That’s the primary area where we see some level of drawback for the product. They do offer meaningful efficacy, and they hang their hat on seizure freedom data that have been well-received in the marketplace. But again, placing the product leader in the treatment paradigm. What we hear from our research is both the rapidity of onset, which simply can’t be seen with a product that requires lengthy titration, as well as the other attributes and use of use associated with 1101 and compelling efficacy as mentioned before, reinforce the open-label experience with the data we’re seeing for a six-month and 12-month seizure freedom data. That pushes 1101 earlier in the treatment paradigm. And often, it’s compared to the impact in its positioning prior to loss of exclusivity, which was really that first product you pull for after you have one or two failures of generic medicine.
And that’s really the primary distinction between what we’re hearing from the profile for XCOPRI as well as what we’re hearing for XEN1101.
Rudy Li: Got it. Very helpful.
Operator: Our next question comes from the line of Laura Chico from Wedbush. Please proceed.
Laura Chico: Hey thanks very much and good afternoon. Just two quick ones for me. First, on X-TOLE4, can you remind us the rationale here for this study and I know the data submission package is going to be focused on X-TOLE and X-TOLE2. But how does X-TOLE4 actually fit into a regulatory submission for XEN1101? And then just one question for Sherry on operating expense trajectory into 2023, quite a heavy clinical trial load this year. So, how should we think about the cadence of spend versus 2022? Any further headcount expansion? Thanks very much guys.
Ian Mortimer: Laura, just a point of clarification, X-TOLE4 or X-TOLE23, do you want us to comment on?
Laura Chico: X-TOLE4?
Ian Mortimer: Okay. Yes. So, maybe I’ll just take a quick step back and make sure we’re all aligned on the nomenclature. So, our Phase 2 study that we’ve completed, we call X-TOLE, our two Phase 3 clinical trials in focal onset seizures or X-TOLE2 and X-TOLE3, those are identical and very similar to the design of the X-TOLE study. And then we’ve got the EXACT study, which is our primary generalized tonic-clonic seizure. So Laura, you’re asking about X-TOLE4. X-TOLE4 is open-label extension for the Phase 3 program. So, patients that complete the double-blind period for X-TOLE2, X-TOLE3, or EXACT can all go into open-label extension starting at 25 milligrams, and that’s what we call X-TOLE4. So, as you mentioned, what we believe is a critical path to regulatory filing in the US is the X-TOLE data that we’ve already generated and the data from X-TOLE2.
And then the data that we generate in X-TOLE3 and X-TOLE4, including all of that open-label data, will be important for the safety database as part of the filing.
Chris Kenney: Can I — sorry.
Ian Mortimer: Yes, yes, go ahead, Chris, and then we’ll pass to Sherry.
Chris Kenney: Well, I just wanted to — I mean, that’s purely from the regulatory perspective, which is obviously important. But these patients based upon the open-label extension in X-TOLE they’re doing really well. And we didn’t feel comfortable removing them from study drug. The other thing I’ll add is more back to kind of the regulatory question. The development program for XEN1101 was extremely efficient, right? Go from Phase 1 to this Phase 2b study, very quick. And so as a result of that, there’s a little bit of work to be done in terms of making sure that we have enough unique exposures in order to adhere to ICH guidelines. So, there is a touch of regulatory in there, but we thought it was just the right thing to do. And then on top of that, recruitment, I think, would be a major issue to the point, brought up, I think the very first question was about recruitment rates. That would be–
Laura Chico: Chris can I–
