Hi, I'm Catherine Okoukoni. I'm one of the biotech associates at Citizens JMP. Today I'm joined by Altimmune's management team. I have Vipin Garg, the CEO, and Scott Harris, the CMO of Altimmune. So just kind of to begin, I guess maybe you could give a little bit of an overview on Pemvidutide as a molecule. I know that it's a dual GLP-glucagon agonist, and balance that. Maybe a little bit of background on what the advantages and the mechanical rationale behind. Yeah, absolutely. So as you said, it's a GLP-1 glucagon dual receptor agonist. Our perspective on the whole obesity NASH space is that there's going to be need for multiple mechanisms of action. If this is ultimately going to be a $100+ billion market, the patient phenotype treating different patients with different mechanisms is going to be important. And that's really what we bring to the table. We are combining the benefits of GLP-1 with glucagon, GLP-1 for appetite suppression, and glucagon for increased energy expenditure. And we'll talk more about it. But that really, ultimately, if you think about it, that brings many different benefits. For instance, by adding glucagon, we're having direct effect in the liver. So we are actually converting from carbohydrate as the fuel, from carbohydrate burning to fat lipid burning. And that has many benefits. We're seeing very profound changes in triglycerides and serum lipids. There's a very large proportion of patient population out there that they're not diabetic, but they have dyslipidemia. So they need to lose weight. But ultimately, we need to improve their underlying lipid profile, their serum lipid profile. So we think Pemvidutide especially fits that kind of patient population. Similarly, in NASH, the goal there is to have a direct-acting agent in the liver. Because of glucagon, we are showing that very clearly really class- leading reduction in liver fat. But at the same time, people are also losing weight, which is a good thing in this patient population. So by combining these two benefits, we think it really would appear would suit a very large proportion of patient population where we need to address both weight loss as well as dyslipidemia. That makes a lot of sense. And just kind of talking about kind of benefits of these drugs beyond weight loss of course, we know GLPs are great on weight loss, like the incretin class in general. Just maybe you could touch a little bit more on the benefits beyond weight loss that people care about and the ones that are kind of most important you think are going to be the differentiators in the field? Scott? Well, we saw in the recent SELECT trial the 20% reduction in major adverse cardiac events. So it's attributable just to the drug alone. Because GLP-1s have very little effects directly on serum lipids, the reduction of LDL cholesterol is only about 3%. So with the 20% reduction with just weight loss, one can imagine, if you also had the lipid effects that glucagon affords, what the effects in a SELECT-type trial would be. Also, we've seen an excessive loss of lean mass with the GLP-1s. With semaglutide, the loss of lean mass was about 40% of the total weight loss. And in the prescribing information for Wegovy, it cites a higher rate of bone fractures in women and the elderly. It's known that with excessive lean loss, you lose function. You lose bone strength, and you lose muscle strength to prevent falls. And especially in the vulnerable populations, this could be a real problem. Glucagon appears to preserve lean mass. We think it's because, as Vipin mentioned, it basically mimics a ketogenic diet. It shifts metabolism away from carbohydrates to fat. And that shifts away from the burden of supplying amino acids from the muscle to make carbohydrate from pulling it from fat. We think that's extremely important. We also know that liver fats are a risk factor for cardiovascular disease. And we have very, very potent lipid-lowering effects in the liver. So all on that, when one looks at the obesity marketplace in the differentiation, one sees the acute weight loss that the GLP-1s afford and then the quality of the weight loss that glucagon offers. One other thing is that we focus tremendously now on the acute weight loss. How much weight loss do you get in one year without asking the question, how are you going to sustain it? What's the market there? And in fact, the market for sustaining weight loss is probably sevenfold great severalfold greater than in the acute marketplace. So does the drug have the potential for altering the basic metabolic tone? GLP-1s suppress appetite. And when you withdraw them, the appetite returns. And in fact, the weight you regain when that happens is actually mainly fat. So if you end up with the same weight, it's not a net neutral. You've actually replaced some of your lean loss with lean with fat. With glucagon, there's potential