Good morning, everyone, and thanks for joining the Altimmune session. I'm pleased to have CEO Vipin Garg and the new Chief Medical Officer, Christophe Arbet-Engels, with us today. As you all know, Altimmune has a GLP-1 glucagon agonist being developed for MASH, but also, I guess you can coin it as a one-stop shop for weight loss and with more liver-targeting capabilities than your indirect ingredients. Maybe we can just open with a few minutes of an overview, and we'll launch into Q&A. Thank you. Yeah, thank you for inviting us, Annabel. We're excited to be here. As you mentioned, we are developing a glucagon GLP-1 dual receptor agonist for the treatment of serious liver diseases such as MASH, AUD, and ALD. We have recently completed enrollment in our 48-week MASH study. We had a 24-week readout from that study in June, and we're looking forward to the 48-week readout coming up here in the fourth quarter. Just a few things about the drug that we are developing. It's called pemvidutide or Pemvi. It's a one-to-one balanced agonist of glucagon and GLP-1. Basically, it brings equal potent activity for both of these receptors: glucagon for its direct effect in the liver and GLP-1 for its metabolic benefits. As you know, the best way to treat MASH is really to combine these two effects: have a direct effect in the liver, anti-inflammatory, as well as anti-fibrotic effect in the liver, and then have an impact on metabolic components of the disease as well. It is really the best way to treat, and we think we have both of these mechanisms built in a single molecule. As people are developing liver-directed agents, as well as, you know, at this point, we've got two drugs approved for MASH. One is a liver-directed agent. The other one is more of a metabolic drug, semaglutide. What we are doing, we're really combining both of these functions in a single molecule. That is really what's exciting about pemvidutide. In our 24-week data readout, we showed class-leading improvement in MASH resolution, anti-fibrotic activity, significant weight loss, very compelling weight loss, and the quality of weight loss, as we have shown in the past, is quality weight loss that preserves lean mass, which is going to be very important in this patient population. Really a whole package in terms of treating both the root cause of the disease and the disease itself. We think that's a very good value proposition for a drug like pemvidutide. Great. So, you know, we have seen a decent amount of activity recently in the MASH space. Obviously, we had two approvals now after many decades of having nothing. Now we've got a lot of large pharma activity looking at FGF21s. It seems to me that they're looking to possibly combine it with other things. I guess, first of all, you know, clearly large pharma has not lost interest. Second of all, it seems that the combination approach is the correct way. Maybe you can put your mechanism in context with how they're approaching it with the FGF21s and I guess how we should think about the competitive landscape in that sense and just what your thoughts are around all the activity here. Right, right. No, absolutely correct. As you know, all of the advanced stage FGF21 assets have recently been acquired by large pharma. Every single one of them has mentioned either they're already combining it with a GLP-1 or with a metabolic approach, or they're looking to do so. Really the best way to treat MASH is combining these two mechanisms. That's exactly what we have done with pemvidutide by combining, having this balanced ratio of glucagon and GLP-1. We're bringing both of those benefits in a single molecule. We think we are very well positioned in that landscape in the background moving forward. People are going to look for a single agent that can do both of these activities. The dual mechanism of action here is the key. Christophe? Yes, so I'm Christophe Arbet- Engels. I just joined Altimmune not even six weeks ago, but I'm joining Altimmune at a very exciting moment. As Vipin mentioned, Altimmune has this molecule one-to-one ratio, and that has a lot of implications because, as a reminder, there are no GLP-1 receptors in the liver. People tend to either use the GLP-1, and it takes a very long time. The tolerability is not very favorable for this chronic disease to treat MASH, or they use the FGF21, which has a direct targeted effect on the liver. We have the opportunity with the glucagon piece of the molecule to really target the liver. In addition, we are also doing the GLP-1. Why is that important to have a ratio one-to-one? It's because there's some side effect of glucagon where you don't want to see the glycemic level go up. For example, in the meantime, you want to see also the defatting of the liver, the weight loss. We were able to demonstrate this in our recent phase II-B data that were presented at AASLD. To your point on the competition, whether you were at the Obesity Week or where we were at