Altimmune, Inc. Aktie

Good morning, and thanks for joining us here on the third day of the Goldman Sachs Global Healthcare Conference. Thrilled to be joined on stage today with the management team from Altimmune.

And Jerry, I wanted to start with this question because you joined the team in the -- like last year, what drew you to the assets pemvidutide into the company such that you wanted to kind of take on this?

Thanks for the question, Corinne. And more importantly, thanks for having us, glad to be here with you today. So it was pemvidutide the asset that really attracted me to Altimmune. Last year, I have been approached first to join the Board and having spent a long time in liver disease and in MASH specifically previously. For me, I looked at the opportunity, the potential. This was prior to us getting the Phase II data sets. And really, in the game of MASH as the market matures, it's going to be all about differentiation and ensuring that you're able to fill a need in the marketplace in some important segments, that's where value is going to come from and seeing a product like pemvidutide that had the potential to bring first 2 important elements of therapy impacting from the GLP side of the molecule, the metabolic factors, weight loss, et cetera, but also the direct action of the glucagon component of pemvidutide bringing direct activity on the liver.

For me, it was a mechanism that was uniquely due for liver disease, which is why you see us really stepping towards liver disease as the primary focus. But importantly, when you look at the molecule, additionally, the proprietary U-port domain, which is impacting the tolerability is also going to be an important piece. So it was the molecule, the product that first excited me as I learned more, saw the potential and then -- the CEO role.

Great. And then maybe for both of you, you guys kind of both joined relatively recently, when you joined, what were the key priorities that you had strategically? And could you just provide like a report card or a mark-to-market on those.

Yes. So it's been a busy time, and I think a time with a lot of progress for me, importantly. First step was really about the foundation of the company, and I think that, that takes on several fronts importantly as we got to the end of Phase II and then look towards the potential for Phase III capabilities that is required for a biotech of this size, evolve and change. So getting the right kind of experience, talent, first in the management team and then ultimately in the rest of the organization that can support the kind of work that is really critical when you think about folks that have experience in late-stage development experience and preparing the commercial business case and ultimately, the commercial strategy, also folks that know how to assess and keep the company open on the right strategic options that are going to evolve. So you did see really a new management team evolve and then importantly, reinforcements under as you need folks that can drive a big execution requirement in a Phase III program.

So importantly, the talent and the people and the capabilities was one component. Another element of the foundation was really about clarifying and fortifying the opportunity as we saw with pemvidutide. So you've seen us refine the way we digested and then discuss the data and importantly, clarify how we're going to translate those important elements of potential differentiation into the Phase III design. So kind of step 2 is really around solidifying the understanding of what the pemvi story could be and how we communicate that so people get a good understanding of where we're trying to go. And then third, and maybe Greg can jump in on this, obviously, a move to Phase III requires a lot of capital. We felt it was important that we were as financially sound as possible, giving us the strength and the optionality and the clarity as we move forward.

So maybe you want to highlight a little bit the progress made on the financial side, which again was a really important element of this first step, which was about making sure we're as strong as possible from a foundational standpoint.

18 months into the CFO role. And it really is early days. I remember it was really about the financial situation. What it's going to take to get through that MESH Phase III, where we were and how we get there, what optionality we had. Investor engagement. And then third and importantly, it's been enhanced by Jerry first on the Board and now CEO is the clear messaging on where the company is going and the focus in MESH and liver disease. And then the financial side, yes, we -- you see that MESH trials cost in the range of $400 million. And so we've raised approaching $500 million over the 18 months. And so we're well positioned now with that Belson suspenders with some additional optionality going forward, if needed. But that's where we stand on the balance sheet. I think the investor engagement has been important too.

I think getting the clear messaging about where our focus is and what the opportunity where the value is going to be enhanced going forward. Pretty excited about all that.

So a lot of progress and a lot of work to do ahead of us.

Yes, absolutely. Maybe taking a step back as you think about MASH, and you obviously, you alluded to this earlier, we have a long history in the space. How do you think about like the direction of travel for the MESH market or NASH market as we look to have multiple new mechanisms coming in over the next couple of years?

So I think importantly, it's been really great to see the maturing of the treatment space, having the first approved options for patients is really important. It's been said from the beginning when we were first starting to execute the first Phase III in MESH that this is probably a disease because of the complexity, because of the diversity of patient situations that's going to require multiple mechanisms, combination therapy, so to speak. And I think that all of the conversation continues to go in that direction. I think again, to bridge back to your earlier question, Corinne, that was, again, 1 of the points of attraction of pemvidutide because you do have combination therapy with 1 molecule because you're bringing the benefits of a direct acting mechanism on the liver with the glucagon side and the GLP side bringing the metabolic approach.

And I think you're going to continue to see that. I think importantly, more entrants into the space, and this is already occurring with the 2 that have been approved. You're seeing diagnosis increase. You're seeing more patients, appropriate patients, get the opportunity to seek treatment. And I think from all the analogs you can look at from any big, large chronic treatment condition, which MESH will ultimately become, I think, another large chronic class where it takes multiple mechanisms where you have to be clear on which segments of patients might be the best choice for certain therapies. And I think you're going to see all of those dynamics evolve. So I think when we all of our thinking about pemvi is about the market we will enter, not so much the market as it exists today, although, of course, you're monitoring as things go on.

So I think you will anticipate more treatment options, more patients treated. And again, I think you're going to see some classic segmentation evolve, and that's the way that we think about the market as always which are the segments where the unique benefits of pemvi, one to one, glucagon GLP, that's bringing strong efficacy with tolerability that allows patients to stay on therapy for chronic treatment, which is critically important. There will be segments that we feel that this profile will be uniquely positioned for, and that's how we think about the preparation that we're doing now.

That's a great point. But as you think about maybe you could be a little bit more specific, Look, what are the kind of key metrics or parameters you think will stratify patients or features of the patient population? And which are the groups that you think are best suited for a drug like pemvidutide?

Yes. So I think you're going to have a general approach around severity of disease and then some of the other patient characteristics. So what do we mean? So I think you're going to continue to see potentially GLP monotherapy be a kind of an early choice. Physicians are experienced with those drugs, although we know from -- even from the data, the real-world data that's evolving. Patients have a difficult time staying on those options for a long period of time. You also might have some mechanisms, if you think about FGF21, that seemed to be well positioned for the later-stage patients. They've shown some efficacy in the F4 population. We think that middle of the road are the segments that pemvi will be well positioned for. I think that you're going to have patients that have difficult times tolerating some of the other options that will be, I think, a really good segment.

We know there are patients that are naive, the therapy haven't been on anything, but maybe at a high risk of sarcopenia, which might be, again, another interesting segment for a drug that potentially not only delivers liver efficacy, but strong weight loss, high-quality weight loss, sparing lean muscle mass. Again, I think you also have a potential with pemvidutide a very simple titration. You don't have to go through a long number of steps that some of the other injectables require. So patients that generally have a difficult time complying with therapy might also be an important segment. And then another area that we think in this context of combination therapy, which we know is of high interest. When you have a drug profile like we believe pemvi will show in Phase III with a good safety profile with excellent tolerability with a simple titration.

It also makes it an ideal partner if physicians want to combine 2 drugs because you don't have some of the complexity that might be there with some of the others. So we'll continue to do all the deep work on understanding exactly the segments and where we will go. I'm sure we'll talk a lot about this as we continue to do the required deep market research here, but we feel good about the potential differentiation. And then importantly, we always look at it in the context of how things are going to evolve in the future. And we believe that importantly, there will be more options, and there's a positive benefit of there being more options because it will help accelerate the overall growth of the number of potential patients being treated, which is important.

Yes. One of the things you mentioned early on was kind of the differentiating features of pemvidutide, one of which is this balanced agonism between GLP-1 and glucagon, how do you anticipate that could translate to the clinic? And perhaps you could couch that against also the servadutide programs in NASH?

Yes. So we do talk about the balance of 1:1 ratio of glucagon and GLP agonism. And again, for us, the concept is this -- the ratio we think is important. That's one component. So you take a drug like pemvi, that's 1:1. Servo is about at 7:8:1. So much more weighted on the GLP side. And that may be one of the explanations why you do see if you compare the data sets of difference in patients' ability in the Phase II MASH trials to stay on the drug through the 48-week course of treatment. As a reminder, for pemvidutide in our 48-week data. You had an extremely low discontinuation rate. You had actually more patients stay on the 1.8-milligram dose than stayed on placebo. And you compare that to the Phase II data -- MASH with Servadutide where you had over 20% discontinuation rate on that.

So again, we think the ratio is important. The molecule is important -- and we do have, as I mentioned before, the port domain, which is one of the elements connecting. That's part of the molecule that we also think is impacting the tolerability. So the mechanism, all -- and this is one of the themes at the recent EASL meeting that we saw in some of the discussions that the mechanism of action is important, but all glucagon GLP combos are not the same. And I think this ratio and the molecules themselves are you're going to see more and more discussion around that as the data set emerges. So when we talk about the differentiation with pemvi, we think out both within the class and on a broader basis against some of the other options that are out there.

So speaking to the data that you've shared over the past 1.5 years or 1.5 years, I guess, at this point, in NASH. I guess could you just remind us some of the highlights of that data? And particularly, what did you guys kind of share at the recent EASL meeting? And what it highlights you want investors to take away from that?

Yes. So we read out the Phase II data set in MASH last year with 2 readouts, one at 24 weeks, one at 48 weeks. I think at 24 weeks, we saw the drug starts to take effect quickly hit strongly on the match resolution endpoint. So you're seeing good efficacy quickly. Although there are a lot of indicators of the antifibrotic could benefit at 24 weeks, did not hit the statistical significance. But so again, on the noninvasives that just 24 weeks, good activity was occurring already. I think importantly, was probably an aggressive assumption to think you're going to hit a biopsy on this mechanism at 24 weeks. Fast forward at 48 weeks, we saw a real improvement at 48 versus 24 weeks on all the noninvasive NITs.

Importantly, there was in a biopsy at 48 weeks but we saw on fiber scan, on ALF, real strong improvements in the antifibrotic effect, which is why we've positioned the Phase III at 52 weeks on the biopsy read. We think that's the right point in time to read out on biopsy for fibrosis. We'll also read, obviously, on the second endpoint in MESH resolution at 52 weeks, but we did hit that quickly at 48 weeks. So what we think we have at a year of treatment is a drug that patients stayed on as I mentioned. Importantly, the weight loss was good, and it was not yet plateauing on the 1.8 milligram dose. We saw good, strong anti-fibrotic activity that makes us importantly believe that 52 weeks is the right time to read that biopsy. We reinforced some of that data set at EASL showing at 48 weeks, some broader benefits on some vascular elements around lipids, waste or conference, had some depth of the weight. So again, good solid understanding of what this drug might be doing at a year, which makes us really encouraged when we designed the Phase III to readout at 52 weeks.

Great. That's an excellent segue to the Phase III program, which you guys have recently disclosed more detail. And maybe you could step through the key parameters of that study and why some of those design decisions were made?

Yes, I think what we tried to do, as you would expect, is we took all of the insights from our Phase II program, had a real active discussion with at our end of Phase II meeting and landed on a Phase III that we think puts us in the best position to not only succeed on important clinical questions but also to reinforce some of this differentiation that we talked about. So first, as I mentioned before, the primary endpoints on the histology phase of the study is 52 weeks. Now this study is set up to read out on confirmatory outcomes eventually, the 52-week is the interim look kind of the classical data set that would support and accelerated approval filing. We're taking 2 doses in the 1.8 milligram, which I mentioned was kind of the -- it was the higher dose than our Phase II, but a dose that we're really felt good about the totality of the data.

We also believe that there is an upside because of what we saw in terms of tolerability, weight loss, et cetera, to also as an upside, put the 2.4 milligram dose. Now as a reminder, we did test 2.4 milligrams in an obesity population previously. And we think there's an upside both on efficacy and potentially for some subpopulations. So we thought it was a good approach to add in the 2.4%. Again, we look at that as an upside. The powering of the study is around what we're expecting in the 1.8%. We did put a simple 1- or 2-step titration into this study. We did not titrate pemvidutide in Phase II. Nonetheless, we saw the kind of tolerability and adherence that I mentioned before where more patients stayed on the 1.8 dose than stayed on placebo. But we think that a simple 1- or 2-step 4- or 8-week titration phase depending on the dose probably has the ability to mitigate even more some of the GI side effects that you tend to see mechanistically with GLP.

And again, it's simple and is very different from some of the 6 or 8 or 10 step titration phases that you see with some of the other options. We also -- it's the first Phase III program, utilizing the AIM MASH assist tool. So as everyone knows, 1 of the components today for Phase III program in MASH that the agency has asked for is a histology read consensus read from pathologists. And this is an AI tool that assists that pathology read. It's meant to reduce the variability, help with the speed of reading and some other elements. So we're also encouraged to be the first program to be able to incorporate that into the Phase III.

Great. There are 2 parts embedded within the study. One measures the biopsy histology endpoint, another is kind of noninvasive test. How did you arrive at the sample size required for statistical significance on that histology endpoint given you don't technically have 1-year fibrosis data based on histology.

Yes. So the study design, it's a few components that contribute. Again, the primary endpoint of the study is those long-term outcomes. So you have to figure that into the equation of how many patients you need overall. The histology cohort, 1 study, as you mentioned, 2 cohorts, one are patients with biopsy-proven F2 and F3 MASH. I think that we continue to frame our powering as conservative. We looked at the NITs. We looked at what other programs have delivered and we tended to take a conservative approach in terms of the sizing of that biopsy cohort at 52 weeks. We had the second cohort, which are patients with NIT screened F2 and F3. That group is contributing to both the long-term outcomes, so that will contribute to the long-term outcomes phase as well as to the 52-week safety database that the FDA guided us towards in terms of the right number of patients to support an accelerated approval while you have the biopsy cohort as the efficacy portion of that -- the 2 groups together will be the safety cohort.

Okay. NASH has been somewhat of a tough indication from a trial conduct execution perspective. You already mentioned the AI tool. Anything else you'd flag in terms of practices embedded in the Phase III to ensure its success?

So I think as you mentioned, we have these 2 cohorts, which is interesting from a site standpoint because you're giving them options. We are definitely prioritizing the enrollment in the biopsy portion of the study because we know that those are were challenging to enroll. However, we feel good about the initial -- all of the initial feedback on the study. We're taking all the learnings. I think that many have learned along the way, as you mentioned, as the CROs have become more experienced as the sites themselves have become more experienced in how to find and screen the right patients. The profile of the drug is attractive. We do know from experience that the weight loss component is another dimension and that sometimes helps attract both sites and individual patients.

And again, we feel good about the progress we're making. We are continuing to move through the start-up work of the study and continuing to guide to patient enrollment in the second half of the year.

Okay. You mentioned some of the things you can do to help enrollment. I guess what are you anticipating in terms of time lines for site initiation and enrollment?

Yes. So all of that work is ongoing now with the sites, the deep work that's the start-up phase in terms of the site of verification. It's a global study. We're working across all the continents that are appropriate and that you would expect. And then you've seen from some of the other global trials. These trials do take typically 18 to 24 months of enrollment. We are targeting the lower portion of that based on some of the elements that I mentioned, and we continue to guide that we'll begin enrolling patients in the second half of the year and that the readout is anticipated in 2029. Obviously, as we get deeper into the picture over the coming quarters, we'll have a lot of discussion around those elements and enrollment and progress on the study as is typical.

Yes. You mentioned already, but you did embed the outcomes piece of this into the Phase III program. How long do you anticipate it will take to accrue sufficient events in an F2, F3 patient population to see a benefit on outcomes?

Yes. So as always, you do the modeling, I think the 60 months is the estimate on that. We'll see how things progress -- and again, I think we feel good about our ability to enroll the right patients along the way to be able to get us to the outcomes portion. It's a requirement of the approval pathway, which is typical for MASH. And again, we're setting up the study to -- with that always as part of the right consideration, keeping the right patients in the study for the long term. So while we'll talk a lot about the 52-week endpoint because that's the first milestone. We're always managing in the context of delivering the full study and the important outcomes.

I think a lot of companies use an F4 patient population to think about outcomes. Why did you feel like this was a better approach for the molecule or for the team?

Yes. I think for us, we're basing it on what we know about the molecule to date. Obviously, the F4 population is an important population. We've seen over time, different products take different approaches. We'll -- we have a clear prioritization on the F2, F3 population at this point, and we'll continue to assess the opportunity as we move forward.

Okay. Maybe pivoting a little bit, pemvi is also in development for alcohol use disorder and alcohol liver disease. Maybe talk to us about why those made sense in the context of this particular agent and its properties.

Yes. So Corinne, that comes back to what we believe is the value of bringing both the direct acting liver impact of the glucagon side of pemvidutide and the metabolic effects I think if we think about both of those patient populations, the drinking is an issue, we know that it leads to implications on the liver over time. So we're approaching it with the potential to be able to address both sides of that. So the emergence of the understanding of the role that GLP can play on the craving mechanism and on the impact of the drinking. We think is only part of the equation even for the AUD population, which tends to be -- although this is a continuum, there are ALD patients who are obviously also suffering from AUD. There has been a perception that the AUD patients weren't always suffering liver complications yet. And I think there's an emergence of thinking progress, you have to be thinking about the liver, maybe even earlier than anticipated.

And so while the Phase II data is primary is the data set that we'll read out next quarter in AUD is primarily focused on the impact on drinking. We see the opportunity over time to really bring the benefit of both an impact on the liver and hopefully, a positive impact on the level of drinking to the equation. We don't look at this as only solving 1 part equation. We think because of pemvi's broad benefit on both sides that could be being different than some of the other options that might be approached.

