Luca Issi: Alright. Thanks so much for taking my question. I have two. Maybe circling on A1AT, circling back on the prior question, Javier, can you just talk a little bit more about the powering assumption here in the Phase 3 at 160 patients in the primary endpoint of 2 years, what is the minimum delta in fibrosis between the active arm and placebo that is actually sufficient to hit the stat? Any color there would be great. And then maybe on DUX4, can you just talk a little bit more about that program. I think in the past, you have mentioned that expression could be quite variable there. So, wondering how you are planning to mitigate their risk, I mean maybe more broadly how confident are you in that program?
Javier San Martin: Yes. Luca, so I don’t know how much detail I can provide on the specifics that the Takeda team and this situation, the work they did to power the study or to size the study with 160 patients. And like I said, the primary endpoint or the primary analysis is at 2 years, 106 when all patients with F2 and F3 that would be about 110 or so complete the 2-year study. So, that gives you really for what we learned so far and we can take this 50% reduction in fibrosis that we observed twice in two different studies with the same and similar patient population as a good point of reference, I would say. And then, you need to look at the natural history data versus the SEQUOIA data and go somewhere in between. And if you do that exercise, you will come out with the same number, more likely. So, that’s how I will address this comment. But Chris…
Christopher Anzalone: And importantly, as Javier mentioned that, that 2-year time point is at around 110 patients, not the full 160. And importantly, it was powered based on that. So, given their assumptions, they determined that 110 should be sufficient. James, do you want to
James Hamilton: Sure. Yes, the DUX question. It’s correct that the expression of DUX4 is static . And or the measurement of the protein in the muscle and the downstream DUX4 affected genes can be challenging at least one other company has demonstrated. And that was one of the reasons, if you recall that we wanted to be sure that we had the tox coverage to cover a longer Phase 2 study, something if we weren’t able to see any knockdown in gene expression that we could do a longer study and see some proof of concept efficacy with imaging, specifically with MRI or with functional endpoints, things like reachable workspace, we now have that tox coverage at least from the chronic monkey study. I think the chronic rat readout should be available shortly.
So, we have the ability to design a study that not only could potentially give us biomarker readouts if we are able to measure DUX4 and downstream gene expression, but also a study that would have MRI and functional endpoints built into it as well.
Luca Issi: Got it. Thanks so much.
Operator: Thank you. Our next question comes from the line of Prakhar Agarwal of Cantor. Your line is open, Prakhar.
Prakhar Agarwal: Hi. This is Prakhar from Cantor. Thanks for taking my questions. So, first on ARO-AAT, how long do you think will it take to enroll the Phase 3 trial, the clinical trial entry for it suggest primary completion date of March 2027. So, that would imply roughly 2 years for enrollment. Is that the right proxy to think about the timing of this readout, or would the timelines be expedited? And I had a quick follow-up.
Christopher Anzalone: Yes. I think it’s inappropriate for us to opine on that since Takeda will be running that. I think probably best to ask them what their expectations are.
