Hey, good morning and welcome to Evercore ISI's HealthCONx here in Miami. I'm very pleased to be joined by Altimmune. Altimmune is working at the intersection of obesity and MASH, or maybe I should say MASH and obesity. I feel like that's probably where things are headed, at least from my perspective. They're both equal. How's that? They're both equal. So we have Vipin and Scott joining us here today, and we'll go ahead and get started. Let's just start out with a company overview just to get everyone on the same page. Yes, as you mentioned, we're working on both obesity and MASH. We've got a dual agonist, GLP-1 glucagon dual agonist that we are developing for these indications. The unique feature of the drug called pemvidutide, call it pemvi for short, is that it's an equal balance between GLP-1 and glucagon. Now, we're very familiar with GLP-1s for appetite suppression, so we've got that component, but glucagon brings a unique added benefit in terms of energy expenditure. So glucagon provides energy expenditure, particularly in the form of fat burning. So it burns fat in the liver, it improves lipid profile, serum lipid profile. All of those are good things in people with obesity because ultimately people don't really die of obesity. It's the cardiovascular events that are more important. So what we're trying to do is really develop this compound for both obesity and MASH. It's really a complete solution for both of these indications. We'll talk more about it. So let's start with kind of the weight loss you've seen. It seems sort of like maybe in the range of semaglutide, is that fair to say? And maybe you can describe that a little bit better and which doses, et cetera. Yeah, Scott. At comparable time points, we had about the same amount of weight loss at 48 weeks. However, unlike the semaglutide curve, if you look at the curve of our weight loss, the trajectory was much deeper. Taking it out to that same 72-week time point, we think that we would actually be better than semaglutide. Do you think that's because you start with kind of more drug on board to begin with or because you don't have the same titration schedule? Is that part of the magic there, do you think? And then would that linear curve continue? That pattern is established by the end of the titration for semaglutide, which is 16 weeks. 48 weeks is a lot further out than 16 weeks. The answer is no. Okay. Yeah, and I think the other thing I would emphasize is that there has to be an adequate amount of weight loss. It's not just about weight loss. As this whole obesity space evolves, there's going to be a lot of focus on what else are we doing in terms of comorbidities of obesity. The first generation of drugs, GLP-1s, they're very good at addressing diabetes. There's really a much larger patient population that has dyslipidemia. And again, cardiovascular outcomes are driven by that. So having glucagon, really, if you can achieve significant weight loss, adequate weight loss, and have these added benefits, that's going to be a very compelling drug as this whole obesity space evolves. Let's talk a little bit more about the weight loss and sort of lean loss of lean body mass versus fat. And that's something I think sort of distinguishes you. Why is that? What have you seen that's different from semaglutide? Because this has become a hot topic in the field, obviously. We've seen tirzepatide as maybe more similar to what normal weight loss would look like in terms of the effects on lean body mass versus fat. So maybe you can speak to that with pemvidutide. Yes, as Vipin mentioned, glucagon fundamentally changes the metabolism of the body and shifts it away from the carbohydrate axis for burning for energy needs to the fat axis. The substrate for carbohydrate is muscle, so by shifting from the carbohydrate axis to the fat axis for your energy needs, especially during calorie deprivation, that is what preserves the muscle in our opinion, so we think that this is unique to glucagon, and the more glucagon that's in the molecule, the more this will be seen. Okay. It's going to have a positive impact on the overall quality of weight loss because it's not just about 48 weeks. The question is, what happens long-term when people are on these medications? Preserving lean muscle mass is going to be critical. So you've completed your studies in obesity and you've got a phase three program planned. Do you want to talk about that a little before we move on to sort of MASH and what's coming next there? We've completed our end-of-phase 2 meeting with the FDA, which is a very important de-risking milestone for the whole program, not just for obesity, because obviously one of the things that FDA looks at is comprehensive safety profile of the drug. And we got a very clean bill of safety. So that's really will cut across all of the indications across MASH or anything else we want to develop pemvidutide for. So this is a very important de-risking milestone. Scott, do you want to talk more about the details of the phase 3 program? The FDA was very complimentary. The meeting actually ended before its allotted time. They raised no safety concerns. That's extremely important. We proceeded with four efficacy trials. The FDA used the word innovative. We came in with a program that highlighted the attributes of glucagon, the profound effects on lipids, the effects on liver fat, and also the lean muscle, lean mass preservation. So unlike other programs, they came in with step one, step two, step three, step four. We came in with a program where all of the subjects were obese or overweight in order to get the indication to get the approval in that population. But each of the trials highlighted a different aspect of glucagon. For example, can you give us some detail? For example, with LDL cholesterol, let's look at statin use. About 50% of people who take statins don't achieve their LDL goals. About 30% of people don't tolerate statins. We showed in our data, number one, that in people with elevated LDL cholesterol, the reduction was 20%. That's statin territory. So you have a trial that's going to highlight that. It's important to note that that