But, Pemvi, the data, and the pipeline, and the partnership discussion, and obviously we have a lot going on in the field, in terms of the glucagon and the GLP-1 for obesity and NASH. Before we do that, maybe Vipin, if you can give us some more, you know, updated elevator pitch to cover some of the recent updates at a very high level, and then we can go into the Q&A.
Yeah. Well, thanks, Roger. Thank you for inviting us. It's a pleasure to be here. As you know, we are developing a GLP-1 glucagon dual agonist called pemvidutide for two separate indications for obesity and for NASH. We have completed a phase II study in obesity that we, you know, had data late last year, and we are preparing for an end of phase II meeting with the FDA on that. So our plan is to have that meeting sometimes in the towards the end of the third quarter, and that would give us the path forward for phase III. Our goal is to have a partner lined up to move us into phase III on obesity. On NASH, the study is currently recruiting patients.
This is a phase II-B MASH study, a biopsy-driven trial, and we expect to have data in the first quarter of next year. So a lot of exciting stuff going on. Because of the combination of GLP-1 and glucagon, we believe it's ideally suited for both of these indications. Obesity patients that have dyslipidemia, hyperlipidemia, high liver fat, would benefit from having glucagon. Similarly, the MASH patients would benefit from having weight loss on top of, you know, improvement in their liver fat and serum lipids. So it's an ideal combination for patients who need both weight loss as well as improvement in their liver, in their lipid profile.
Excellent. Maybe Vipin or Scott, you can set us for the level set is how pemvi, pemvidutide is molecularly designed to be differentiated from other GLP-1 and glucagon co-agonists? And then, as secondarily, you have done quite a few kind of clinical study. So far in clinical, what are the key kind of features you have seen is pretty differentiated from other glucagon or, you know, incretin-based therapies?
Right. So, pemvidutide was designed with trying to incorporate as much glucagon in the molecule as possible. We're well aware of the beneficial effects of glucagon, the profound effects on liver fat, the profound effects on serum lipids, more recently, data that we have showing preservation of lean mass. These are all characteristics of glucagon. So we have the highest ratio of glucagon amongst all of the GLP-1 glucagon dual agonists in development. And the molecule was designed to incorporate that, yet maintain blood sugar control. So by having a one-to-one ratio, we're actually able to do that, and we've demonstrated throughout all of our trials that we're maintaining glucose homeostasis, and we're not seeing these excursions in glucose control. The drug is ideal either for a non-diabetic or for a stable diabetic. We're not shying away from treating diabetics.
If a patient has diabetes and does not have glucose under control, there are better drugs suited for them, but for the majority of patients who have glucose control, and have these comorbidities of obesity and MASH, this would be an ideal drug. Now, with regards to the data, we're seeing the following: We're seeing across all of the glucagon compounds, much greater reductions in liver fat and much greater reductions in MASH, both MASH resolution and fibrosis improvement. That relates directly to the amount of liver fat reduction. It's been shown across trials that the more liver fat reduction you have, the better the effect on MASH endpoints, and we have the highest glucagon content of our molecule across that class of drugs. We're seeing profound effects on serum lipids that we're not seeing with GLP-1 monotherapy or GIP.
The reduction in serum lipids is in the range of about 3%-5%, typically. So when we look at the SELECT trial, for example, which was the semaglutide outcomes trial, that 20% reduction in MACE events, major adverse cardiac events, was noted despite not having much LDL cholesterol reduction. We can only anticipate the better effects that we would have in that kind of outcomes trial had we had our lipid effects supplementing the weight loss effects they've seen. In addition, we've also seen sparing of GLP-1 effects with better tolerability, 'cause glucagon does that, and now more recently, the improvement of body composition because glucagon appears to preserve lean mass. It's essentially the same as a ketogenic diet. It shifts metabolism away from burning carbohydrate to burning fat, and the substrate to burn carbohydrate is muscle.
So that shift from carbohydrate to lipid metabolism, which we achieve with glucagon, is really quite important. Now, these effects are by and large, at this point, short-term effects. The majority of the weight loss market in the future is gonna be maintenance of weight loss. It's not gonna be how much weight you lose in a year. That's only gonna be a minority of the prescriptions. It's gonna be how you maintain it and maintain it safely. If you're losing excessive lean mass, that's gonna be associated with ill effects. That's been known to be associated with higher morbidity and mortality. More directly, it's known to be directly associated with bone fractures.
So we think that the focus will shift in the future from acute weight loss to chronic weight loss and maintenance of weight loss, and for that reason, we think, that glucagon is ideally suited for that population.
