All righty. Welcome, everyone, to Jefferies 2026 Global Healthcare Conference. My name is Roger Song, senior analyst covers med tech. It is my pleasure to have the fireside chat with the company from Altimmune. We have a CEO, Jerry, Greg, CFO, and then Christophe, CMO. Welcome, gentlemen. Glad to be here, Roger. Thanks. Excellent. All righty. Jerry, why not you give us a state of our Altimmune. We have a lot going on in terms of MASH and then some of the related disease. A lot of exciting things ahead of you. Yeah, it is an exciting year for Altimmune. Obviously coming off, and I'm sure we'll have a chance during the discussion, an exciting meeting at EASL last week. Really continuing to stay focused and make progress in the areas that we've talked about throughout the last couple of quarters. Importantly, we're continuing to move forward in the startup phase of our phase III MASH program for pemvidutide, where we anticipate we'll be enrolling patients in the second half of the year. Continuing to deepen our understanding of what pemvi can bring to the MASH population. Definitely enhanced data from the recent EASL meeting. I'm sure we have a chance to touch on, but really getting a good, deep understanding of really the potential for differentiation of pemvi for the MASH population, which as we all know, as that market continues to grow up and get more competitive, the differentiation is going to be key. We have two additional phase II trials that are ongoing. Exciting the fact that we'll read out on our AUD trial next quarter, so it comes quickly, that we anticipate being fully enrolled in our ALD, our second phase II ALD, also in the third quarter of this year. A lot going on, and importantly, as we do all of the deep work towards phase III, the fact that we've made a lot of progress importantly on our balance sheet and felt it was important to get the balance sheet in a strong position prior to initiating the phase III. The financing that we did throughout the first part of the year, again, I think gives us clarity and strength of the work ahead. Excellent. All right. I think we just are right off the press from the EASL. I think you presented a couple interesting new data points there, including the AI-generated imaging review and then also some of the metabolic endpoint. Maybe just give us some highlights of why those can increase your confidence about the phase III. Yeah, Christophe. Sure. No, we were really happy with EASL. We had a pretty big presence with our booth, with our team there, met a lot of the KOL. We had receptions as well. We got the best of EASL abstract with the oral presentation on our 48-week data. We were also presenting additional data on cardiovascular risk and the benefit that pemvidutide can bring to the patients with cardiovascular risk. We had some data as well on our non-invasive testing and a different presentation, more comprehensive approach to those non-invasive tests. Finally, to your point, we had this qFibrosis, which is a different way to analyze our data from the 24-week biopsy. As you know, we showed during the 24 week already some trend in the fibrosis, anti-fibrotic effect of pemvidutide. We looked at this different ways. The biological marker, PRO-C3/CTX, that were clearly showing a fibrolytic effect there. We looked at also AI-generated. The first was the Liver Explore. That gave us a sort of a continuous demonstration that we had that anti-fibrotic effect already at week 24. The qFibrosis, which is a second harmonic generation approach that demonstrated this as well, and we were really happy with this data. As you all probably know, this is a new way of looking at those biopsies, and all these different approaches were consistently showing that anti-fibrotic effect of pemvidutide. Excellent. All right. I think maybe, Christophe, if you can give us a little bit more detail around that qFibrosis, because that can be interesting. Remember the phase II, your 24-week MASH resolution is statistically significant, which is very good already. It's fast. The fibrosis part is generally missed a little bit, I believe you have some early AI analysis also suggesting it's positive, but this qFibrosis may be more correlated with the fibrosis you're expecting to read out for the histology. I'll start with just saying that the histological reading of biopsies is in general very variable between different pathologists. It's a little muddy sometimes. They all have different approaches that they like to focus on. That leads to placebo responses that can be fairly variable. Also 24 weeks is fairly early, so there is more variability, and that could explain some of those differences. qFibrosis is a way that subtract the steatosis and calculates without any staining the amount of collagen in those biopsies. It's a fairly more accurate maybe perceptions of exactly what the level of fibrosis is in there. It's a different approach that PathAI is using with their LiverExplore approach, but they're all complementary. For example, Madrigal, who is resmetirom, has been using also and has recently presented such data. We had the opportunity to look at this. I would take all this in the more general consistency of the data. We think that's why we design our phase III at 52 weeks, because 24 weeks is probably, we are in the zone of variability there for the biopsy, and that will be the case