How should we think about the market opportunity in each of those indications and the unmet need in terms of patients that might be candidates for therapeutic intervention.

Yes. So the unmet need is high. We know that if you look at some of the data, they are large populations, 12 million or so with AUD might be half of that or so with ALD, no approved drugs in ALD, the few older options with AUD, but we know a high level of unmet need. So I think importantly, again, it's going to be about defining what the therapeutic impact you can deliver. It is a market development need. You have to understand how to find the right segments of patients to be able to bring on board. Large unmet need. We think we can deliver if the data supports it, something unique there. And if that's the case, then it's going to be about understanding the right business case and how best to pursue. But we're encouraged by the level -- the potential of the mechanism the unmet need is high and it's kind of indications that we feel a company like Altimmune should be exploring.

To that point, what do you need to see from these Phase -- programs.

Yes. So we'll see the AUD study -- obviously, we set up that study, as I mentioned, primarily around impact on drinking, although we'll capture the full liver enzymes, et cetera, we will look at weight. We want to see the impact on drinking. The decrease in the number of heavy drinking days is the primary endpoint of that study. We have some of the potential regulatory endpoints as a secondary impact on the WHO classification, for example. We'll look at the totality of the data. see what we're seeing have a discussion with the FDA, make a determination what we think the potential is and then come back and an update on what the options and the plan will be. We have talked about it if we're in that positive scenario where we believe there's value there.

Maybe, Greg, you want to mention how we think about the financial element on that because, of course, we have some milestones to get through in terms of understanding the data and the regulatory endpoint. But of course, we're always thinking and working about the what ifs along the way.

Well, a Phase III thinking as we go forward in these 2 new indications is important. And the framework of existing balance sheet and MASH imperatives as a foundation but yes, we are beginning to do the work. I think as we turn over the card in AUD, get the regulatory feedback we'll in parallel be looking at optionality on how we might position that Phase III funding and take that forward. I mean if the value is there, we'll get it done. I think the likely preference is going to be nondilutive, could be a partner, it could be strategic, it could be regional, it could be some other flavor and not a default to new equity issues. But we're excited about it. This is a very exciting time for the company between kicking off the MASH trial, the AUD reading out, ALD moving forward and just all the detailed work that's going on to on the financial side, create a little more decision around the forecasting a little more certainty around what that use of cash and burn rate could look like going forward. .

Great. So maybe just to clarify, I guess we'll have the data next quarter. When do you expect we'll get kind of a broader update on the program and -- there?

Yes, we'll guide to that when we think it's appropriate. Again, I think we want to make sure we're digesting the data. We've got a lot of important focus on MASH execution. We'll digest the data, can't always predict exactly how long it's going to take us to have the right discussion with the FDA, but we'll be working on all of that with a lot of focus, and then we'll come back and give some more clarity. And again, really encouraged and looking forward to releasing the data when we have it.

Awesome. Well, that brings me basically to the end of my questions. I thought this was a super productive conversation. I appreciate the time this morning. and thanks to everyone who joined us here in online.

Thanks, Corinne. Appreciate it.

Thank you.

Good morning, ladies and gentlemen, and welcome to the Altimmune First Quarter 2026 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded. I'll now introduce your host for today's conference call, Luis Sanay, Vice President of Investor Relations. Luis, you may begin.

Thank you, operator, and good morning, everyone. Thank you for joining us for Altimmune's First Quarter 2026 Financial Results and Business Update Call.

On today's call, you will hear from Jerry Durso, our President and Chief Executive Officer; Dr. Christophe Arbet-Engels, Chief Medical Officer; Linda Richardson, Chief Commercial Officer; and Greg Weaver, Chief Financial Officer. Following management's prepared remarks, we'll open the line for the Q&A session. Our first quarter 2026 earnings release was issued this morning and can be found on the Investor Relations section of our website.

Before we begin, I would like to remind everyone that remarks made about future expectations, plans and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For a review of the risk factors that could affect the company's future results and operations, we refer you to our SEC filings.

I also direct you to read the forward-looking statements disclaimer in our press release issued this morning. Any statements made on this call speak only as of today's date, May 13, 2026, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date.

As a reminder, this call is being recorded and will be available for audio replay on our website.

With that, I'll now turn the call over to Jerry Durso.

Good morning, everyone, and thank you for joining us today for our first quarter 2026 financial results and business update call.

During our last earnings call, I discussed that one of my first priorities as CEO was to strengthen Altimmune's foundation to equip us for the continued successful advancement of pemvidutide and support our evolution into a late-stage development company. Since the start of the year, we've made significant progress across multiple fronts and are excited about the opportunities ahead of us.

Let me take a moment to highlight our recent progress. First, we have continued to enhance and build our team strategically to ensure we are best positioned to deliver on our vision as we enter a new phase for Altimmune. We've also remained focused on strengthening our financial foundation. Importantly, in April, we completed an oversubscribed public offering resulting in $225 million in gross proceeds. The proceeds from the April offering, along with our existing funds, resulted in a cash balance of approximately $535 million as of April 30. We now have the financial resources to fully fund the company through our Phase III MASH 52-week data readout, which is expected in 2029. This financing highlights the confidence and the conviction of participating top-tier biotech investors in the potential of pemvidutide and represents another key step towards bringing pemvi to patients.

We're entering a new phase for the company with the right team in place and a very strong balance sheet, and we're now focused on execution and believe we're well positioned to successfully execute our strategy. We believe that pemvidutide has the potential to bring meaningful benefit to people affected by a variety of hepatic diseases. The balanced 1:1 agonism of glucagon and GLP-1 in a single molecule achieved with pemvi makes it potentially well suited for the liver conditions we're targeting.

Additionally, pemvi incorporates our proprietary U-port structure, which slows absorption and is believed to drive improved tolerability, potentially reducing GI and other side effects. This can lead to greater treatment adherence. Importantly, keeping patients on therapy at the right dose is crucial to the management of chronic diseases such as MASH. Recent market research we've conducted points to attributes that would drive prescribing in MASH, including the highly favorable tolerability profile that does not sacrifice efficacy and quality weight loss. These are two of the potentially differentiating characteristics of pemvidutide based on our clinical trials to date.

As the MASH market continues to evolve, there remains a significant unmet need, and we believe pemvi has the potential to offer a differentiated profile for patients. Furthermore, the potential of pemvi has been recognized with breakthrough therapy designation in MASH by the FDA. We're continuing to advance our efforts and expect to initiate our global Phase III study in MASH in the second half of this year. The MASH Phase III trial will be called the PERFORMA trial. We've now finalized the study protocol and submitted that to the FDA as part of the standard process.

We've also completed the scientific advice process in Europe, and the final study protocol is aligned with the feedback we've received from EMA. So Altimmune is fully focused on the start-up phase for a large global Phase III trial. We're moving quickly, partnering with the CRO, who brings deep know-how in the MASH Phase III space. The Altimmune team is working closely with them, and we're progressing to activate the most experienced trial sites, and then we look forward to initiating patient screening.

While we have significant focus on our lead MASH program and initiating the PERFORMA study, we're also progressing on two additional indications. First, in AUD, an area of high unmet need, we remain on track to report top line data from our Phase II trial next quarter. We remain encouraged by the strong scientific interest in this indication and look forward to the data readout. In ALD, we now expect to complete enrollment of the RESTORE trial in the third quarter of this year.

Pemvidutide represents a unique and compelling opportunity to improve the lives of people with MASH and other liver conditions. It has had the potential to become an important tool for physicians as they look to improve upon the current treatment paradigm and meet the needs of their patients. With a stronger team in place and cash runway through the top line readout of our PERFORMA Phase III MASH trial, we're now laser-focused on execution. We're moving with urgency on bringing pemvi to patients who may benefit from its promising therapeutic profile and creating long-term value for our shareholders.

With that, I'll turn the call over to Christophe for a clinical update.

Thank you, Jerry. The start-up activities for the PERFORMA Phase III MASH trial continue to progress as planned, and we are well on our way towards initiating the study in the second half of the year.

In the last few weeks, we have finalized and submitted the study protocol to the FDA, and the Altimmune team is working closely with our CRO partner. We are ensuring the global infrastructure, vendors, labs, and clinical supply chains are in place to support a successful trial. These activities will allow us to initiate screening and start enrolling patients in the second half of the year. We are also pleased to report alignment on the Phase III trial design with both FDA and now, EMA. As we expected, feedback received from EMA validated our planned trial design and represented the final regulatory step in our Phase III preparation. This is an important milestone in our global development strategy as the data from the PERFORMA Phase III trial will form the basis for regulatory submissions in multiple regions.

Importantly, we achieved strong efficacy results at both 24 and 48 weeks in the Phase II IMPACT trial, particularly at 1.8 milligram. We will introduce the 2.4 milligram pemvidutide dose in Phase III, which has achieved additional weight loss in the previous obesity study and could potentially show increased liver efficacy beyond what was observed at the 1.8-milligram dose in Phase II. We also observed improved adherence to treatment and low discontinuation rate, lower than placebo, which is critical to addressing a serious chronic liver disease such as MASH. Based on the strong Phase II data and based on the design and the powering of the pivotal Phase III study, we are looking forward for pemvi to continue showing benefits for MASH patients.

We have announced this morning the 48-week results from the Phase II IMPACT trial will be the subject of an oral presentation by Dr. Mazen Noureddin at the EASL conference later this month in Barcelona. This abstract for the oral presentation has been selected as the best of EASL abstract, which highlights the most noteworthy contribution to the scientific program at EASL. In addition, our presence at EASL conference will increase this year with another three posters about cardiovascular risk factors, including weight loss, NIT, and qFibrosis. We believe that the oral presentation and the interest from the scientific community through these activities speaks to the excitement around pemvidutide. We will also have a medical affair booth and participate in many interactions with KOLs and potential investigators for the PERFORMA Phase III trial. We look forward to engaging with the liver community and supporting their excitement on pemvidutide.

While our near-term focus is now the execution of the PERFORMA Phase III MASH pivotal trial, we have another milestone approaching this year with the top line data from the Phase II RECLAIM trial of pemvidutide in alcohol use disorder expected in the third quarter. We believe the AUD population, who has a high unmet need, is particularly suited for pemvidutide therapy because of the expected GLP-1 action on alcohol cravings. The direct glucagon activity on the early liver disease, including steatosis, inflammation and early fibrosis, and the excellent tolerability, which we have observed to date and is critical in this population.

As a reminder, the RECLAIM trial is evaluating the 2.4 milligram dose of pemvidutide with a simple 2-step monthly titration scheme versus placebo in 100 subjects with moderate to severe AUD. Subjects are dosed once weekly for 24 weeks, and the primary efficacy endpoint is the change from baseline in heavy drinking days, which are defined as five or more drinks for men and four or more drinks for women in a 24-hour period. Key secondary endpoints include 0 heavy drinking days, a 2-level reduction in the WHO risk drinking level, change in measures of alcohol consumption and change in body weight and BMI. An important exploratory end point is the change in phosphatidylethanol or PEth, which is a more objective blood-based biomarker of alcohol consumption that represents alcohol intake over the most recent 4 to 8 weeks. We look forward to sharing the top line data next quarter.

In addition, the RESTORE trial in AUD evaluating pemvidutide effect on liver-related NIT, markers of alcohol consumption and body weight is continuing to enroll, and we now expect to complete enrollment in the third quarter of this year. In summary, with a heavy focus on the execution of the PERFORMA Phase III trial, we continue advancing our clinical development program for pemvi with important milestones expected throughout the rest of this year. These efforts are integral to our long-term value creation strategy, which centers on optimizing the therapeutic potential of our balanced 1:1 glucagon GLP-1 dual agonist, pemvidutide, in serious liver diseases.

And with that, I will turn the call to Linda.

Thanks, Christophe, and good morning, everyone. The MASH market is evolving as approved drugs and a number of others in late-stage development represent a range of modalities that aim to address various segments of the broader MASH patient population. This reinforces our belief that as the market continues to evolve, distinct patient segments with unique needs will begin to emerge. Satisfying those needs will be a key driver of success.

As Christophe mentioned, our PERFORMA Phase III trial design has factored in key learnings from our Phase II data sets, and we believe this positions pemvi well for future competitiveness in the market. The potential target product profile for pemvidutide in MASH includes strong early metabolic benefits, significant improvements in inflammation and fibrosis, and quality weight loss that also helps preserve lean muscle mass, combined with the patient-friendly simple titration that leads to a low rate of discontinuation due to GI side effects. This combination of features and resulting potential benefits resonates with HCPs and leads us to believe pemvi may provide real advantages to patients facing serious liver disease.

During our last two earnings calls, I shared key data points from market research studies we commissioned engaging health care professionals in both the U.S. and Europe. The feedback collected from these exercises highlighted the importance of potential key differentiating attributes for pemvi that would influence future prescribing decisions in MASH. A highly favorable tolerability profile that does not sacrifice efficacy and quality weight loss.

First, let's discuss the highly favorable tolerability profile we've seen to date in our IMPACT trial, which did not include any dose titration. Results showed that both the 1.2 and 1.8 milligram doses of pemvi were efficacious, showing early evidence of MASH resolution and NIT-based antifibrotic effects while being well tolerated. In fact, there were fewer AE-related discontinuations in the two pemvi arms than in the placebo group.

To potentially further enhance efficacy and optimize tolerability, our PERFORMA trial design includes a simple titration schedule that begins with an active starting dose of 1.2 milligrams and escalates to either 1.8 or 2.4 milligram dose, after only one or two titration steps of 4 weeks. In a real-world setting, this patient-friendly simple and quick titration could readily translate to patients remaining on treatment longer, allowing for a greater likelihood of achieving therapeutic benefit, especially in a chronic condition like MASH.

Now let's compare this combination of simple titration and favorable tolerability to other therapies on the market or being evaluated for use in MASH. GLP-1-based therapies, in particular, have been associated with GI side effects that lead to discontinuations in both clinical trial and real-world settings. One competitor's Phase II trial included a titration schedule that used 12 different strengths over 20 weeks to get to the maximum dose, and at least seven steps to get to the lowest effective dose, all with a proactive attempt to manage GI-related side effects. And still, approximately one in four patients discontinued therapy due to GI side effects.

In clinical practice, dropout rates are typically even higher than those in clinical trials, where patients are actively managed and encouraged to stay on treatment. From our own market research, we know that physicians are now indicating that there is an emerging unmet need for new options for patients who could not tolerate semaglutide. How can patients get the efficacy they need when tolerability is a real barrier?

Shifting the discussion now to the quality of weight loss as an additional potential differentiator for pemvi, we saw steady weight loss with our 1.8-milligram dose in our Phase II MASH trial, with no evidence of plateauing over 48 weeks. This pattern also occurred in our obesity trial, where pemvi demonstrated less of an impact on lean muscle mass that has been reported in other GLP-1 trials. Rapid drops in weight loss have been associated with a greater negative impact on lean muscle mass.

Current projected average age of diagnosis for MASH patients in the U.S. is between 55 and 60. This represents a high degree of overlap with the ages where preservation of lean muscle mass becomes a concern. Patients diagnosed with MASH and sarcopenia are at a significantly higher risk for adverse outcomes. Therefore, the importance of preserving lean muscle mass in the MASH population should not be underestimated. We naturally begin to lose lean muscle mass as we age, with an acceleration of loss around age 60. By age 70, many people have lost 25% to 30% of the muscle mass they possessed in their prime. Over time, loss of lean muscle mass and muscle weakness can lead to metabolic dysfunction, reduced mobility, difficulty performing activities of daily living and falls and fractures. Clearly, therapies that helped reduce the impact of lean muscle loss in patients with MASH are needed for this at-risk population, and we will be evaluating this in our Phase III MASH program.

We continue to believe very strongly in the potential of pemvidutide to offer meaningful benefits to patients with MASH and that its potential unique attributes position it well to stand out in a commercial setting. We look forward to generating additional clinical data to support these benefits in our Phase III MASH program and to sharing additional insights from our pre-commercial work along the way.

With that, I'll turn it over to Greg for the financial review.

Thanks, Linda, and good morning. Starting with the balance sheet here. A key strategic focus for the company was securing access to the capital required to successfully drive our clinical programs. And to that end, in April, we're pleased to complete an oversubscribed public offering with gross proceeds of $225 million with participation from top-tier biotech investors. And as of March 31, we reported total cash of $332 million. And on a PERFORMA basis, our cash position as of April 30 was $535 million. This very strong cash position now provides us with the operating cash runway through the PERFORMA Phase III MASH 52-week data readout expected in 2029.

Now moving to our financial results for the quarter. R&D expense in Q1 2026 was $16.2 million as compared to $15.8 million for the same period prior year. The increase in R&D spend was driven primarily by the ongoing AUD and ALD trials as well as the start-up costs for the PERFORMA Phase III trial in MASH, partially offset by a decrease in expenses related to the completion of the IMPACT Phase II trial in MASH, which was ongoing in 2025.

The Q1 2026 spend includes $9.5 million of direct costs related to pemvi development, of which $3.7 million was for MASH and $4.2 million for the Phase IIs in AUD and ALD and $1.6 million in CMC-related expenses. Q1 '26 also included $1.2 million in total non-cash stock comp.

G&A expense in Q1 2026 totaled $8.1 million as compared to $6 million for the same period in 2025. The increase in G&A primarily driven by an increase in severance costs and professional fees. The first quarter '26 G&A included $2.1 million in total non-cash stock comp.

The net loss for the first quarter of '26 was $22.6 million or $0.18 a share compared to a net loss of $19.6 million or $0.26 per share in the first quarter of 2025.

