I will say, Dae Gon, the other thing that we’re also doing, and while this hasn’t been confirmed with payers, I think our instinct is that payers will require a confirmed genetic test of FSHD before approving the product. And as of right now, because there are no treatment options for patients with FSHD, very little genetic testing is done. And of the genetic testing that is done, it’s clunky, in that it takes a lot of time to get these genetic tests back. They’re expensive. Sometimes the insurance company will pay for it, sometimes they won’t. So that’s an area that we’re going to spend a lot of time on in 2024 and 2025 to really streamline that process of genetic testing, because right now, it is not as efficient as we feel like it needs to be at the time that we launch, given our instinctive assumption that payers will require confirmed genetic testing before agreeing to approve the drug.
So on the second question, Iain, maybe I’ll turn that one over to you.
Iain Fraser: Yeah, sure. So, briefly, just to recap, the ReDUX4 reachable workspace data, as you indicated, showed that ten percentage point treatment effect difference that was derived from a repeated measures model that was used to assess that endpoint. And that is the same model that will be used for the REACH study. And just to recap, that includes evaluations at baseline, week four, week 12, 24, 36, and 48. So it’s not just a single comparison of the week 48 out to the baseline value. So it incorporates all of those measures over time. And the treatment effect difference on an RSA unit score was about 0.05 with a baseline reachable workspace score in those patients of 0.54 to 0.53, that’s five quadrants of the theoretical max there would be 1.25, just to contextualize that.
So those were the data points that were used to power the Phase 3 REACH study. 230 patients originally projected, and 260 originally — finally enrolled in that study. With respect to the test, retest, so we do have that — I don’t have that number in front of me, and we can circle back to you with that. That’s in the published literature, and certainly can confirm that aspect outside of the ReDUX4 study. The variability in the change from baseline in reachable workspace, that standard deviation went into the power calculations for the REACH study. And so, we’re incorporating not just the treatment effect size, but also the variability from that in ReDUX4.
Dae Gon Ha: Okay, appreciate the color there. Switching gears to pociredir. Alex, on the site activation, it seems like you’re making some progress on certain sites that have already been activated, but you’re also going out to activate more. Just wondering, for those that you’re working on now, what are some pushes and pulls you’re hearing from them before they can get on board? And sort of separate to that is, what pieces of data are you looking to collect to further expand the TAM of pociredir longer term? Thanks so much, guys.
Alex Sapir: Yeah, great questions, Dae Gon, and thanks for asking those. Yes, I think the — or actually, let me back up a little bit. So at the ASH meeting, we had an opportunity to probably interact on a one-on-one basis with maybe 30 of the top thought leaders in sickle cell. And I think while there were a minority of physicians that said that they weren’t interested in participating in the study, primarily because of the fact that it is a small study, and it’s a new site, and it’s going to take nine months to get that site up and running and they may only be able to give us sort of one to two patients, they said, for the time being, we’re going to sit on the sidelines and come back to us once you are ready to enroll in a larger sort of Phase 2, 3 study.
So the sites that we’re talking to right now are all sites that have expressed an interest, and a lot of those or many of those physicians that we spoke to at ASH, I would say the majority of those physicians that we spoke to were very interested in the potential that pociredir could bring to their patients. So all the sites that we’re talking with right now, we’ve sort of screened out all those that are no longer interested. And so, we’re essentially — have identified a series of sites that are very interested in participating, and essentially we’re just going through — going through the, you know, getting the IRBs to approve it, getting the contracts through. And the second question? Second part of that question, Dae Gon?
Dae Gon Ha: Yeah, with regards to the trial, the PIONEER trial, I mean your long-term goal is to eventually expand the TAM, right, given the high severity of disease right now? So what kind of data are you looking to collect in PIONEER before you can look to expand that?
Alex Sapir: Yeah, great question. And I think some of that has to do with conversations that we’ve had with the agency to date, and Iain has been intimately involved in those conversations. Maybe I’ll turn that one over to, Iain.
Iain Fraser: Yeah, absolutely, Alex. And it’s clear that the agency thinks of this in terms of risk and benefit. And they articulated that certainly in terms of their dealings with the gene therapy approaches in particular, which we know are associated with pretty significant risk, including malignancy, with a black box warning going to the bluebird product. However, they feel that they understand the upside and the benefits of those therapies much better than they do with something like pociredir, which is still in early development. So I think the initial approach here is in the context of the PIONEER study, this three-month study is really to articulate fully at doses that we think are likely to be therapeutic, which are the 12 and potentially the 20 milligram once daily doses, what sort of fetal hemoglobin inductions we can see in those patients.
