Thanks very much. Good morning, everyone. I'm Seamus Fernandez, one of the senior biopharma analysts here at Guggenheim Securities. This is our SMID Cap Biotech Conference, and I'm really pleased to be joined on my immediate right by Scott Harris, who's the Chief Medical Officer of Altimmune. Altimmune is a company that we've covered for several years with the context of both an opportunity with their drug, pemvidutide, in the MASH space, as well as a potential obesity asset as well. But maybe just to kick us off, remind us a little bit of the Altimmune story and maybe update us where we stand today. Sure. Well, thanks, Seamus. So Altimmune is a public biotech company. We're based in Gaithersburg, Maryland, about 60 employees currently. Our main product in development is pembedutide, which is a GLP-1 glucagon dual receptor agonist. We are developing this for metabolic diseases, obesity, and for MASH. With regards to obesity, we completed a very successful study. Phase II study was 48 weeks, and we'll describe the results of that in a minute. We also conducted a very successful end of Phase II meeting with the FDA in November of last year. With regards to MASH, we will be reading out on a biopsy-driven Phase II- B study in the second quarter of this year. We made the announcement that we completed enrollment in the third quarter, and we're really looking forward to that. We've also announced that we may be developing pemvidutide and up to three additional indications, and we announced that we intended to file at least one of these INDs at the end of last year. Great. Maybe talk about the differentiation of pemvidutide itself. Obviously, there's a number of products pursuing obesity now. There's two 800-pound gorillas in the market reporting results as we speak, basically. So just interested to know your points of differentiation with pemvidutide in particular. Right. We see the obesity marketplace as being in two fundamental lanes, the first being compounds with glucagon and those without glucagon. Compounds without glucagon include semaglutide, tirzepatide. Compounds with amylin, all of these compounds do is mainly suppress appetite. That's how they achieve their weight loss. With glucagon, you fundamentally change metabolism, increase energy expenditure, but more importantly, you have profound effects on serum lipids and also liver fat. You get this because there are glucagon receptors in the liver. There are no GLP-1, GIP, or amylin receptors in the liver. All of their effects on ectopic fat, like liver fat, is through weight loss. With glucagon, you have the potent defatting effects in the liver, which leads to potent effects on MASH, but also potent effects on serum lipoproteins. In addition, glucagon appears to be sparing of lean mass. We've reported out the fact that we have class-leading preservation of lean mass among GLP-1 agents, and if time permits, we can talk about what we believe that mechanism is, so glucagon fundamentally changes how you approach obesity. With higher lean mass and higher muscle, you have a greater chance of preserving your weight loss because muscle burns more energy than fat. Preserve more muscle, greater chance of maintaining the weight loss over time. We believe that we have the first in class glucagon receptor agonists, or compounds that are being developed as dual agonists with GLP-1 and glucagon. We believe we have the best molecule because we have the highest ratio of glucagon. The molecule was designed to drive the glucagon effects, yet maintain glucose homeostasis because the GLP-1 balances the effects of glucagon on serum glucose. We got confirmation of the safety of pemvidutide in diabetics at our end of Phase II meeting. Great. So let's take a step back and we'll sort of go to the MOMENTUM study, the MOMENTUM study results, which really kind of forms the basis of your dialogue with the agency. Maybe we can just kind of tie those two together. Right. So we reported out the results of the study at the end of 2023. It was a 48-week study in contrast with many other studies that have gone 68 - 72 weeks. At the end of the 48 weeks, we had achieved 15.6% weight loss. However, the trajectory of the weight loss was still steep, and had we continued the trial out to that 68 to 72-week point, we would have had very competitive weight loss. Importantly, we had very profound reductions in serum lipids. We saw a greater than 20% reduction in LDL cholesterol in people with elevated levels at baseline. 80% of these subjects achieved normalization of liver fat, and as I mentioned previously, we saw class-leading effects on preservation of lean mass, and with this, we also saw preservation of glucose control. Great. When we kind of go to the sort of next steps, just remind us a little bit of the sort of incremental or the specifics of that lean mass preservation. How many patients did you actually study as part of that patient group? Right, so the MOMENTUM trial was 391 subjects, and we had a sub-study of 67 subjects who underwent Magnetic Resonance Imaging, MRI, for assessment of body composition. This is felt to be the gold standard for assessing lean mass and visceral and peripheral fat. We also saw very profound reductions in visceral fat along with the preservation of lean mass, and the reduction of visceral fat is very important because