Looking ahead, we're looking forward to initiating the PERFORMA Phase III MASH trial in the second half of the year and top line data readout from the Phase II AUD trial next quarter. With a stronger balance sheet, providing us with the cash runway through Phase III data, we're now really focused on execution and looking forward to continuing to advance pemvidutide.

This concludes our prepared remarks, and I'll now turn the call back to the operator for the Q&A session. Operator?

[Operator Instructions] Our first question comes from Ellie Merle with Barclays.

Congrats on all the progress. So you announced this morning some presentations at EASL. Can you go into some more details on what new information we'll learn from these?

Ellie, thanks for the question. Christophe, can you take that one?

Sure. Yes. So the different presentation we're going to bring at EASL are regarding our -- some qFibrosis. So additional evidence of early fibrosis, antifibrotic effect that we had at 24 weeks on our biopsy. It's a different type of reading from AI-generated reading. We're going to have, as well, some look at our weight loss and potential lipid data, cardiovascular risk in this population. And obviously, very importantly, we'll have our 48-week data that we'll be sharing in this oral presentation, that's been where the abstract was selected as Best of EASL. So we're really happy with this. It's an important contribution to the scientific program based on their selection, and we believe it is the case as well. So excited about it.

Our next question comes from Roger Song with Jefferies.

Great. Congrats for the quarter and then all the progress. Since you're finalizing the Phase III MASH trial starting in the second half, I'm just curious, any interim analysis has been updated to the design potential for security or the sample size adjustment. So that's a question for MASH. And then for AUD, can you just elaborate on what will be the go/no-go decision criteria before you can commit more investment into the pivotal stage?

Okay. Maybe you start on the MASH, I'll take the AUD.

Sure. So on the MASH, the study is designed as an event-driven study to reach the final clinical outcome for final registration. The interim analysis is the 52 weeks based on biopsy that will be -- that will support the accelerated approval and for which we're going to have those -- finish that trial having to read out in 2029. There is no other interim analysis that is planned than these two, and we are, again, very well powered in order to reach this outcome, and then I'll let Jerry answer the AUD.

Yes. Thanks, Roger. We're definitely encouraged by all the interest emerging in the AUD indication overall and definitely look forward to the readout, and good to say that we can say the readout will happen next quarter at this point. Obviously, we'll assess the data fully once we get it, and we'll look to disclose that to the market. We'll also then undertake the right conversation with the regulators. And so all of that will factor into what we think about is the potential value.

If we get to a situation where we believe there's value to move ahead, with that indication, then we would definitely have a preference in that scenario to really explore non-dilutive options in terms of thinking about funding, moving that program ahead. So again, next important step for us is to get the Phase II data readout, and that will give us some additional insight on it. Again, an indication where we think pemvi can play a unique role potentially not only the impact on drinking, but also on the direct liver benefit, which is such an important part of that disease as it progresses.

Our next question comes from Annabel Samimy with Stifel.

Just a follow on the AUD questions. So thank you for laying out the differentiation that you see versus semaglutide. What I'm wondering here is, given that they have recently shown some pretty meaningful data in AUD, with the addition of glucagon, are there any measurements that you're looking at for AUD that could show the benefit of the direct liver targeting that you'll have with pemvidutide over Wegovy? Any other things that you think that you should be incorporating into the trial or looking at the trial to further differentiate pemvi from Wegovy, given that Wegovy might be generic by the time you come to market. And then I guess another question on AUD. In terms of the clinically meaningful endpoint, you have heavy drinking days, clearly, and you also have some abstinence. Is it clear what the final endpoint should be for Phase III from a regulatory perspective? Just curious on that.

Okay. So maybe, Christophe, we'll take that in order first, the question on the differentiation and how do we see that evolving, and then second, on appropriate endpoints from a regulatory context.

Right. So no, thank you. So first, we are really excited to see those semaglutide data because this is clearly validating the hypothesis that pemvidutide has a real potential to show benefits in this population. In addition to this, as you mentioned, the glucagon part is really important. So we believe that -- and we know this has been demonstrated, there has been presentation in the past conferences, scientific conferences, that these patients have early markers of liver disease, including steatosis inflammation and even early fibrosis. So targeting the liver is really a critical aspect for us. That is something that the GLP-1 alone will not be able to achieve since there is no GLP-1 receptor in the liver.

In our study, we have markers of liver healthiness that we're going to be looking at. And to your last point, we will obviously look at all the data that we will have and see how we can incorporate those differentiation factors into our Phase III into the registration program, how to do this best because we believe here that we have, again, a product that is really well suited for this population. The last piece that I would remind you about is the adherence to treatment of the tolerability in a population that is fairly healthy otherwise and for which pemvidutide, if we continue to show what we've seen in our IMPACT Phase II MASH data, should be, again, having a clear advantage with that population. So that's important.

Regarding the end points. For Phase III, right now, the FDA has proposed to two end points, the 0 drinking days, heavy drinking days or a change in 2 steps, 2 levels in the WHO drinking ranking there between those. So we'll explore this, too. We'll see how -- where our data will lead us, and we'll have those discussions with the FDA when we reach the end of Phase II meeting.

Our next question comes from Michael DiFiore with Evercore ISI.

Congrats on the progress. Two questions for me. At your December IMPACT call, you said that there was no obvious path to reevaluate the 24-week biopsy data in an AIM-MASH-like way because LiverExplore is a different quantitative tool. That said, the EASL poster now says quantitative digital pathology showed fibrosis regression at 24 weeks. So can you clarify what exactly is new in that analysis? And the second question is, just given Roche's proposed acquisition of PathAI, does that change anything in how you plan to incorporate AIM-MASH assist into the Phase III biopsy read process?

Maybe I'll start with the second question first, and then Christophe can clarify. There are a lot of different AI tools, so it is a little important to track what we were -- exactly which one is being used there. First, I think on the question of the acquisition by Roche Diagnostics of PathAI. As you would imagine, the teams are working extremely closely between Altimmune and Path on the Phase III incorporation of the AIM-MASH assist tool. And that conversation has continued fully since the announcement, and we don't anticipate any change to the process that's already been mapped and all the planning around how execution is going to work on being the first program that we'll be able to incorporate the AIM-MASH assist tool to the pathologist in the Phase III.

Maybe just some clarity then, Christophe, on the qFibrosis data versus the AIM-MASH assist tool.

Again, I mean, sharing my enthusiasm, we are going to be the first registration study using that AIM-MASH assist, so we are looking and working with the PathAI team really closely. So no change there. We are just moving forward directly. With the qFibrosis, so it's a little different approach that is assessing -- so the AIM-MASH cannot because you need to do that in prompting the pathologists to the reading, et cetera. Going back, we'll have some -- created some internal -- I mean clearly some biases, et cetera. So we cannot go back to the AIM-MASH assist as you mentioned.

The qFibrosis is different. It's an approach that subtract basically the steatosis around to allow to read in a more accurate manner through the AI process, just the fibrosis itself. And those data are important. We believe that our drug, pemvidutide, is decreasing MASH or leading to MASH resolution very rapidly, very early, and that could be one of the factors that makes it harder for the pathologist to identify the changes in the fibroses with some of the features. So it's an interesting poster that we're going to be presenting, and we're really excited about showing this data and showing, again, that what we believe is that we see some very clear antifibrotic effect early, even at 24 weeks. So putting those together, it's very exciting to see what we're going to get at EASL.

Our next question comes from Srikripa Devarakonda with Truist Securities.

Congrats on getting Best of EASL. So a couple of questions on the Phase III trial design. Beyond the 52-week biopsy endpoint, I was wondering if you can provide a bit more details. You're moving from the new titration Phase II to starting with 1.2 mg and titrating. So can you just remind us for the -- of the rationale for the strategy, and then with the inclusion of -- you have both the 1.8 mg and the 2.4 mg arms for the primary endpoint. Can you talk a little bit about the statistical design there? Does it need to get on both, or how does that work?

No, that's -- thank you for the questions. The first thing is I want to remind you about the 48-week data that shows that basically 1.2 and 1.8 milligram dose were efficacious dose. The 1.2 milligram dose had a tolerability similar to placebo, and 1.8 had a little more GI effect, but there was no titration. So we believe we have an upside that we can propose to the patients with a very single step titration that will help them just improve in tolerability. We've seen our GIAEs occurring within the first 4 weeks max -- in general. So we believe that, that first step will really help because of that placebo-like tolerability. So that's why we design it that way.

And then with regard to the other, each of the other part of the question, what we have done is we've established those two arms. Our first key dose based on our Phase II data is the 1.8 milligram dose. We believe it's a very efficacious dose. Our data supports this. And on top of this, the tolerability and what we've seen at 48 weeks confirm this. So that's our anchor dose, if you wish. We've seen added weight loss in the obesity program with the 2.4. And based on this, we believe that there is a potential for added efficacy. That's why we included it. However, on the powering and the statistical approach, we've taken a more conservative approach to powering the study and we've powered on the effect size of the 1.8 milligram dose, both the 1.8 and the 2.4-milligram arms because clearly, this is more of an exploratory approach, if you wish, where we expect added benefits for these patients. So that's how we've -- we believe it's the upside on the efficacy part that we could see, and we're going to be looking at these end points at the end of the 52 weeks.

Our next question comes from William Wood with B. Riley Securities.

All right. Sort of two from us. Just curious how you're seeing the long-term treatment of patients with MASH on pemvidutide. Has there been any sort of evaluation of dose reductions or what happens when patients' dose reduce or even taking less frequent dose or -- and is that expected to be looked at in some of your upcoming trials, maybe possibly even after your Phase III reads out? And then also just a quick add-on or a follow-up to your EASL data that you're expecting, it looks like in the abstract of your CV presentation that we'll be getting some visceral adipose tissue data or just that. Could you just sort of confirm that we'll be getting the VAT data in that poster, just given with what we've seen on the importance on sort of the CV benefits?

Right. So on the dose reduction, first, I mean, this is something that we've explored in our Phase II. We've seen very few patients reducing the dose, no discontinuation. And obviously, we'll be looking at this in our Phase III. We have put in place even for all the way to the 2.4, where these patients can reduce the dose. However, we are incentivizing that the patients in order to stay at the most efficacious dose, which is 1.8 milligram dose or even all the way to 2.4. So there is a whole system that is put in place to really have those efficacious doses tested and allowing if there were any GI tolerability. We believe even with the current titration scheme that we proposed, that we're going to be even able to eliminate most of those and limits really to just a few patients, those aspects. So that's the upside.

On the lipid and the cardiovascular risk, we'll be looking at the lipid profile. To your questions, we have shown some lipid benefits through our previous studies, and patients look at this. But we don't have like VAT assessments in the poster itself.

Our next question comes from Arabella Ng with H.C. Wainwright.

I was just wondering, will PERFORMA used a prefilled syringe autoinjector? And then if it is given as an autoinjector, have you secured a partner for that? And then just generally, are there any gating items you need to complete before you initiate the trial?

So maybe I'd start on the last part first, and then we flip it to Christophe. As we said in the prepared remarks, and we'll stress, we're in the full start-up phase on the trial. So it's about really establishing the global infrastructure, ensuring the vendors are online and ready, initiation of the trial sites and ensuring that the clinical supply chain is ready to support the initiation. So all of that activity is ongoing, and the start of the trial with initiation in the second half is what we're moving towards. Christophe, maybe you'll take the other part.

So for the PERFORMA Phase III study, we're not using the autoinjectors. We're going to do separately a comparability type study to use the autoinjectors at launch. And that's how we've approached that aspect. We've got some good adherence with our approach right now to the Phase II. So we're going to continue using that approach and have the autoinjector ready for launch.

Our next question comes from Corinne Johnson with Goldman Sachs.

This is Anupam on behalf of Corinne. Maybe can you just tell about in terms of digital pathology for fibrosis, how should we think about translating the outcomes based on these measures to the fibrosis improvement as it will be evaluated in the Phase III trial?

Yes. So there's two -- I mean, obviously, there's the regulatory path that requires the biopsy, and that's the way regulatory agencies are looking at this. The digital pathology, you have different aspects. You have like the AIM-MASH assist, which is a tool that assists the pathologists in reading and prompt the pathologists to the features on the biopsy slides, which is in itself should be able to decrease the variability, increase consensus between pathologists as they all come into the same features, and that's one approach.

The other approach is some of the things we've done in our Phase II study, that we'll be continuing to look into this LiverExplore that was highly significant at 24 weeks, demonstrates the impact on fibrosis directly in a continuous manner. And the other one approach, which is this qFibrosis that we're presenting at EASL, that is very interesting. I think here, we have a little bit of a story when you decrease the fat in the liver very rapidly, as we've seen at week 24. It becomes a little more challenging for the pathologists to read the fibrosis changes. And so being able to subtract it in a way that's consistent with staging of those fibrosis is very valuable. So these will be added assessment and confirming the biopsy read from the pathologies through the AIM-MASH assist. But clearly, in our Phase III, the primary endpoint will be done on the biopsy using this AIM-MASH assist tool for the reading. So we'll have a whole bunch of evidence that we'll cross reference at the end of the study at week 52 for the accelerated approval.

Our next question comes from Jon Wolleben from Citizens.

Two for me. MASH trials are large and take a long time to run, but incretin trials go pretty fast. I'm wondering if you think about the pace of enrollment potentially being faster than we expect the MASH trial because of the potential obesity benefit. And then big picture-wise, you talk a little bit about differentiation. We're seeing more and more triple agonists get announced. You have more data now, but do you think down the road, dual agonist get leapfrogged by the triples that are all becoming more popular and crowded as well?

On the first question, look, we are expecting that the weight loss benefit, to your first question, and the overall profile of pemvi will help. We've seen in the other trials. And as you referenced clearly, Jon, the other -- the speed of the incretin trials that typically go quickly. So we're understanding -- we're building a robust study here and what we're targeting for good, efficient, effective enrollment, and the profile and the weight loss is one of the components that we think will help with that.

Yes. No, I have nothing else to add. I mean maybe the design of the study is also attractive because we have a couple of cohorts. So more chances for our patients and the PIs to include their patients. So all in all, they're absolutely correct. I mean the rate of enrollment is much higher for obesity when there is the weight class. In addition, we have these features in the design of the study that will help...

Jon, on your second question, we are developing. And then when we talk about differentiation, we always have in mind the other combinations, including the triples. Maybe, Linda, you touch on how we see the ability of pemvi to be differentiated, not just kind of in -- with the products available today, but also with the coming therapies that might be available in the future.

Yes. Certainly, I think that we have an opportunity with pemvi to focus on our attributes of being both direct acting on a liver with a glucagon and with our ratio of 1:1 GLP-1 statin. And the package of benefits that we're seeing delivered there are very competitive, even vis-a-vis the very metabolic forward as we've seen at this point, metabolic forward triple Gs. The direct-acting components haven't been as defined as ours in the 1:1 ratio. And I think looking at a tolerability profile and efficacy on multiple points, our ability with our safety profile, frankly, to be used in combination with other agents that they need to, we're delivering the full package and our titration, unlike some of these others as we've talked to, is very simple and not complex.

So you see we have that tolerability and we have that effect on metabolic and even the opportunity to have additional weight loss. So we're seeing ourselves as a pretty fulsome well-rounded package that can hold our own and that we see early effects, sustained effects with weight loss, maybe some more efficacy with the 2.4 even on antifibrotic and weight measures. So right now, until we're really seeing things that aren't based on weight loss studies, really want to -- we'll keep an eye on the market, of course. But I think looking at even our quality of weight loss could be a differentiator. You're not dumping a ton of weight loss right away and then leading to more muscle mass being lost. So obviously, always keeping an eye forward, but confident in our ability to continue to display the differentiating benefits of our Phase III trial and associated trials to make sure we have a very solid place in the MASH landscape in the future.

Our last question comes from Andy Hsieh with William Blair.

Just a question on ADA data presentation. The other GLP-1 glucagon asset, survodutide, will have both the obesity data set and [ muscle ] data set. So I'm curious about how you would interpret that data when the full results come out. And secondarily, I think you emphasized [Technical Difficulty].

Andy, you're cutting out. Can you repeat your initial question?

Sorry, let me just use my phone. Sorry about that. So it has to do with the GLP-1 glucagon competitive asset, survodutide, that's going to be presented at ADA. So I'm curious about how you would interpret their both the obesity data set and also the muscle data set without biopsy. So that's question number one. Question number two, you mentioned about the tolerability a lot during the call. Looking back in the Phase II trials that you've conducted MOMENTUM and IMPACT. I'm curious if you have any persistence or adherence data. So for example, percentage of patients persisted throughout the trial or towards the end, that could really paint a picture of patients staying on therapy for pemvi.

Yes. Maybe we'll start with that one because I think it's an important one, which we've talked about a bunch. We do see in the 48-week data when we talk about the strong tolerability profile that this adherence and the fact that such a large percent of the patients on pemvi at both doses, frankly, stayed on therapy even more than placebo. And when we talk about tolerability, we're not just talking it as an avoidance of some side effects, but it's also being able to get to the effective dose and stay on therapy, which we know are such a large part of the important real world treatment concerns for physicians. And that kind of leads right to your other question, which was around survodutide and what we're seeing there. Maybe, Christophe, you want to pick that up?

Yes. No, again, so first, I mean, in the IMPACT and MOMENTUM, et cetera, we see a clear dose response in favor of the higher doses of pemvidutide where patients stay on treatment. So this is very encouraging for us, especially, I mean, on my end as a physician, I mean in a chronic therapy setting, keeping the patients on an efficacious dose on the long term is a key aspect of what we're trying to achieve here. So really encouraging data that we've seen here. Also, we have anecdotal evidence from some of our PIs telling us, that are running different studies, also other GLP-1 or even those triple agonists, et cetera, and they are telling us that pemvidutide is a very different kind of approach for the patients and the treatment satisfaction is much different. So we feel that we have some advantage here, and that's really important in that chronic setting in MASH, in AUD, in ALD, et cetera. So these are the kind of things.