AASLD, everyone is mentioning that you need to have those combination therapies. Here we have the ability to propose this. I will just add one piece on the tolerability side. This is really something that is important, and that was highlighted in the late breaker that was presented by Professor Nuridin, is the fact that our molecule has a proprietary U PORT system that delays the Tmax and decreases our Cmax. Instead of having a huge peak where you see a lot of nausea or GI effect or discontinuation because of this, actually in our phase II data, we were able to show just below placebo discontinuation rate when even other glucagon GLP-1 receptors had a discontinuation rate within 20% or 26% even from Mazdutide, for example. That was the presentation just before. The combination of pemvidutide is actually a very unique proposition for patients, and we look forward to getting our 48-week data, going to the FDA, and moving towards our phase III program. Okay, great. And just, you know, while you mentioned AASLD, you obviously just came out of that. How was the visibility relative to some of the other glucagon programs in development? Were they presenting any data there, or did you have any kind of interactions that give you some confidence that your program is the right approach? Oh, so we had, so first we had a poster on our phase IIb data. We also had that oral presentation in the late breaker session. We had a lot of engagement with KOLs, with the scientific community, with the patients' advocacy community as well. This was really exciting. I think we've been probably a little bit under the radar. Through this AASLD, what I observed was that there's a lot of enthusiasm. There's a unique approach here that is different. Again, this is when you look at Mazdutide, it's really much more the ratio is much more in favor of GLP-1. It's more like a GLP-1 compound, for example, that can explain all this tolerability. Here we have really that unique aspect. I will just add as well that we have a weight loss that is different from our obesity study. We can show that the lean mass is preserved. More and more in the current environment for this chronic disease where we're addressing a population that is aging in their 50s above, tolerability for the chronic disease and the quality where you preserve the lean mass is a key aspect of pemvidutide and very important for people. Again, I think we're starting to see a lot of great feedback, a lot more interest towards, I think Professor Nuridin called it a unique proposition or something like this in his talk. As people get to know the molecule, get to know how it's related, it's not just a clinical finding. It's inherent to the molecule. We're having some very good feedback from this congress. Yeah, one thing was very clear that every physician you talk to will tell you that they want a drug that's going to have both direct effect in the liver, anti-inflammatory and anti-fibrotic, but they want their patients to lose weight. 80%-90% of the subjects with MASH will benefit from losing weight. That's really the key benefit of pemvidutide is combining these two mechanisms in the single molecule. You're approaching your 48-week data that is measuring fibrosis with non-invasive testing. Before we go into what your expectations are around that, maybe you can just give us just a quick summary of what you saw at the six-month data that gives you confidence into the 48-week data. Sure. We had the ambitions to look from our biopsies at 24 weeks. This is a little unusual. Most trials look after 48 weeks first. It is very early on. We were successful in showing clearly MASH resolution after only 24 weeks. The results of that study are now published in The Lancet. The editorial shows that there is great surprise or enthusiasm to see such a rapid effect. I mean, we were really happy. On the fibrosis, we saw also very comparable effects to what you see with the FGF21. For example, we saw 36% of fibrosis improvement without worsening of MASH. However, we were a little non-lucky, and we can debate how and why with the placebo that was quite high. We did not reach statistical significance. On the MASH resolutions, we were at par with studies that have lasted for 48-72 weeks, but already at 24 weeks. On the fibrosis, at least numerically, we had a very striking effect already. This was also supported by a very consistent, and this was in the poster, very consistent results on those non-invasive tests, whether it's VCTE, it's the ELF. I mean, a 0.5 decrease in ELF when the placebo was increasing at 24 weeks is not a small thing. We see this mostly in compounds that are studied for 48 or more weeks. Very powerful, very strong. The tolerability, again, is extremely good. There was no increase in glycemic levels. Our HbA1c were flat or actually even slightly decreasing over time. That allowed us to now move into the phase III and have the interaction with the FDA. We were able to