for just simply altering the metabolic tone. So for longer-term weight loss, glucagon may actually have greater implications than GLP-1s. That's really helpful. Just kind of going along those same lines as far as kind of longer-term weight loss, I know that Nature just published an article about Wegovy and kind of longer-term weight loss. I know that kind of the Momentum trial had pretty impressive weight loss at 48 weeks. I'm just wondering kind of whether you think that that's sort of you're at the peak, how close to the peak you think you are, and if there's any I guess there's no way to predict, but just kind of your thoughts on peak weight loss and longer-term weight loss you mentioned. Right. Well, as you mentioned, at 48 weeks, there was still a very steep weight loss curve. So people started our weight loss at 15.6%. But if we had continued to the duration of a semaglutide trial at 72 weeks, that weight loss might have been even much more impressive. So we've considered the possibility of going to longer trials in phase three. That decision certainly has been made. But we have to recognize that once you get to 15% weight loss, from the metabolic health point of view, you've accomplished what you need to accomplish. The major comorbidities of obesity reverse at 15%, the diabetes, much of the lipids, osteoarthritis, sleep apnea, things like that. So beyond 15%, you might say and this might be a bit generous it's cosmetic. I don't think that's totally true. The more weight loss, the better. When you get to 15%, you're playing in the field of benefit. Now the question is, what else do you bring to the table beyond the 15%? We think that's glucagon. Just kind of maybe touching upon kind of the next steps in the pivotal study, I know you mentioned on your earnings call that you're in the process of kind of regulatory discussions and trying to figure out kind of what kind of a trial Pembe's best fit for. Maybe kind of touch upon regulatory discussions and kind of what regulators want to see versus kind of what the investor community wants to see and how those are different. Well, you know clearly, there's a basis for what you have to do in phase three. You have to be about 5,000 patients. You're expected to probably do a trial without diabetics and diabetics. Then beyond that, the question is, how else can you develop value? Clearly, we'd like to also conduct trials looking at lipids, liver fat reduction, and body composition. That discussion will take place with the FDA in the third quarter, late in the third quarter of this year. I think it'll be tremendously value-enhancing. It'll give us a very firm footing in what we need to do. More importantly, advise companies that want to partner with us. It will de-risk the program for them. It'll give straight answers about what we can do to differentiate based on the glucagon. Yeah, I would just add that I think we have a unique opportunity here to add certain claims on the label by including a unique patient population that we think glucagon is specially suited for. So our goal going into this meeting would be to identify those patient population. Because when you're doing a 5,000-patient trial, it gives you a lot of flexibility. You don't have to do just three trials and three subpopulations. We can look at different sub patient subpopulations that will further enhance the label. And we'll obviously discuss more with the FDA and decide what are those indications that we can go after. That makes a lot of sense. It kind of touches upon sort of my next question as far as kind of the inclusion criteria and how you think that it's going to vary. I know you talked about kind of diabetic populations. How are you kind of looking at thinking about this inclusion criteria versus the inclusion criteria on MOMENTUM, which I guess was kind of more of a preliminary trial where you wanted to kind of be broader? Well, you start with the basis of taking people who are obese. I mean, it is. The approval is for obesity. That's the primary indication. But then you get your secondary claims. You get lipids. You get liver fat reduction, preservation of body composition. So the question is, what else to include in the inclusion criteria or in the endpoints in order to get those claims? We talk generally about that. That discussion will take place with the agency later. That makes a lot of sense. I guess just touching upon body composition, I know earlier you mentioned the fact that that's important. I know that MOMENTUM did collect some body composition data. Maybe you could just touch a little bit upon how pemvidutide's differentiated in this respect from, let's say, tirzepatide or some of the other agonists. Well, we'll start with semaglutide because we'd mentioned it before. And that seems to be the basis because that was the first one to report out. And that's at about 40%. Now, the