Pushkal Garg: Sure.
Operator: And one moment for the next question. Your next question comes from the line of Paul Matteis with Stifel. Your line is now open.
Paul Matteis: Hey, thanks so much for taking my question and congrats on the progress. I was, I thought it was really interesting that you included potential sales from ONPATTRO in TTR cardiomyopathy in guidance, given that it’s under review, given that there is an adcom, and I guess is it the right interpretation of that decision, that the company continues to have very high conviction that the APOLLO-B data should lead to an approval, and that was enough for you to plan financially and guide around that? Thank you.
Yvonne Greenstreet: Yes, well, I mean, I’ll start and then hand it over to Jeff in terms of how we thought about planning. I mean, clearly, we do believe that the APOLLO-B study has delivered actually very impactful results, both in terms of health status and disease progress. We’ve talked about the efficacy endpoints in some detail. And clearly we are planning for the advisory committee as notified by the FDA. And obviously you know, we will have to await the FDA’s determination on our submission. But you know, we believe that we have an efficacy and safety package here that is pretty compelling. Jeff, do you want to speak a little bit to how we thought about ONPATTRO CM revenues?
Jeff Poulton: Yes, I mean, Paul, you’re right. I mean, we flagged that in the guidance on the slide that we assumed that. Again, given the timing of that, given that it’s in the fourth quarter, the impact of that from a revenue perspective, that this year is going to be relatively modest. And so, not, that doesn’t really have a significant impact on the financial guidance we’ve given for the year as a result, if approved, we would expect more significant impact next year.
Paul Matteis: Thanks so much.
Operator: And one moment for your next question. The next question comes from the line of Gena Wang with Barclays. Your line is now open.
Gena Wang: Thank you. I have one question regarding the APP program. What will be the ideal clinical profile regarding percentage of knockdown and the frequency of dosing? Any negative review from vutrisiran by any dosing data regarding frequency of dosing for the APP program?
Pushkal Garg: Yes, Gina, thanks for your question. So I guess a couple things in there. You know, what’s the ideal profile? So look, I think this is the, you know, we’ve said before that we don’t have the, from genetic data, we would imagine that we would want get to close to about 50% knockdown of ALN-APP of amyloid precursor protein. We think that’s probably around the target range to get to a therapeutic effect, but at the end of the day, no one really knows. And so that’s kind of where we’re shooting for. But this is again an initial single ascending dose study. We’ll be providing some interim data and so we’ll be working our way up to get to higher levels of knockdown as the data allow and so that’s point one. In terms of the frequency of dosing, look, the preclinical data that we have suggests that this may be a relatively infrequently dosed molecule.
We’ve seen knockdown lasting over six months in the non-human primate studies that we’ve done with ALN-APP. So we’re very encouraged with the potential that this could be a quarterly or potentially biannually dosed drug in the CNS. But again, the data will inform that. I don’t think there’s any particular read-through from the increased randomized treatment extension that’s a different molecule given to a different space. It’s a different conjugate. And as you know, we continue to — our scientists continue to hone our chemistry all the time, but a lot of that is also molecule and target dependent. So we’re very encouraged by the data we have so far non-clinically and really looking forward to the clinical data emerging shortly.
Gena Wang: Thank you very much.
Pushkal Garg: Thanks, Gena.
