Vipin Garg: And Corinne, in terms of the timelines, as you know, those of us who have done deals, it’s very difficult to sort of lay out a timeline, but our focus has been always to have a partner in place before we start Phase III towards the second half — in the second half of this year. It would be nice to have a partner alongside with us when we have our end of Phase II meeting. It’s not critical because it’s pretty standard at the end of Phase II meeting for obesity program. So we’re very comfortable having that conversation with the FDA, but it would be nice to have a partner alongside with us, and we’ll see if that’s going to be possible.
Operator: Our next question comes from Mayank Mamtani with B. Riley.
Mayank Mamtani: I appreciate the comprehensive update here. Just few more precise technical follow-ups there. So regarding the liver fat normalization data up to 79%, which is a little higher than what you saw in Apple study, but still, what’s the sample size? And I assume it’s a pooled analysis from top dose levels? Could you please clarify that?
Scott Harris: Well, the body — the liver fat data mine comes from the body composition study, right? So patients have MRI scans, and they got an MRI-PDFF when the liver was being scanned. So we’re seeing a very high rate of liver normal as fat normalization. We think this is very similar to what we saw in patients in the NAFLD study who started with much higher levels of liver fat. The liver fat — mean liver fat in the NAFLD study was about 22% to 23%. And in this study, it was about 5%. So the barrier for normalization was less.
Mayank Mamtani: Got it, Scott. And a related question I have on the body fat composition data the methodology used here, you just clarified that MRI-based, but there are additional approaches like [dexa bot pod], that could be helpful to also compare against what we have for semaglutide. Are those analysis being conducted and could be presented in the future? Or was that not part of the protocol?
Scott Harris: Well, MRI is the preferred technique for body composition. We think that many experts think the DEXA is not a good surrogate for the specificity and sensitivity of MRI. So that’s the technique we relied on for this study.
Mayank Mamtani: Okay. Understood. And then on the IMPACT MASH trial execution, any color you can provide on pace of enrollment and if you’d expect later in the year doing a placebo-controlled study could be impacted now that an approved MASH therapy is on the market? And to the prior commentary you had that some of the approved drugs will start showing more [indiscernible] anti-fibrotic effect than we’ve seen before. Anything on the MASH trial execution through the course of the year we should be aware of?
Scott Harris: Yes. So enrollment in the trial is going quite well. And the feedback we get from investigators and their subjects is that they prefer to come into their trial because patients can lose weight. So faced with the possibility of choosing amongst different trials available to them in community, we’re seeing patients come into our trial because this trial offers weight loss and also potent effects. We believe that, that reflects the commercial potential of the drug when these drugs are being offered. We’re seeing [resmetirom] recently being approved, but there’s no weight loss associated with that. And we think head-to-head, we’re going to do extremely well in that regard. Regarding the other benefits of the drug, remind you that we’re seeing class-leading effects on liver fat reduction and other biomarkers of inflammation, which is going to allow us to actually read out and differentiate from the pack in this area by reading out on fibrosis improvement in 24 weeks, and we think that we can do that.
But repeatedly, the effects of glucagon here are being shown to be very differentiating and very valuable, especially with regards to the quality of the changes that are being seen, especially in the weight loss front. And we look forward to generating more data in the future.
Vipin Garg: And Scot, you may want to talk about the direct anti-fibrotic effect that we are seeing.
Scot Roberts: Sure. But actually, before I get there, I just wanted to reaffirm that the — we’re in the sweet spot, when it comes to MASH, we’re in this sweet spot. Scott just talked about [resmetirom] and also the FGF21s are doing great jobs on directly acting on the liver but there’s no weight loss associated with those. With drugs like tirzepatide, they’re hitting MASH resolution, but the liver defatting of a straight GLP or GLP/GIP is just not that great. And that’s why we believe the fibrosis endpoint wasn’t hit. So here, we have a direct acting agent that can defat the liver very quickly and control inflammation very quickly, but we also have the weight loss. And you don’t find those 2 qualities in the competitors that are out there.
As far as the direct anti-fibrotic effect, we think that we talked about here today are exciting and really offer a second mechanism that could certainly push things along for F2F3, which is our intended population and our — is the population in our IMPACT study, but also may have implications for late-stage fibrosis F4, for example. So we’re continuing to look at that and try to understand the mechanisms by which this is occurring, but we’re excited about the data, and we think that it certainly adds to the value of pemvidutide for MASH.