comparison is to natural weight loss diet and exercise, which is 25%. So when pundits have talked about this field, they've said, look, for pharmacological therapy to play in this space, especially with older people and with women, we have to be as close to 25% as possible. So as mentioned with semaglutide, with the 40% lean loss, they actually have in their label a higher rate of bone fractures. That had actually been described in prior obesity trials when there was successive weight loss. So with retatrutide, which is also known as GGG, it came in at about 37%, not much better. Tirzepatide came in at about 26%. We were comparable about 25.5%. But there's a big difference here. They read out at 72 weeks. We read out at 48 weeks. It's known that the percentage of lean mass lean mass loss, the percentage of total weight loss goes down over time. We know that from the bariatric surgery literature. For example, in the first three months after bariatric surgery, about 50% of the weight loss comes from lean. Then it declines over time. So we're at 25% at 48 weeks. We think if we actually followed people out to 72 weeks, that percentage would drop. We'd have a clear superiority difference over tirzepatide in terms of the preservation of lean mass. Again, we attribute it directly to the glucagon effect. Tirzepatide works mainly by stymieing appetite. That's how GLP-1s and GIP work predominantly, whereas glucagon shifts the basic metabolic tone away from muscle burn to fat burn. So we think that if patients were followed over a longer period of time, that the preservation of lean mass that we demonstrated in Momentum will actually be enhanced going forward to a longer duration, which, as we said, is extremely important for maintenance of weight loss. We have the acute effects. But then the question is, how are people going to do over time? If they continue to take these drugs, they continue to have lean loss, the bone fractures over time, we think that we're going to do quite well in that scenario. That makes a lot of sense. And just kind of just a little bit of a follow-up on that and just the glucagon agonism and preservation of lean mass in general. Is there any precedent for that, like as far as other mechanisms that have glucagon agonism that have sort of seen? I know you mentioned retatrutide that also has glucagon agonism. Are you guys kind of just paving the way as far as glucagon agonism and. I don't believe there's a lot of information out there in the literature. As you know, we have more glucagon in our molecule than Retatrutide. So any differences could potentially be explained by that. But I think we're really at the cutting edge here in terms of reporting and results. But every time we look at glucagon, we look at the benefits of glucagon, we just see more and more, especially for chronic weight loss, where you have to maintain good lean mass. You have to maintain lipids, cardiovascular effects, and actually the ability to maintain the weight loss. So every time we look at glucagon in that regard, we see more and more. That makes a lot of sense. Just kind of along one more, I guess, on body composition because it's such a kind of an interesting topic. Once we've already seen kind of the numbers look good as far as weight loss, it's interesting to see, like you said, quality of weight loss. What other data are we going to see potentially from Momentum that's sort of going to help make this claim? Because I think that's a really nice differentiator between, I guess, the classes when you're in the obesity war. Well, as we mentioned, we're going to report out more data on Momentum this year. At upcoming meetings, we're not at liberty to say because of embargo rules which meeting. But you're going to see a lot out there at prominent meetings coming up in the near future body composition, Momentum, lipid effects. These are all going to come out at future meetings. So you're going to see us building on the Momentum story with scientific data that really substantiates the value of glucagon. Perfect. Perfect. I guess on that note, maybe switching gears to NASH. And I know that that's also a very hot topic currently. And I think maybe I'll start with a question about the first approved NASH drug, resmetirom, and how you kind of view that playing into the newer generations coming up, like pemvidutide, and how you see kind of your drug fitting in and sort of how this might change your views of the just general opportunity in NASH. Well, first, we think it's great that Resmetirom got approved. We think that was a great advance for the field. But there are two differences between Resmetirom and pemvidutide. The first is that Resmetirom gives no weight loss, period. And the major comorbidities of NASH initially are not the liver disease. It's the comorbidities of obesity. NASH patients die of heart attacks more