Unidentified Analyst: Okay, thank you. And maybe a quick follow-up question, if we may. So how do you view some of the evolving data in the field include the most recent update from Roche Trontinemab? Thank you.
Daniel O’Connell: Sure. I can take that. I think we noted at the ADPD that Trontinemab data, which is early but encouraging. We took the view that targeting oligomers as a differentiated mechanism from a Gantenerumab shuttle construct, which is the Trontinemab. And so we’re very much committed to exploiting the oligomer targeted mechanism of Sabirnetug and generating evidence in support of it as a treatment option and feel — that the field in general, is large enough to accommodate a variety of different product formats and options. So it’s interesting and something we’re looking at but staying very focused on execution for Sabirnetug.
Operator: One moment for the next question. The next question comes from Geoff Meacham with Bank of America. Your line is open.
Unidentified Analyst: Good morning. This is Jason on for Geoff. Thank you so much for taking our questions. And congratulations on the progress. I wanted to ask maybe a little bit more broadly, we’ve seen the publication of a number of recent studies that have found that a number of the signals or biomarkers for amyloid beta appear quite some time before the symptoms. I think specifically regarding the ratio of A-beta 42 to A-beta 40 pops up 14 years prior to the onset of symptoms. And I’m curious, has that influenced the design of some of your clinical studies, do you think you may need to go a little bit earlier, or do you feel that kind of early AD is sufficient enough for kind of either a reversal of the symptoms or delaying them?
Eric Siemers: Yes. So Dan, do you want me to take that one, it is a great question. So yes, one of the ways that the field has made some real progress in the last 10 years and maybe even the last 20 years is the understanding of this fact that, as you point out, that you develop the plaques 15 to 20 years before you develop any symptoms. And there has been a thought in the field that if you were going to target amyloid or A-beta in one way or another, that because of that time period, you actually had to do it before people had any symptoms at all. And there are ongoing studies and they have been ongoing. There have been studies of what’s called preclinical Alzheimer’s disease. So in other words, you have the plaques, but you don’t have any symptoms yet.
Thus far, none of those studies have been successful. I think there’s a lot of reasons for that. Partly, the study design is much more complicated. The studies need to be longer or some technical reasons why that’s a challenge. But what’s really important, I think, is that for drugs like Lecanemab and Donanemab and potentially even Aducanumab, you’re seeing a signal in people who have either MCI or mild dementia with Alzheimer’s pathology. And the reason why that’s so important is that means you don’t have to go all the way back to that preclinical stage where the study designs are much more challenging and not as well worked out. So we feel really good about the fact that we are in this population of MCI plus mild dementia. Other drugs are starting to see a signal there.
And apparently, what that means is that’s not too late in the process. And that’s, I think, a really good insight for the field broadly.
Unidentified Analyst: Interesting, thanks for the color. And then maybe a quick follow-up, if I may. The FDA released draft guidance for Alzheimer’s earlier this month. I think one of the big takeaways here is that really codified the driver push to maybe shorten the length of clinical studies potentially using, again, kind of biomarkers and other indicators rather than waiting for several years that it might take to detect a meaningful change. And I’m again kind of curious, has that translated to your discussions with the regulators and again, are we thinking ahead to maybe a shorter Phase 3 if need be?
Eric Siemers: Yes, having read the draft guidance like a lot of times for these draft guidance, it’s a little hard to read between the lines, and they certainly did have some language in there about shortening timelines based on using biomarkers, but then they talk about a validated biomarker but what is validated to really mean. So there’s still a number of things that need to be worked out. It may be that they were directing some of those comments to just taking an antibody that is IV and then converting it to subcutaneous. I think that’s probably the most straightforward case for more of a reliance on the biomarkers. But at this early stage, we’ve not really considered using a biomarker alone to try to get accelerated approval for Sabirnetug because, of course, the payers, at least to this point, haven’t really offered to reimburse for accelerated approval.
So we’ll continue to watch that very closely. But at this point, I don’t think we have enough information to make any real changes in what we would anticipate would be our Phase 3 design.
