Allison Bratzel : Just one for me on the Phase 2 GOLDEN trial in GA. Just curious, is there any update on your view of the geographic atrophy space and potential opportunity for a therapy targeting complement factor B, just given some of the recent safety and regulatory updates in the GA space in recent weeks. Could you just frame what you’re looking for in the Phase II readout next year to warrant further investment in that space?
Brett Monia : Thanks, Allison. Yes, we’re — and our partner, Roche, are very enthusiastic about our GA study, our Factor B-LRx geographic atrophy study GOLDEN. We’re pleased that there’s a benchmark to get drugs approved for GA. This helps set a path forward for all drugs that are being developed for GA, including ours. We like our drug. We like our profile. So far, the GOLDEN study is a large study, around 300 patients to dose cohorts, dosing groups, in which patients are going to be treated for about 15 months. So it’s a good study. And what we’re looking for is the primary changes in geographic atrophy area in the study. So it’s an efficacy study, a proof-of-concept study, and that study is due to read out next year. We like this.
We like to target, Factor B in the alternative play, we think is the right target for GA, we think systemic approaches to the complement pathway, particularly Factor B is the right approach for treating GA. And we think that the overall safety profile and tolerability profile that we’re going to have with Factor B-LRx is going to be a very significant advantage versus IBT drugs, which are administered directly to the eye and have side effects as a consequence to that. We expect Factor B-LRx to have an excellent safety profile, much like the rest of our LICA platform that has eplontersen, pelacarsen, olezarsen, donidalorsen. So that — it’s in Phase 2, and we’re seeking to achieve proof-of-concept for the next year. If the data is strong or the data supports, I should say, Roche is preparing to go to Phase 3, and they’re equally enthusiastic for the program as we are.
Operator: The next question comes from Paul Matteis with Stifel.
Paul Matteis : Congrats on all the progress. I wanted to ask about olezarsen in light of how much the cardiometabolic space has really changed since you initiated the pivotal program. Just specifically looking back at the Phase 2 baseline characteristics, I think most patients in the study had type 2 diabetes, most patients had comorbid hypertension. BMI was overweighed on average. I guess, how do you think about the impact of this recent WEGOVY data and more broadly, the takeoff of these weight loss drugs on the market for olezarsen? And I guess, what percent of patients with trigs above 500, would you say demographically wouldn’t actually qualify for one of those drugs on label?
Brett Monia : Onaiza, you want to take that?
Onaiza Cadoret: Yes. Hi, Paul. Yes, been on it’s a lot of good data for the GLP-1s recently as well. So a couple of important things to note. First of all, they’re not going to be indicated, right, for triglyceride lowering. And if you looked at some of their TG — just their TG lowering data, it’s very much in line with what current standard of care is. So they’re not getting to the really high levels of TG lowering that APOC3 target can actually deliver here. So that’s kind of the first thing. If physicians do use it off-label, it’s a very important reminder, and I think most of the endocrinologists know is that the GLP-1s have a warning in their label for not being used in patients with risk or a history of acute pancreatitis.
And as you know, in the 500-plus severely elevated triglycerides where olezarsen is being studied, we have many, many patients who are at risk for AP. So we do think both the magnitude of triglyceride reduction along with the risk for these patients who are over 500 for AP, we do not expect that to be a direct or an indirect competitor.
