So that’s been one experience and then we’ve also broadened our net and are looking at a number of sites that treat exclusively adults that obviously do have many of these more severely impacted patients and so we are bringing them into the fold as well. So we’re costing a wide net. We’ve noticed those subtleties of the patient populations at the different sites and we’re meeting with lots of investigators.
Operator: Our next question comes from the line of Joseph Schwartz with SVB Leerink. Your line is open.
Joe Schwartz: Hi, it’s Joe Schwartz from Leerink Partners. I was wondering if you could talk some more about how the new inclusion criteria negotiated with the FDA could influence the profile of disease severity, which will be reflected in the future cohorts for the Phase 1B for pociredir and do you think that pociredir will still be able to generate an increase in fetal hemoglobin, which is sufficient for generating a clinical benefit in patients with more severe disease? I guess I’m wondering if you think the patients in future cohorts will have as much of an opportunity to reach the 20% range you referenced earlier, if they’re starting out at lower baseline levels compared to those who were treated previously?
Alex Sapir: Yeah, great question, Joe. I think to answer that, let me turn that one over to Iain.
Iain Fraser: Yeah, absolutely and it’s one that we’ve given a lot of thought to and I think it’ll be interesting to see the data as it rolls out. I think I’d make a couple of comments about it. One is in the 16 patients that we’ve treated thus far in the 1B study, there’s a pretty high rate of baseline fetal hemoglobins and while we don’t have full three months data in all of them, the initial trajectory of increase in HPF is pretty consistent across all of those. So it didn’t seem as though it was a steeper rate at the higher baseline HPFs and the lower ones appeared to be responding just as well. So that’s the first point. The second point is, I think the mechanism of action being distinct from that of HU has some advantages in this respect.
Obviously, we’ll need to demonstrate that as we move into the more severely impacted patients, but it’s not operating through a stress erythropoiesis type response, which HU is. There’s some discussion about whether that mechanism might be susceptible to depletion of stem cells or fatigue in the marrow or whatever description you want to append to it. So I think that the differentiated mechanism of action acting through alterations in gene transcription are likely to be successful in that more severely impacted patient population, but we’ll get the patients in and we’ll have to demonstrate that in the clinic and that’s our expectation.
Joe Schwartz: Interesting. Thank you. And then could you just walk us through the calculus you employed to develop the estimate that your inclusion criteria for pociredir covers 7.5 [ph] to 10,000 sickle cell patients in the United States? And I’m just wondering how confident you are in that estimate as you engage with the sites now and what do you expect the screen failure rate for patients to be going forward?
Iain Fraser: Yeah, maybe as it relates to the screen failure rate, I’ll ask Iain to answer that, but yeah, let me give a bit of color, Joe, in terms of how we got to that number. I think what’s important to remember in looking at the inclusion-exclusion criteria, these are people that have either tried or failed on some of these advanced therapies or for whatever reason don’t have access to the advanced therapies, Voxelotor and Crizanlizumab, because of the simple fact that they don’t have proper insurance or their co-pays are too high. So let me give you some high level numbers. We know that from 2019, when both Vox and Criz launched through 2022, both of those products each generated about 10,000 prescriptions. We know that about 25% of those prescriptions never converted to a patient start and our assumption there is that those patients simply didn’t have proper insurance cover or didn’t have access to the drug due to payer related issues.