schedule a meeting that's going to be, even with the government shutdown, an in-person meeting. I think the FDA is very engaged to see molecules like pemvidutide move forward. In addition, we also looked at AI-based reading of the biopsies and again, consistent results. The totality of the data shows that the fibrosis improvement is taking place and given longer time and larger trial, we will hit that endpoint. Can you just go over the post on the PathAI and the poster that you presented or the presentation that you had regarding, I guess, high-grade fibrosis versus low-grade fibrosis? Maybe you can help us understand the significance of that because the low-grade, I guess, was not as significant as the high-grade. Maybe you can just talk about that a little bit. Yes, so just the difference. Biopsies in general are read by a pathologist or multiple pathologists. I like to say that it's a little bit like tasting wine. You can give the same wine and people will have different reading. There is a lot of variability. What we're asking them, especially on the fibrosis, is to start to look at a change from one stage to the next. They look at a small part of it, and then they see a little bridge here on the fibrosis or a filament there, and then they say, "Oh, we cannot have or that patient has not changed." Now, the AI is much more comprehensive and objective. What they're looking at is the comprehensive slide. They grade that slide by percentages of fibrosis, and then they look at the early and the late or advanced fibrosis. Obviously, the advanced fibrosis takes more time and is more difficult to break apart, but you can see some effect there as well. The early is a little bit easier because it's not as advanced. Having those distinctions was really very nice for us. The big impact is the consistency, again, of the number of patients, the percentage of patients that reach 30% or 50% of improvement in fibrosis. We see this very clearly. The poster has that information, and that AI has, I mean, as a reminder, it is already approved in Europe. The FDA is reviewing the PathAI AIM approach and will probably move in that direction from our understanding. This is really a tool that helps alleviate those variability that you can have with the pathologist in staging those patients. I guess in terms of some of these, the PathAI and some of the non-invasive testing that you're doing, there was a lot of discussion at AASLD about that. I guess one of the things that kind of emerged is that there's, I guess, no real cohesiveness as to which tests to really put the greatest importance on. There's a little bit of variability from test to test. Where do you think the market is as far as adopting non-invasive testing either for diagnosis or for screening or for clinical studies and even the PathAI for that matter? Do we think that the FDA is anywhere close to accepting any of these methodologies to assist in MASH development? No, I would agree with you. I think we are much closer because the EMA approved already the artificial intelligence reading of the biopsies. These are still biopsies. I think the FDA will move fairly rapidly, I mean, in a reasonable timeframe towards approving something like this. They're well aware of the. It's still biopsy-based, clearly. It's still biopsy-based, yes. The needs is a little more complicated because the needs you need to relate this and from a regulatory perspective, they want to relate it to long-term clinical outcome. There were a few debates. The FDA was in the room at AASLD whether a single non-invasive test like the blood testing, like the ELFs or others like FIB-4, et cetera, or FAST are things that you should be using by themselves or whether you use a combination with some imaging with the VCTE, for example, things to that extent. I'm not sure there's a complete consensus to move right now. Some folks are trying to definitely link those outcomes and help the FDA. There are clearly discussions. We've seen the letter of intent. The scientific community is really pushing in that direction because biopsies are really difficult, but for patients and for trials. We will see that moving, but I think it will come at a slower pace than the year. Yeah, one thing I'd like to point out, Annabelle, is that we looked at every marker of every non-invasive test, whether it's for inflammatory markers or for fibrotic markers. Across the board, every single one of them, we hit statistical significance. For us, that's very important because the drug is clearly working both on the anti-inflammatory side as well as on the antifibrotic side. In the end, it doesn't matter what we end up with as the final marker that the FDA will choose. We think we can hit those. Okay, great. Just as we're approaching this 48-week data, what are your expectations? First, how many patients move from the 24-week into the 48-week component? Did all the patients stay in? That's, I guess, the first question. What