effect was also seen in people who were taking statins. So now we're talking about synergy between statins and pemvidutide. Statin, excuse me, LDL reduction is kind of like hypertension. It's silent. It's not something you rush to treat. But people rush to treat their body weight. So combining statins with pemvidutide, you have an ideal combination where you can increase the effects of statins, achieve effects that are not achieved with statins alone, particularly in patients who aren't compliant with them or don't tolerate them, and actually drive the use of these drugs to the desire to have weight loss rather than cholesterol reduction. Okay. So that phase 3 program is up and running. An important thing you said was safety. And can you distinguish this? We've seen with glucagon some signals here and there. You haven't seen any signals. Can you talk a little bit more about what signals we've seen from other programs and why you think maybe you've sort of dodged some of those? Yeah. We want to start first by saying that if this were a class effect of glucagon, FDA would have told us to do a safety study. Okay, fair. They didn't. So what we're talking about are not the effects of glucagon, but other compounds. So regarding other compounds, I'll say this. You're aware that one compound was told to do a safety study. That's which one? For cardiovascular harm. Right, but which compound? It was survodutide. Right, right. Rather than talking about other compounds here, talking about pemvidutide, we were not told by the FDA that we needed to do that study. They had no comments at all about our safety profile. As Vipin mentioned, carrying this forward to all of our indications, we start with an agreement or an alignment with the FDA. This compound is safe. And that's extremely important for development because compounds fail because of safety. This end of phase two meeting was extremely important to establish that agreement with the agency. Okay, wonderful. So now you've got a MASH study ongoing. Just to get everyone on the same page again, maybe just talk about sort of the design of the study and what you're hoping to show there. So the study will, as you know, read out in the second quarter of next year. We're very excited about that. This study probably enrolled faster than any other study to date. It's probably because people enjoyed the safety profile and tolerability of the compound. And also, they had the opportunity to lose weight. So this tells a lot about how the drug will be used in the future compared to other compounds, the enthusiasm of patients to come to the trial. 190 subjects. The primary comparison is between placebo and the 1.8 milligram dose. We have it well powered. Which is your middle dose? It's not even your dose with the highest weight loss. That's because in our phase 1 studies and liver fat reduction, and liver fat is what drives all the effects and also the accompanying inflammatory markers, the markers for fibrosis and the like. Everything seemed to point to the fact that the effects were plateauing at 1.8 milligrams. So it would make total sense that the effects on liver fat and in liver inflammation, that dose response is not the same as the dose response to obesity. It plateaus out. So we decided to study the 1.8 milligram dose. Now, we could always use the 2.4 milligram dose in a phase 3 program. That primary comparison of that 1.8 milligram dose placebo was well powered at 76 per arm. That's important because you don't want to have a type two error and miss out on the effect. We're always asked about sample size calculations. I would point out that other compounds have gone in with about 60 per arm or less. So this study is well designed and well powered for a positive outcome. The primary endpoints are NASH resolution or fibrosis improvement. So it's a dual endpoint where success is achieved by hitting both, although we have a lot of confidence based on all of our data that we're going to hit fibrosis improvement. The study population is F2 and F3, and we're going through biopsy reads the same as other sponsors. You have no diabetics in the study. Oh no, that's not true. Okay. No. This study enrolls both diabetics and non-diabetics. And what's the ratio there? We don't want to talk about the actual data at this point, but in most studies, it's been about 50%. Okay. Because there's been some controversy with diabetes and glucose control and that kind of stuff, right, with your drug. We've had excellent control of. I guess it wouldn't be a diabetes treatment. Treatment, right. Right. Yes. Yeah, that's fair to say because this drug wasn't designed to treat diabetes. It was designed to treat obesity or MASH, but it's quite safe in diabetic patients. So in controlled diabetics, we can go and treat their MASH. So that's the idea. I mean, these patients will benefit from liver fat reduction, and that's what the drug is designed to achieve. And that's why it's important to point out that we have the highest glucagon levels of any other GLP-1 glucagon dual agonist because we believe it's important to have as much glucagon as possible. And the best you can do is one-to-one ratio GLP-1 to balance out the glucagon. So you have the benefits of glucagon, but you can also counteract glucagon by having enough GLP-1 in there as well. Okay. And no dose titration? No dose titration. We did allow dose reduction, which we have not done in the past. And we're very, very pleased with the results that we are seeing so far. Have you seen people dose reduce? We're not really talking about that at this point, obviously. But all I can say is that we're very happy with the profile, the tolerability profile that we are seeing. Okay. In terms of one of the key things that people focus on in these MASH trials, what's placebo going to be? How are you analyzing the slides? Can you sort of review those components and how are you thinking about what a placebo response would look like? It seems that it's hovered around 20% for a lot of folks. Yeah, that's a very important question. Scott, do you want to go through that? We've been benefited tremendously from the other trials that preceded