it corresponds to what we consider to be central obesity, which is a clear risk factor for cardiovascular disease. Right. Kind of tying us back to the old dialogue around metabolic syndrome. Exactly. Yeah. Okay. Great. The MASH opportunity and the learnings from the obesity opportunity, as well as your sort of Phase I exploration, can you just sort of tie a little bit of that together? It seems like the visceral fat reduction that you saw in the Phase II obesity study really also helps to inform some of the decisions that you've made in the incremental decisions to move forward with your current biopsy-driven study. Right. Well, we're well aware that in the SELECT trial, they saw a 20% reduction in major adverse cardiac events, also called MACE events. And that was accomplished with much lower effects on fat. semaglutide's effects on LDL cholesterol was generally around 3% - 5% at most compared to what we've reported out before. We believe that pemvidutide has one of the greatest potentials to reduce cardiovascular risk. You sum it all up. The profound reduction in LDL cholesterol, liver fat is a known risk factor for cardiovascular disease. And in addition, we've done studies, and we've reported this in recent meetings, on the reduction of a whole variety of inflammatory lipids that circulate in the serum, ceramides, diacylglycerol, sphingomyelins that are also known to be responsible for cardiovascular disease, as well as for MASH. So we believe that when we finally do conduct a cardiovascular outcomes trial, we can exceed the effects that we're seeing in the SELECT trial. Great. In terms of the MASH opportunity, you talked a little bit about the unmet need opportunity in MASH and where you see, again, you talked about the limitations of weight loss exclusive approaches to MASH. We have seen some data with survodutide, another competitor. Maybe you can kind of compare and contrast what you've seen so far from a liver defatting in your NAFLD patient population that's already been published, as well as some of the visceral fat and then your expectations for the upcoming 24-week data, which I think is coming in the second quarter. Right. So recognize there's a need in MASH to not only get potent effects on fibrosis, but also weight loss. Patients with advanced fibrosis go into cirrhosis. So you have to have an antifibrotic effect, but earlier in the disease, they die of the cardiovascular complications. So the binary effects of liver fibrosis reduction and also weight loss is extremely important for the MASH patient. Right now, we have a drug that has some effects on fibrosis, resmetirom, which has been shown to affect reduced fibrosis in F2 and F3 MASH. We have some data now on efruxifermin and FGF21 on the reduction of fibrosis in patients with early cirrhosis. But none of these drugs achieve weight loss. Now we have semaglutide, which affects good weight loss, but its effects on fibrosis are not considered to be very potent. As you know, it actually failed the trial in F4, a well-powered trial. It failed to then, and it even failed in an early well-powered Phase II study in reducing fibrosis. So if you survey physicians in the field who are using these drugs, they'll use semaglutide for weight loss. They'll use resmetirom for reduction of fibrosis. But there's no one compound that would address both. pemvidutide is the complete solution. The effects in fibrosis are driven by the amount of liver fat reduction you get. We've shown class-leading effects at 76% at 24 weeks. We're seeing these effects rapidly as early as six weeks. So we believe that we have among the best liver defatting compounds in development, and it's the reduction of liver fat that drives the reduction of fibrosis. We've also shown in animal models without liver fat that we can reduce fibrosis. We think that pemvidutide has a fundamental anti-inflammatory, antifibrotic effect in the liver. Combined together, we think that we can have the best antifibrotic effects as well as offering weight loss. With the FGF21s, with their successful readout, the liver fat reduction is about 62%. We actually beat that. So we believe that we can be competitive in all phases of fibrosis, even F4, while offering weight loss at the same time. So it offers, unlike other compounds, the complete solution for MASH. And we think that based on that, when pemvidutide is eventually approved, it will be the go-to drug for the treatment of MASH. Great. Can you talk a little bit about the dosing and the dose selection, 1.2, 1.8, and then in the obesity setting, the 2.4 dose is selected. So just trying to get a better understanding of what you're exploring in the MASH patient population and why you wouldn't necessarily go all the way up to a 2.4 milligram dose, or is that exploration still possible? Right. Well, the dose response curve in obesity is fundamentally different from the dose response curve in MASH. With obesity, that you see the more drug you give, the more the weight loss. We've seen with the recent 7.2 milligram semaglutide trial that it eventually plateaus off, but above the doses that we're currently using. So there is a linear relationship between dose and weight loss and probably goes beyond the 2.4 milligram dose for pemvidutide as well, meaning that if we dose higher, we could get even higher weight loss, although