that might differentiate from valbenazine and that would include the potential for using tardive dyskinesia indication, but obviously beyond that into other neuropsychiatric disorders. And as we get some of that information, we understand the potential areas of differentiation, we’ll be more specific about that.
Operator: Your next question comes from Sumant Kulkarni with Canaccord.
Sumant Kulkarni : On your Phase 1 studies for 567, 69 and 70 muscarinic agonists, are there any differences in enrollment criteria by age? And are any of those being specifically run in older adults?
Eiry Roberts : Yes. I mean — so the initial studies for each of those that we’re just starting up are in healthy subjects of the kind of normal age range, not including elderly subjects. However, each of those plans is designed in order to address specific questions relating to those molecules. And so we do understand that, particularly, with those molecules that impact both M4 and M1, that cognition can be an important part of the potential indication space moving forward. And so similarly to what was done for 568, we will be exploring those molecules in older subjects at some point during the plan to enable us to be ready for the chosen Phase 2 path forward.
Operator: Next question comes from Evan Seigerman with BMO.
Evan Seigerman : I haven’t really heard much recently on your push for INGREZZA in the long-term care market. Maybe highlight what you’re doing in this space as this used to be a pretty big part of the narrative or at least where we were going to see INGREZZA growth?
Eric Benevich : Yes. It’s still an important part of the INGREZZA growth story. Frankly, we’re seeing good progress across all three of our business segments in psychiatry, neurology and long-term care. We’ve been in the long-term care segment now for coming up on two years. I’m really pleased with the growth that we’re seeing and the progress that the team is making. Today, long-term care is contributing approximately equal to neurology in terms of our overall business. And so we’re going to continue to develop that segment. And the only other thing that I would add is that on a relative basis, it’s earlier in the overall development phase, commercially speaking that is in the sense that we’ve been in psychiatry and neurology now for seven years with INGREZZA and less than two years in long-term care.
So there’s still a lot of HCPs that are learning about drug-induced movement disorders in tardive dyskinesia and becoming more familiar with INGREZZA as the most prescribed most preferred VMAT2 inhibitor. So we’ll continue to see good growth coming out of long-term care going forward.
Operator: Our next question comes from Uy Ear with Mizuho.
Unidentified Analyst: This is [Leo] on for Uy. So we were under the impression that 845 could differentiate on cognition. Do you still believe this is the case? How else do you expect 845 to differentiate? Could it also differentiate on onset of action?
Eiry Roberts : Yes. We’re just going through all the information from the trial. We also shared the top line today. I mean, I think we’ll be — once we understand data sets and the totality of the data, we’ll be able to comment more around where we think this can truly differentiate and will be designed. Well, Jaz will be designing the Phase 3 trial appropriately so that we can ensure that we always like to do here that we bring the best options to patients that we possibly can.
Operator: Our next question comes from David Hoang with Citigroup.
David Hoang : So I just had a question on the 770 molecule. This is, I think, the NMDA NR2B allosteric modulator. What would be your expectations there around that mechanism and drug profile and how could that differentiate from what you’re seeing with 845?
Eiry Roberts : Jaz, do you want to comment on that?
Jaz Singh: Sure. So NR2B NAM mechanism is a validated mechanism for treatment of depression or potential efficacy even in treatment of system depression. So the initial study we’re looking at is understanding the dose and whether we can determine efficacy. Once we have some data from the Phase 1, Phase 2 studies, we will be able to much better to be able to profile in aware what the efficacy safety profile looks like and how best to position it for further growth.
Operator: We’ll then move on the next with Ami Fadia with Needham.
Ami Fadia : I had a quick question on 845. The trial design mentions that patients would have had to have failed the prior treatment? Was that just SSRI or SNRI? Or were there other modalities that patients were either already on a background therapy or have failed at?
Jaz Singh: So the study requires patients who have had non-response to at least one antidepressant. And that could be any that they’ve taken. We didn’t have any specific restrictions as to which one. So what was seen in the study was a combination of SSRIs, SNRIs, use of conjunctive antipsychotics with propiontis. It’s a mix of what the standard of care looks like.
Operator: Our next question comes from David Amsellem with Piper Sandler.
David Amsellem : I have a CAH focused question. With crinetics having its data coming up for its orally CTH antagonist. Just wanted to get your thoughts on how you’re thinking about that agent and more broadly, the potential for coexistence of multiple novel agents in the broader CAH space?
Eiry Roberts : Well, I mean, a couple of things. First thing, I think it’s really great to see so much focus on trying to bring new medicines patients living with congenital adrenal hyperplasia, both pediatric and adults. It’s been a long time coming, I mean, 70 years in the making before getting to the Crinecerfont data. So we kind have a flow of Crinecerfont playing in that space as well. And I think that’s great. The second thing is, we’re very focused on Crinecerfont right now. We obviously are ahead. We have very robust Phase 3 data in both pediatric and adult patients. And as you heard, we just submitted our NDA yesterday. And so we’re waiting to see the crinetics information on the [NCR2] agonist. And I think that patients with CAH have so few options that additional research in this area is always a good thing. And we’re looking forward to our opportunity to serve this patient population hopefully in the very near future.
Operator: And I will now turn the call over to Kevin Gorman for closing remarks.
Kevin Gorman : Thank you very much. You know what I’m struck by from all of the questions this morning is it reaffirms the perception that we all have here and what we’re experiencing each day. I would say in over 32 years with the company, I’ve never seen us in a better position than we are today from every aspect of the company. We’re talking about from commercial all the way to late-stage clinical trials and NDA submissions. And then clearly into our mid-stage, which 845 has proven itself and then now into our Phase 1 program. And even several of the questions we’re reaching back into what you will learn over the next 24 months is one heck of a robust research pipeline that’s making its way into the clinic. The best days of Neurocrine are in front of us by far.
I have no doubt about that. I want to remind you, what we talked about at great length in our R&D day, and what we outlined is that we understand that in — we’re tackling difficult diseases, and these are psychiatric diseases that we’re tackling that are very difficult. And one of the ways that we do that is we attack them with multiple mechanisms. And in addition, we choose mechanisms that can have multiple disease applications. Thus far, this is proofing to working out for us. Is it going to guarantee 100% success? No. But will it ensure success? Absolutely. And so that’s how we’re conducting ourselves. And I really appreciate all the questions this morning. We look forward to talking to you about all of our pipeline projects and INGREZZA and INGREZZA SPRINKLE going forward.
And thank you very much.
Operator: And this does conclude today’s program. Thank you for your participation. You may disconnect at any time. Goodbye.