probably if we had chosen that again. We're putting ourself in the phase III with some evidence that we have early anti-fibrotic effect. We're going to wait later, and we've demonstrated that at 48-week in our phase II, we have very strong anti-fibrotic effect. In the phase III, we'll have these at week 52. That's all putting the story together there on the direct role of glucagon and pemvidutide on the liver. Understanding from investor's perspective, when you show data then they have to take the face value and say, "Okay, phase III didn't hit that." We have a lot of evidence to support even 24-week, your fibrosis is very close, then the 48-week, probably even better. Right? I think that's understood and obviously, you need to show us in the phase III. In terms of the qFibrosis versus, I believe you're using another MASH in your phase III as well. How are those two correlated? I think you also use the qFibrosis in your phase III. That's correct. MASH is a little different. The LiverExplore that we've used or the qFibrosis are analysis of the biopsies themselves and quantifying the fibrosis into the liver. MASH is actually a tool to assist the pathologist on how to read the biopsies. We're going to use this. We're the first phase III registration trial that is using MASH. Basically, in a nutshell, you have the digitalized image in front of you. It points to the features, and then it clearly scores, and then the pathologist has the final say whether they agree or disagree with the scoring at the end. It's a very good tool. Hopefully, it decreases the variability, and it will help us in that phase III to read this. The qFibrosis, we're using this as well in the phase III, not as a post hoc analysis as we've done in the phase II, but we include this as a secondary endpoint. As you know, it's not an approved tool first for primary endpoint, clearly at this point in time. Many of the people in the field are looking at this as an evidence of the anti-fibrotic and will complement our primary endpoint reading on the biopsy with the qFibrosis. Got it. Okay. Then you did get the alignment with the FDA using all the AI tool, including MASH, which will be supporting the histology read. Correct. We have alignment with the FDA, also with the Europeans. At this point in time, they have the protocol enhanced, and we're all good to go with the phase III. Excellent. Okay. On the other part, I believe your phase III is a pretty comprehensive, very thoughtful design. You also have an arm or cohort is using the NIT as the primary endpoint, or at least a part of the endpoint. With the potential, if FDA change mind or the field evolve, and then maybe the NIT become approvable endpoint, at least for the accelerated approval. Tell us a little bit more NIT, and then also your phase II, how the data support the potential kind of positive on the NIT endpoint. Sure. I'll start with the phase II. Our data on the phase II were really convincing around our non-invasive test results. When we looked at either the ELF or the VCTE results, we have combined even these that could become potentially an alternative to a biopsy read, we show clear dose response, very strong difference versus placebo at our 1.8 mg dose. Very encouraging in the phase II. In the phase III, as you know, it's an event-driven study with the final approval that is based on liver-related events. Our interim analysis serves to support the accelerated approval. For this, we need to read on biopsy, and that's where the MASH assist will be very helpful. We have a cohort that is supporting that efficacy assessment. We also need to have a safety database to support the accelerated approval. This is the second cohort that this time between both cohorts will have the total amount of patients that's required for that safety database. This cohort is more on the NITs. The good news is that for sites, they have two opportunities, basically, to include their patients. Their patient could be included on the biopsies, and if they fail the biopsies, but they meet the NITs, they are having that opportunity to bring the patient. It's quite exciting. With the feedback we received from the PIs, it's quite positive, and we hope that it will help us with the enrollment. Got it. The enrollment criteria is slightly different between the histology versus the NIT. I believe you all enroll Stage 2 and 3. [audio distortion] Correct. We're focusing right now on our F2, F3 populations. The Cohort 1 is going to be F2, F3 biopsy proven. The Cohort 2 will be either the biopsy, they have failed, for example, in ballooning, but they are matching the NITs on the F2, F3 and the criteria that we've determined with our academic experts that are representative and high probability of being F2, F3 patients. Roger, as you reference. Yeah. Mm-hmm. We're capturing all the NITs for all the patients. Should something evolve on the regulatory side, we would be in a good position to have all of the appropriate information to pivot should that be an opportunity during the execution of phase III. That's right. That would be a huge upside because that's what the field want to look like, and then the physician side and the scientific community want to see that, but regulatory seems a little bit lag behind. I think the conversation is ongoing. Yeah. We would need the agency to move their position. Yeah, that's right. The other