On the survodutide aspect, so we've seen weight loss similar to ours. It's been comparable. The big challenge in my mind is back to that tolerability. They had one -- I mean, first, they needed a very long titration to get up to the efficacious dose. They even have set up some aspects where if they down titrate, you need a whole kind of new scheme to restart the patients, which is absolutely not our case. You've seen in the Phase II, you can jump the patients straight into their 1.8 milligram dose without any titration. So we are in two very different scenarios here, and the discontinuation rate is almost one in four patients that is not staying on the drug. So I believe there's a couple of aspects that we have here, survodutide look more like GLP-1 with a little bit of glucagon. That's the 8:1 ratio. We've heard people saying just a little splash of glucagon on top of GLP-1.

And we believe that this ratio 1:1 is really important. And again, I cannot reemphasize in the chronic setting the importance of having adherence to treatment into an efficacious dose. I mean this is a key aspect. Patients will stay. I'm sure that payers will be very happy with this. But that also -- we've seen it already in our study. We'll continue to look into it in the Phase III PERFORMA trial.

That concludes today's question-and-answer session. I'd like to turn the call back to Jerry Durso for closing remarks.

Thanks, operator. So we've made significant progress as we evolve into a late-stage company. Altimmune is focused on execution, and we're committed to further advancing our promising meaningfully differentiated liver therapy and creating long-term value for our shareholders. It's really an exciting time here, and I definitely look forward to updating you on our progress as we progress. Thanks a lot for joining today, and everybody, have a great day. Take care.

This concludes today's conference call. Thank you for participating. You may now disconnect.

Hi. Good morning, everyone. I'm Ellie Merle, one of the biotech analysts here at Barclays. Very happy to have Altimmune here with us for a fireside chat. Joining us from Altimmune, we have Jerry Durso, Chief Executive Officer; Christophe Arbet-Engels, sorry, if I butchered your name, Chief Medical Officer; and Greg Weaver, Chief Financial Officer. Thank you all so much for joining us.

Happy to be here.

To begin, maybe if we could start with a brief overview of the key highlights of Altimmune's progress over 2025 and into the first quarter of '26, including on the financial front as well.

Sure. So we've been busy as a company and a lot going on and really an exciting year ahead of us in 2026. Last year, significant progress on the clinical side. The Phase II MASH trial read out in 2 different time periods. We had the 24 data -- 24-week data that came out in June and then right at the end of the year in December, the 48-week data set. I think we got a really good view of the potential target product profile on pemvidutide in MASH. I think the 48-week data really reinforces what we may expect to see in the same time frame that we're designing the Phase III trial.

I know we'll go into some details on that, but really starting to see the potential of pemvi as a significantly differentiated product in the MASH space. I think the dual mechanism, the balance glucagon and GLP ratio that we bring, which is unique to some of the other combos coming along. And again, I think the 48-week data gives us a good sense of what we have and then how best to position some of the evolution in the Phase III design.

Progress on the financial front has been an important part of the last several quarters, and maybe Greg can kind of touch on some of the highlights as we continue to progress towards initiation of our Phase III this year.

Yes. Thanks, Jerry. Ellie, we've taken the progress on building out the balance sheet very seriously. It's the highest priority, made some progress -- significant progress over the last year and using the various tools available to us, a combination of debt, equity and active and open to speaking with strategics as well. Just really want to be in a position here as we move into the start of the Phase III trial to have that capital allocation necessary to drive that trial to fruition. And so excited about the path forward.

And then in addition to MASH, progress on our other 2 Phase IIs. So in AUD first alcohol use disorder, where we enrolled in the latter part of 2025, actually ahead of schedule and are now guiding to a quarter 3 readout of that top line data set. Again, another really interesting opportunity that we think pemvidutide might be well suited for.

And then our second ongoing Phase II is an alcohol-associated liver disease, where we're in the process of -- we launched a trial last year. We're in the process of enrolling and we anticipate enrollment completing this year. So lots of activity, lots of progress.

And then the last piece of that is an evolution as we moved towards the end of Phase II, looking at how best to position the capabilities of the organization to deliver in Phase III as a late-stage company, a significant evolution of the leadership team. I had joined the Board last year and then transitioned into the CEO role at the beginning of this year. Several other members of the leadership team, Christophe, Linda, Robin, who's our new Chief Legal Officer, came on board again, as we get ready. Greg had joined about a year prior. So ensuring that we have the capabilities, the means and the team to deliver in the next phase. So lots of progress, lots of work to do, and we think some exciting catalysts to come in '26.

Great. So let's talk about the MASH space. You have Rezdiffra approved. You have other drugs in late-stage development across PPARs, FGF21 and other incretins as well. Where do you see pemvidutide as being differentiated in MASH and the opportunity?

So maybe, Christophe, you can pick up from there.

Yes. So pemvidutide is a unique 1:1 ratio of glucagon. And GLP-1, why it is important? Because the glucagon has the direct effect on the liver and the GLP-1 treats the metabolic context that this liver disease is happening. We have data that have shown that pemvidutide is now clearly having a great effect on fibrosis on MASH resolution, very early MASH resolution at 24 weeks. And we also have the tolerability. In my mind, the tolerability is a really important aspect because we were able to demonstrate that our patients in the Phase II were staying on treatment, much more patients were staying on treatment at our active doses than in the placebo, the discontinuation rate was lower than placebo.

And in the current context compared to many other -- like the survodutide that has a 7 to 1 and demonstrated the discontinuation rate that's close to 23%, 25% or the GLP-1s, this will be a very big differentiator. We also have the lean mass preservations in the -- that's associated to our weight loss that is different than what you can see with other compounds. And as we're moving in the MASH, it's important even in combination therapy to not have the bone loss and the lean mass loss and trying to address those things. So there is different opportunities like this that are really differentiating pemvidutide in that area.

So lots of potential for differentiation, and we think lots of opportunity to make that even clearer with the way we're thinking about the Phase III design.

Yes. Certainly, the ability to have the strong liver targeting as well as weight loss, I think, is an interesting approach in MASH. Can we talk about some of the data that you've seen so far, both the 24-week data as well as 48-week NIT data? And I guess what are the key parts of the data set so far that give you confidence in the profile?

So as a reminder, we read out at 24 weeks, which was the primary endpoint of the study where we captured the histology. The 48-week result that we read in December and presented, we captured all the NITs again and safety and whatnot. I think one -- a couple of points of reflection. One, we saw good early activity in the 24-week result, which Christophe can describe. We hit on the MASH resolution, did not reach statistical significance on the fibrosis endpoint. Was an aggressive and optimistic time frame, frankly, to read out with this particular mechanism. And I think we get some indication in the 48 weeks that the process you would expect to occur with this mechanism took a little bit longer to play out, and we like the signals that we get in the 48-week data.

Yes. Just to add to what Jerry just mentioned is that at 24-week data, so we were able to show that very strong MASH resolution. The biopsy readout was a little confusing because the placebo was very elevated. The numbers were good by themselves. But what is important is to see also all the other elements, and they're all pointing to the same direction from the AI, the Liver Explore that we used that was statistically significant on fibrosis to all the needs that were also statistically significant all the way to our molecular levels where we had a very antifibrotic impact on this lever.

And looking at all this picture, we were able to go to the FDA and having a very positive end of Phase II meeting with the FDA because we felt we had strong data. So the 48-week results were not a surprise. They just demonstrated added value, a clear dose response and clearly a very strong antifibrotic effect.

And how should we expect the NIT results at 48 weeks to translate to histology as we think towards the Phase III?

So the NITs are different tests than the biopsies. So the way we've designed our Phase III, we're going to be designing it for a readout first at week 52. That's one step. So we should be able to see this. We've done modeling. We've done also other things, but we powered our study taking into account the biopsy read from the pathologist, the histological read, so -- because we understand there is more variability.

What is an upside for us is we're going to do this with AIM-MASH Assist. And that's the first study, pivotal study, Phase III that we will use that. It is supposed to help decrease the variability, streamline the process, accelerate how the pathologists by prompting them where to look at exactly. And so hopefully, will help us 2 things. The duration now will help us having a clear dose response and also decrease this variability and the potential placebo effect. Second, with the AIM-MASH, same thing, decrease that variability. So we consider that as several upside for us in that direction.

Yes, let's talk more about the Phase III design. You recently announced the Phase III initiating this year and details of the design. Can you go over the Phase III design and any areas where it differs from some of the trial design we've seen in the MASH space in the past?

So our design is fairly standard in general. What is we have 3 arms. We have our placebo. We have a 1.8 milligram dose, and we're going to also look at the 2.4 milligram dose. What allowing us to do this is the good tolerability that we've seen in the Phase II. And with this good tolerability and adding the upside of a very simple 1-step or 2-step titration, we should be able to see added benefits on the 2.4 milligram. Having said that, we're not powering based on the 2.4 milligram. We are powering based on the 1.8 milligram dose.

There is 2 cohorts. They will be the cohorts for the F2/F3 proven biopsies. That first cohort will support the subpart H efficacy. And then we have the NIT F2/F3, Assist F2/F3 that we'll be able to complement for the safety assessment as a subpart H, both cohorts continue and go all the way for the long-term clinical outcome and the final approval.

The good things about this setting and the way we've looked at this is the fact that now we have the -- for sites, we understand that they're interested to given the screen failures on the biopsy that they have different options for the patients, and there is actually some good feedback on the way we've designed the trial. And obviously, on top of this, we have the AIM-MASH Assist that is part of how we are going to read that. So we have designed -- that's the big picture of what we designed for the Phase III.

Can you elaborate on sort of the AIM-MASH Assist? I mean that's pretty novel. And I mean, certainly, like, look, there's human error involved in the histology in all the MASH trials, but can you elaborate on some of the implications and how this could improve?

Sure. So I'm going to go through actually the physical parts of how it goes. So you get -- you take the biopsy. You put it in the slide, you stain them. And in the past, now the pathologist was looking at those slides. And the slides are fairly big when you look at those, and you can see different things in different corner, but you can miss things or you cannot always look at the same -- as the same things. That's why there were some disagreement between pathologists. The AIM-MASH, we'll take those slides, digitalize the slides, put the slides on the computer and prompt the pathologists to the features. And it will help them score the NAS score or the F2/F3 type of scoring or any differences in fibrosis. So it will clearly help them look at the same thing from one pathologist to the next.

Having said that, it's still a consensus process where at the end, they are responsible to agree or not with what the computer says and they will -- if there's 2 pathologists that disagree, there's a third one that comes into play. But that process should help decrease the variability by pointing every single pathologist to the same features and then also streamline because it's faster to go through those areas that are already identified by the computer.

What do you think it will do to the placebo response?

What the placebo response will be on this?

Yes. I mean the effect of using this AI assist?

So I think this could decrease the placebo response because we're -- it should be a bit more objective. And then we believe we're working through those things now. We will see the training of the pathologists. These are things that are really important. So we are putting in place the right process now to identify the appropriate pathologists to make sure they have the right training and to incorporate that AIM-MASH. So we're hoping that this will have an impact on decreasing that placebo response and decrease that variability that we have seen in some trials.

So several opportunities, hopefully, all working together to do whatever we can to limit the placebo response. But as Christophe mentioned, we powered the study not assuming any impact of those measures. So we're trying to be conservative with the powering and also to bring these other elements forward. And again, for us, a good opportunity to be the first sponsor to utilize this recently cleared tool.

And there's been conversation in the MASH field for some time around the potential for NITs to be used. I mean, if that were to happen, that would be a huge positive for you and other companies that still have trials underway or just beginning. How should we think about this? You just met with the FDA, I assume this came up.

So we asked that specific question. As you know, that process that the agency signaled occurring last year is ongoing. The FDA told us it was premature to consider noninvasives at this time as endpoints. We are capturing all of the data, as Christophe outlined on the noninvasive side, should that evolve on the FDA front, we have the information, and we think we'd be in a good position to discuss with them a potential pivot. But at this point, we haven't gotten the clearance to move in that direction. That process continues. We have some opportunity as part of that formal process to have a separate discussion with them on that topic, and we'll take that on at the right time.

Interesting. Yes, that certainly could accelerate development. And there's -- I mean, in my opinion, a lot of data that suggest that ITs are perhaps more reliable but...

And we were encouraged that the first step towards trying to help manage the variability was the clearance of the AIM-MASH Assist tool. And again, we'll incorporate that into the program as is planned.

Interesting. How should we think about enrollment time lines?

The time lines for the enrollment. So what we -- biopsy trial usually are between 18 months to 24 months. We're aiming at the lower end of this because we have, like I said, the setup of the cohorts. We also have great learning and engagement from our Phase II trials. So we have those relationships with the sites. And so these pieces together, the tolerability is a big attractiveness. We've seen in our AUD people were enrolled really rapidly as well. So we believe that those pieces altogether will help us going towards rather the low end of this 18 to 24 months.

Great. And AUD and ALD, I think there are some interesting opportunities. I think there's like pretty clear biology, at least from what we've seen from the GLP-1s and some of the like case studies there around the motivational impact it has on people. So as we head into the AUD data in the third quarter, I think this is a newer indication from a data standpoint to a lot of investors. So like help us think about like what's clinically meaningful in terms of like reduction in number of heavy drinking days or alcohol being consumed?

So the drug that has been approved has been approved on 0 drinking days, heavy drinking days. And heavy drinking days, it's 5 drinks for males, 4 drinks for female. Our study captures this, capture also the new endpoint that the FDA is considering around the WHO risk levels. And we are capturing as our primary endpoint actually the weekly average of those heavy drinking days. So we'll have all this information. We have to consider that these are patient-reported outcome. And so we have been taking the study is 90% powered for showing a difference, but we've taken a sort of a conservative approach with an assumption that there will be some impact of just being in the study for a patient, and they will see some drinking decreases there.

We also have more objective ways of looking at this. We have that phosphatidylethanol, which is a blood test that looked at the impregnation -- the alcohol impregnation of patients over 4 to 6 weeks or 2 to 4 weeks, I think, something -- it's a little bit like the HbA1c that you could see for glucose that helps understand what is the level of glucose that those patients had over the past and we're looking at 4 weeks at baseline and 4 weeks at the end of the study after 6 months. So we'll have a good information to move forward and potentially based on the data, we'll be looking at having discussions with the FDA.

The good news is the FDA just said that one trial might be sufficient given the safety database we will have between the MASH and our previous study, this is an approach that could help us move into that direction.

Great. And turning to ALD, how is the enrollment in that trial going?

The enrollment is going as planned. We're going to finish the enrollment this year, and the study has 2 main readouts at 24 weeks and a week 48. It's a longer study than the AUD. So this will be coming after the enrollment clearly.

Okay. So we look forward to that data potentially next year. So AUD, okay, to say we see statistical significance, reducing the number of heavy drinking days, you see a difference versus placebo. What are the next steps from there look like?

For AUD? So for AUD, we're going to be -- the next step is to define the endpoint, having the discussion with the FDA. Based on the data, again, it depends what we're going to see with this data. We're going to be looking at this. I think there will be -- we are learning now that pemvidutide could be actually very well suited for AUD patients because they do have already early -- they have the fatty liver, but they also have early fibrosis. And having that direct impact on the liver in these early stages of fibrosis could be a huge benefit. And we know that physicians think that this is a really attractive mechanism of action for this.

So we're going to build around that. We're going to build around the potential benefit on the cravings on the liver and defining the endpoints in align with the FDA. Hopefully, we can do this with one single Phase III trial and move forward, and then we could and then we'll see. But our data will drive all those discussions.

And the quality weight loss and the lean muscle sparing might be another important element. We know many of these patients are at risk and can't necessarily afford to lose lean muscle. So that's another dimension. Again, we'll see what the data looks like as we consider next steps. But there's clearly a large unmet need in the AUD population. Again, we think that the mechanism might be well suited. And it's good that we're going to have data on hand by the third quarter of this year. So we look forward to that.

Yes, certainly an exciting readout. So how should we think about the size of the population for AUD, I guess, the addressable patient population relative to MASH and how you think about the relative sizes of these potential opportunities?

So the AUD population is large. If you look at some of the data, some of the estimates, 12 million or so that fall into some of the categories. I think it's going to be -- and we know that very, very few of those patients get any sort of drug therapy now. There are several older drugs available. We know there are some challenges with that. So we're in the process of looking at the market now. We know the total patients out there that are "eligible" according to the strict definition. We'll continue to do the work on defining the market in a robust way and looking at where these patients are, how many are seeking treatment. It will be for new entrants into AUD, a therapeutic area and a market that needs to be built.

And I think the interesting opportunity for us is that we have the potential to bring a broader solution in that we hope will impact the drinking and then some of these other benefits, particularly on the liver, might allow us to talk about what we can bring in, in a more medical way that, yes, the drinking reduction is important, but we think, again, the dual action of the mechanism can also be impacting the liver disease that we're finding more and more is developing even for these patients that are considered "earlier" in their journey.

Okay. And when you think about kind of the development pathway, how do you see the evolution of price in the MASH space relative to, say, AUD?

Yes. Again, I think that there is a different dimension that occurs in each. I think that we're seeing as MASH therapies get approved that there are -- there's value in the market. I think there's also going to be some segmentation of different options at different points in the treatment cascade. You might see GLP monotherapy be an earlier choice in treatment, maybe at a different price point than other drugs. Again, we think that pemvidutide is going to bring a broader benefit than GLP monotherapy, and we think about potential future pricing in that context.