Great. You know, it's very good to see the pretty good translation from the molecular design to the clinical feature you have seen so far, right? So all the kind of pleiotropic kind of various effect getting to the clinical profile. Good. So maybe we talk about the most recent kind of updates from the latest conference EASL. They're happening exactly the same time as this conference. So, understanding you also have some poster there, you just put out a release. Maybe give us some highlights, what pemvidutide is showing there, what's new? And then also this morning, tirzepatide, they have some data, you know, detailed kind of fibrosis, NASH data. And then what else, what the other glucagon-targeting agent you are tracking maybe have some impact to Altimmune as well?
Thanks, Roger. I'll first talk about the data that we're presenting at EASL. There are three presentations that we're making that meeting, then I'll talk about tirzepatide and perhaps even survodutide, which is another compound in the GLP dual class. So we have three presentations at EASL. They all reinforce what we're seeing in the clinic. The first are biomarkers of histologic response. One is the FAST score, which predicts fibrosis progression. We're seeing statistical significance in that compared to placebo. We're also seeing a very high rate of what's called the combined MRI-PDFF and ALT response, which according to the Loomba data, is highly predictive of NASH histological response as well. And that supplements all the other data that we've presented so far, showing high likelihood of histologic improvement based on biomarkers.
We've actually generated a computational model that looks at the effects of glucagon compared to GLP-1, and the combination of GLP-1 and glucagon versus GLP-1 alone. That model predicts superior effects of our compound and combination and also predicts a high likelihood of seeing a 1-point improvement of fibrosis in our clinical trial, and we're conducting that trial right now, and we'll read that out in the first quarter. And the final, perhaps most interesting, is lipidomics data. You know, we think about LDL cholesterol, we think of total cholesterol, triglycerides, but some of the more important lipids we may not be tracking, and this is what lipidomics gives us. Sphingolipids, phospholipids, ceramides, diacylglycerols, triglycerides, for example. And these are highly inflammatory and known to be associated with the development of NASH, and we're showing very significant reductions in those as well.
We interestingly also have data in the cardiovascular population that'll get on stage in the presidential plenary at the AGA, so we're excited about showing that data at that meeting as well. Now, with regards to tirzepatide, we're excited to see new data. This data is extremely interesting. We would start by emphasizing the fact that the effects of tirzepatide in the liver are all indirect. The effects are entirely mediated by weight loss. If you don't get weight loss, you don't get liver fat reduction in the liver. And the liver fat reduction that's been seen with tirzepatide has been relatively modest, in the range of about 39%-40% at the conclusion of a year. When you add glucagon, you get much, much more effects.
We see twice the amount of liver fat reduction in one quarter of the time. So by and large, we're happy to see the data come out, but we want to emphasize that we think we're gonna get better effects and more rapid effects as well. And in fact, we'll be the only incretin to read out on MASH data at 24 weeks. The other data is coming at 48-72 weeks. Their data is interesting because they're not showing an intention to treat, at least in the abstract. They're showing completer analysis. I think we have to see all of the data, understand it, because completer analyses are not accepted by the scientific community or the FDA. They want to see the intention to treat.
A bit worrisome that they have a 30% placebo response rate in their fibrosis improvement. It raises the question about the robustness and quality of the readout. That readout should really be in the range of, for placebo, about 15%. With regards to survodutide, we'll see that data in a couple of days as well. The initial data looks promising from the efficacy viewpoint, and we believe that relates to the presence of glucagon. Once again, highlighting that we think we'll do better than that because we have more glucagon on our molecule. Our ratio of glucagon to GLP-1 is 1-to-1. Their ratio is 1-to-8. But what really characterizes that molecule is poor tolerability.
In their interim data that they presented last month at another meeting, they had a 31% adverse event discontinuation rate in just 24 weeks, and now we have to go 48 weeks, so that number will be higher. That's the highest adverse event discontinuation rate that we've seen in any molecule in this class, in any study. So the tolerability is extremely important. We believe they're getting their efficacy by pushing the molecule very hard at the expense of tolerability.
Excellent. Thank you, give us the highlights of the EASL presentation and then some of the comments around your competitors, which is very helpful. So I think our other investors will stay tuned on the BI drug and obviously the tirzepatide. We're gonna take a closer look at the analysis. So moving on. Moving back to pemvidutide in terms of the next step, understanding you are having the end of phase II meeting with the FDA in at the end of Q3. What are the key topics really gonna you know materially you know matters to the program? Understanding this is relatively standard, but specifically for pemvidutide, investor you know interested in knowing, okay, how you gonna address the diabetes population?