than they die of liver complications, except as they get out towards cirrhosis. And even early cirrhotics have more cardiac events than liver events. We've seen great interest in enrollment in our IMPACT trial. That's because patients come in and they say, well, there are other trials out there, but you give us weight loss. So we think that when physicians and patients choose in the future between a drug like Resmetirom and pemvidutide, NASH is a silent disease. But if you say you can lose weight, that's something of immediate benefit. So we think that's going to drive preference. The second thing is that Resmetirom's effects were driven by about 50% reduction in liver fat over about 24 weeks. We're at 75%. And that reduction in liver fat drives the NASH resolution and also fibrosis improvement. The data clearly shows that the more liver fat reduction you have, the better NASH effects. So not only having better weight loss, but also driving better NASH effects, we think we're very well positioned. That makes great sense. And I guess kind of a follow-up on that would be just talking about differentiation, like you said, differentiation of Pembe within the NASH space and some of the other mechanisms. How are the GLPs and the dual agonists sort of differentiated? Well, the effects of the GLP-1s, the fat loss in the liver is mediated indirectly by the weight loss because there are no direct effects of GLP-1s. And for that matter, GIP in the liver. So if you don't get weight loss with these drugs, you don't get liver fat reduction, period. And even the liver fat reduction that you see is pretty modest. With tirzepatide, the level of liver fat reduction at 48 weeks was only 39% at the 15 mg dose. We saw a 75% reduction at 24 weeks. And in fact, we saw a similar reduction at 12 weeks. So the effects that we're getting are not only more robust, they're much more rapid. And this is going to show up in clinical trials. All of the incretins have read out at 48-72 weeks. We have so much confidence in our compound that we're actually reading out at 24 weeks because of the potency of the liver fat reduction. We've also had some preclinical data recently that pemvidutide has direct antifibrotic effects on the liver. And we have mechanisms around that. So based on the potent and rapid reduction of liver fat and also the direct effects on fibrosis, we have a lot of confidence that we're going to separate and differentiate from the pack of the GLP-1s by being able to read out in both NASH resolution and fibrosis improvement in just 24 weeks. And that's going to maybe be a statement about the potency of the molecule. Yeah, I just want to add that there's been a lot of discussion out there that how GLP-1s will really become also a therapy for NASH because people are losing weight. And that should so what we're doing, we're actually bringing the best of both worlds. We have GLP-1. We have a drug that you have weight loss benefit. But we also have direct effect in the liver. So by combining the two, we're getting rapid resolution of liver fat, ultimately rapid resolution of NASH and fibrosis. And people are also losing weight. So if you're a doctor, you're a patient, why wouldn't you want to take that? That is basically combining two mechanisms that are ideally suited for improving these patients. Yeah, that makes a lot of sense. Like you said, the dual agonists, it seems like common sense. Like you said, your readout's going to be earlier than kind of what we've seen in the field. So are you guys giving any guidance as far as what efficacy you expect to see on the biopsy endpoints at 24 weeks and kind of how that'll guide sort of next steps? And any color on that would be helpful. Well, it's difficult to give numbers. Obviously, we have power. We've made calculations. We're confident in the power of the studies and the size and the treatment effects that we're going to get. And then just kind of thinking about sort of prioritizing the two, like you said, great obesity drug, great NASH drug. So what is kind of the thought process in kind of how you plan to advance those two very large indications? It seems like you got the molecule. But now, what do you do with it? Yeah, so I mean, we're doing a number of things as far as obesity is concerned. We've been very clear. Our goal is to have a partner before we start phase 3 trials, actual phase 3 trials. We are getting ready for the end of phase 2 meeting with the FDA. So we'll know the path forward. That That would obviously de-risk the program. NASH, we're going to read out on the phase 2b data. Very excited about that. We think NASH is an indication we can take forward on our own. So that gives us that flexibility. We're also looking at additional potential indications for pemvidutide that perhaps we can also take forward on our own. So it's sort of a multi-pronged approach. We're