are the expectations for that 48-week data? What exactly are we going to see? As mentioned, we have a really good tolerability and safety. The discontinuation rate is maintained. I mean, in a blinded manner, we can see that it is maintained as what it was for the 24 weeks, which is really encouraging. That is, again, quite rare even among the glucagon GLP-1 agonists, the dual agonists. There is only pemvidutide that has such numbers. With regard to the 48 weeks, just again, we had very strong data at week 24. Some of those markers, I want to remind you, the 48 weeks, we are not reading biopsies again. We are going to look at those non-invasive tests. Some move at different levels. Some have already maxed out at the liver fat content and those kind of things are very close to be already at very high efficacy at week 24. We may see a little bit of an improvement there. The others on the fibrosis, we can see some added on the liver stiffness, added values here. They move all at different speeds. We'll see. What we would like to see is something that will continue to confirm what we expect. One is our weight loss did not plateau at week 24, so there will be added benefits there in these patients. We want to continue seeing the consistency in our needs and trying to see that happen. Again, some additional benefits on liver stiffness and that usually on the fibrosis side in particular takes a little bit more time. Okay, great. I mean, I guess going into phase III now, you're designing the trial. What are your expectations from FDA on what your requirements will be for the phase III design? The FDA has not changed for now the guidelines. They still want to see for what they call the subpart H at 52 weeks to reach the accelerated approval based on biopsies. We will follow this. Then you need to follow the outcome with the appropriate patients' population. We have designed our program in order to address these two, clearly in that. Where we are a little more unique is the flexibility that we have introduced in our program so that we could switch endpoint to the point we discussed just before. If the FDA or the regulators are moving away from biopsies, are considering needs or other things, we are collecting, as Vipin was saying, we are collecting all this information. The change can happen in a seamless manner between the traditional endpoint in biopsy to the needs. We will be prepared for this. We've learned a little bit, I would say, at AASLD around where their mindset is. We will learn more when we meet with them. That might give us also additional colors on how to best approach those endpoints. We have put that engineer, that flexibility into our program in order to be able to adapt because in the time, in the duration that we're doing this program, we may see some changes at the regulator. We will have also some information because we will be going to scientific advice from the Europeans. Combining all these pieces of the puzzle, I think we're going to be in a really strong position with our phase III program. Yeah, I mean, our goal is to be in a position that we can start the program based on biopsies. Whenever the FDA changes the requirements, we'll pivot to those. That's why even in our phase two program, we collected all of the data, all of the needs data with that in mind. We'll continue to do that in our phase III program as well. Are you going to be looking at any measurements at a six-month time point from a needs perspective maybe so that you can monitor how quickly the fibrosis improves? Correct. That's one of the benefits of needs. You can monitor them over time. We'll do that for sure. In our case with pemvidutide, what is really great and will be an important asset is to be able to have an early efficacy and those early reads. The reason for this again is because with the GLP-1, we know that most patients drop GLP-1. There were some information on posters even around that on semaglutide very rapidly or definitely 80% within a year. The titration doesn't help on all those aspects. It was for us keeping the patients for market access and reimbursement, keeping the patients on track, keeping seeing the efficacy, strengthening the profile and the benefits that patients will see is of paramount importance. Yeah, I mean, this was one of the themes that came across at AASLD. Every physician told us that they were really impressed with our tolerability. If you can't keep the patient on drug, these are long-term chronic therapies. You need to keep them on the medication. We're seeing that best-in-class tolerability. I think that's one of the features that's going to be very important as we go into the long-term treatment of MASH. Yeah. I guess on leaving MASH and moving into some of your other programs, you're clearly leveraging pemvidutide into AUD, alcohol use disorder, as well as alcohol liver disease. How does that profile play into those two markets? Are they as motivated as MASH patients? I