Eiry Roberts: Yeah. I can’t really comment on the market and maybe Eric might want to make a comment there. With respect to the second part of your question, though, I mean, that combination has not been studied together. Obviously, that would need to happen before we make any comment on clinical implication of combined therapy. Mechanism of action would be somewhat similar in terms of the direct reduction of androgen for both an ACTH inhibitor and a CRF1 antagonist. And I think what we’ve seen so far in our data is that treatment with crinecerfont can result in a very substantial and clinically relevant reduction in androgens alone and so I think in the context of need for combination, we do not have evidence of that up to this point.
Sumant Kulkarni: Thank you.
Eric Benevich: Yeah. It’s, obviously, very early with regards to commercial plans. But what I will say is that we’re very excited about the opportunity to potentially make a meaningful difference within the CAH community. We estimate that there’s between 20,000 and 30,000 people living in the U.S. currently with CAH, classic CAH, similar number in Europe. The standard-of-care today is suboptimal. It’s high dose, supraphysiologic glucocorticoids to suppress the excess androgens. And so these patients are faced with a difficult conundrum, either having excess androgens or living with high GC exposure and the consequences of that. And so, I believe that crinecerfont offers a real shift in the treatment paradigm, which would directly reduce the androgen excess in patients and enable the reduction of supraphysiologic GC doses.
So, obviously, we’ve got a lot of work to do to build the market, but that’s what we’re good at and we’ve demonstrated that with INGREZZA and TD.
Operator: Next question comes from David Amsellem with Piper Sandler. Please go ahead.
David Amsellem: Thanks. Just a couple of quick pipeline questions. So on NBI-770 and MDD, those in license from Takeda, when are you going to be in position to disclose the mechanism of that asset? And then, secondly, any thoughts on the M1, the selective M1, and what your general thoughts are on the potential utility of selectively targeting M1 in psychiatric disorders? Thank you.
Eiry Roberts: All right. I’ll take the second part first. M1 agonist, I think we’re excited about the prospect of being able to bring forward an M1 preferring agonist in due course. I think there’s been quite a lot of research in the past in this field. It’s not clear that all the molecules have been of the quality they’ve been able to go forward appropriately in clinical development. So I don’t really think the paradigm has been tested fully. And the range of indications could be quite broad, ranging from cognition in both neurological disorders to some degree of potential in the psychiatric space. With respect to 770, in terms of that program, we actually have just completed the Phase I and are entering Phase II, hopefully in the near future, in the United States, in major depressive disorder.
We have not as yet disclosed the direct mechanism of action there, and obviously, once we get to being in the clinic in Phase II here, we’ll consider whether or not to do that at that point in time.
Todd Tushla: Nikki, let’s go on to the next question, please.
Operator: And we’ll move next with Mohit Bansal with Wells Fargo. Please go ahead.
Unidentified Analyst: Hi. This is Serena [ph] on for Mohit Bansal. Thanks for taking our question. I wanted to ask about the reimbursement prospects for crinecerfont and if you can help us understand what factors payers might take into account beyond shortening of chronic steroid use. For example, if there’s any therapies like puberty blockers in the pediatric population that crinecerfont could help mitigate use of and how this would differ between the adults and pediatric population? Thank you.
Eiry Roberts: Yeah. I mean, I think, it is obviously very early to be talking about reimbursement in a very specific way. What is very clear from the discussions that we’ve had up to this point with KOLs, payers and regulators around the world is that the impact of long-term steroid use is detrimental in this patient population, particularly at supraphysiologic doses. And so the reduction in steroids that we have already been able to demonstrate in the context of our Phase III program, we believe is very impactful and meaningful for in the context of all the key stakeholders that will be supporting crinecerfont’s use. Beyond that, obviously, we have ongoing clinical data that we’re generating that will focus on some of the other functionally related endpoints and clinical endpoints in this space that are relevant, including metabolic bone and in pediatrics growth and development.
And so as those emerge, I think, they will be helpful and useful in the context of these discussions, but it is really very early days.
Unidentified Analyst: Thank you.
Operator: Our next question comes from Ash Verma with UBS. Please go ahead.
Ash Verma: Hi. Thanks for taking my question. Just on margin, I mean, looking beyond the next few years, just in the long run, like where do you see operating margin shaking out and have you considered providing a formal long-term outlook on this?
Matt Abernethy: This is clearly something that we discuss quite frequently with our Board in terms of what our priorities are in terms of financial profile over the long run. We’ve not provided a guide at this point, but clearly you can see we’re on a path of generating improved operating income. You can see the SG&A leverage, but I’d say, from an R&D perspective, we’re committed to continue to invest at a very similar rate from a percentage perspective as we are today in R&D to continue to build our pipeline and develop medicines to help patients here in the future. So we’re not going to provide a specific guide, but know we are intending to drive operating leverage through SG&A margin improvement.