looking at a partnership for obesity, sort of main obesity indication. We're also looking at additional indication that we can develop on our own, including NASH. That's the beauty of this molecule. There's really multiple different indications that you can take it, different directions that you can take it. It gives us flexibility as to how we move forward. And then kind of another question I had is just about you guys are going to have the readout in NASH. You're going to read out the phase 2b data. And how do you expect weight? What do you expect as far as weight loss on that trial? And how do you think that'll be sort of interpreted by the obesity community? Because I know that sort of the two indications are different. The patient populations are different. So kind of getting some of your thoughts on the messaging in there. So keep in mind that the NASH drugs today really have no weight loss. So any weight loss is going to be better than no weight loss. So rather than giving numbers here, obviously, it's only a 24-week study. So you have to take that into account. But we think anything that's statistically significant would be value-creating in terms of weight loss. Scott? Yeah, I mean, I think with Semaglutide, they saw about a 12% weight loss. Clearly, that's very attractive to patients. I mean, people are out there when the longer-term Semaglutide studies, they were 10% weight loss. So to offer this to a NASH patient who doesn't have the prospect of any weight loss at all is going to be very attractive. That makes a lot of sense. Then as far as just general, I know that the NAFLD study sort of gave us a little bit of a taste of sort of what weight loss might look like in this subset of patients, patients that have NASH. How does weight loss compare between the two patients? Let's say you have a healthy, obese patient versus a patient that has NASH and is overweight. How does weight loss compare in those two? Yeah, it's a little hard to say. In the NASH population, you have diabetics, which traditionally lose less weight than non-diabetics. Although in our diabetic population, interestingly, we're seeing about the same amount of weight loss in diabetics as in non-diabetics. That's really fascinating because typically, with other drugs, you get a haircut with diabetes. Currently, with the data that we have, which is still a small subset, but we're having weight loss in diabetics comparable to, if not better, than tirzepatide, but only at 12 weeks. So it's going to be interesting to see how that works out in terms of the whole blend. But I think we're going to have very potent weight loss. Thank you so much kind of for that rundown. I guess just kind of in the last couple of minutes that we have, just maybe going through some of the upcoming catalysts and sort of what we should watch out for. I know you have kind of a number of programs going on. So it'd be interesting to hear. Sure. So So as Scott mentioned, we're going to be very active during summer and fall at various conferences. So we're going to be presenting more data, more analyses from Momentum, as well as from NAFLD study that we have completed. So stay tuned for that. We are also preparing for our end of phase 2 meeting with the FDA. We expect to have that towards the end of the third quarter. So that would be an important milestone. And then, of course, the NASH data in the first quarter of next year. Great. Great. And then, just to finish up, maybe you remind us on cash runway and just all that's included in that. Yeah, so at the end of first quarter, we reported $182 million in cash. And so we're very well positioned to execute all these milestones. Perfect. Perfect. Yeah, sure. Would a partner want to have some say when you go into that end of phase 2 meeting? You wouldn't want to walk in with a partner into that end of phase 2 meeting with the FDA? They're going to be, presumably, I think that's what you're saying, helping pay for that trial. Right. Right. No, that's a good question. And clearly, it would be our intent to, to the extent the partner can be part of those discussions, even discussions we're having or we've had with partners, guide us as to what people are looking for. But having said that, obesity development is pretty well laid out at this point. There have been two drugs already approved. The FDA has their own guidelines. We know what's the number of subjects. It's really a question of how do we customize it to our molecule. And that's pretty standard. We know all the benefits of glucagon. So there's sort of going to be a base program in obesity and then these add-ons that we will think about how to enhance that. So yes, I mean, if there was a partner ready to go with us, we'll certainly welcome that partner to join us. But with or without the partner, it would still be value-creating having that meeting behind us. Great.