Well, I think, the cleaner the profile looks, the better XEN1101 emerges in the eyes of clinicians. So that very well could be a positive differentiator if one sees an AE profile that is similar to the 10 milligram profile that emerged from X-TOLE. But to be clear, we also spend time in our market research, diving deep into the perspective on an AE, such as dizziness, which is a little less common in the current standard of care, but in the context of it being a mild and potentially transient AE was something that clinicians viewed in the totality of the risk benefit profile to be certainly within reason and would ultimately result in the product being used in their armamentarium.
Ian Mortimer: And maybe I would just add one other point to Chris’ comment. If we — we have a huge body of data on XEN1101 now. Just as a reminder in Chris Kenney’s comments earlier, we have our first patients out more than four years of dosing. We have hundreds and hundreds of patient years of exposure now and we’re seeing this consistency in profile. And we know that not all patients are going to tolerate these drugs the same. So in our epilepsy experience, as we move an X-TOLE from 10 to 20 to 25 milligrams, you get a step up in efficacy and you get a step up in some of the CNS adverse events based on the potency and activity of this drug. And we know that when we think about epilepsy or we think about depression, there would be multiple dosages available.
And so if you don’t tolerate a certain dose, there’s an opportunity for you to move to a lower dose, which can address some of the tolerability. So I think we have — when we think about XEN1101, we know a tremendous amount about it and we have that flexibility, because we know patients will tolerate the drug differently from patient to patient.
Operator: Our next question comes from the line of Paul Choi from Goldman Sachs.
Paul Choi: I have two, first for the team. With regard to the pace of enrollment in X-TOLE2, I appreciate your comment that it’s tracking faster than X-TOLE. But could you maybe just comment on it, if you’re seeing any competition for recruiting patients and whether any of your clinical trial sites overlap with others developing potassium channel drugs for epilepsy? And my second question is under a scenario where X-NOVA reads out positively. Can you maybe comment on how the recent FDA rejection of zuranolone has or hasn’t affected your thinking on potential future development in MDD?
Ian Mortimer: So maybe I’ll make a couple of comments first on X-TOLE2 and Chris Kenney, you’re very close to the investigators on the site, so please add your perspective as well. And then we can get to the X-NOVA question. So as we think about X-TOLE2, I mean, I think one of the messages we’re communicating today is that obviously we have a lot of experience in running global epilepsy studies. I think, if we look back over the next few years, we have run the largest number of significant epilepsy studies when we compare ourselves to any other sponsor. So I think there’s a huge amount of experience that we’re gathering. Often we don’t find that a clinical site will take on two competing studies to focus on one, but I’ll let Chris provide his perspective there.
And then when we just look at the recruitment rates in X-TOLE2, when we look at other companies over the last number of years that have run epilepsy studies, I believe that our recruitment rate and our ability to complete these studies have outperformed others. And so obviously, we’re very proud of the work that the team has done. But Chris, any other specific comments that you’re seeing at individual sites on competition?
Chris Kenney: I mean, the challenges that have come up, probably the number one challenge at the sites is more about making sure that each site has the appropriate resources to be able to support the study. And the issue of competition with other anti-seizure medications hasn’t slowed down to my knowledge even a single site. So if you think about the timing in terms of, I believe, when you say Kv7 drugs, I believe you’re alluding to the public information that Biohaven is going to start Phase 3 by the end of this year. We were going out to sites quite a while ago. And so we’ve locked in those sites already that we were most focused on. So that really — competition with other Kv7 has not had any rule in terms of slowing us down to date.
Ian Mortimer: And then Paul, your other question on X-NOVA and maybe the regulatory environment. We haven’t had regulatory interaction with the psychiatry division. Obviously, if X-NOVA is positive and we move into late stage clinical development, we do an end of Phase 2 meeting. So I think maybe we’ll just pause on that question until we have more interaction. When we look at the zuranolone summary basis of approval and we’ve looked at the regulatory information that’s publicly available, we don’t see any read through to the work that we’re doing with XEN1101 in major depressive disorder with the caveat, as I mentioned earlier, that we still need to have detailed regulatory interaction as we would think about the late stage program.
Operator: Our next question comes from the line of Joseph Thome from TD Cowen.
Joseph Thome: Maybe the first one on the upcoming Neurocrine data. How are you thinking about potentially moving forward with that co-fund option, what are some considerations you have? And can you remind us when you have to make that decision, is it immediately after data, is it after an end of Phase 2 with the FDA or is there time on that? And then for the 1101 NDA filing, can you just remind us what kind of safety database is required to initiate that? Is having patients through that 12-week double blind period sufficient or will you need some additional time after the data readout before you could start the filing?
Ian Mortimer: Sherry, do you want to tackle the first one on co-fund? And then, Chris and I can provide perspective of on the safety database.
Sherry Aulin: So as a reminder for our collaboration with Neurocrine, we have a tiered royalty structure. So ultimately, if the drug progresses, we would be eligible for royalties that are based on sales. So the co-fund option allows for us to opt in to pay for or fund 50% of the Stage 3 development costs. And in return, we would get an incremental step up in the royalty, which at the highest tier would amount to a [20 royalties]. We’re going to have the benefit of having a lot more information in hand before we have to make the decision around [Technical Difficulty] we want to trigger the co-fund. So importantly, we’re going to have data from this upcoming Phase 2 study, which we’ll be able to evaluate in addition to all of the information around the Phase 3 development program.
So an agreed upon protocol with FDA on Phase 3, a full budget around what the Phase 3 development program will look like, and we’ll be able to make a decision based on that, the totality of that information. I do want to point out, I think given our experience in the space, we are very well positioned to be able to review all of that and make a very informed and educated decision. And also, I will say that at this stage, Neurocrine is driving the development next steps of the [352] program. And ultimately, we’ll have to see what their next steps are. So it is possible that from this Phase 2 signal finding study, they may decide to proceed into larger Phase 2b study rather than directly into Phase 3, in which case the timelines around [Technical Difficulty] longer.
So don’t expect that it’s a decision that we need to make in the near term. I’d say at the fastest if they are going straight into Phase 3 probably, I’d say at least 12 months, maybe more like 18 months until they have regulatory interaction and all of that information I discussed.