thing, now you reminded me this, because some of the patients, they qualify histology, some of the patients only qualify the NIT. How should we think about the ultimate outcome in terms of histology result, the ultimate, the liver event result will be different to those, huge difference between those two populations? The F2, F3 might have difference, and it's known that on the liver-related events, they have different risks. The F3s are clearly more advanced. The F2s are less advanced and have a hazard ratio for liver-related events that is usually smaller. We have the opportunity to adjust. We've determined based on the literature, there is no current study that has demonstrated outcome. Based on our knowledge and the literature and the academic experts, we have a hazard ratio that we feel is reasonable. We're going to monitor that event rate, and we have the options to adapt this in our enrollment based on this. We'll have that flexibility. Our primary focus, obviously, is to get to accelerated approval, and these are the biopsy-proven patients on the efficacy side. Got it. You have the flexibility to change the ratio between the F2 versus F3. How about the Cohort 1 and the Cohort 2 in terms of the histology validated and then the NIT validated? For the Cohort 1 and 2, those ratios have been determined. We are going to have 990 or approximately 990 patients in the Cohort 1. This is based on an effect size that we've determined on our own phase II data on the prior products that have been approved so far and what was the effect size. We've powered ourself based on MASH resolution, this one is easy to achieve, we're well north or even 99% powered. On the fibrosis, this is the most difficult to achieve. We've taken a rather, I would say, a bit of a conservative approach on our assumptions, there is a few upside. One, we're having the 2.4 mg dose that has demonstrated the added weight loss and potentially could demonstrate added benefit on the fibrosis. That's not been part of the powering, we're powered based on the phase II on the 1.8 mg. We see that as upside. We have, as I mentioned, the decrease in variability potentially on the MASH assist. That could also play in our favor. One additional aspect that I think is really important in all of these MASH trials is adherence to treatment. We've demonstrated with pemvidutide that more patients stay on treatment. Discontinuation rate could be lower than, for example, other competitors or GLP-1s. If the more patients we keep in our study, obviously, the more chances we have to demonstrate strong efficacy. All these are kind of added upside that have been put in the design of the study, but they are not factored in our sample size. Got it. In terms of the Cohort 1 and Cohort 2, I believe both of them are well-served to the final endpoint, which is an event-driven endpoint. Sure. Will those two population difference in terms of natural history and then the reaction or response to the incretin? No. The two population will not be different. It's not because you do the biopsy and you fail on the biopsy that you have lesser risk, et cetera, to evolve towards progression to cirrhosis or other liver-related events. That's part of some of the challenges of the biopsy and where the scientific community is trying to push regulators to understand that the NITs could be sufficient to determine the risk of those patients. They will be extremely similar, and we hope to have the same progression for these. We've built as well a little bit of what we call NITs-triggered biopsies to follow those patients and identify events. Hopefully, that could help us either wrap the study a little faster or figure those things out as they come with given the event rate. We build a few things like this that we think can help us and can ultimately be more efficient for the MASH patients. Got it. Okay, great. It going to take a while to read out, but I think we have a lot of evidence to support the phase III could be positive. If that's positive, and then you can get accelerated approval, and then waiting for the final approval. If you get approval at the interim based on histology, how should we think about the market? A lot of investor discussion or pushback, I would say, is incretin also show benefit there, and they will go generic pretty soon. The pricing point is different. You as a, now it become a more liver-specialized kind of a compound, pemvidutide. How should we think about the dynamic there, why people want to not use the generic incretin, rather using pemvi, what's the pricing strategy there? Yeah. As I mentioned on the front end, the whole opportunity is going to be about differentiation and making sure in market you're identifying the patient segments that can best be served by pemvidutide. Importantly, the market's going to continue to grow up. It's been great to see since the first couple of approved drugs have come out that the physicians are able to identify the MASH patients at risk non-invasively. The payers have been supportive. You see the utilization of MASH therapies, which we talked about for a long time. Once some drugs are available, you'll start to see the structure of the market evolve, and it has. Importantly, I think when you look at the potential profile of pemvidutide, we're meeting some of the needs that will be there in spite of the fact that there are drugs approved