Ian Mortimer: And then, Joe, I think your question on NDA and safety database when you specifically sat around after the double blind period, I’m assuming that you’re kind of referring more to long term exposure. So I’ll answer it that way and then if you have a follow-up, let us know. So this is a large market opportunity. So we think about ICH guidelines in terms of exposures, the long term exposures that are required, there’s 300 subjects. So this is the guidance, there’s 300 subjects of six months of exposure and 100 subjects of 12 months of exposure. And as I’m sure you can appreciate, we have a significant amount of long term data. Actually, I think that’s one of the things that is continuing to differentiate us versus even those in the competitive space is that we now have so much experience with this molecule that long term safety is not going to be gating to an NDA filing by any means.
Operator: The next question comes from the line of Danielle Brill from Raymond James.
Danielle Brill: I was wondering if you could talk about the decision to permit enrollment of patients with PTSD in X-NOVA. We asked this since PTSD can be associated with lower treatment response rates to more traditional antidepressants. Specifically curious if you stratified enrollment and if you plan to break out treatment response rates with inpatients with or without PTSD or other comorbid anxiety disorders?
Ian Mortimer: Chris Kenney, can you provide perspective there?
Chris Kenney: Well, the top-line analysis of X-NOVA is going to focus on the MADRS and the SHAPS top-line safety, et cetera. So it’s not part of the top-line. The second round of data, we can look at those sorts sort of things but that isn’t a major — looking at PTSD, it’s not stratified in the study. And looking at whether those patients are spawning differentially isn’t part of the plan. Danielle, I don’t know the numbers off the top of my head, but I think we’re talking about relatively small numbers. And so I think that in the context of a study this size, I think even doing that may have limited utility.
Operator: Our next question comes from the line of Marc Goodman from Leerink Partners.
Unidentified Analyst: This is Madhu on the line for Marc. Could you just give us an update on your pediatric formulation of XEN1101 and also your second gen molecules that are in preclinical development? Could we expect to see any data from these candidates in the near term?
Ian Mortimer: Yes, we have, as we stated, I think, in previous calls, we’ve got alignment from regulators on what the pediatric plan is for XEN1101. So there’s some layers to this in terms of focal onset seizures, we have an ability in the US to take advantage of the, what’s called, the PK extrapolation rule where we can do open label work in younger cohorts of patients. We’ll start with adolescents and then move into children. With our exact study or our primary generalized tonic clonic seizure study, we have, based on feedback from regulators, move the lower bound of age to 12 and above for that study. So we’ll be enrolling some of those patients in the Phase 3 program. And then in terms specifically on a pediatric formulation, so obviously, an oral capsule can go down to a certain age group and then when we get into much younger age groups, we’re going to need to work on a pediatric formulation.
So that work is ongoing internally. In terms of next generation Kv drugs, yes, I think we’ve communicated a number of times that we have a number of different chemistries and different molecules that we’re interested in preclinically, that target the potassium channels in the CNS. And we don’t talk a lot about kind of stage of development where we are publicly with those. But we would expect over the next year or two we would have molecules that’ll transition into clinical development and that’s probably an appropriate time to start sharing some of the preclinical data publicly as well. Operator, we can move to the next question.
Operator: Our next question comes from the line of Laura Chico from Wedbush.
Unidentified Analyst: This is Ingrid on for Laura Chico. Wondering if you could speak at all to any efforts to coformulate 1101 with another ASM? Would this be something that could be explored in vocal epilepsy space? I realize this may be challenging to dose optimize. But would there be any advantages to this type of approach?
Ian Mortimer: Yes, really interesting question. Chris Von Seggern, I know you’ve done some time thinking about this and obviously, the types of anesthesia medicines that have been developed over time. So maybe you can start and then, Chris Kenney, if you have anything to add as well.
Chris Von Seggern: Yes, what I can say is and what we expect from a commercial use standpoint and the focal onset seizure mark it is most certainly combination use with other commonly used anti-seizure medications. And there are a handful of those products, which are used quite frequently early in lines of therapy, Levitiracetam, lamotrigine and increasingly lacosamide, are products that would be potentially ideal candidates for thinking about co-formulation opportunities. It’s definitely something that’s been on our radar for consideration. Although, there are technical complexities to consider when you think about the range of doses that exist as well as the requirement for other products to be titrated to full efficacy. One of the key advantages of XEN1101 and the treatment of FOS is that we don’t require titration and that gets us to a therapeutic dose with the initial dose selected.
So there’s a little bit more technical complexity to that question than the obvious desire to think about co-formulation with other commonly used anti-seizure medication and something that still needs to be explored.
Ian Mortimer: Chris Kenney, anything to add?
Chris Kenney: Nothing to add, Ian.
Ian Mortimer: Yes, I think, as Chris said, there’s a real challenge there as you have a lot of these drugs that are titrated, and not everyone gets to the same dose. And so that provide some inherent technical challenges on co-formulation.
Operator: Our next question comes from the line of Mohit Bansal from Wells Fargo.
Unidentified Analyst: This is Serena on for Mohit. Thanks for taking our question. So I have two, the first is that if the monotherapy study in MDD doesn’t work or even if it does. Is there a possibility of studying the 1101 as an adjunctive and MDD to see if there’s any synergistic effects? And then my second question is if you can help us understand why there are no treatments specifically approved for anhedonia when it looks like some antidepressants have shown a benefit on anhedonia scores?
Ian Mortimer: Chris Kenney, do you want to start on — and maybe I’ll start with a global comment and then maybe you can provide your perspective on monotherapy and potentially future development and in the adjunctive setting as well. And any perspective you have, I think, both you and Chris can weigh in on. I think if — just turning to the very first part of your question on if X-NOVA isn’t positive, would we move ahead with adjunctive studies? I think that’s unlikely that if we don’t see a signal in this study that we would be running an adjunctive study separately to this. I think in the scenario where XEN1101 is positive and X-NOVA and we’re moving ahead, then I think it’s a question that we’ve definitely thought about. And it’ll be somewhat jurisdictionally dependent also based on interaction with regulators. But Chris, why don’t you provide your perspective there and then we can move to the anhedonia question.
Chris Kenney: I think you covered it, Ian. I don’t have anything to add to that.
Ian Mortimer: And so, yes. I mean, maybe just add a different way if we’re positive in X-NOVA and we’re moving ahead into registration studies, then I think we would look at both potentially monotherapy or adjunctive studies in future development. On the anhedonia sides, either Chris or Chris, your perspective on maybe why we haven’t seen — I know anhedonia is definitely showing up as an endpoint in a lot more studies now, but we haven’t seen that used as a primary endpoint in development.