How you gonna y ou're gonna include those differentiation to be, you know, for the phase III, how to design the trial to reflect in the potential label for your phase III? So maybe.
Yeah, that's exactly right, Roger. I mean, as you know, obesity trials are relatively large. You know, you don't need that many patients to show efficacy, but for safety, you need fairly large patient data set, anywhere from 4,000-5,000 patients. So that gives you an opportunity to study subpopulations within that large phase III program. So that's our plan, is to really discuss with the FDA what are some of the subpopulations that we can study to really demonstrate the benefits of glucagon in our molecule. You know, one example would be dyslipidemia or hyperlipidemic patients with obesity. So but there are others as well. So our goal is to really clarify that.
We think that's gonna be very value enhancing as we come back with that information as to what patient populations we can study and how we can get them on the label eventually. So that's really the game plan. As far as diabetes is concerned, this is not a diabetes drug, so we're not treating you know, we're not treating diabetes, but we will treat diabetic obese patients, so there will be diabetic patients that would be included in the trial. But beyond that, you know, stay tuned. We'll figure out, you know, what are these subpopulations and what benefits we can draw in terms of designing specific aspects of molecule that we can enhance in these studies for the benefits of glucagon.
Maybe also comment on some of the, you know, potential endpoints regarding those subpopulation and the, the benefit of the pemvidutide you have seen. What are the potential endpoints for those subpopulation can be included in the clinical development program?
Right. So there are a number of opportunities to get information in the label about serum lipids. Obviously, a lipid endpoint. We thought about the possibility of enriching the population, take individuals with high lipids that are not being controlled by other therapies. The same with liver fat, although there are no w ell, there's been the approval of resmetirom. But let's say that to take a population that needs to have liver fat reduction and achieving that as well and getting that on the label for obesity. And there are some other things that we've considered with body composition as well, building on the effects that we've seen in our phase II study.
Excellent. Good. And then, you know, one of the key topics investors have been very, very interested, and, you probably hear that every single day, is the partner discussion. So I understand it's ongoing, not necessarily you can comment too much, at this stage, but maybe I ask a different way, is what are the key things can potentially trigger the partner decision, you know, one way or the other, maybe from different, you know, type of the partners, right? So your NASH data, the competitor, glucagon data, or what are the key data points they are waiting for? Otherwise, you have your phase II momentum data last year, right? So I think, what are people are really looking for, waiting for?
Yeah, so I mean, there are a number of things. It's not just our data; it's also the overall landscape. People are trying to figure out how they want to get into obesity because getting into obesity space, it's a fairly significant commitment. This is not about just funding one phase III trial. It's a real program. Manufacturing capacity comes into play, all of those things. So there is a fairly significant investment that's required by any partner or any player who wants to get into this space. So there are external factors, and they're looking at, you know, information that we are providing. I think the key component of analysis is what are the differentiating features, you know, because people aren't really interested in yet another GLP-1. That's already very crowded space.
So what we bring to the table is really differentiation over and above the existing GLP-1-based therapies. And there's a lot of data coming out on top of that, so people are also waiting for that. So I think all of that put together, you know, there's not one thing that they're waiting for. Our end of phase II meetings, for some potential partners, that's going to be important. Some people are equally interested in NASH. The NASH data may be important. So, you know, these are different things for different partners, but overall, we are looking for large multinational players who can, you know, who can actually progress both of these indications in parallel because the opportunity is now. So basically, we don't want to wait for, you know, just develop one and not the other.
We want a partner who can move this forward in parallel and do that quickly.
Good. I think it's a hot debate out there. You know, some people speculating the boat, the ship are they already gone, so you'd not no longer be able to sign a partner. But for me, I'm still kind of looking forward to the news every single day, right? So you're gonna sign a partner. So how should we think about the timing? Because you say you're gonna have the end of phase II meeting by the end of 3Q, and then you get phase III ready with the partner. So how should we think about the timing, maybe the match.
Yeah, and that's for obesity, to be very clear.
Yeah. That's right. Yeah.
We will move forward with NASH on our own if we don't have a partner by that time. But again, our goal is to have a partner lined up by the time we start enrollment, let's say, in phase III. But I think it's important to realize that there are many factors that go into these, this decision-making, and a partnership is not like a deadline that if you don't do it by December 15th, that's it, it's over. You can never find a partner. So I think it's a, it's an evolving process. It's a continuum. We'll have more information, and that would help, and all of it has to come together for, you know, for the right partnership for us to put it in place.