today and that we anticipate more coming. Where might pemvi play? I think first and foremost, we continue to get strong feedback that the dual mechanism impacting high-quality weight loss along with direct liver activity is one of the key treatment goals. It's why from the beginning when the first phase III were set up for MASH, the scientific experts always talked about combination therapy because we know it's a complex disease that's going to bring multiple mechanisms at play. Pemvi, we believe, is going to bring good solid weight loss addressing many of the elements on the metabolic side and bring the direct liver action. I think that the GLP monotherapies, by the time that a drug like pemvi gets to market, will be often a first -line option. You mentioned might be at a lower price point. We know the access to and experience with the therapy. Even today, we know that the majority of patients, MASH patients who are put on GLP monotherapy, don't stay on the therapy for the long term, right? Chronic therapy, getting patients at the target dose and keeping them at the target dose in the real world is the whole key to effective treatment. I think that's where the profile pemvi can play best. We saw in the phase II the dropout discontinuation rate on the 1.8 was lower than placebo. Again, keeping patients on in the real world I think is going to be one of the opportunities to differentiate from GLP monotherapy. We know there are significant portions of the population that have difficulty tolerating GLP monotherapy. We know that some of the oral options which aren't bringing weight loss to the table, there's a desire for a drug that can bring both, and at times avoiding having to take two different drugs, which they are doing already. Some of the patients that are starting on the oral option that's available and, sema are getting both together. The opportunity here is you bring something to the table that can do both. Roger, we continue to see, again, good strong segments of patients. We can talk about the group of patients that are at risk of sarcopenia, which might be, again, an ideal candidate for a drug like pemvidutide, if the phase III data is as we anticipate. Again, we believe there's a middle of the treatment cascade here that may not be first on. There might be some later-stage patients, F4 patients that where FGF21 are a good option. We think there's a really good solid several segments of patients where pemvi's going to be a good option. Yeah. We're going to continue to focus on the differentiation. Some of the data that came out enhanced that. The way we're setting up some of the elements around phase III play in that direction. Again, the market will grow up, and the key to success is going to be not just getting into the market, but getting into the market with clear opportunity to differentiate for important segments, and that's the approach we're going to take. Got it. Yeah. I think it's maybe as a down the road, but I would think that this is also a branding strategy because you want to differentiate yourself from the top is not just another obesity incretin. You are rather it's a more glucagon liver targeting agent because a lot of the other, you do have a couple GLP-1 GCG, but their ratio is basically the GLP-1. Yeah. It's a very little kind of a GCG. Rather, you are one to one, so it's more on the GCG side. When you do the branding or the pricing. Yeah. This is a more kind of a liver-targeted agent. That's a key point, Roger. It was one of the, I think, themes that we saw at the EASL meeting, the growing understanding of the importance and the potential of combining glucagon and GLP. On top of that, the fact that all of these compounds are not the same. The ratio matters. We believe that the balance ratio we see in pemvidutide is important. We think that the EuPort domain, which is again, a core component of the connection of the peptides is important on the tolerability side. Again, I think ultimately yielding a profile that's going to be different not just from other combinations, which might be the GLP-GIP, but also significantly different from the other glucagon GLP combos out there. These combos are not all the same. It's about the molecule. It's also about the formulation. It's about how the drug is delivered. I think all of these are going to be contributing to what we believe is a differentiated profile. I agree. Okay. Greg, I know you've been busy and successful, right? You try to finance this kind of major massive phase III MASH. Tell us where is the balance sheet so far, and then how this whole program is funded? Thanks, Roger. Yeah, let me start with sort of how I think about the financing strategy as we came into the year. We had a pretty good line of sight on what the investment in the MASH trial was going to take. We broke that down and through two different equity offerings, most recently the $225 million on top of the $75 million raised back in January, bring us to a total balance sheet north of $500 million. The so what is that that will cover the runway to deliver on the MASH results in 2029. That's three years out, and the effort that Christophe and his team just end to end the efforts to take the MASH phase III through the gauntlet that were covered there. I think we also have a budget for the AUD and the ALD phase IIs. Those are also covered. As we go forward, we have