Matthew Hagood: Hey, guys, thanks for the question. I will also jump on the FSHD bandwagon here. I wanted to ask maybe about some different scenarios for REACH-3 and specifically if you saw a path forward if the study doesn’t hit or maybe narrowly misses the reachable workspace endpoint. Like, do you think the biomarker endpoint might be sufficient? I guess taking a page out of Sarepta’s playbook and what we’ve seen now over the last couple weeks, kind of what are your thoughts there? Thanks.
Alex Sapir: Yeah, great question, Matt. Thanks for that. So let me turn that one over to Iain.
Iain Fraser: Yeah, yeah, thanks, Matt. So just to be clear, in terms of biomarkers in REACH, we’re not evaluating the DUX4 transcriptome, which was evaluated in the Phase 2 study because that’s not really a feasible clinical trial measure to make. What we do have, however, are a number of secondary endpoints that are different than the reachable workspace endpoints, and those include the MRI endpoint, which I guess could be considered a biomarker which evaluates the accumulation of fat in muscle tissue that still has what looks like normal contractile muscle interspersed with fat. So that we also showed in the Phase 2 study as for the reachable workspace that you’ve got a stabilization of that fat accumulation relative to the placebos who showed an increase.
So we think that that’s clearly an important secondary endpoint. We also have an evaluation of dynamometry, so conventional muscle strength testing, which we’re evaluating. We have some patient-reported outcomes that reflect on both patient global impression of change, but also some specific questions related to FSHD itself and so there are a number of those secondaries that I think will be important to consider, irrespective of what happens to the primary endpoint, but if, as you articulate, the primary misses narrowly, I think having all of those secondaries trending in a favorable direction towards losmapimod over placebo, will be extraordinarily helpful and persuasive in that context.
Matthew Hagood: Yeah, I agree with that. Thanks for the question.
Alex Sapir: Yeah, and Matt, this is Alex. The only other thing I would add to what Iain said is going back to something I said earlier regarding pociredir and how the FDA looks at everything from a risk-benefit perspective, I think what’s also important to note is that when we file our NDA with the FDA, we will have over 3,600 patients in our patient safety database and this has been shown to be a very, very safe drug and so I think that that is a really important piece of information that the FDA will look at as it considers the safety and efficacy data in totality and decides whether to approve this drug or not for patients, for which they have none.
Matthew Hagood: Yeah, makes sense. Thanks.
Operator: We have a follow-up from the line of Dag [ph] with Stifel. Your line is open.
Benazir Ali: Hi, just one more question from us. For FSHC, can you remind us of the powering for REACH and the assumptions that went into it for the reachable workspace? Given that it’s a mobility test, how should we think about it in the context, again, of the recent embarked trial failure and what read-through for the powering assumption for REACH?
Alex Sapir: Yeah, great question. Let me turn that one over to Iain.
Iain Fraser: Yeah, so REACH was powered based on the observed data from Redox 4 from the Phase 2 study and you may recall that was an 80 patient study, 40 in each arm and essentially, what we took was the change from baseline, so the treatment effect, losmapimod minus placebo on the reachable workspace, and also assessed the variability in the measurements in that particular cohort, and then applied it to the power calculations for the REACH study. The REACH study was originally powered on a total enrolment of 230 patients with an expectation that 210 of them would be FSHD type 1 and 20 of them would be type 2 and that’s a reflection of the relative epidemiology of type 1 versus type 2. Type 1 is overwhelmingly the most prevalent, 95% or so of that.