we're very happy with the weight loss that we have right now. Now with MASH, it's different. The dose response curve for reduction of liver fat plateaus off at what we see at the 1.8 milligram dose. So for the efficiency of doing this current trial, we decided to give placebo 1.2 milligrams and 1.8 milligrams. That we felt was a much neater trial to do. We recognize that we could get greater weight loss with 2.4. We always have that possibility of adding it in phase three if that's an effect that we'd like to show. We don't feel that we would get additional liver fat reduction, MASH resolution, or fibrosis improvement by going to 2.4 milligrams. However, in the Phase III setting, if we also wanted to demonstrate class-leading weight loss, we could add that back to a Phase III trial. Got it. Okay. And when we talk to endocrinologists, one of the sort of challenges is finding assets in MASH that will both defat the liver and improve the HbA1c and be able to manage blood glucose. Where does pemvidutide sort of sit in that scale? But on the flip side, hepatologists are the ones who actually treat the more severe patients at the same time, and they're laser-focused on the opportunity to defat the liver. Where do you sort of see that trade-off emerging over time? Starting with obesity, only about 20% of obese patients have diabetes. Of that 20%, half of them are well controlled. Now, if you want to treat both obesity and better control hemoglobin A1c, there are better drugs to do that. semaglutide and tirzepatide do that quite well. However, the great majority of obese patients have dyslipidemia or fatty liver or MASH. That is a more prevalent problem in patients with obesity than diabetes. Pemvidutide was not designed to treat hemoglobin A1c. It was designed to maximize the effects of glucagon, as I've described, the reduction of liver fat, the reduction of serum lipids, now the preservation of lean mass, the reduction of visceral fat, but at the same time, maintain blood sugar. It's an ideal drug, either in non-diabetics or people, that half of the diabetics who have already have glycemic control. So we believe that we have a drug that really fits not only the MASH population, but the obesity population as well in terms of the unmet need. Great. So now we're in the expectation-setting game, which is the hard part of the job. So in terms of your MASH upcoming data, maybe just sort of set the stage, the endpoint, when we're going to see the data, or sorry, not when we're going to see the data, but when we see the data, what are your expectations for those data as it relates to the key endpoints? Maybe just remind us the primary endpoints of the study and maybe some of the exploratory endpoints that you might be excited about. Yeah. So the two endpoints of the study and the dual endpoints, they're not co-primary endpoints, meaning you don't have to hit both. The study is powered to hit either, and that's the traditional FDA endpoints of MASH resolution and fibrosis improvement. So we're very enthusiastic about how we've designed the trial to hit both. With regards to fibrosis improvement, which we think to be probably the most important endpoint in MASH, that was achieved with statistical significance by other sponsors with about 62 patients per arm. Liver fat reduction that these compounds had generally in the range of the low 60s, 62%-65%. So they were in the 60s. We've actually cushioned our study in order to have a higher likelihood of a successful result by going to 76. And we're starting with a compound with 76% liver fat reduction. So we're very optimistic about reading out on that fibrosis endpoint. We'll obviously also have biomarkers. I think the key differentiator here is the fact that we're reading out at 24 weeks. semaglutide read out at 72 weeks. If successful at 24 weeks, we will be the first and only incretin to show that level of potency. Speed is potency. The FGF21s have been able to do that. They have potent antifibrotic effects. We believe that we will hit this endpoint and, unlike the FGF21s, offer the complete solution, something the FGF21s don't do, something resmetirom doesn't do, which is significant weight loss. And this is also going to drive prescriptions. MASH is a silent disease. The doctor tells them they have it, they better get treated. What drives people to treatment is the weight loss. We know it. We saw it in our MASH trial. We had one of the fastest enrolling MASH trials to date, and the reason always given is that patients wanted weight loss, so when you put the pen to the prescription pad, which I've done a lot in my career, you negotiate with the patient, and the patient always want weight loss. Consequently, we think this is going to be a real driver for prescriptions. Now, we'll have that readout at 24 weeks, but we're going to be following patients all the way out to 48 weeks for safety and also for their biomarkers. We're going to be looking at FibroScan. We're going to be looking at ELF, ProC3, and the like. We will be able to project what the biopsy results would have been at 48 weeks had we biopsied at that point as well. It's not really feasible to expose people to two biopsies in such a short period of time. But whatever we see at 24 weeks, we'll double or triple over the course of time. We saw that in the FGF21 data. Our