Onaiza Cadoret : Yes. So Robert I think that we would expect that again the two indications are both rare disease indications, but they are priced differently if you looked at analogs in the marketplace. Based on all the work that we’ve done, we don’t believe there is any reason to kind of shift from that in terms of our pricing strategy. So I would expect that as the price is set by AZ that we would expect polyneuropathy to be priced according to the analogs and benchmarks of other polyneuropathy products.
Brett Monia : And regarding our newest Phase 3 program our Alexander disease program most of the time we’re enrolling rare disease indications can be challenging, because they are rare in finding patients into your study obviously can present challenges. But what’s unique about our Phase 3 program for Alexander disease is that we designed a seamless Phase 1 through 3 design such that it’s all the same sites. It’s all the same — the protocol has already been baked and everything like that. And after our Phase 2 results, which was when we reviewed it we had two decisions to make not really. One was to dose escalate or to move into Phase 3 development. And during that review process when you go through all the data you’re collecting the data you’re cleaning the data and before we actually review the data enrollment is put on pause right?
Because we don’t know what the next step will be for the program. And what happened in this situation is that patients were on the sideline waiting to get into either the dose escalation phase of the next step or the Phase 3 part of the program. So with that said, we think actually enrollment will go well for the Alexander program because we have patients on the sideline waiting to qualify to enter our Phase 3 program now that we’ve activated it. So enrollment is ongoing and we expect data in 2025.
Operator: The next question will come from Yaron Werber with Cowen. Please go ahead.
Unidentified Analyst : Hi, guys. This is Brendan on for Yaron. Thanks so much for taking the question. Just a couple of quick ones from us. Just another one on Matt Tau — excuse me, sorry if I missed this but — just wondering if there’s any plan for any interim look at the Phase 2 study or any possibility of any additional data updates there before the full Phase 2 readout assuming maybe 2026 for the full Phase 2. So just wondering if we can expect anything new there in the meantime? And then quickly on donidalorsen. Obviously you have a few different studies ongoing there. But I think you’re planning to incorporate into one filing maybe including the switching study, et cetera. So can you just maybe give us a sense of timing for data beyond the top line readout in the first half of next year?
Maybe how long thereafter do you think you’d need to collect and analyze data, and if you’re thinking to maybe file in the second half of next year if that’s fair to assume. Thanks very much.
Brett Monia : Sure. So there’s no plan for an interim look in the Phase 2 study for the tau program at this time. So that’s a short answer quick answer. It’s very important to get this study right, and you get the richest dataset as you possibly can. And as I mentioned earlier, it’s — this is — what we’re looking for here is actually evidence to support a Phase 3 decision that we’re improving cognition impairment. So that’s going to take time that studies over a year long, as I mentioned earlier, more than 700 patients. So no interim look at this time. For donidalorsen, I don’t think we’ve said that we’re expecting to include switch data in the filing for the NDA. Really the Phase 3 data along with all the other data that we’ve generated from Phase 1 and Phase 2 will be sufficient to support a filing assuming positive outcome.
With that said, we expect Switch data from our Switch study which as a reminder to our knowledge we’re the only sponsor that has actually conducted a true Switch study in which patients that are on an existing treatment therapy Prophylactic Treatment are switched over to power of investigational medicine Donidalorsen to and Onaiza mentioned which in our case is Donidalorsen. And then we assess everything, including protection against HAE attacks on identifying demonstrating that there’s, no gaps between one treatment switching to, another treatment. Tolerability sustained efficacy and actually be able to generate the information that prescribers are going to want to have to understand how do I do this? Okay I want to switch to your drug. I want my patient to go on your drug, but how should I do this?
And that’s really the goals of the Switch study. We expect that data to be out next year or at least a cut into that data next year that’s going to really allow us to actually demonstrate the value of Donidalorsen in this market which is a Switch market. But we have no plans to include that at this time to my knowledge in the NDA filing.
Onaiza Cadoret: If we believe that the publication will be more than sufficient to be consistent with label to be used actively by our sales teams in promotion. And to the extent if it’s all ready alongside of it, we could actually add it in, but it’s really not a requirement nor that we think it’s really necessary for commercial uptake. We like it in the publication. That’s what we’re really looking for is our strategy going forward.
Unidentified Analyst: Okay. Great. Thanks very much.
Operator: The next question will come from Jessica Fye with JPMorgan. Please go ahead.
Unidentified Analyst: Hey guys. Good afternoon. Thanks for taking my questions. Can you remind me of your expectations around whether in addition to a clear impact on triglycerides, whether you believe you could show an impact on pancreatitis for Olezarsen in sHTG? And then second forgive me if you stated this, but for CARDIO-TTRansform, I believe the ball is up to 140 weeks. I just wanted to clarify is there a minimum planned follow-up for those who do not reach 140 weeks. I noticed some of the endpoints are assessed a week I think 121. Is that the minimum assuming the study has not stopped early? Thanks.
Brett Monia: Eugene, do you want to take those?
Eugene Schneider: Sure. Happy to, maybe I’ll start with the last one. So as you said of course the fair excruciating level of detail on the statistical analysis plan, but just to summarize it the exposure on the study is up to 140 weeks which means that in some patients if the study reads out early the exposure will be less than that. We’ve defined the minimal exposure and the time point specific time points for those early look in our SAP. And I don’t think that we’ve come out and included specific time lines on those other than sort of the general statement about early opportunity for closing the study earlier based on some specific conditions being met. And then,…
Unidentified Analyst: In the event you don’t stop the study early what the minimum would be?
Eugene Schneider: Well, if we don’t stop the study early we go — all patients will be treated for 140 weeks. That’s the double-blind period.
Unidentified Analyst: Yeah. Okay.
Unidentified Analyst: Okay. And then, likelihood of achieving AP in sHTG?
Eugene Schneider: Yeah. So sHTG again it’s of course a very different population from FCS in terms of risk for AP events. Having said that again the program that we designed the two very large studies certainly we believe we’ll have an opportunity to show an effect. And what we are also going to be looking at is a combination of those two studies. So looking at sort of integrated analysis of efficacy combining those two large studies which together amount to about almost 1,000 patients. So we’re fairly confident of course today we don’t know what the data will show. What we can say is that we were extremely pleased with the effect on AP events in our FCS population. So we do believe that the thesis is very strong, but we need to wait until the data read out.
Operator: The next question will come from Kostas Biliouris with BMO Capital Markets. Please go ahead.
Kostas Biliouris: Hi, everyone. Thanks for taking our question. One quick question from us on ATTR. This morning [Indiscernible] presented data from the literature demonstrating that in addition to the percentage of TTR reduction, the absolute serum TTR levels after treatment are also very important as they can contribute to the ongoing fibril formation and they actually have an impact on survival. That said I’m wondering whether you have any thoughts around that given that most of the discussions in this space focus on the percentage of TTR reduction rather than the absolute levels of TTR post treatment? Thank you.