Right. Good. Since you, obesity conversation continues with more data gonna help your partner discussion, but also the NASH data is upcoming, 1Q next year. So maybe tell us a little bit more, what should we expect from there? I think, Scott, you laid it pretty well. You may be the only company or only incretin in try to do biopsy data at 24-week. So which is final, I think it's a final analysis, not like an interim analysis. So tell us what gives you the confidence you can see that. I understand the liver fat, maybe just remind us and then, how, what, what, what can we expect from that data?
Yeah, there are a variety of factors there, Roger. First, there's a very clear relationship between the level of liver fat reduction and your NASH resolution and fibrosis improvement. We have class-leading effects in liver fat reduction. We also have class-leading effects on reduction of liver inflammation. We base that on an imaging technique called corrected T1. We have the best results with that and also the best results with ALT reductions as well. We've recently generated data that's being presented at EASL in looking at biomarkers that are highly correlated with fibrosis improvement, and that would be the FAST score in the combined MRI, PDFF, ALT, response. In addition, we've generated computational models looking at this. All of the data consistently point to a positive readout at 24 weeks.
We also have preclinical data in an animal model showing that glucagon has a direct effect on fibrosis. So in a lot of these animal models, they're done in what's called diet-induced obesity animals. So when you treat and you lose liver fat because of weight loss, you also reduce fibrosis. So then it's not clear if the fat fibrosis reduction is due to the liver fat or direct effects. We actually took animals in a carbon tetrachloride model, where the animals were lean, and we showed in two weeks a 33% reduction in fibrosis that was statistically significant. So glucagon itself, in addition to all of the effects that we've described, has direct effects on fibrosis, which we think is gonna increase our chances of having a positive readout on that fibrosis improvement endpoint.
Great. Maybe, Scott, if you can remind us what's the powering and assumptions you have, if you have disclosed. If not, what should we benchmark, pemvidutide, this 24-week versus any other drug probably not having that early on, maybe, you know, 48- or even 72-week data. What is the appropriate benchmark we can see, say, "Okay, pemvidutide is getting towards our biopsy data is very promising?
Right. We have three prior trials that have shown statistically significant improvement of fibrosis at week 24. We have two FGF21s. We have the efruxifermin data, that's Akero, and we have the pegozafermin data, that's 89bio. We also have positive 24-week data from the PPAR-gamma lanifibranor . So there is precedent for hitting this endpoint at 24 weeks. I can't get into the details of the power, but the sample sizes per arm in those studies range between 45 and 62 patients, and we've actually overpowered it, despite having similar, if not better, effects in our earlier data with 76 per arm.
So we think that based on the precedent of hitting this endpoint with smaller trials and having a larger trial and having as good, if not better, biomarkers, it gives us confidence about hitting that 24-week endpoint. And again, the compounds that I've mentioned are not incretins. We feel that incretins are gonna dominate this space and are gonna be preferred for the treatment of MASH going forward. But we will have the most potent incretin 'cause we'll be the only one able to show both MASH resolution and fibrosis improvement at 24 weeks. And we think that will set us apart from the other compounds in the field.
There's also been talk of the GLP-1 based compounds dominating the space between F1 and F3, and the compounds that are more anti-fibrotic, the FGF21s, perhaps resmetirom, being in the F3 to F4 population because they don't produce weight loss, right? And the goal in the early MASH is to get weight loss because of all the other comorbidities wrapped around the condition. But we feel that with our data, both MASH resolution and fibrosis improvement, the effects I've described, that we can play in all of the areas of fibrosis, no fibrosis F1, F2, F3, and even F4. We think we can cover it all, and we think we can be uniquely situated as an incretin-based compound of doing that, whereas the other ones would be only in the F1 to F2 or F3 space.
Excellent. I think the more we talk about it, I think this MASH 24-week biopsy data can be game changing for the incretin space, for the MASH at least.
Right.
Absolutely.
Yeah. Okay, good. So we have a last minute. What's your cash runway, and then, what else, we haven't talked, but, you know, you wanna highlight for us?
Yeah. So at the end of March, at the end of March, we reported approximately $180 million. We, you know, as you know, we have the, the readout coming, on, on MASH, biopsy study in the first quarter, so we have plenty of cash to go through that. And really, this, our runway is into 2026 at this point. So we're well situated. Stay tuned. We've got a lot of information coming, both internally from Altimmune as well as from the outside world, and we're looking forward to it.