AUD is a more open space in terms of the drugs that are out there, again, aren't used very often, are low priced, not utilized, bringing a limited amount of benefit there. So we'll, of course, over time, think about potential pricing in a franchise basis, but we're developing our program and ultimately, our data sets and ultimately our commercial offering with value in mind, and that's -- we'll have a lot of conversations in the coming time about pricing because it will always be something that's a work in progress as data evolves and the competition evolves, and we clearly look at both. But in the middle of the pricing and value discussion is always differentiation, which is why the profile for us is so exciting.

Great. Well, thank you all for joining us. Exciting year ahead. So I appreciate you making the time.

Thanks, Ellie. Appreciate it.

Thank you very much. Thank you.

Good morning, ladies and gentlemen, and welcome to the Altimmune Year-End 2025 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded.

I'll now introduce your host for today's conference call, Lee Roth, President of Burns McClellan, Investor Relations Adviser to Altimmune. Lee, you may begin.

Thanks, Gigi, and good morning, everyone. Thank you for joining us for Altimmune's Fourth Quarter 2020 Financial Results and Business Update Conference Call. On today's call, you'll hear from Jerry Durso, our Chief Executive Officer; Dr. Christophe Arbet-Engels, Chief Medical Officer; Linda Richardson, Chief Commercial Officer; and Greg Weaver, Chief Financial Officer.

Following management's prepared remarks, we'll open the line for the Q&A session. Our fourth quarter and full year 2025 earnings release was issued this morning and can be found on the Investor Relations section of the Altimmune website. Before we begin, I'd like to remind everyone that remarks made about future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995.

Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause our actual results to differ materially from those indicated. For a review of the risk factors that could affect the company's future results and operations, we refer you to our filings with the SEC. I'd also direct you to read the forward-looking statements disclaimer in our press release issued this morning, which is now available on our website. Any statements made on this call speak only as of today's date, March 5, 2026, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this call is being recorded and will be available for audio replay on the Altimmune website.

With that, it's now my pleasure to turn the call over to Mr. Jerry Durso, President and CEO of Altimmune. Jerry?

Good morning, everyone, and thank you for joining us today for our fourth quarter financial results and corporate update. This is my first earnings call since joining Altimmune as CEO in January. I'd like to start with some comments to reinforce why I'm excited about the opportunities ahead of us with pemvidutide.

Altimmune's exclusively focused on liver disease, an area where I've spent a good part of my career. Despite a number of therapeutic breakthroughs in the past several years, there remains significant unmet need and treatment gaps among patients living with serious liver diseases like MASH. We believe that pemvidutide has the potential to bring meaningful benefit to people affected by a variety of hepatic diseases. The balance one-to-one agonism of glucagon and GLP-1 in a single molecule achieved with pemvi makes it potentially well suited for the conditions we're targeting.

Glucagon's direct effect on the liver can drive reductions in liver fat inflammation and fibrotic activity, while GLP-1 can mediate weight loss and appetite suppression and may contribute to anti-inflammatory effects. Additionally, pemvi incorporates our proprietary U-port structure, which slows absorption and is believed to drive improved tolerability, potentially reducing GI and other side effects, which can lead to greater treatment adherence.

Importantly, keeping patients on therapy at the right dose is crucial to the management of chronic diseases such as MASH. The data we've generated to date across multiple preclinical and clinical trials, including our Phase IIb MASH study reinforce our belief in the strong therapeutic potential of pemvidutide as well as its ability to stand out among competing therapeutic options, if approved in MASH. As we evolve the pemvi plan, we're focused not only on advancing into Phase III but also ensuring that the potentially unique benefits of pemvi for patients, payers and physicians are addressed in our program with a keen eye to competitive advantages in pemvidutide's targeted product profile.

Based on our ongoing discussions with hepatology KOLs and other practitioners, it's clear that clinical practice in MASH is evolving and will continue to evolve as new therapies become available. The prevailing sentiment is that no single therapy will be able to effectively address the needs of all patients. This is already being acnowledged by the industry as a number of companies are pursuing combination strategies to meet the needs of broader segments of the patient population. With pemvi's dual mechanism, we have a combination therapy in a single molecule with the potential to address both the hepatic and metabolic drivers of disease at once, which could differentiate pemvidutide from these multidrug approaches that aim to achieve the same benefits we're providing with a single compound.

In our Phase II MASH study, pemvi showed strong and early MASH resolution at just 24 weeks and clear antifibrotic activity at 48 weeks. The key measures were consistently moving in the right direction with important noninvasive markers of fibrosis and inflammation improving as therapy progressed in the trial. In addition to efficacy, patients need a therapeutic regimen that they can adhere to in order to realize the full benefit of treatment.

As we've shared the favorable tolerability leading to low discontinuations due to adverse events that we saw in our Phase II MASH trial can be a key differentiator that pemvi may deliver. Likewise, for patients and physicians, the simple dosing aspect of pemvidutide could play an important role. The 1- or 2-step titration scheme will be incorporating into the pemvidutide Phase III trial could prove to be key when compared to the much more complex dosing of other injectable compounds.

The potential of pemvi was recently recognized with FDA Breakthrough Therapy designation and MASH. Breakthrough is granted to medicines that are intended to treat a serious or life-threatening condition and have shown preliminary clinical evidence indicating the potential for substantial improvement over available therapies on a clinically significant endpoint. We look forward to proving this out in our [ opening ] Phase III trial. I hope this gives you some additional perspective into why we're so encouraged about the future of pemvidutide and excited for what's to come.

Now as to how we're preparing to deliver on this potential, one of my top priorities since becoming CEO is strengthening Altimmune's foundation to equip us for the continued successful advancement of pemvi and support our strength as a late-stage development company. I'm pleased to report that over the last several months, we've enhanced our team with the addition of new leaders to bring expertise in liver disease, late-stage clinical development, commercial strategy and other key areas.

We'll continue to build on to the strong Altimmune team strategically to make sure we're able to deliver. We've also remained focused on strengthening our financial position. The $75 million capital raise completed in January was an important step in our ongoing efforts to prepare for the planned initiation of our Phase III this [ year ]. We remain committed to securing access to the capital required to successfully drive our clinical programs and create long-term value. At the end of Phase II meeting with the FDA, which was held in the fourth quarter based on 24-week data from our Phase II MASH study, we received valuable guidance on the Phase III trial and we made excellent progress on the in-depth planning of a major global mass trial like this.

We are clear on the overall design elements and the endpoints, and we're now in the process of making the final detailed decisions on the protocol and the full operational plan. Christophe will share more on the trial with you this morning. While we have significant focus on our MASH program, we're also executing well on our other Phase II trials. As a reminder, last fall, we completed enrollment of the Phase II AUD trial ahead of schedule, and we're now on track to report top line data from this study in the third quarter of this year.

We're also expecting the complete enrollment of our Phase II trial assessing pemvi and ALD in 2026. Pemvidutide represents a unique and compelling opportunity to improve the lives of people with MASH and other liver conditions. It has the potential to become an important tool for physicians as they look to improve upon the current treatment paradigm. This is a very exciting time for the team at Altimmune. We're moving quickly with intent and focus on bringing pemvidutide to patients and creating long-term value for our shareholders.

With that, I'll now turn the call over to Christophe for a clinical update.

Thank you, Jerry. As we shared on our conference call in December, the 48-week data from the IMPACT trials of pemvidutide and MASH which evaluated the 1.2 and 1.8 milligram doses was very encouraging. The 48-week data set, including key noninvasive markers of liver inflammation and fibrosis weight class and tolerability and showed strong evidence of anti-fibrotic effect at week 48 following the early MASH resolution shown already at week 24.

The 48-week data established a clear dose response that supports our plan to focus on the 1.8 milligram dose in the Phase III trial, while also evaluating the 2.4 milligram dose which could provide additional benefits on both weight loss and most importantly, liver efficacy. We saw substantial improvement both from baseline and from week 24 to week 48 in health liver stiffness with the results achieved at the 1.8 million dose being particularly clinically relevant and comparable to or greater than that observed with the approved MASH product. These measures are clear indicators of antifibrotic activity, and we believe that they will translate into measurable histologic improvement, the 52-week time point in Phase III, which, along with MASH resolution, will be the basis for a potential accelerated approval.

In addition to the strong benefit in health and [ vetiveness ] results, treatment with pemvidutide demonstrated statistically significant improvement in liver content, liver health as measured by ALT and CET1 imaging with particularly impressive results observed in the 1.8 milligram treatment arm. While these net tells the story of pemvidutide's robust direct beneficial effect on the liver, the 48-week data also provided evidence of the ability to address metabolic drivers of mass with patients receiving 1.8 milligram pemvi, achieving 7.5% weight loss at 48 weeks with no plateauing.

As noted, the inclusion of a 2.4 milligram dose could result in greater weight loss in the upcoming Phase III trial and be an opportunity for additional efficacy on match endpoints for accelerated approval. As Jerry pointed out, [ alert ] treatment in this chronic disease is currently a substantial challenge. Long-term treatment is key to demonstrating clinical outcomes as well as delivering benefits to patients in the real world.

Therefore, safety and tolerability of [ parent ] importance in addition to demonstrating efficacy in MASH. I am very pleased to say that the low treatment discontinuation rate in the 48-week Phase II study were maintained in patients taking EMV. We attribute these key benefits to the favorable safety and tolerability profile of pemvi with limited GI adverse events despite the absence of titration. The timing of the GI-related adverse events in the IMPACT trial which were predominantly occurring in the first or 2 months of treatment helped inform our plan to introduce a simple one or two step titration depending on the dose in the Phase III program. We expect this to further improve the tolerability profile of what we observed in Phase II study.

On the regulatory side, the minutes from our end of Phase II meeting with the FDA which we received in January confirmed our takeaways from the meeting. We are aligned with the agency, all key aspects of the design for the pivotal Phase III study, which will assess pemvidutide patients with moderate to advanced fibrosis. Participants in the pemvi arms will start at 1.2 milligram and follow a 1- or 2-step monthly titration to either 1.8 or 2.4 milligram dose.

The trial's primary population will enroll 990 patients with biopsy-confirmed F2 or F3 MASH, evenly split between placebo emitted 1.8 milligram and [ MVG ] 2.4 milligram and major improvement in either of two primary endpoints, match resolution of fibrosis improvement at 52 weeks with [ AMS ] assessed used to add the histologic assessment. The 52-week endpoint is designed to support potential accelerated approval with 5-year clinical outcomes data on the liver-related events needed for an eventual final approval.

A second cohort following the same dosing and titration parameter will enroll approximately 800 patients with NET assessed F2 and F3 MASH and measure changes in these noninvasive tests over the same treatment period. This population will support safety and long-term clinical outcome evaluations. In total, we will enroll approximately 1,800 patients in this pivotal study. Other key endpoints in the program will include safety, weight loss and additional potential differentiation attributes such as body composition, quality of weight loss and patient reported outcome. This will be a global trial with sites in North and South America, Europe and Asia.

In addition to the alignment with the FDA, we have submitted rector scientific advice to both the European Medicines Agency and the MHRA. We have incorporated learnings from previous programs and believe that our Phase III design is well positioned for these regulatory agencies. Overall, we've made great strides towards preparing to initiate our Phase III trial this year. We are finalizing our protocol and we have aligned with the FDA on the trial design. We have incorporated feedback from key opinion leaders and we look forward to execution of the Phase III study. We will be providing updates on our progress as appropriate.

Now looking beyond MASH, pemvi has the potential to address major unmet medical needs in both AUD and ALD because of a similar lever physiopathology to MASH in this indication. And both of those Phase II trials are progressing well. First, reclaim our AUD trial completed enrollment in the fourth quarter of 2025 and we look forward to reporting the top line data in Q3 of this year.

In addition to patients reported measures of alcohol consumption, the trial will also assess an objective biomarker associated with alcohol intake, pemvi's effect on body weight and safety in this population. For the RESTORE trial in ALD, which will evaluate avidities effect on liver-related noninvasive tests markets of alcohol consumption and body weight is continuing to enroll, and we expect to complete enrollment later this year. Both trials will further expand the already robust [ party ] evidence for pemvidutide in seriously [ deviated ].

And with that, I will turn the call to Linda for a commercial perspective on pemvidutide.

Thanks, Christophe, and good morning, everyone. As we move toward Phase III initiation, establishing the future commercial competitiveness of pemvidutide in MASH remains a primary focus, both of them design of our trial, as Christophe described, and in identifying and addressing unmet needs in the marketplace.

Despite early excitement with the first two classes of approved therapies for MASH, it is clear there is significant room for new therapies to address treating gaps and needs. We recently conducted market research with 75 U.S. health care professionals who treat mesh patients to assess unmet needs in the market and satisfaction levels with current and future therapies. I'll share some key insights now.

First, we learned that physicians are identifying emerging needs in patient subgroups. This includes options for MASH patients who have discontinued semaglutide for either tolerability or efficacy reasons and now need alternatives. Tolerability failure was seen as an area of high or very high unmet need by the majority of the respondents. Half of all physicians surveyed agreed that there is a higher -- very high unmet need for therapies appropriate for MASH patients at risk for loss of muscle mass.

A recent view of the literature shows that nearly one in four patients with [ Maze D ] is at risk for additional muscle loss for sarcopenia. And this rate is higher in more advanced MASH patients. In addition, health care professionals in our research see several fundamental limitations with currently approved and potential future therapies, setting up a clear need for potential novel options like pemvidutide.

Many physicians acknowledge that the lack of weight loss with FGF21s and Resmetirom are limitations of these options. And 44% agree that the tolerability profile of GLP-1 and GLP-1-based therapies cause many patients to drop off. Over 1/3 believe that lengthy titration schemes to improve the tolerability of these drugs create adherence challenges. A similar number agreed that the loss of lean muscle mass is a concern when initiating GLP-1 or GLP-1 gift therapy, echoing the concerns regarding sarcopenic patients I mentioned earlier.

From our Phase II data seen to date, we believe that pemvidutide and a dual mechanism of action may address many of these unmet needs. Our existing clinical program already shows that pemvi has a favorable tolerability profile relative to current and investigational therapies. This may be highly differentiating and is clearly important in this market where patients must remain on drug therapy to achieve efficacy and weight loss benefits.

Furthermore, other MASH therapies have trial designs with long titration schedules using multiple subtherapeutic doses to try to mitigate side effects. As Christophe highlighted, our Phase III trial will start with an active 1.2 milligram dose in each arm and have only one or at most two titration steps to possibly further improve our favorable tolerability profile. The inclusion of a 2.4 milligram dose with a 2-step titration over only 8 weeks should help maintain tolerability and allow us to evaluate potential further increases in efficacy and weight loss.

Light loss is an important element of managing MASH, and it's clear that lean muscle preservation is a growing concern among HCPs. This is an unmet need that we may be able to address as we've seen lean mass preservation in our pemvidutide obesity trial, then we'll be generating additional data on this element and are further studies with pemvi and MASH patients.

Now I'll share how physicians reacted to our [ trended ] product profile in this market research. We developed our projected product profile based on our current DataCo impact, showing early and significant mass resolution anti-inflammatory and fibrosis effects from [ kits ] and included data we anticipate seeing in our Phase III program, such as quality weight loss in the 8% to 10% ranges with lean muscle preservation. HCP surveyed recognized significant promise in our efficacy, including direct action in the liver with our glucagon agonym, metabolic improvements, straightforward titration, quality weight loss that preserves lean muscle mass and pemvi safety and favorable tolerability.

In fact, in this market research setting, over 70% reported a very high or high likelihood to prescribe pemvi. Physicians projected using pemvi in 43% of their F2 patients and 51% of the three patients. Over 80% of pemvi at [ both ] first- and second-line option. Pemvidutide's potential efficacy, safety and tolerability profile may allow for use in patients requiring greater efficacy than a GLP-1 alone or providing quality weight loss not seen to certain other classes of drugs like FGF21s and resmetirom.

As we add to our understanding of pemvi's clinical performance and data, amplify our storyline regarding our unique combination of attributes, we believe we will be well positioned to enter the MASH marketplace. We see today and continue to hear from health care professionals certainly signaled strong interest in pemvidutide. It is not enough to be differentiated. You must have meaningful differentiation than pemvi's projected profile provides that.

I'll now turn it over to Greg to review our financial results.

Thank you very much, and good morning. I'll begin with a brief review of our fourth quarter 2025 P&L. R&D expense in the fourth quarter 2025 was $18.4 million compared to $19.8 million in the same period of 2024. Variance in R&D spend related to the end of the Phase IIb trial in late 2025.

Breaking that down further, the Q4 2025 R&D spending included $12.8 million of direct costs related to pemvidutide development, of which $3.1 million for the IMPACT Phase IIb trial, 7.4 million for the Phase II trials in AUD and ALD and $1.2 million in CMC-related expenses. Fourth quarter 2025 R&D also included $1.3 million in noncash stock-based comp, which is flat in comparison with the same quarter prior year.

Moving to G&A. The G&A expenses were $10.5 million and $5.1 million for the quarter's end 12/31 '25 and '24 respectively. The Q4 increase in G&A year-over-year was driven by a onetime noncash and cash stock compensation and payroll charge due to executive transition, which totaled $2.6 million along with increases in professional fees and other compensation-related expense. Fourth quarter 2025 G&A included total noncash stock-based comp of compared to $1.8 million in the prior year period.

