Andreas Maldonado: Hi. Thank you for taking my question. I reiterate my congratulations on all the progress. So one quick question from us on 439. So I guess in the context that the goal of next-generation obesity program aims to really hone in and follow the issue of variability of patient response. Could you maybe talk about how much in this variance, you scribe muscle loss, driving that variation in patient response. And then a follow-up question to that would be, given the safety and tolerability of apitegromab and which has been positive. Are some of the treatment-emergent events more worrisome in the context of the combination? Thank you very much.
Jay Backstrom: So okay, maybe we’ll do a tag team with Mo. I think your question is sort of the variability in weight loss that occurs with the current GLP-1 receptor agonist. And you see kind of a range across. Some patients do well, there gets to be a plateau for some. I think it probably, in my — as I review the literature and look at the data, some of it may very well be starting points for the patient’s ability to get to adequate doses. So I think there’s a lot of things that affect the overall waive loss. From the muscle mass loss that we’ve seen, there is a range, but it’s a fairly — it’s what, between 20% and say, 40% that is definitely related to that. And so those are kind of related events, but our focus really is on the preservation of the muscle mass, which we believe we should have a consistent effect across hence, we’ll look at our proof-of-concept studies to move forward.
But I think that’s the thinking there. And again, I think it’s really interesting to your point about safety, and we’ve emphasized this because, it matters, it really matters. I think about weight loss therapies over time, they’ve been effective, but they’ve all been troubled by toxicities and safety issues that have prevented their continued use. I think what we’re seeing with the GLP-1 receptor agonist is to date, and there’s been wide patient exposure. We’re seeing some effects, but nothing like what we’ve seen in the past that would really warrant stopping these therapies. So that’s a good thing. But any additional therapy that comes into this space, that’s an add-on therapy that’s used to kind of offset some of the negative effects like loss in the muscle, in my mind, really needs to bring no additional risk of toxicities if possible.
And that is where I believe, if you look at all of the conversations going on in other areas, other companies coming into lean muscle mass, I do think our approach by hitting myostatin and non-myostatin will avoid off-target effects. And I think Mo walked through that. If you look at what happens when you hit active and receptors A and B, you start to get into some things that you may not want to see, right, that over time could potentially be troublesome and that’s also true with GDF11. So I like our approach. It shouldn’t bring any additional risk to that risk-benefit profile. We’ll obviously see that when we report on our Phase III data, but so far — and we’re seeing that in TOPAZ, we have patients coming on four years with really a very, very clean safety profile.
I think in the cardiometabolic space, we definitely want to continue with that. And I think we’re positioned to show that.
Operator: Our next question comes from the line of Ernesto Rodriguez-Dumont with Cowen. Please go ahead.
Ernesto Rodriguez-Dumont: Hi, thank you for taking my questions and congratulations on the progress. I just have a follow-up on the obesity program functional endpoints for regulatory purposes. So other chromatin programs that show muscle gains in other settings day, are there any hints of functional changes from those programs that could lead the way to identifying a functional endpoint for the obesity program? And then also, do you expect the therapy to be a chronic therapy in conjunction with the GLP-1 or do you expect that there to be some kind of biomarker and limit to the therapy. Thank you.
