Yvonne Greenstreet: Yes, Ritu I mean, I think that’s a – yes, it’s a good question. And I think we’ve been quite clear about how we’re going to be handling the release. I mean, clearly we’re going to show kind of p values for the primary endpoints and key secondary endpoints. So we’re going to provide some information on safety, obviously, that’s an important consideration. And we’ve said we will give some information with respect to subgroups. I know he’s [ph] particularly interested in the tafamidis subgroup, but I think that’s where we stand at this point in time. We’re kind of obviously looking forward to being able to share the top line results. We’re still on track for end of June, early July.
And then, of course, we will present fulsome data at a proximal medical congress. So stay tuned. We will be providing some additional color over and above p values for the primary and secondary endpoints, but that’s probably all we can say at this point in time. Your second question?
Ritu Baral: It was on the…
Pushkal Garg: You were just [indiscernible] the NT-proBNP and the echo data. Look, I think, we haven’t mapped out exactly what will be in the top line presentation. Obviously, we’ll be limited in terms of what we can, we want to make sure that we and we’ll work with the investigators to make sure that there’s a fulsome presentation. But you can imagine with a data set like this that there’ll be a number of presentations to speak to the various aspects of the data. And certainly BNP, echo, et cetera, or two are important parameters that we’ll be reporting on.
Yvonne Greenstreet: Absolutely, Pushkal. I mean, we’re clearly very interested in those parameters, but you kind of have to prioritize how many secondary endpoints you have with respect to managing alpha. And clearly, we’re pretty confident about what we’re going to be able to demonstrate with those additional endpoints. But they’re going to be endpoints that we’ll be able to share. But we really wanted to prioritize, the very clinically relevant secondary endpoints. And we’ve discussed what those are with respect to disease progression, mortality, as well as a six-minute walk test in KCCQ.
Ritu Baral: Great. Thank you.
Yvonne Greenstreet: Thanks. Yes.
Operator: One moment for our next question. And our next question is from Jessica Fye with JPMorgan. You may proceed.
Jessica Fye: Hey, guys. Good morning. Thanks for taking my question. For HELIOS-B, when you talk about any impact on outcomes being clinically meaningful. On the one hand, I completely hear you their outcomes. But then again, when we ask physicians about this, they usually have a magnitude or a threshold in mind that’s not just any benefit. So I’m curious how to kind of reconcile that. Or maybe you could just elaborate there?
Pushkal Garg: Yes. Look, Jessica, I think, I don’t know that I can give you a lot more information other than to say, just have to, again, remember what the unmet need in this disease is that there are patients who currently, a large number of patients, as Tolga has outlined, many of them are undiagnosed and untreated, who have a steadily progressive disease that leads to irreversible damage, and ultimately patients pass away. And so what I think, and as evidenced by, as Yvonne highlighted, our EAP experience after APOLLO-B, and that was in the setting without any outcomes benefit being demonstrated in IV drug. We rapidly enrolled a population of patients, many of whom were progressing on tafamidis, which was the only available therapy to them.
So it highlights the unmet need. So we think that when we come forward with hopefully a positive HELIOS-B, showing an outcomes benefit, a mortality and hospitalization, along with these other differentiating factors that we’ve talked about, and an orthogonal mechanism that rapidly knocks down the disease causing protein of this disease, that we think that that’s going to address the key unmet needs for these patients. So we’re looking forward to that and we’ll let the data speak for themselves.
Jessica Fye: Thank you.
Operator: One moment for our next question. Our next question comes from the line of Kostas Biliouris with BMO Capital Markets. You may proceed.
Kostas Biliouris: Good morning, everyone. Thanks for taking our question and congrats on the progress. A question from us on HELIOS-B, just for a change. How important do you think is the ratio between hospitalization events and deaths as a metric, especially when we compare different drugs? Do you look at this ratio as an important metric, or you just look at those two types of events together as a composite? Thank you.
Yvonne Greenstreet: Thanks for the question, Kostas. Pushkal, this is one to you.
Pushkal Garg: Yes, no, I think it’s an interesting question, Kostas. I think, in general, we look at them together and we don’t make a huge, huge distinction here. I mean, I think part of the reason that composite endpoints like this were created was because hospitalizations tend to correlate very strongly with mortality events. And so these are both clinically meaningful outcomes. And so we would expect that they will both go directly in the same direction. That’s what we’ve seen with other drugs. That’s what we’ve seen throughout the cardiovascular disease area with lots of drugs and lots of different diseases, disease classes. So we would expect them to go in similar directions, Kostas, and I think the main thing is seeing a benefit, hopefully in both of those that trend in the right direction.
Kostas Biliouris: Thank you. Very helpful.
Operator: One moment for our next question. And our next question comes from the line of Ellie Merle with UBS. You may proceed.
Ellie Merle: Hi. Thanks for taking the question. In ATTR, what proportion of patients do you think are mixed phenotype in the real world? And how is this being defined both by doctors and by payers? And do you see silencers as more likely to gain a larger share in this population versus stabilizers longer term, when we look to the cardiomyopathy expansion? Thanks.
Yvonne Greenstreet: I think Pushkal first, and then Tolga will follow up.
Pushkal Garg: Yes. Ellie, I think you raised a very important question, and I think we’ve oftentimes people have sort of classified these as two very distinctive diseases, polyneuropathy and cardiomyopathy, when, in fact, it’s the same protein, when it’s misfolded, that’s causing both manifestations of the disease. And I would – we’ve seen, for example, that in the hereditary population, when we looked in APOLLO and HELIOS-A, that more than half of those patients had concomitant cardiomyopathy. And conversely, studies that have been done in cardiomyopathy patients suggest that a significant proportion of those patients may have polyneuropathy manifestations. So, there are reports ranging from 15% to 30% or more of patients with wild type ATTR or V122I, for example, which might have a primary cardiomyopathy manifestation, have concomitant polyneuropathy.
And certainly we’ve seen that with the silencer class of drugs, particularly with patisiran and AMVUTTRA, that the magnitude of effect in polyneuropathy is really quite unsurpassed in terms of its clinical profile. And so it’ll be interesting to see, and Tolga can probably comment more about this, how clinicians will make decisions when they have patients who have multiple manifestations of this disease, when they hopefully have multiple classes of therapies available.
