Tazeen Ahmad: Yes. The question is on what you’re going to present at the top line? What should we include in that assumption of what you’re going to be presenting? So would you be
Yvonne Greenstreet: Fine, that’s really clear, so top line
Tazeen Ahmad: Yeah.
Yvonne Greenstreet: Topline data from the ALN-APP study. Pushkal?
Pushkal Garg: Yeah. Thanks, Tazeen. So, yes, we’re really excited about the ALN-APP program. It’s our first foray into the CNS. We’re still on track to have top line data in the first half of this year. As a reminder, this is a study in patients with early onset Alzheimer’s disease. We’re in the single ascending dose phase of that study. And what we are hoping to report out on will be safety and tolerability, which is the primary endpoint. This is the first time we’re giving intrathecal injection with the C16 conjugate, and then looking for target engagement, a knockdown of soluble APP alpha and beta. So we have very good pharmacodynamic markers that can point to target engagement. And we will want to see evidence of target engagement there that we’re seeing good pharmacology in the brain. So those are really the key things that we’ll be reporting on later in the first half of the year.
Yvonne Greenstreet: Thanks Pushkal. Next question?
Operator: One moment for the next question. And your next question comes through the line of Salveen Richter from Goldman Sachs. Your line is now open.
Unidentified Analyst: Hi, this is Tommy on for Salveen. Thanks so much for taking our questions. For HELIOS-B can you remind us of the rationale behind using all-cause mortality instead of cardiovascular mortality in the composite primary endpoint? And is there one that’s preferred by physicians and regulators? Thank you.
Yvonne Greenstreet: Thanks. And I guess that’s a question straight for you, Pushkal.
Pushkal Garg: Yeah. So Salveen I think when we, you know, when we look at, when we designed the HELIOS-B study, we really want to ultimately show the benefit of the drug on the totality of the experience of patients with this disease. And an all-cause mortality and recurrent CV event endpoint really captures, maximizes the number of events that we can capture in the course of the study which aids in the powering of the study and also becomes a very clinically meaningful effect. Certainly there can be analyses that are looked at under that as secondaries or post hocs that look at the various types of mortality events. But that’s the basic explanation.
Yvonne Greenstreet: Next question?
Operator: One moment for the next question. The next question comes from the line of Maury Raycroft from Jefferies. Your line is now open.
Maury Raycroft: Hi, good morning. Thanks for taking my question. I was wondering if you have a tentative date scheduled for the adcom and you’ve mentioned adding the 120-day safety data from APOLLO-B open label extension, but I’m wondering if you can discuss possible scenarios where you may be able to supplement the sNDA with additional efficacy or safety data from APOLLO-B, open label extension and or the HELIOS-B study.
Pushkal Garg: Yes, so Maury, maybe a couple questions in there. You know, we don’t have a formal date yet. That’s something again, we’ve released what we understand at the moment from the agency’s correspondence with us. So we’ll look forward to getting additional information on that. And in terms of the 18-month data, look we’re in the process of getting and reviewing the APOLLO-B open label extension data. As a reminder, everybody crosses over to active drug at month-12. And we’ll certainly share those data at an appropriate scientific meeting. And with regard to the agency, we’ll be supplying whatever they need to facilitate their review. And so, we’re looking forward to sharing things, the data with them, both from the main study and as they need from the open label extension. The day 120 safety update is primarily focused on safety update data, so that will also be a parallel process.
Maury Raycroft: Understood. Okay, thanks for taking my question.