us. Lots of learning. The learnings. And we've seen how other sponsors have read the biopsies. For example, in one recent readout, it was a single reader. And the placebo response rate was 30%. So obviously, you have to have a panel. There has to be some adjudication or agreement between the readers. And without getting into details, we've taken the learnings that we've had from all the KOLs and the experts who have been involved in these trials, and we designed an adjudication scheme that maximally reduced the placebo rate. Recently, we announced that we are going to reread all of the biopsies. Right. That in itself will drive down the placebo rate. You could lose a lot of patients though too. Are you worried about N or powering or anything like that? The studies that have been successful with rereadings, and as you know, with rereadings, you can lose patients, have been successful with 60-65 per arm. And we are sitting at 76 subjects per arm, so we have a greater buffer than those studies. So we've built in that insurance policy in cases. Meaning you can lose about 10 patients per group right now? I can't give you an exact number. In fact, I don't know the exact number. But what I can say is we're using pathologists who have read out other studies. There's no magic here. There's a group of pathologists. We do all of these studies. We'll probably have the same loss of patients in a reread as other studies that have been successful at 60- 65 per arm and we're at 76. So without focusing on the number, I think what we have is adequate. So you're at an interesting juncture here. You're on the cusp of getting in the second quarter some really interesting data in MASH. And you've got this obesity program planned. There's a big price discrepancy between obesity and MASH. And I think you're equipped to go forward in MASH by yourself, maybe obesity leave for a partner. How do you get this all done together? Do you need to pursue actually the obesity, or is that just sort of extra at this point? How are you thinking strategically about how you want to position this drug? Yeah, I mean, look, both of these indications are very large indications, and they're both important. So our strategy is to continue to focus on finding a partner centered around obesity while we pursue MASH on our own. We think this is an ideal drug for both of these indications. I mean, if the data readout in the second quarter shows what we expect, we'll be the only drug for MASH that's going to have both significant weight loss and improvement in liver fibrosis and MASH. I think that's a very powerful combination. At 24 weeks, that's a very powerful combination. And that speaks to the potency of the drug. So now if you take that 24 week forward to 72 weeks, you should see even more effect than what others are seeing at 72 weeks. So that really becomes a very compelling story going forward. On top of that, these patients are going to be losing weight, which is very attractive for this. So this is really a complete solution for MASH as well as for obesity. As you think forward, and I think it's so funny, I mean, several years ago, we would never think about a phase 3 ahead of a phase 2B because biopsies never worked in MASH, and now we just assume they'll work, right, so with that assumption, you're thinking into phase 3. How are you thinking about the F4 population? Is this drug properly suited for them? There is weight loss. Do you want to lose weight if you're a cirrhotic patient? Do you think this drug can work there? Is it appropriately suited? Is that something you'd pursue in phase 3? Right, so this is a drug that can work across all phases of fibrosis. Early on, phase F1, F2 because of the effects in obesity, F3, F4 because of the potent antifibrotic effect. You know, we have preclinical studies that show that pemvidutide have a direct antifibrotic effect. So comparatively, we may even do better in cirrhotics than other compounds, F4. Patients with advanced cirrhosis lose weight. Early on, patients with MASH cirrhosis are overweight and still need to lose weight. In fact, many of them still succumb to cardiovascular disease. So in the second quarter, we have an important liver meeting in Europe. Is that a place where we might think about this data being presented, or would that be too early? It's hard to be specific in terms of the timeline. We're very comfortable saying that we'll have data in the second quarter. It'll be great if we can have the data at that meeting. But either way, we'll have the data in the second quarter of next year. Okay. All right. So I guess as we wrap up, tell us about your plans for the oral version of pemvidutide. What's going on there? We're continuing to make progress on that front. Pemvidutide is a peptide. I think it's important to keep in mind that an oral peptide, because we are hitting two different receptors, it's likely not possible to come up with a small molecule. It has to be a formulation of pemvidutide that's orally bioavailable. We've made significant progress on that. We're not quite there yet in terms of declaring a compound for preclinical, but stay tuned. Hopefully, next year we'll have that. Okay. So maybe we can talk about your cash position, how much cash you have, how far can that get you? And then let's review 2025 catalysts. I think we know the big one. Anything else? Yeah. So So we just announced the quarter. We have approximately $140 million at the end of September. And that's sufficient cash to reach all of these milestones that we are talking about and well into the first half of 2026. As you said, we've got some very interesting catalysts coming up. We just completed our end of phase two meeting. That was a very important de-risking milestone for the company. We continue to have partnering discussions around obesity. We're also talking about exploring additional indications for pemvidutide, and we hope to discuss more of that. We expect to file our first additional IND by the end of this year, and we'll be able to talk about it in the first quarter. And then, of course, the data on MASH. Okay, excellent. Thanks for joining us, Vipin and Scott. Thank you.