Net loss for the fourth quarter of 2025 was $27.4 million or $0.27 a share compared to a net loss of $23.2 million or $0.33 a share in the fourth quarter of 2024. Total full year 2025 cash OpEx was approximately $67.5 million, excluding noncash comp of $16 million. We anticipate the use of cash will trend up this year as we approach the launch of the MASH Phase III trial. As Christophe mentioned earlier, we're actively finalizing the last details of the study plan and the other last important details for the Phase III. When ready, we will update you and come back and provide more guidance on the timing of cash flows and related details.

Now moving over to the balance sheet. We reported total cash of $274 million at year-end 2025. We've made a great deal of progress in building the financial position, having recorded net proceeds totaling approximately $208 million last year, in a combination of $174 million in net equity capital raised and $35 million in fund of the Hercules tranche loan facility. And in addition, we raised $75 million in a registered direct offering announced in January with Alyeska Investment Group. The proceeds from this offering, along with $8 million raised off of our ATM facility in January, equates to a pro forma cash position today of approximately $340 million. We forecast that our current cash position would provide an operating cash runway into 2028 based on our current expectations for the scope and timing of the MASH Phase III plan along with the cost of both the AUD and ALD Phase II trials.

Our intent is on having the cash resources necessary to execute the MASH Phase III trial. We'll continue to be strategic and opportunistic in our approach to securing access to the forecasted capital needed to fund the Phase III and we'll keep you updated on our progress.

And with that, I'll turn the call back to Jerry.

Thanks a lot, Greg. As we highlighted today, we've entered 2026 with a great deal of momentum. We've made significant progress as we evolve into a late clinical stage organization and we're committed to further advancing our promising differentiated liver therapy and creating long-term value for our shareholders.

So this concludes our formal remarks, and we'd now like to take questions. Operator?

[Operator Instructions] And our first question comes from Roger Song of Jefferies.

So first question related to the Phase III. We all see the FDA have some new single pivotal framework. Just curious, have you talked with the FDA about that potential change? And then is that possible you can further save the cost from a Phase III if FDA allow you to do some amendment for the Phase III?

Thanks for the question, Roger. Christophe, maybe you get on one?

Yes. No. So we discussed this -- we haven't discussed this at the end of Phase II meeting, the path for approval for the MASH programs is the one single trial for accelerated approval and then all the which final approval for clinical outcomes. So this doesn't really apply directly for us. That knew it doesn't change anything from how we're approaching our development program towards approval.

Got it. That makes sense. And then just knowing you're still finalizing the protocol, just any strategical plan you can share at this point in terms of the interim versus the final outcome of a split and then different two primary endpoints for the interim, if anything this year.

Yes. Thanks, Roger. A lot of progress there. Maybe Christophe can give the big picture on that.

Yes. So the first is that we are having a fairly standard design for the Phase III, so we have our two primary [ Ponte ] guidance, which is MASH resolution without worsening of fibrosis and fibrosis improvement without MASH worsening. And this is how we powered our study. Our study is powered more than 90% on this endpoint. And that gives us a sample size that is around 990 patients, so 330 patients per arm.

As we highlighted, that power should give us the sufficient patients to reach the approval and the split of the alpha is, as you know, for the accelerated approval, the part one is 0.1 and then the other -- the rest of the alpha goes all the way to the clinical outcome. The live [ thanks ] is with powered based on our assumptions for the 1.8 milligram dose. So as mentioned, we're very well powered for this. In our trial, we have the option for an upside with the 2.4 milligram dose. And so we're really hoping that we'll see some added benefits there.

And our next question comes from [ Eli More ] of Barclays.

This is Jasmine on for Eli. I have two. So first, from your conversations with the FDA, what does the agency stand now on flexibility to consider NITs as a potentially registrational endpoint is the thinking for including the NIT cohort that we could potentially need more flexibility on this in the future. that you might be able to amend and use discount work for approval more quickly? And then secondly, can you talk about your plans in NASH F4 and potential time lines there?

Thanks, Jasmine. Maybe I'll start and then turn it back to Christophe. On the first question, we did broach the point of end points on NITs in the end of Phase IIb process, the agency at that point said it was premature to consider that, which is why you see the biopsy driven end points. Nonetheless, we'll capture all of that data. So that process at the agency will be ongoing. But again, the -- as we finalize the protocol, you'll see the biopsy-driven endpoint as part of that. Maybe you want to pick up the second?

Sure. No. I mean in the context of the [ a ] MASH assist approval, we see agency slowly moving towards that direction. So we've incorporated it in our trials, and we've put everything in case they change during the conduct of the study. So we are in a good shape here if they were to go there.

The other questions on the F4. I mean, our current focus is clearly on the F2 and F3. We believe there is some potential here with the mechanism of actions and the direct effect on the lever to impact the F4. At this point in time, our teams and is really dedicated towards the execution of the Phase III and putting all the last pieces in place to start.

And our next question comes from Yasmeen Rahimi of Piper Sandler.

This is [ Jon Mick ] on for Yas. So we just got a few here. The first one related to the Phase III for NASH. What are the great limiting steps to kick off that study? And how are you thinking about the time lines for [ and ] top line data?

Okay. Maybe I'll start on the first half and then Christophe can take the second. We're very focused on bringing pemvi to patients as soon as we can. I think we're approaching the preparation on both the financial and the operational fronts, as Christophe outlined, we like where things sit on the clinical side. Good clearance from the FDA, good insight on our proposal regarding Europe. So all things are moving in parallel. We expect that all will be in line to start the trial as we progress through this year, and we'll narrow the guidance as things come to fruition. Again, the teams are moving quickly here and this parallel approach is going to lead us to initiation of the trial.

Yes. I mean, I can just add to what Jerry says, we are in we're preparing everything on the regulatory side. We have alignment with the FDA. We have done our homework on what is expected from the European or we're in good shape here. We don't expect any major changes on our approach. So it's about now execution, getting the team to finalize the last details. whether it's in our protocols, some of the key aspects of the protocol and then moving forward to be ready to start as soon as possible.

Okay. Great. And then I just have one more question on reclaim. We decided for that trial. Your thoughts on what you hope to see and what would you consider clinically meaningful on alcohol usage for that.

So this study of the AUD is analyzing the heavy drinking days over a period of 7 days or a week. And we have powered the study to see a fairly conservative change. So hopefully, we'll see that. We are also capturing other endpoints like the zero drinking days, as well as some of those WH risk because this could be endpoints that will be discussed with the FDA if we move that program forward.

So we have -- we're going to look at all these aspects when we get the data and hopefully, we'll see some improvement. As a reminder, the mechanism of action is well suited for this, both on the reward system through the GLP-1 side of it, as well as the direct effect on the liver, which is quite unique compared to what other progress currently in development.

And our next question comes from Corinne Johnson of Goldman Sachs.

This is [indiscernible] on behalf of Corinne Johnson. Maybe can you just tell us about the additional financing through the year? And what you are anticipating needing to lift the completion of the Phase III in the MASH program? Any color on that?

Yes. So maybe I'll start on that, and then Greg could pick it up. As we -- I mentioned a couple of times already, including in the prepared remarks, we're preparing on both the financial and the operational side. On the financial side, as Greg outlined, we've improved our position.

He referenced roughly $340 million on the balance sheet at the end of February that gives us runway into 2028. We'd like to make further progress as we progress to initiate trial. We believe we have good line of sight on some options on how we would approach that in parallel to all the good operational work that Christophe and his team is doing. And then we'll access the appropriate tools along the way. Greg, anything else you want to reiterate?

I'll just pick up that. I think we have a sense of purpose here in making sure we've got the strength of our resources in hand as we begin the next necessary steps to launch this trial this year. Just basically just have a clear line of sight on what that looks like, how much that's going to take and confident that we'll get there.

And our next question comes from Annabel Samimy of Stifel.

Thanks for all the color on the profile and the physician receptivity. So I just want us from a competitive landscape. We'll likely be seeing more data from [ Reta ] and servo in obesity this year with the full knowledge that this is in obesity. What are some of the key data points that you as a team are looking for that may translate into NASH and could potentially have implications for the competitive landscape on the glucagon agonist front. Maybe you can just give us an idea of how you're thinking about the entire competitive landscape for these specific dual agonists?

Sure. We're always paying attention to what's happening in the marketplace. And we look at ourselves and what we have in terms of great tolerability, quality weight loss that we haven't seen with these other agents. Our simplicity of our titration and tolerability, which we've emphasized is really seen as something quite important.

For very obese patients, I think that there is going to be a role for managing that. but that has to be balanced with tolerability and efficacy elsewhere. And the direct acting effects that we have shown in the ratio that we're showing in the 1:1 ratio, we believe, are very important. If you're talking about the results of obesity, there may be some read over there, of course, but the trial that they're looking at shouldn't read out for quite some time on outcomes.

Our trial will be very heavily focused on mash patients. So that's our focus F2, F3 and the size of the market is such that there are going to be enough patients who need help that there will be ultimately many roles, I think, for pemvidutide, particularly if we deliver on the differentiation and the profile that we just talked about.

I think just maybe one other -- just maybe one other point Linda touched on. The ratio matters. I think you think about the BI compound, for instance, I mean, obviously, we'll see some additional data from them. But I think the work we've done with our own compound, we believe the balance ratio is part of what's driving some of the elements around the tolerability profile, which again -- we saw a good solid picture in our Phase II without a titration.

Now we have the opportunity to put a simple titrate and then maybe move forward on that as well. So we're looking at all of the competitive entrants. It's why we focused on this call, frankly, a lot more detail on the differentiation story because it's how -- we view the work that we are doing currently in executing the Phase III and also really always understanding how we're going to position pemvi to bring the benefit to the patients that needed the most.

Yes. And let me -- I just want to correct myself right now. The pemvidutide study is with their 8:1 GLP glucagon. And that is in the mass population. I was looking at the [ RETT ] trial in my head. So I just want to make sure I correct that. Either way, I think the tolerability for server was going to be quite significant for them. And when you look at the complicated titration schedule, that is going to be of concern as well.

Our next question comes from Patrick Trucchio of H.C. Wainright.

Louis Santos here in for Patrick. Congratulations on all the progress. My question is regarding the match noninvasive tests that you are using. So now that you have alignment with the FDA, did they provide any clarity on using it as primary rather than just surrogate as well as the AI biopsy reads or [ pemvidutide ] accelerated approval?

Yes. So on the discussion with the FDA, so as mentioned, the needs are not -- are too premature now, and we just want to be really ready on this. However, I mean the opportunity with our two cohorts is actually several fold once it fulfills some of those -- the requirements for the safety as well as the long-term clinical outcome but also to enroll a little faster our Phase III trials because we know and we've done that we'll look into it.

I will be happy to actually have the patient having different options, so to the biopsies and the [ knits ]. So that will give us some advantage there, and we're hoping this will be playing in our favor. With regard to the AIM MASH, this is still a consensus based on the pathology reading. At the end of pathologist is responsible, where we believe this could help us is actually in reducing variability potentially if we do the right training, et cetera, having a lower placebo response and trying to play in our favor.

So we're putting those pieces into place right now. We're having a lot of discussions with key pathologists and with the AIM MASH assist company that's AI. And we're putting all the pieces of that and getting very close to having a really a really strong path toward biopsies, but also, as mentioned before, having the flexibility around the needs in case [ DAA ] changes their mind.

That sounds great. Very quickly, can you update us on your CMC manufacturing readiness. And do you plan to scale for global trial manufacturing supply for both obesity and MASH simultaneously? Or do you plan to partner on then?

Scott Roberts can take the question. Just one point on the front is that we're focused on [ thematic ] trial, okay? We're focused on positioning pemvi as a liver compound.

Yes, that's exactly right. And as far as writing this for the Phase III, we believe that we're there, we're ready to go on that. As far as MASH, a global trial, that's really not an issue before MASH. We were really developing the process for obesity. We can scale to that size as necessary, but the company is focused on MASH and for those indications in the U.S. and the rest of the world where exactly where we need to be.

And our next question comes from Michael DiFiore of Evercore ISI.

Two for me. I just want to -- the first one, I just want to drill down on a prior question that was asked. Now that you received the FDA minutes, were the key elements that are fully locked and what is the single biggest remaining variable that you're still optimizing? And secondly, with the request for EU scientific advice now submitted, is there any early read on whether EU fee that could change anything meaningful versus the FDA aligned plan?

Thanks for the questions, Michael. Christophe?

Yes. So on the FDA unit, and the discussion with them, I mean, the -- we are really in the last phases of finalizing our protocol. We have all the elements, like I mentioned, the sample size. We talked to all of our biostatisticians. We have the primary endpoint aligned, the population, et cetera. What we're looking at is finalizing some like, for example, the biopsy is a critical point, and we want to really take the time to do it in the most comprehensive manner and having our team of pathologists with us.

So we're taking the time to do this, the most appropriate way and these are the kind of last details, some of QC, for example, things like this. So these are really the final stages of those aspects.

With regard to the EU, we've worked with regulatory consultants. We have a good understanding. We actually even have biostatisticians that are advising the EMA that worked with us. We've put together all the PCs. So we don't expect anything to hold us back and we -- our protocol and the design of the study shouldn't change based on the scientific advice.

Our next question comes from Jon Wolleben of Citizens.

Two quick ones. Mostly on the reclaim program. Firstly, how thinking about the mechanism of action? Like as far as having GLP and glucagon specifically maybe being beneficial over just GLP-1 agonism in the collated diseases? And also logistically, how do you guys plan on kind of moving forward on the Phase III program. Are you guys going to kind of move forward with AUD and then wait for ALD data? Or do you want to kind of see both before moving forward?

Yes. Maybe I'll start with the second question and then Christophe can take the mechanistic one. So we'll -- as we said, we're going to expect the readout on the AUD trial in quarter 3. They'll assess the data and then plan next steps. That would happen immediately upon receipt of the data no need to wait for ALD. We like the fact that we have a second Phase II going in ALD. But as the enrollment will finish this year, that will be a later readout.

Yes. On the mechanism of action, so it's well recorded in the literature that GLP-1 have a central effect on the reward system and the type of alcohol use that those patients will have. The difference is the direct effect on the liver. They are now more and more -- and recently in January, at the MASH [ Mastek ] conference, it was clearly talking about the fat in liver of these patients, but also some elements of early fibrosis, so it would be very suited for these populations to not only treat the alcohol use and the cravings and that reward aspect but also to directly deliver because the liver is already substantially damaged.

And even with early fibrosis with clearly the dual mechanism of action and the tolerability I will add in that particular population is extremely suitable for a product like pemvidutide. This population feels good. they are not having -- you don't want to add side effects or implications to [ dams ], so they really want to get their lever treated as well as the cravings.

And our next question comes from Andy Hsieh of William Blair.

We have two questions. One is related to the prepared remarks that you made, highlighting that Sema failures might be a potential segment to provide clinical differentiation. So can you tell us a little bit about the exclusion, inclusion criteria regarding the length of the washout period in the upcoming Phase III trial. So that's question number one.

Question number two has to do with kind of the pathologist panel that you decided. I'm curious if it's just like a 2-person panel, a 3-person panel. Can you talk about the education process, if you don't mind?

So I'll start with the first one. Clearly, what we hear and what's been presented in the past conferences is that sema is hard to tolerate that most patients do not reach the MASH effective dose that the titration is complex for them. and that there are a lot of dropouts of treatment after already 6 months to a year. So this is a challenge there.

If that's the case for us, clearly, we will accept these patients in our Phase III trials and we want to be able -- if they have not tolerated sema to bring them on board because they will have an option which we decide again to have and I want to remind you to the extremely strong efficacy we've seen in our Phase II study, as well as the [indiscernible].

So both together is a perfect option for this population with a real chance now to address the liver and their metabolic causes for that match. With regard to the pathologist, we're still finalizing these details where towards the end of this, our thinking right now is to have -- it has to be a consensus. So we're thinking to have a few pathologists and the reading would be two plus one type of reading with the consensus, the plus one would be if there is no consensus between the two pathologists.

Clearly, the advantage here for us is the AIM MASH assist. If really that decreases the viability and help that consensus, it should also accelerate and streamline the process. And so for us, these two aspects, decreasing variability and streamlining the process are good positive perspective to execute our study in the best possible way.

And our next question comes from William Wood of B. Riley Securities.

Two from us, if we may. All your reclaim trial, it's focused on drinks per day in alcohol consumption but I was curious if there are any NITs looking at the liver or additional measurements that could read through to either your ALD or Phase III trials since you'll be evaluating the 2.4 mg dose in both the AUD ALD and then obviously, the Phase III as well as could you provide any color on how far along you are in your ALD trial enrollment? And then I have a second follow-up.

All right. On the AUD, so we don't have too many -- we have the typical liver enzyme, et cetera. We're looking at a heavy drinking days. We're looking at the zero day of drinking, we're looking at those the WHO risk classification, if you wish, and how these patients will change. But also since it's a patient reported outcome, we also have blood tests such as the test, which is a little bit like you would see in the HbA1c, which reflects the alcohol impregnation.

So we believe that here, we have -- and we have all the other markers of the effectiveness of the drug such as weight loss, et cetera. So we have in our a number of things that will be very helpful to be -- to prepare for discussions with the FDA granted the data come out positive on this. On the we are enrolling as per plan. As you know, this is a more severe population. So it will be more difficult to enroll.

I mean, we successfully enrolled very rapidly our AUD trial. Much faster than anticipated. But here on the ALD, we're on track for as per plan and moving forward smoothly as I can't give you any more forecast on that at this point.

Okay. And then in your Phase III trial, maybe I missed it, but will you be evaluating any cardiovascular benefits? Or maybe how do you plan to assess MACE since you're not conducting a separate CVOT trial.