goal is to get statistical significance. That's the starting point. Other compounds haven't done that. If we do that at 24 weeks, again, we'll be the first incretin to get that effect at 24 weeks, and the treatment effect is only going to grow with time. Let's follow up a little bit more on the dynamic specifically around FGF21s. You've mentioned them several times. There is, I think, a bit of a differentiation in some of the data between F2, F3, and an F4 population. One of those dynamics that we've raised in our own publishing and we've all talked about is this reduction in BMD. What effects does pemvidutide have on bone mineral density? Is there any evidence of bone loss, especially bone loss at the hip? Yeah. We don't have those measurements right now. I would tell you that generically, with weight loss, you lose bone density. It just simply makes sense. You're carrying less weight. You need less bone density. So the physiological, not pathophysiological, response to weight loss is to drop some bone density because you don't need it. And that's going to happen with any weight loss. We know that in the bariatric surgery literature. With the FGF21s, it's different. They don't have weight loss, but they also have the drop of bone density. So it's not a weight loss-driven phenomenon. It can't be compared to GLP-1s, where you get the benefit of weight loss and the bone loss is physiologic. There appears to be a direct effect of FGF21 on the bone. I believe that it was reported in the Cirrhotic population at 96 weeks. It was about 5% over placebo. You pointed this out in a recent report that the placebo could be expected to lose quite a lot in Cirrhotics. I think at 24-48 weeks, it was about 2%-3%. It was just projected out what would happen. Let's say it was 5% at 96 weeks. The 5% placebo plus the 5% on top of that is a 10% loss of bone mineral density. That's in a population where 40% of the subjects are already osteopenic coming into the trial. So one has to be very concerned about that. We know with the semaglutide data in their SELECT trial with 17,000 patients, they had a higher rate of pelvic and hip fractures in patients taking semaglutide. They have an unexplained 40% loss of lean mass, something that's about twice of what we see. So it is a significant issue, and it's going to sort out with larger studies over time. Got it. And then can you talk a little about what's differentiated in your own obesity program? As we kind of go back to it, you've basically had your post-Phase II meeting with FDA. You have a well-defined program. Can you talk about the program and then how you hope to move forward, whether it be alone or with a partner? Sure, so we had a very successful meeting with the FDA. The FDA identified no safety signals. They told us to proceed with our program. This, in contrast, we believed other sponsors that were told they had to do cardiovascular safety trials. They did not find a safety signal. Our incidence of cardiac adverse events were the same as placebo. We saw no increase of arrhythmias. That's in contrast to some other programs, and the FDA said that they agreed that we maintain glycemic control. We have four pivotal studies. The first, the linchpin study, looks very much like STEP 1 and SURMOUNT-1. It's basically a non-diabetic weight loss study. It kind of is the linchpin. It allows you to compare to other programs, but we're taking the dosing out now to 60 weeks. VELOCITY-2, VELOCITY-3, and VELOCITY-4 are differentiated. VELOCITY-2 looks at reduction in LDL cholesterol in people coming in with elevated levels at baseline. We saw reduction of LDL cholesterol in these patients even if they were taking statins. That's very significant because what it means is that this is a synergistic effect for further drive LDL cholesterol reduction in people taking statins. It's known that as many as 50% of people do not achieve their LDL goals taking statins, and the FDA jumped on this immediately and complimented the study, so we will read out on the LDL reduction in that population, and in addition, look at the subset of patients coming in on statins. VELOCITY-3 looks at liver fat, another driver of cardiovascular disease, and VELOCITY-4, which the FDA termed innovative and complimented us on, is looking at lean mass and preservation of function in patients with obesity. It's important again to note that no safety signals were identified, and this is extremely important as a platform for all of our studies and all of our indications going forward. Great. And then in terms of opportunities in MASH and the programs that Altimmune can fund on their own versus needing a partner, can you just walk us through the differentiation there? We've announced that we're not planning to proceed into Phase III in obesity without a partner. But for MASH and the additional indications that we will announce on soon, it's full speed ahead. These are programs that we feel that we can develop on our own all the way to the finish line. We announced that we would file at least one of these INDs at the end of last year. That goal has obviously been met and that we will make announcement on other INDs in the very near future. Great. Well, Scott, I think we're out of time. Thanks so much for joining us. Great to have Altimmune here at our conference again this year. Great. And.