Mayank Mamtani: And just maybe staying with you, Scot, final question on that preclinical anti-fibrotic study data you report, I think 33% level fibrosis in less than 2 weeks. In the same experiment, chemical experiment with incretinand non-incretin drugs, are you able to comment on what you’ve seen? And then also lastly, an update on the oral formulation of pemvidutide, I believe you were pursuing a couple of technologies there. Is there any early data emerging that you can talk about of the overall peptide format. And thanks again for taking our question.
Scot Roberts: Sure. Absolutely. So as far as in comparison with other drugs, there’s really not a lot out there for MASH drugs that have really looked at this nonsteatotic, non-obese model. So it’s been difficult to really tease apart, are we defatting the liver, and that’s why we’re getting anti-fibrotic effects or is there some direct activity? I will mention that lanafibinor, for example, has done the same sort of study that we’ve done, very similar, and we see comparable effects on the amount of fibrosis reduction. And as you know, lanafibrinor is certainly demonstrating anti-fibrotic effects in the clinic and is currently in Phase III testing. So there’s not a lot out there, but I think that that’s an important touch point there with the [indiscernible] data.
As far as the oral formulation, we are making good progress there. When we look at the levels of pemvidutide that are detected in the in vivo studies, we’re seeing a significant fraction of what we achieve clinically, for example, at the 1.8 milligram or 2.4 milligram dose. We know what those levels are. And in these drugs, we’re able to achieve a significant fraction of that. And so we feel we’re on the right road here, we still have 2 different approaches that we’re evaluating, and both of them look promising. So I think that those — that effort is looking good, and we hope to report that we’ll putting one of those candidates into IND development by the end of the year.
Operator: Our next question comes from Jonathan Wolleben with JMP.
Jonathan Wolleben : A couple of follow-ups on the body composition study. I’m wondering if you could give some context for how what you’re seeing with pemvidutide compares to semaglutide and tirzepatide? And if you expect to see similar changes with other dual and triple agonist that include glucagon work this is specific to pemvidutide?
Scott Harris: Yes, Jonathan. So in the same analysis, I remind you that we were at 25.5%, semaglutide is at 40%. So compared to semaglutide, we’re clearly preserving more lean mass. Within the semaglutide prescribing information, the higher rate of bone fractures in women in the elderly is highlighted, we believe that that’s associated with the lean mass loss, and it emphasizes the importance of preserving lean mass as people lose weight and to get as close to the ratio seen with diet and exercise, which is about 25%, and we’ve achieved that. The tirzepatide data has only been presented in abstract form. It’s a bit difficult to see the exact number, but we believe it’s at about 26%. So clearly, we’re in that class of the leading drugs in this space.
And renitutide reported out a lean ratio, in other words, how much lean was being lost compared to body weight, of about 37% to 38% in a recent trial. Now we believe that the effects that we’re seeing are being driven by glucagon. We would point out that we believe that we have more glucagon in our molecule in our [indiscernible], and that’s why we’re differentiating on the body composition. So we think the more we’ve done, the better in a variety of areas, including reduction of lipids, reduction of liver fat and now better preservation of lean mass.
Operator: And our last question comes from Patrick Trucchio with H.C. Wainwright.
Patrick Trucchio: Just first a clarification on the lean mass data. I’m wondering if the — how the lean mass preservation and body composition compared across dose levels of pemvidutide or if it was consistent across doses? And then separately, I’m wondering if the updated preclinical or clinical data reported today has impacted the way you’re thinking about a potential Phase III program in obesity in terms of trial design, such as dosing titration or end points? And separately, can you tell us how the data reported today would be expected to read through to the IMPACT program?
Scott Harris: Patrick, I guess I’ll take that. So the lean to total loss ratio that we quoted a 25% — 25.5% was the same in all dose groups. So you achieved that ratio regardless of the dose. So 25%, 25%, 25% at all 3 doses. The data on body composition clearly has to be thinking — make us think about incorporating this into a Phase III design. The largest change that we’ve made in the program so far has been [indiscernible] dose reduction, which we think is going to remarkably improve the tolerability of the compound program in Phase III. We certainly have the optionality to look at longer titrations. That’s not a decision that’s been made yet with the partner but that is something that we could consider if there’s felt to be value there.
Our current position is that we do not feel that we need to longer dose titrate. We think, as Vipin mentioned, especially at the 1.2 milligram dose, it is differentiating for other compounds — against other compounds, particularly for primary care. But the — is the opportunity in the future program to go to higher doses, if we chose, all the evidence suggests that we would get higher weight loss. But I want to emphasize that we are very happy with the fixed 15.6% weight loss that we achieved at 48 weeks getting even longer — larger with longer durations of treatment. The endpoints in these studies are pretty much established by the FDA at least for the nondiabetes and diabetes trial. We’ll look to see if we actually do a — we actually look to see if we will do a study that includes body composition.