No, this is a great question. First, I mean, we've already seen some great improvements on the lipids. On the inflammation, we clearly have a decrease in inflammation in -- with pemvidutide. We've seen improvement in lipids at week 24 in our latest data similarly at week 48. So we believe there is a real potential here to see some cardiovascular benefits. We will clearly look at the scenario of Phase III MASH trial. However, the FDA doesn't want us to include this as the clinical outcome for liver-related events, clearly, these are two separated aspects, but we'll have the data built in, in our Phase III.

And our next question comes from [ Boris Peaker ] of Titan Partners.

Great. I guess I just want to focus on the muscle preservation and obviously, it's one of the key differenting elements of the drug. I'm just curious, the observed weight loss today, can you comment whether the muscle preservation was stronger at the lower or the higher end of the DMI scale? And what can you potentially do in the Phase III study in terms of enrollment to maximize the impact of this muscle preservation, particularly considering to the large and international study?

Yes. So the muscle of preservation in the lean mass is critical, as you say, because this is something that in that population, that's aging. Our average patient is 55 and older, and that's -- they start losing their bone, their muscles. And so we don't want to add anything to this. So we want to keep the muscles in this population. We've demonstrated some very interesting data already in our [ VCT ] trial, and we would have to continue demonstrating this. How we are integrating this in the Phase III, we are actually in some discussions right now, whether it's a full mechanistic study or if it's a substudy that is put into the trial is something that we're defining as we are speaking today.

Regarding the BMI, I mean, there's no difference between the it works. It's all different type of BMI and it's consistent throughout. That's what we've seen in our VCT study.

Got it. I'm just curious what specific test to biomarkers are you monitoring to better understand this muscle preservation. So is it just a DEXA scan, hand strength, MRI, where are you specifically monitoring? And what do you think you'd need potentially get a claim in the label on some kind of muscle preservation.

Yes. That's I mean, that's a complicated question because you're getting a claim would require some clearly will have MRI. We'll have this kind of, like you mentioned, Dexa, we would like to better understand. We have some ideas how this is working as well. We believe that one-to-one ratio is one of the key aspects that could lead to this. So if we can make that link.

And during our Phase III, clearly, that would be an important distinction and differentiator at launch. So we're putting all the pieces together as we're first -- first, we're finalizing that protocol for the MASH and putting the pieces on that lean MASH preservation as well in parallel.

I show no further questions at this time. I'd like to turn it over to Jerry Durso for closing remarks.

So thanks, everybody, for joining us today. A lot going on in the company, a lot of progress. We're moving forward towards the Phase III execution. We have work to do, but we're in a good position, and we definitely look forward to providing further updates as we progress. Thanks, everybody, and have a great day.

This concludes today's conference call. Thank you for participating, and you may now disconnect.

Good morning, and welcome to the Altimmune conference call. [Operator Instructions]. As a reminder, this call is being recorded. I would now like to turn the call over to Lee Roth, President of Burns McClellan, Investor Relations Adviser to Altimmune. Lee?

Thanks, operator. As a reminder, a press release summarizing the results of the trial can be found on the Investor Relations section of the company's website. This call is also being recorded, and a copy of the slides and audio will be posted to the IR site at the conclusion of the live event. Following some prepared remarks from management, we'll open the call to your questions. Before we begin, I'd like to remind everyone that remarks about future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For discussions of some of the risks and risk factors that could affect the company's future results and operations, please see the risk factors and other cautionary statements contained in our filings with the SEC.

I would also direct you to read the forward-looking statements disclaimer in our press release issued this morning and on Slide 2 of the accompanying presentation. Any statements made on this conference call speak only as of today's date, December 19, 2025, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. With that, I'll now turn the call over to Dr. Vipin Garg, President and CEO of Altimmune.

Thank you, Lee, and good morning, everyone. Thank you for joining today's call to review top line 48-week data from the IMPACT Phase IIb trial of pemvidutide in MASH. As announced in our press release this morning, the 48-week data showed marked improvements in key noninvasive markers of fibrosis across treatment arms with continued reductions from the 24-week time point. We were also pleased to see additional weight loss with the 1.8 milligram dose from 24 to 48 weeks with no evidence of plateauing. We are very excited to review these longer-term results as well as share key highlights from our recent in-person end of Phase II meeting with the FDA.

Before we begin, I would like to quickly extend my gratitude to those who have worked alongside me over the last 7 years to help establish pemvidutide as the cornerstone of our company and bring it to the cusp of Phase III development. As announced earlier this month, our Chairman, Jerry Durso, will assume the role of President and CEO at the beginning of next year. There is no one better equipped to take Altimmune into the next phase of its corporate evolution than Jerry, and you will hear from him today as we reviewed this new data set. With this, I welcome Jerry to take the floor. Jerry?

Thanks a lot, Vipin, and congratulations on the data. Let me start by saying that as someone familiar with this liver disease space, I'm very excited to be taking the reins of Altimmune at the start of the new year. That excitement is due to pemvidutide and its potential in liver diseases like MASH. Pemvi is uniquely tailored for liver patients, providing liver-directed effects from glucagon with metabolic effects from GLP. Combining these peptides in a balanced 1:1 ratio via our proprietary domain, which is the linkage between these 2 peptides creates a basket of benefits and a differentiated profile, including a favorable view on tolerability, which will be important in keeping patients on therapy at an efficacious dose.

This tolerability profile is critical in MASH, which, as you know, is a multifaceted disease that might be best addressed with multiple mechanisms. Pemvi acts as combination therapy in one molecule. The 48-week IMPACT data further strengthens our understanding and clearly positions pemvi as an exciting and differentiated investigational product among current MASH therapies and those in development. Now before we review the 48-week data, let me review on Slide 4, the encouraging 24-week data that we announced in June. That readout showed that pemvi worked quickly and achieved significant reductions in liver fat and improvements in markers of hepatic inflammation and importantly, reached statistical significance on the approvable endpoint of MASH resolution. Additionally, we saw weight loss that didn't plateau at 24 weeks for either dose and signs of antifibrotic activity through NITs as well as a favorable tolerability profile.

Now moving to Slide 5 and the 48-week top line results, I'm excited to share that we saw what we were hoping for in this data set. The incremental improvements in the absolute changes, both from baseline and from week 24 at week 48 on ELF and liver stiffness measurement is a clear evidence that this drug has a strong antifibrotic effect. The dose response is also clear and allows us not only to focus on the 1.8 milligram as a key dose in Phase III, but also gives us the confidence to assess a 2.4 milligram maintenance dose, which may give us an upside both on weight loss and potentially on efficacy. Importantly, we also maintained improvements around inflammation, liver fat and tolerability from 24 weeks to 48 weeks. With that, I'll now turn the call over to our Chief Medical Officer, Dr. Christophe Arbet-Engels, to further speak on the data.

Thank you, Jerry, and good morning, everyone. Let me provide a brief overview on the design of the IMPACT trial. Participants with MASH were enrolled and randomized across 3 treatment arms: placebo, 1.2 milligram and 1.8 milligram doses for a duration of 48 weeks. The dual primary endpoint of the study, MASH resolution or fibrosis improvement were assessed by liver biopsy at week 24, and we reported along with the results of a variety of noninvasive tests or NITs and weight loss. The noninvasive test and body weight continue to be assessed throughout the remainder of the 48-week treatment period, and that is the data that we are reviewing today.

To begin our data review, here, we highlight substantial improvements among 2 well-established markers of fibrosis, ELF, a marker of the severity of the fibrosis and the liver stiffness, a marker of the amount of fibrosis. The greater or equal reductions than 0.5 in ELF has been shown to be associated with histological improvement. And similarly, a reduction of 30% or more in liver stiffness has been also associated with histological improvement. On the left-hand side of the slide, the ELF improvement was greater than 0.5 at the 1.2 milligram dose and close to 0.6 for the 1.8 milligram dose with a placebo-adjusted difference close to 0.8. Regarding the liver stiffness, an improvement of approximately 4 kilopascals was around 30% reduction in liver stiffness.

And on the third graph, the combination of these markers which is thought to potentially replace biopsies as fibrosis surrogate biomarkers highlights the proportion of patients who reached at least a 0.5 reduction in ELF and a 30% reduction in liver stiffness. The dose response observed and the strong difference versus placebo, especially at 1.8 milligram are evidence of a clear antifibrotic effect of pemvidutide at week 48 that should translate in histological improvements in a 52-week pivotal study for accelerated approval. While both treatment arms showed statistical significance, here we highlight the improvement over time of the 1.8 milligram dose on ELF and liver stiffness from week 24 to week 48.

As you can see, on the ELF, these had already decreased by 0.5 at week 24 and continue to strongly improve at week 48. We also observed a robust improvement in the liver stiffness measurements from week 24 to week 28. In particular, this data highlights how pemvidutide substantially and rapidly decreases fat in the liver, which leads to decreased inflammation and ultimately improvement in liver fibrosis. These data give us greater confidence that the 1.8 milligram dose should be an efficacious dose to reach both endpoints of MASH resolution and fibrosis improvement at 52 weeks in the Phase III registration program.

Now I will quickly discuss how the ELF and liver stiffness results for pemvidutide at 48 weeks compared to published data from other MASH therapies. On this first slide, as you can see here, the improvement in placebo-adjusted ELF score achieved by pemvidutide at week 48 compares very favorably with other options. For example, the 2 currently approved therapy, resmetirom and semaglutide showed comparable improvement in their Phase III. In the next slide, with regard to placebo-adjusted liver stiffness measurement, similar improvements were observed with pemvidutide at week 48 compared to other compounds.

Next, let's look at liver fat content, which is a driver of MASH and ultimately fibrosis. Multiple studies have shown that liver fat reductions of 30% or more are highly associated with histological evidence of MASH resolution. This data highlight a clear dose response with pemvidutide, maintained similar reduction from the rapid 24-week improvement and reached more than 50% at week 48. Turning now to liver enzymes such as ALTs, these are an important measure of hepatic inflammation and liver health. Based on published literature, a 17-unit reduction in ALT is strongly associated with MASH resolution, and we achieved more than double that in both pemvidutide doses. Moreover, participants with an ALT level of 30 or lower are considered to be within the normal range. And as you can see on the right of this slide, a significant majority of pemvidutide-treated patients, greater than 70% of them achieved ALT normalization at 48 weeks.

On the next slide, we show the results of corrected T1 or cT1 imaging, which is an advanced MRI-based technique to measure hepatic inflammation. According to a 2020 study published in Frontiers in Endocrinology, a cT1 reduction of 80 milliseconds or more is strongly associated with both MASH resolution and fibrosis improvement. The reduction in cT1 achieved with both pemvidutide doses were well above this 80-millisecond threshold.

On Slide 14, weight loss continued beyond 24 weeks, showing a clear dose response and at the 48-week time point, both the 1.2 and 1.8 milligram doses achieved statistically significant weight loss. The performance of the 1.8 milligram dose, which did not plateau at week 48 was particularly impressive, considering that approximately 45% of our populations were patients with type 2 diabetes. Because of this, we anticipate including the 2.4 milligram dose in our Phase III study, which could give us an upside with greater weight loss and potential increased efficacy on MASH resolution and fibrosis improvement. As a reminder, the quality of the weight loss observed in the Phase II obesity trial showed lean mass preservation similar to diet and exercise alone.

Now looking at safety and tolerability. Pemvidutide maintained its very strong safety profile throughout the 48 week of the study. There were no serious or severe adverse events or AEs of special interest related to study medication. The majority of AEs were mild to moderate, and there were no heart rate increases observed. Importantly, approximately 45% of the patients in the trial were diabetic, and they were able to maintain good glycemic control throughout the entire duration of the study. Here, we take a closer look at GI tolerability.

As a reminder, MASH is a chronic disease, and it is critical to maintain patients on therapy for a prolonged period of time for successful treatment. Tolerability is key to keeping patients on an efficacious dose of drug. Excellent tolerability of pemvidutide was observed throughout the 48 week of the trial and the GI AEs at the 1.2 milligram dose were very close to that of placebo and a very compelling tolerability profile at the higher 1.8 milligram dose was observed in the absence of titration. The majority of AEs were mild to moderate and predominantly occurring within the first 4 to 8 weeks of treatment. Most importantly, the discontinuation rate due to AEs was lower than that of placebo and more patients stayed in the study in the 2 active drug arms than in the placebo.

To put this data into perspective, being able to maintain patients at an effective dose over the long term is again critical to address the causes and the complications of MASH as a chronic disease and is also critical for the success of the Phase III registration program. On Slide 17, in addition to the exciting 48-week data presented today, we are equally pleased to update you on our completed end of Phase II meeting with the FDA. The in-person meeting was highly productive with a great deal of engagement among the members of the FDA team, and we will receive the final meeting minutes in January. During the meeting, we have aligned with the agency on the registrational Phase III program in MASH patients with moderate to advanced fibrosis with biopsy-based endpoint.

Importantly, the agency was open with our intent to incorporate a MASH AI Assist, which recently became the first FDA-qualified AI pathology tool to improve standardization of the biopsy readings and reduce variability in the consensus read process. The FDA was also open with our intent to evaluate multiple doses of pemvidutide in the Phase III trial, including the 2.4 milligram dose, which, as I mentioned earlier, may be an opportunity for added efficacy given its important weight loss benefit in the Phase II obesity study. We intend to seek scientific advice from the European regulators, which will be considered as we finalize the Phase III protocol. Our goal remains for the Phase III data to support regulatory submissions in both the U.S. and Europe, and we expect to initiate the trial in 2026. I will now turn it back to Jerry.

Thanks, Christophe. So as you can see on the left of Slide 18, 2025 has been a very busy year for Vipin and the team on our clinical programs. We completed the IMPACT trial, held our end of Phase II meeting that Christophe just described and began preparation for the registrational program in MASH. We announced 2 additional indications for pemvi, AUD and ALD, initiated Phase II trials in both and have already completed enrollment in the AUD trial. Now looking ahead to next year, we expect to initiate the Phase III MASH trial, report top line data from the RECLAIM Phase II in AUD and complete enrollment of the Phase II RESTORE trial of pemvi in ALD. 2027 will see the continuation of execution on the Phase III MASH trial, the expected completion of the RESTORE-ALD trial and the potential Phase III readiness of pemvi in AUD.

So finally, to recap, the 48-week IMPACT data was what we were looking for and achieved key measures of success. Treatment with pemvi showed improvements in key noninvasive markers of fibrosis with continued reductions versus what we saw at 24 weeks. We saw additional weight loss as well as reassuring safety and tolerability reinforced by low discontinuations. These data enhance our confidence as we look to Phase III and map the longer-term competitive profile of pemvi. We've aligned with the FDA on a path to Phase III development in MASH, and we have a steady stream of expected catalysts over the next several years. Finally, we're building the right capabilities for the next phase of Altimmune. As I said at the opening, this is a very exciting time for us at Altimmune. We believe strongly in the potential of pemvi to be a meaningful treatment option for the MASH patient community, and we look forward to sharing all of the progress as we continue to move ahead. So thanks. And with that, we'd be happy to take your questions. Operator?

[Operator Instructions] Our first question comes from Yasmeen Rahimi with Piper Sandler.

Congrats on the data and really a big win of getting all to the regulatory alignment to you move to an AI-based biopsy reading. So team, I guess, if you could help us understand as you think about these really profound liver fibrosis benefits that you're seeing, which continues to get at 48 weeks. Can you help us understand like would you contemplate doing a longer Phase III study to capture that? And maybe just squeezing that the question will come up is, given that's AI-based, could there be an opportunity that the size of the Phase III could be smaller given that you use variability or biased in any way? Or is it just going to have to be over 1,000 patient data given the safety data requirement? I appreciate any color, and I'll jump back in the queue.

Yes. Thanks a lot for the question. I'll turn it to Christophe. But obviously, on the front end, we are really encouraged with what we see here at 48 weeks and our thinking around the Phase III design will include a 52-week readout on biopsy and then a continuation of the patient population to outcomes for the confirmatory trial and potentially the full approval. Christophe, do you want to get into kind of the sizing consideration and how AIM-MASH assist might play on that?

No. Again, the data that we've seen are really encouraging and in particular, the 0.5 reductions and 30% reductions are very striking. We discussed this with our academic experts. They're also very encouraged by this data. The role of the AIM in the Phase III could potentially help reduce the size of the trial. However, at this point in time, it is PathAI who's speculating that there should be some improvement around the variability, some improvement in standardizing the process for reading the biopsies. So our consideration for our Phase III is to power and sample size the trial as per the biopsy reading, the consensus reading and the upside of AIM could really help increase even the power of the study.

Our next question comes from Annabel Samimy with Stifel.

Congratulations on the really consistent data. So a few questions here. Just going back to the design of the study, realizing this is going to be a 52-week study. Anything that you're doing to bake in an endpoint that's going to demonstrate the rapidity of effect because I think that's one of the standout characteristics here. And then you mentioned that you're adding a 2.4 milligram dose for maintenance only. Is this only maintenance? Or are you considering it as one of the actual arms of the study?

Christophe, why don't you jump in?

Yes. So the rapidity of the effect is actually really important. Obviously, for patients to stay on the drug, for payers to respond favorably, it is critical that they see this effect occurring rapidly. And we've demonstrated that at week 24. We will build that in our Phase III design to be able to see again and demonstrate further that rapidity of effect early on, especially on the MASH resolution. The inclusion of the 2.4 milligram dose is an opportunity and upside for us. The way we're thinking about it at this point in time is potentially a very simple 1- or 2-step titration to go to the 2.4 we have here with the 1.8 very efficacious and established a very efficacious dose. So that dose, we want to continue to demonstrate its in the accelerated approval, its ability to provide an efficacious treatment for MASH patients, both on the MASH resolution and the fibrosis improvement, and we see the 2.4 milligram dose as an upside. So we -- probably, at this point in time, we would separate the 2 arms, the 1.8 milligram dose and then the 2.4 milligram dose.

