Gary Nachman: Thanks. Good morning. So, in ATTR-CM, are you still just thinking of [indiscernible] as primarily a monotherapy drug as tafamidis continues to grow as standard of care in ATTR-CM, if the combo data with TAF are positive enough and show enough of a benefit over TAF alone, would you reconsider that thinking? And what are you doing now to prepare for the launch in CM? Just some details there would be helpful. Thank you.
Yvonne Greenstreet: Yes, some really good questions there. So, Tolga, maybe you want to talk about how we’re looking at the cardiomyopathy market and how we’re preparing for launch. I mean, clearly we’re playing to win in this space. So we’re very excited about the opportunity of getting into this very rapidly growing category. Tolga?
Tolga Tanguler: Yes, no, thank you. That’s exactly right. We’re really here to play to win. And look, at the end of the day, we need to look at the fundamentals of this category. There are 80% of the patients remain undiagnosed. This is a rapidly and progressing disease with irreversible damages. And frankly, patients and physicians are both looking at quickly be able to deal with the disease as quickly as possible. So if you look at the pharmacodynamics of what AMVUTTRA has to offer and how we impact the disease causing protein at the upstream and rapidly knocking down that toxic protein, that is going to be a key clear differentiator. At the end of the day, we know that AMVUTTRA provides speed, depth and duration as early as it first dose.
And this is what physicians are really looking for. It is true, and it’s great to see that tafamidis is making great progress. But it’s not just the standard of care, it’s the only care in this category. So one needs to remember that. And I think they have just reiterated the fact that the LOE in the U.S. in particular, is going to remain until the end of 2028, which really means, mainly because of the access pressures, but also, again, the way this product is going to be positioned. And obviously, depending on the data we need to demonstrate. We believe we’re going to be able to actually be the first-line agent and after all, there are going to be, as Pushkal indicated, a substantial number of patients who are being treated that are continuing to progress.
And we believe physicians and patients are looking for an alternative. And in that case, we believe it’s going to be a very important option in the armamentarium of the physicians in this difficult disease.
Yvonne Greenstreet: That’s absolutely spot on, Tolga. And I think it’s just instructive when you reflect on our expanded access program, where within a matter of very short space of time, we max that on the program. I think that, again, is just an illustration of the level of unmet medical need in space and the fact that patients continue to progress on tafamidis and are looking for alternative therapies. Next question.
Operator: One moment for our next question. Our next question comes from the line of Tazeen Ahmad with BofA Securities. You may proceed.
Tazeen Ahmad: Hi. Good morning. Thanks for taking my questions or question. I appreciate all the color you’ve been giving about expectations for what to show at the top line. But in terms of trying to drill into the detail on mortality, specifically fully understanding there’s a lot of undermet need, even with what’s available right now, how important is it going to be to know when the mortality benefit kicks in for vutri? So, I think for tafamidis that benefit in the Pfizer studies started around month 18. Is it going to be important to have a number at the end that hovers around that month 18, or potentially, could it be better than that? Thanks.
Yvonne Greenstreet: Pushkal that’s one for you.
Pushkal Garg: Yes. Thanks, Tazeen. Look, I think, what we’ve seen in terms of mortality separation, if I call both for tafamidis and the acoramidis data that are under review, is around month 18 is when we start to see the mortality separation. Look, we’re encouraged by what we saw coming out of actually the original APOLLO data and then the APOLLO-B data where we seem to see evidence again in underpowered studies of separation on mortality occurring earlier, roughly month nine or so. So, we’ll have to see in HELIOS-B if we’re able to recapitulate those results in this larger powered study. Again, I think it’s going to be important to look at the totality of all the data that come out. Obviously that will be one parameter.
What is the mortality difference when is it emerging? What about hospitalizations? And then again, what’s happening in terms of disease stabilization? So, we think all of those are going to be important parameters. But look, the early data that we’ve seen from APOLLO and particularly APOLLO-B, which is in the same patient population gives us a lot of confidence that we should be able to see a substantial effect in potentially earlier separation.
Yvonne Greenstreet: Thanks, Pushkal. Next question?
Operator: One moment for our next question. Our next question comes from the line of Ritu Baral with TD Cowen. You may proceed.
Ritu Baral: Good morning, guys. Thanks for taking the question. I want to thank you for the detail that you’ve given on the top line release, but I wanted to just dig a little further if I could. Pushkal, and Yvonne, when you mentioned that you would give us some more details on subpopulation. Will you be able to give us sort of drivers of potential composite benefit of the TAF subpopulation or the composite, I’m sorry, combined subpopulation as well just given the conversation – investor conversation and focus on hospitalizations, driving previous data sets where we get sort of a tell on what the major drivers are. And then just a very quick follow-up on data release. You drop proBNP and echo parameters to exploratory endpoints, and those are ones that at least our KOLs actually deeply, deeply value. We were wondering if those would be released with first medical presentation. Thank you.