think the tolerability obviously plays into keeping patients on drug. I'll just say one thing that we enrolled our AUD trial five months ahead of schedule. That's a good point. That was really, we were surprised ourselves. I think part of the reason is that people know that people knew and physicians could tell their patients that, "Hey, by the way, you might also lose weight on this drug." Again, having this weight loss benefit, these are metabolic diseases. In the end, AUD leads to liver damage, leads to overall liver health deterioration. It is really a metabolic disease in the end. You want to treat cravings as well as weight loss at the same time. It is very similar to MASH where we are having direct effect in the liver and combining it with weight loss. Here, we are reducing cravings for alcohol and combining it with weight loss. That is the added benefit. Same thing with ALD. ALD is MASH basically that results from alcohol. This idea of having a dual mechanism of action is very appealing, very attractive for all of these indications. Yeah, just sorry. To add to Vipin's, this is a continuum. Those liver diseases have similar features. You see in the AUD patients some fatty liver. You see in those ALD patients some fatty liver. You see some fibrosis as well as they evolve. Pemvidutide has the ability now to target directly those aspects. In addition, which is not the case again for just semaglutide or others because we are seeing now some others coming into that field and some more interest. That gives us additional value we can bring with pemvidutide. Again, we have that direct effect on the liver. It's not just shutting down the reward system or craving system. We are bringing these direct liver benefits to these patients if they are more advanced. There's a sort of a continuum from the AUD to the ALD. A percentage of those patients will be coming from slightly fatty liver and those cravings all the way to having those related alcohol liver disease. We need to be able to treat them all along their patient's journey and all the way. I think pemvidutide has an, in that particular case, you're absolutely right. The tolerability is a point that is critical because these patients are not really sick. You don't want to make them more sick. You want them to be able to take the drug, feel less rewards, defat their liver, become more aggressive. They have a little fibrosis here and try to bring them to a healthier place. We have that options. The weight loss and the quality weight loss, which is even more important in these populations that do have sarcopenia that lose their muscle, is something that's unique to pemvidutide. We're excited about moving there. And as Vipin said, I mean, not only we as Altimmune are excited, I think the patients are as well because they came to that study and we were able to enroll that really rapidly. Just on the point regarding the reward system. It is clear that pemvidutide has direct liver effects. We understand that. How comfortable are you with the actual primary endpoint of these studies, though? I think reduced drinking days, I believe. How comfortable are you with the actual reward signal or reduced reward signal that is coming from the GLP? I know we have anecdotally heard about it, but are you comfortable that it is actually a real effect? I believe it is a real effect. I mean, we are not the only ones that believe this. Other companies and other products are trying to test that. They do not have the one-to-one ratio. They do not have the direct liver effect, which is a little older tolerability. I think it is clear that there is an impact. We'll see with the results. We'll see when those results come. It's something that is central that is based on the GLP-1 mostly for that. There are also some other mechanistic aspects around the delayed gastric emptying, around all these that may decrease the impact, if you wish, of alcohol. Putting all these pieces together, I think we have confidence. We were able to have a molecule that will address these different mechanistic aspects of alcohol. This is good. Yeah, I'll just remind everybody we have as much GLP-1 in pemvidutide as semaglutide does in its highest dose. At the 2.4 mg dose, we have equivalent amount of GLP-1 in our molecule. We have preclinical data showing reduction in alcohol intake using pemvidutide. It is really not just anecdotal information, but we have got preclinical model backing up that information. Okay. I guess one last question. Catch position, where does that take you as far as being able to complete the development program? Yeah, so we just reported our quarter. As you know, we have been strengthening our balance sheet throughout the course of the year. We reported about $211 million at the end of the quarter. We are in very good position moving forward into looking into 2026 and 2027. Okay, great. I think we're out of time, but thank you very much. Thank you. Thank you very much.