Iain Fraser: Yeah, I think the advantage of reachable workspace is that it provides a quantitative assessment that treating physicians typically use in a more qualitative sense, to understand how their patients are doing. So it allows us to put some numbers around those qualitative terms. And since there haven’t been any therapies that alter the course of the disease available to date, there’s really been no need to do that, all the therapy is symptomatic to this point. So it’s really adding a little bit of quantitative measures around the more qualitative sense in the clinic. I think the important pieces to point out here are, number one, that reachable workspace has been shown previously, prior to Fulcrum’s involvement, that FSHD patients exhibit a decline in their reachable workspace over time.
That’s in a small natural history study that was published several years ago, and that’s consistent with clinical observations around measuring muscle strength by more traditional measures like dynamometry, for example. We know that, in addition, the reachable workspace correlates with instruments, patient-reported outcome instruments, such as the Neuro-QoL Upper Extremity questionnaire and that work has been published. And we’ve also shown from our Phase 2 data a correlation between the reachable workspace and the shoulder abductor dynamometry. And it’s the shoulder abductor dynamometry, because obviously reachable workspace is focused on the upper extremity, and the shoulder abductor is a major muscle component of that. So there are correlations that have been observed in the reachable workspace.
And as I say, probably most importantly, it’s that documentation of the decline experienced by these patients, and that’s what the patients report is this inevitable decline over time. And that’s something that the treating physicians and caregivers also report. And so there’s consistency in the measure from that respect as well.
Joori Park: Okay, got it. Thank you. And then my second question is on pociredir. I know that baseline characteristics like HbF can play a role and how much HbF you can achieve. So would it be possible to provide patient baseline characteristics ahead of your next update so we can better contextualize and appreciate the data when they are released? Thank you very much.
Iain Fraser: Yeah, this is Iain again. So maybe I can just add that we do have in our corporate presentation on the web, the data from the initial 16 patients that were enrolled in the study that includes a plot of their HbF, and it includes the baseline fetal hemoglobins that they went in with. The comment that I would make there is that there was a range of baseline HbFs, and I think, speaking from memory, it was about 3% at the low end and just under 20% at the high end. And we know that in the sickle cell patient population in general, it’s around 5% to 10% is sort of the average baseline. So we’ve seen to date a pretty widespread across baseline HbFs. And while we don’t have three months data in all of those patients, certainly the initial slope of the increase in HbF across all of those baselines looked pretty similar.
So it didn’t appear that those that were starting out higher had a lower response or vice versa. I think where — the critical piece of this is where do the patients end up with after three months. Looks like from the six-milligram data that we have, which is the highest dose that’s gone out to three months, may not even be plateauing fully at the three months mark. And so that will obviously need to be evaluated further as we move through the process. But we will, once we have the data around the fetal hemoglobin, we will reveal those baseline HbFs as well, because it is an important component.
Operator: Thank you. One moment, please. Our next question comes from the line of Dae Gon Ha of Stifel. Your line is open.
Dae Gon Ha: Hey, good morning. Thanks for taking our questions and congrats on all the progress. Three questions, if I may. One. Alex, have you guys actually started some pre-commercialization work with the payers specifically? I think there was quite a bit of questions around physicians and their comfort as well as the regulators. But how do payers feel about the reachable workspace and the magnitude you showed so far? Second, sticking with losmapimod, the 10% change you detected in ReDUX4, I was wondering if you could go into a little bit more on the test, retest variability you mentioned to an earlier question. Any other evidence you can point to that kind of gives us some comfort around your Phase 3 REACH powering, and then I’ve got a follow up on the pociredir story.
Alex Sapir: Okay, great. Yeah, why don’t I — I’ll take question one and then I’ll turn question number two over to Iain, and then we’ll come back to you for question number three. Thanks, Dae Gon, I think really good question. So, yeah, we have done some initial payer work both in the US as well as ex-US, and I don’t remember the specifics of the study that we did, but I think it was around 10 payers that we had spoken to, and shared with them the target product profile and shared with them the results of the ReDUX4 study. And they obviously were well aware that there was no available treatment options for these patients. And the objective of the work that we did was really to try to understand their thoughts around pricing.
And what we heard loud and clear from those payers is that they would expect that when this drug gets approved and comes to market, that it would command rare disease type pricing, such as in the hundreds of thousands of dollars. I think probably a really good comp to look at would be the pricing that Biogen has with SKYCLARYS. So it’s — SKYCLARYS targets Friedreich’s ataxia, again, neuromuscular disease. Not a lot of mortality, but high morbidity. So very, very similar to what we see with FSHD. The biggest difference between FA and FSHD is the prevalent population. FSHD is about four times the size. So the payer work that we’ve done, albeit somewhat limited to date, has really been around pricing. And the feedback that we’ve heard from payers that they would expect this as the first entrant in a rare disease to be priced in hundreds of thousands of dollars, similar to other rare disease therapies.
