James Hamilton: Yes. So for RAGE, I would say, based on our animal data, we were in the Alternaria model that we presented at ATS, we were wanting to get better than 50% knockdown, 60% to 70% knockdown in that particular animal model. And then for MUC5AC, I think if you look at the patient data versus the healthy volunteer expression level for MUC5AC that patients have maybe tenfold more MUC5AC compared to what the healthy has. So I think that — and you probably don’t have to bring the patients back to normal levels to have a benefit. But particularly in the patients, I think there’s pretty significant dynamic range in terms of MUC5AC knockdown such that if you get 50% reduction in MUC5AC expression, we may see an associated clinical benefit. I don’t know if that addresses your question.
Madhu Kumar : No, that’s helpful. Maybe on AAT, I guess kind of — how much different would you expect the SEQUOIA data to be from the Phase 2 of label extension given kind of like patient recruitment in SEQUOIA relative to the open label extension? Like is there any reasons are going to be a significant difference in kind of the disease course in the SEQUOIA patients relative to the open label extension?
Christopher Anzalone: I don’t believe so. No, they should be similar. Look, we always viewed that open-label data as important in terms of pegging a story. It was a small number of patients, but we thought it pegged the story. And we have been looking for — we’ve been hoping that SEQUOIA would confirm that story.
Operator: And our next question comes from Mayank Mamtani from B. Riley.
Mayank Mamtani : Thanks for squeezing me in and I appreciate you putting out the 2025 campaign. So maybe on the SHASTA study, a quick follow-up on the two pancreatic events that you saw there. Admittedly in a blinded manner, but is that what you would expect for a study this size? And in general, like what would be the event rate for SHTG study? And maybe a second part, as you think about validating triglyceride as an approvable endpoint for either SHTG or for larger mixed dyslipidemia indication, how are you sort of thinking about that next year?
Javier San Martin: Yes. So with regards to the two cases of pancreatitis are well within the expected event rate, which is about 3% to 5% per year in this patient population. So we saw two cases in about 200 patients and by the time we — I mean, by now we have almost one year follow-up in most of those patients. So yes, the event rate is what we expected. And the second part with regard to the Phase 3 study, I think we commented on this before, the registration program for ARO-APOC3 in the severe hypertriglyceridemia indication does not need pancreatitis endpoint for approval. But of course, we would like to enrich the patient population as much as possible to provide information about pancreatitis risk reduction, which is the goal of therapy.
And that would be very important for many other reasons really to translate the clinical benefit, to define the value proposition and so forth. So the approval path does not require pancreatitis, but we will do our best to have enough number of patients at high risk, so we can see the risk reduction in pancreatitis as a consequence of normalizing triglycerides levels.
Mayank Mamtani : And then just a quick one on A-1 AT. Are you able to comment on how — as you think about Phase 3, how are you thinking about placebo response? Because there have been studies recently put out independent of this program and also by Takeda about how to sort of think about F2, F3 patients differently. So is there anything you could comment on that on the placebo response for Phase 3, how you might be thinking about?