some flexibility and optionality. We think about the use of perhaps some strategic investments also in combination with perhaps our debt facility and/or an ATM. Again, going forward, we would focus on non-dilutive options as our preferred go-forward plan. I think it was also important in all the work that Greg helped lead, that we brought in some real top-tier biotech investors into the story. It had been clearly one of the objectives and an important element as we look at the long-term opportunity with MASH and hopefully with AUD and ALD also. Yeah. Okay. Let's talk about the AUD and ALD. Honestly, I'm very interested in those two program as the liver, more specialty in the liver, and then the unmet need is even more than the MASH, considering how many options are there available to them. You will have the data pretty soon, I believe it's 3Q. Yep. The ALD a little bit later. That's for AUD first. Then, I think at this point, we treat them as the optionality and how excited are you internally in terms of the upcoming phase II and then what is the profile can trigger you to tell Greg, say, "Okay, we're going to fund this a little bit even more, and then let's do more?" Yeah. We're excited. We're looking forward to the data. I think that this was a real important expansion of the potential for pemvidutide. We always hope to go into areas where there's large unmet need and where we believe there can be differentiation in what pemvi can bring versus what some of the options might be, and it's the context upon we designed the two studies. Maybe Christophe, you can give a little insight in the data we're anticipating, just what we're going to read out on and how you see the mechanism of pemvi playing in that indication. Sure. AUD and ALD are those next indications we're looking into. Pemvidutide fits really well because through the GLP-1, we address the reward and the cravings on the alcohol aspect. Through the glucagon, we are very uniquely positioned to address the liver aspect, in particular, obviously, in ALD patients. AUD patients also already have liver steatosis inflammation and even at EASL, some KOLs were telling her that it's underestimated the level of fibrosis they have in their liver. This is a great opportunity for us. Our AUD study will read on heavy drinking days. We were really encouraged to see the semaglutide data. It was one single center study. We're multi-center. There are differences with our study. It looks like it's validating our approach with the GLP-1 at least component of pemvidutide. As you mentioned, it's going to be helping us moving, we'll see with the data, but moving to based on this data, what else can we do next? Starting planning to engage with the regulators and moving forwards, I'll be bugging Greg to accelerate more funding efforts to support it. Yeah, Roger, you can expect in quarter three, we'll read out the data. A traditional top line release from the company. We'll put the data together. If it's positive, request an interaction with the agency, and then continue to update on our plans there. We look at that as a good solid bet and excited for the data to come. We'll see what it looks like. How many days reduction on the heavy drinking days you think it will be clinically meaningful also? I believe a powerful one-day difference, is that right? That's correct. We've been fairly conservative in the sense that these are PROs, that the placebo effect can be fairly important. We're measuring more objectives assessment through some blood markers like the PEth, the phosphatidyl e thanol measurements. We'll get a good sense of where those things are. We've assumed only a one-day difference between the effect of the pemvidutide arm versus our placebo. Obviously, we'll get a sense of how that plays out when we read out the data. You think the one-day difference also clinically meaningful in terms of the advisor or the feedback you're getting from physicians? Yes. I think it's already clinically meaningful. It's an average, so in some patients it will be more than that. It's what we believe as a starting point can be important. Based on this, we'll look also other endpoints that have been validated and regulators look at it for the phase III, such as zero day of drinking or WHO levels changes. These will be aspects all together clearly will tell us how far and where we can get with this data. By the way, the time period, the one week, within the week, a heavy drinking day, and then you reduce it by one day, right? It's an average per week, but we're measuring four weeks in a row. Four weeks. At the baseline and four weeks in a row at end of study at 24 weeks. Got it. It's not just one week like this, it's an average, and we'll get a sense as well as what's happening throughout the study. Got it. Okay, great. Jerry, any closing comments? No. Except just to say that the company stays extremely focused. We are in an era of execution. We're executing towards the readout. We're executing towards getting the MASH trial up and running. Again, I think at the heart of it all is our belief that pemvi is an important potential therapy for patients and can bring elements different to the table than any of the other medicines out there. A lot of work to do, but good progress and we'll keep you informed. Excellent. Thank you, gentlemen. Thank you, everyone. Thank you. Thank you. Thanks, Roger.