Now, with respect to the body composition, we know the loss of lean mass is associated with loss of function and also a higher rate of bone fractures, particularly in the elderly and also in women. So we saw the semaglutide trial. They had a 40% loss of lean mass which exceeds the natural weight loss, the natural loss of lean mass from diet and exercise which is about 25% which is what we achieved. But with that 40% lean loss in their label, they report a higher rate of fractures in women and the elderly. So now you can see the immediate implications on the market and the differentiation on the segments. For example because of its preservation of lean mass could tend to do tie be ideally suited for treating the elderly, especially frail or individuals or women with osteoporosis risk which is a huge segment of the population recognizing that women with lean bone mass are carrying around extra weight which increases the risk of fractures.
So all in all, these are discussions that we’ll have with the FDA’s which is our target population and our endpoints.
Mayank Mamtani: Super helpful. I think you covered a lot if you could comment on the outcome trial scale and scope given you have a big lipid benefit?
Scott Harris: Right. Obviously that’s going to be a great benefit to us. I think that’s where we can really differentiate because as you’re aware in the SELECT trial there was a 20% reduction of MACE major adverse cardiac events just in the basis of weight loss alone and their effects on serum lipids are minimal at best. I believe there if I’m quoting the data correctly, the reduction of LDL cholesterol and total cholesterol only in the range of about 3% to 5%. Recognize that in our population of subjects with elevated serum lipids at baseline, we saw a 21% reduction of LDL which is comparable to the effects of statins, so going into that trial. We can have really very excellent effects that exceed that seen with them with semaglutide.
We also have reported out data on lipidomics in the past showing that not only this penveu tied reduce the amount of LDL and total cholesterol, it also changes the very nature of the lipids that are circulating, inflammatory lipids. That are known to damage the cardiovascular system and liver, like ceramides and diacylglycerols. So we’re very optimistic about conducting that trial. Optimistically, that is a trial that we’d like to start with in Phase 3 and get those results as soon as possible, so that we have it around the time of market authorization and that would be something that we’d hope to achieve in the discussion with the FDA.
Mayank Mamtani: Got it. And then just on the MASH development, you have fast track. There’s another glucagon-directed program, which has now Phase 3 based on NIT endpoints, weight loss, and MRI-PDFF, no biopsy. I was just curious if you could also get some preliminary guidance on what your late-stage MASH development could look like. And maybe just remind us on the enrollment for impact. Are you on track to complete enrollment in 3Q? Thanks again for taking our question.
Scott Harris: Yeah. Thanks for the question, Mayank. The obesity meeting is going to be with the endocrine division. Our NASH program is going to be with the liver division. So I don’t really think there’s going to be immediate opportunity to get information about the NASH development. Of course, there’s overlap and interchange of ideas, and clearly any information we get from obesity we can take forward to enhance NASH development. Regarding enrollment, it’s going extremely well. We this reflects the fact that patients with NASH are seeking treatments that have visible, clear effects on them that they can see. MASH is a silent disease. And what they see on a day-to-day basis is their body weight. So given the opportunity to lose weight in the trial, they’re coming into the trial at very handsome rates. And this robust rate of enrollment is going to support, as we’ve said, the readout in the first quarter of next year.
Mayank Mamtani: Got it. Thank you.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Jon Wolleben from Citizens JMP.
Jon Wolleben: Yeah. Thanks for taking the question. We had some data last night from another GLP glucagon agonist. I was wondering if you guys saw. Because we’ve heard some critiques that glucagon agonist may not be effective and even detrimental for diabetics. But this data said that Chinese patients showed superiority to dulaglutide. And I was wondering, your thoughts on that data set? And do you see any read-through to pemvidutide and others in the class? And how are you thinking about the diabetic population as an opportunity for pemvidutide?
Scott Harris: Well, thanks, Jonathan. So, just to emphasize, we’ve seen excellent control of blood glucose in our program. And this drug is not designed specifically based on its ratio of GLP-1/glucagon to drive down blood sugar or hemoglobin A1c. But it clearly maintains it safely while patients derive a whole variety of other benefits. So we continue to believe that the data that you’ve talked about, as well as our own data, supports the safety and effectiveness of the drug in all populations, including diabetics. I would emphasize that we are seeing in our studies weight loss in diabetics equivalent to the weight loss in non-diabetics. This is something that’s of great interest to us as we go forward into Phase 3, because it is possible that there is something unique about a glucagon mechanism where the weight loss is preserved in diabetics, which would be extremely attractive, because, as you know, diabetics with the GLP-1 based compounds, like semaglutide and tirzepatide, seem to take a haircut in the diabetic population.
So we are extremely interested in pursuing that and believe that we could operate very nicely in the diabetes space.
Jon Wolleben: Okay. And then one more, if I may. Just — as you guys are planning for your Phase 3 program, can you talk about the trade-off between the shorter titration, which you guys have talked a lot about in the past, versus, improving the tolerability profile with the slower titration, like we’ve seen from other programs, and how you think about the importance of both and your thoughts going into the Phase 3?
Scott Harris: Well, thanks. Great question, Jonathan and something that we’re giving a lot of thought to. The first thing I would say is that 1.2 dose of pemvidutide is extremely attractive. It has an adverse event profile, an adverse event discontinuation rate similar to placebo, and want to remind everybody is given without dose titration. So we’re going to pursue that dose as well as the 1.8 milligram, 2.4 milligram doses going into Phase 3. But literally a physician could prescribe a dose of pemvidutide that’s approved not have to titrate up to it and some patients were achieving 20% weight loss on that. And the natural use of the drugs in clinical practice is that these drugs are started on the lowest dose. The doctors wait see how the patients do and then increase to other doses like 1.8 milligrams and 2.4 milligrams as they go forward.