And if I could just ask a quick follow-up. Obviously, the discontinuations were very impressive, barely any dropout actually. So can you actually talk about that relative to the other MASH drugs, what you typically see, not just from the GLP-1s, but also from the FGF21s? How does it compare?

So in general, the discontinuation compared very favorably. This is a unique feature of pemvidutide that is built in within the molecule, as Jerry mentioned, that EuPort linker between the 2 peptides delays the Tmax, decrease the Cmax, and we see it clinically in the data that we just presented. It's very, very important for a number of aspects, clearly to demonstrate the efficacy in the Phase III program. But again, we see now with other compounds, some very significant number of patients discontinuing. So for example, survodutide has close to 23% of discontinuation. FGF21 vary around the 5 depending on what is reported during clinical trials. But then in real world, it is becoming more challenging for some of these drugs. And we see, for example, with the GLP-1 close to between 2% to 6% in clinical studies, but a much, much greater amount of patients dropping out or not reaching efficacious doses after 6 months to a year. So we feel extremely comfortable and extremely encouraged by this. Again, in a chronic disease setting, it's absolutely critical to be able to keep these patients on an efficacious dose.

The only thing I'd add, this is a really important finding for us. I think when you consider we know that the MASH patients in the real world are complicated patients. They're on multiple different therapies often for diabetes, for cardiovascular risk and being able to provide a therapy in MASH that allows them not only to stay on therapy, but to stay on at the right efficacious dose, I think it's going to be a real differentiator, not just from the drugs that are already on the market. But as Christophe mentioned, those coming through the pipelines now.

[Operator Instructions] Our next question comes from John Wolleben with Citizens.

Two for me. You mentioned you saw consistent safety in the diabetic population included. I wonder if you could talk a little bit about any differential responses you've seen on any of these efficacy measures. And then for Phase III, when you're jumping into the 2.4 milligram dose, can you talk about expectations for response rates at that higher dose? How do you think about your statistical projections and modeling for the Phase III?

Sure. So on the safety in diabetics and the efficacy, we haven't -- so this population, we haven't seen any difference. So in our mind, what we've established clearly here is that we can use pemvidutide in both populations, the MASH patients with diabetes or without diabetes both on the efficacy and clearly on the safety side, as you have seen, there is nothing, no imbalance, nothing that led to any differences in this population. The only thing that may be different is they have a harder time to lose weight. So we were extremely happy with the weight loss that we've seen considering that there were almost half of our population that had diabetes.

Regarding the expected efficacy of the dose or the response with the 2.4 milligram dose, we've demonstrated that the 2.4 milligram dose in the obesity population could reach close to 15% of weight loss. So we are hopeful that we can do that and that we can increase the efficacy seen on the MASH resolution and the fibrosis improvement with that dose. One part that is allowing us to do this is the exceptional tolerability and safety of pemvidutide. So we believe in the 1.8 milligram dose as a very competitive, very compelling dose for MASH, but there may be some population that could benefit from a little added efficacy, and that's why we are trying to explore this a little further with our 2.4 milligram dose in the Phase III program. And the FDA was very much on board with this approach.

Our next question comes from Michael DiFiore with Evercore ISI.

Congrats on the very impressive data. Two questions from me. For Phase III for the 1.8 milligram dose, will it incorporate titration given the relatively high nausea rates seen in Phase II? And the second question is the FDA's openness to using PathAI. It sounds like they still need, I guess, more convincing on the variability of this modality. Has there been any change in the expected timing of Phase III given this -- the openness to use? Or is the base case still that the agency needs more data to fully embrace it?

So again, on the AI MASH assist tool, the agency is opening to incorporate it, obviously, the clearance came almost concurrently with our FDA discussion. And as Christophe framed, they are completely open to us using the tool now that it's cleared. We will capture the way we're going to incorporate it in the final protocol when that will go in. And as you can imagine, working closely with PathAI as we finalize that. So no hesitation from the agency standpoint. We do just have to acknowledge we will be the first to utilize the tool in a Phase III setting. So from that standpoint, again, we think there's a good opportunity based on potentially reducing the variability and incorporating the tool. And again, we will frame exactly how we will do that in the final protocol, which will go to the agency.

Correct. And on the 1.8 milligram dose titration. So I just want to this is an upside for us. When we saw the safety and the tolerability profile, we have an extremely good efficacious dose with the 1.8 milligram. So the 1.2 milligram had a placebo-like type of tolerability. We believe that with a very single step titration, not something like you can see with the GLP-1 like 5 steps, 5 months, something like that, with a very single step, we might even be able to improve a little further the tolerability of the 1.8 milligram dose. And so that is one of the considerations for the Phase III. And obviously, now we could allow the 2.4 milligram dose to increase on the efficacy side. And both of those together brings us to a very strong package for our competitive Phase III program.

Our next question comes from Patrick Trucchio with H.C. Wainwright & Company.

Congrats on the data. Just the first follow-up was just, I think you mentioned that the data in diabetics compared to non-diabetics was similar. I'm wondering if you can comment on the consistency of the NIT responses across baseline fibrosis stage F2 versus F3.

Yes. So at this point in time, we haven't done all -- these are the top line results that we have here. We haven't done all the sub-analysis. We do not have evidence that there is any differences, but these are some of the further analysis that we intend to [Technical Difficulty] later.

Got it. And just maybe just a clarification for the Phase III design and regulatory strategy with FDA alignment at the end of the Phase II, the endpoint hierarchy in Phase III, particularly the balance between biopsy endpoints and noninvasive tests such as ELF and LSM?

So the FDA is still with -- we asked the questions about the NITs to the FDA. They believe it is premature to use the NITs as primary endpoints. So we will go ahead with our Phase III program with the biopsy endpoint that uses the consensus, and that is -- that consensus, being streamlined and hopefully decrease viability with the AIM-MASH. The NITs, we believe that at one point in time, given the movements that we start to see with the agency on the AIM-MASH, we believe that they will be changing towards the NITs, and there's a good pressure here from the scientific and clinical community. So we have incorporated these in our Phase III trial, and we'll have the flexibility to adjust our endpoint if need be, when the agency moves in that directions during the Phase III trial.

Great. And if I could, just one on -- from a payer perspective. So actually, from a payer and physician perspective, how important is it to demonstrate this objective improvement in the NITs by 48 weeks compared to waiting 72 or 96 weeks just from an adoption and reimbursement decision perspective.

So we think it's important because, obviously, there's 2 things, I think, 2 angles around the payer that start to become evident when we look at our data. The quick action and starting to see an impact on the NITs quickly is important for payers. Again, they want to understand whether there's an early response for the patients that have been put on. The second piece, which is crucial, payers have a big challenge with adherence on chronic therapies. They do not like to pay to start patients that are either dropping off therapy after a small period of time because they look at that as wasted cost.

Additionally, patients that are maintained at a suboptimal subtherapeutic dose is also an issue that they have. And that's why we feel with the low drop-offs we see here as well as what we believe will be a very simple approach to titration, very different from what you see with up to a 5-step titration approach with some of the GLPs, for instance. So again, we think that combination of keeping patients on and at the right dose will be a strong part of our value proposition with payers. And they tell us that in the conversations that we have in the market research setting.

Our next question comes from Corinne Johnson with Goldman Sachs.

I was hoping you could be a little bit more specific about the number of patients you anticipate in the Phase III program, given some of these considerations around both efficacy and safety. And then I also wanted to just follow up on a point you made a bit earlier about using a maintenance phase for outcomes, assuming that's in the F2/F3 patient population. I'm curious if you anticipate also doing outcomes in an F4 population and how long you'd kind of anticipate it will take to generate that outcomes data depending on the patient populations you're looking at? Thank you.

Thank you. All right. So on the Phase III sample size, as most standard program, they are ranging between approximately 1,000 to 1,500 patients on treatment plus the placebo group. We have had that discussions with the agency, and they're open for us. We have not determined yet the exact number, but we should be on the lower end of that range. With regard to the outcome part of the study, the way we can build this, and we are thinking about building this right now is developing this F2/F3 populations for the accelerated approval, both on biopsies and on and following them throughout then up to approximately 60 months for liver-related events. And we are also exploring an opportunity to look at pemvidutide given the very strong antifibrotic effects into our Phase IV -- F4, sorry, population.

So this is kind of how we're building this and how we believe we're going to have all the appropriate population, both for the accelerated approval and then in the future for the final traditional approval with the clinical outcome.

And our next question comes from [ Fiona Gia ] with Jefferies.

This is Fiona on for Roger. Congrats on the data and also the regulatory advancement. Just a clarifying question on the Phase III design for the primary endpoint. Is the understanding the conversation with the FDA is still evolving. Is your current goal using the noninvasive measurements or PathAI data for the primary endpoint?

So for the primary endpoint, the FDA is very clear that for now, we follow the guidance and we follow the biopsy consensus approach for this primary endpoint. There are 2 pieces that are moving. The first one is that AIM-MASH AI, which is supposed to improve the variability. And when we discussed this approach with the FDA, they were very open on how we can use it. And hopefully, it's going to be an upside for us on our power and sample sizing of the study. But the primary endpoint to be again very clear is still the biopsy-driven endpoint. And then because the biopsy -- the FDA is still having a lot of these discussions around new approaches to avoid biopsy as we all know, there's associated risks and complications for patients, et cetera, and limitations. So we are, as the sponsor anticipating that the FDA or the agency or the regulators in general will move in that direction and using those NITs. And therefore, we're building this in our program to make sure that if this were to be the case, we are ready to move in that direction as well.

Our next question comes from Andy Hsieh with William Blair.

Congratulations on your career. And Jerry, I look forward to working with you. Just a clarifying question for the Phase III. So the goal for AI is to assist the pathologists, right? So I just wanted to make sure that the final call on MASH resolution and fibrosis will be made by pathologists. And maybe a follow-up on that. I'm curious if you decided on kind of the pathologist panel in terms of consensus building, how many of them will be there for your Phase III program? And my second question has to do with the 2.4 milligram dose. I'm just curious about how much you can leverage the MOMENTUM trial from a safety database perspective where you need like a safety lead-in kind of a Phase II portion leading into a Phase III in order to kind of make sure that the agency is comfortable with using that dose?

Yes. So maybe I start on the path -- the AIM-MASH question and then Christophe to the second one. So the discussion we had with the agency, they clarified that utilization of the tool is consistent with what they've published on the context of use. So essentially, as part of a pathologist-led consensus reading process. So the pathologist, as you say, will make the final call as part of the process, but that the tool will help each pathologist in the panel with that individual slide read. And so again, I think there's a lot of reason to believe that this will potentially have an impact on variability. But the pathologists will be the final say as part of that consensus process. But again, the tool assists on each individual read.

Yes. Just to that point, I mean, to understand the tool, it shows you the entire slide, and it prompts you to the features on the slide. So that piece will be similar for all pathologists and the pathologist ultimately agrees or disagrees and that's the consensus Jerry is referring to. So that -- we hope it will reduce some variability there. On the 2.4 milligram dose, there won't be any leading. What we are trying to do here is to make sure that we can have that opportunity for added efficacy, maybe in some subpopulation or in the general benefits for the patients. But the way to approach that is to try to keep the tolerability that we have seen and trying to find that very simple 2-step titration basically and bring the tolerability in the same range as what we've seen with the 1.2 or 1.8 milligram dose.

So the upside and the great weight loss we've seen in the obesity population might be slightly different than in the MASH because we have to understand comparing the obesity weight loss and the MASH weight loss is very different. But the opportunity to go even further into the efficacy on MASH resolution and the fibrosis is clearly there, and we will be -- make sure that this doesn't jeopardize the tolerability -- excellent tolerability of pemvidutide.

I see. So should we think about it as kind of an opportunity to increase the dose a little bit and not a separate arm?

The way we are looking at this at this point in time is 2 separate arm. One arm that would go to the 1.8 milligram dose because -- and that's what we've discussed with the FDA and where they were open with us to do that. The 1.8 milligram dose has clearly now been established as an efficacious dose for MASH resolution and fibrosis improvement. And then the opportunity is to -- without jeopardizing the tolerability with a very simple, again, little 1, 2 steps from 1.2 to 1.8 to 2.4, a separate arm that could give us added opportunity to understand added efficacy and potentially subpopulation that could benefit from it.

And our last question comes from William Wood with B. Riley Securities.

Congratulations on the results this morning. I think the first question I have sort of centers around the NIT that you look to incorporate. The field has been essentially coalescing around this dual VCTE endpoint, which you've now increased to sort of come in line with your VCTE now at less than -- or greater than 30% improvement. But I'm just curious, given that while VCTE and now MRE are in -- they've had LOIs accepted from the FDA, we haven't seen that type of movement for ELF. And so the question really centers around where is the FDA or what's the FDA thinking in terms of a potential approvable NIT, are you looking at more this dual endpoint? Is that the correct area? Or is it going to be just VCTE or liver stiffness in general or just ELF? And then I have a follow-up.

So we haven't gone into all these details with the FDA to be fully transparent. The FDA is telling us is trying to correlate some of those NITs to the clinical outcome. Right now, they haven't reached that level of information. There are some movements, and they're open to this and some companies, as we know, have been trying to work with the FDA to try to get their tool approved like for the VCTE and the FibroScan. This is where we are. And -- the challenge with the MRE is at this point in time, at least for clinical trial execution, it's not in every center, and it limits the number of sites that you could use. Therefore, the FibroScan being a little broader and given that we would like to enroll this study as rapidly as we can and get to a very good enrollment and run that study efficiently, the FibroScan is probably the best tool to be used on clinical trials at this point.

Operator just -- I am sorry. No, no, go ahead.

Just one last one, if I can. In terms of the AIM-MASH AI tool, you incorporated this into your 24-week endpoint, but only for fibrosis. Is there a means to go back and reevaluate those original biopsy slides at 24 week for your dual primary endpoints and sort of give an adjustment post hoc wise on how that may change your original solely hepatologist read? You already presented the responder rate analysis, but you didn't actually provide -- I don't know if that's an option. That would be very interesting to see how that could improve or change in general, the solely hepatologist based.

Right. So no, what we've used is a slightly different tool. This is kind of the next-generation tool that is looking at the continuous improvement, it's called LiverExplore, and that tool doesn't stage the same way that AIM-MASH does stage. It's not a tool to assist necessarily the pathologists like the AIM-MASH is. So there is no obvious path towards reevaluating our data. I think our data at week 24 were very strong on the MASH resolution and surprisingly early for such a compound. In general, we were really happy with the data on the fibrosis. We just got a little unlucky on the placebo side. But I want to remind you that the numbers that we've seen were numerically quite important already and the consistency between the LiverExplore artificial intelligence reading of the biopsies and all the NITs was extremely strong, which made us really believe that we could go with that package to the FDA, and the FDA was very open to that discussion with that package.

So now we have evidence at week 48 with a clear dose response, a very efficacious dose with the 1.8 and potential for upside, both on the tolerability and on the efficacy in our Phase III program. So we are in a very good position to move that program forward right now.

Okay. So thanks all. It's obviously a very exciting time here at Altimmune. We've made significant progress on both the clinical and the regulatory fronts on the MASH program. And a big thanks to Vipin for all the progress delivered and the ability now to pass the baton to the next phase of the company. We look forward greatly to 2026. Obviously, we'll keep updating you on our continued progress. And last and certainly not least, big happy holidays to everybody. Thanks, and we'll talk soon.

Thank you for your participation. You may now disconnect. Everyone, have a great day.

All right. Good morning, everyone, to Jefferies' London Healthcare Conference 2025. My name is Roger Song, one of the senior analyst covering SMID-cap biotech in the U.S. It is my great pleasure to have the next fireside chat with Altimmune. We have Vipin and Christophe. Good to meet you here.

Thank you for having us here.

Absolutely. All right. So maybe, Vipin, you can start with some elevated pitch and then to see what's the state of the union for Altimmune today?

Yes. So we are developing -- as you know, we are developing a glucagon GLP-1 dual receptor agonist for MASH, for liver diseases, MASH, AUD and ALD, it's a rationally designed molecule with 1:1 ratio of GLP-1 and glucagon. And we think that's very important really in order to drive the glucagon function, glucagon works directly in the liver. There are no GLP-1 receptors in the liver. So GLP-1 works more through the metabolic pathway through appetite suppression and weight loss, whereas glucagon works directly in the liver. So the idea is to combine 2 mechanisms in a single molecule to have both direct effect in the liver and combine that with the metabolic benefits of weight loss.

It's also rationally designed to have a unique PK profile. We have a proprietary domain on pemvidutide call EuPort domain. And what that does, that slows down the entry of the drug into the bloodstream. So we have longer Tmax and lower Cmax. So really, the entry into the bloodstream is more gentle, and that gives it a very interesting tolerability profile, very favorable tolerability profile which we believe is going to be very important.

We have recently completed enrollment in a 48-week trial of pemvidutide in NASH. We recently presented 24-week data from that study. We're expecting 48-week data here in the fourth quarter before the end of the year. We also have a FDA end of Phase II meeting scheduled based on the 24-week data, and that's -- it's an in-person meeting again before the end of the year. So we've got a lot of exciting news coming. We're looking forward to really designing our Phase III program and discussing it with the FDA, which is happening right now. And we're looking forward to 2026 to start our Phase III program.

Excellent. I think it is a very, very unique compound, pemvidutide in the entire GLP-1 space. And then in a way, obviously, you're incretin, but also you're hitting the glucagon, nobody else is kind of designed for. And then also your program is now more liver focused in NASH with diabetes, with obesity. And then you have also other more liver targeted ALD and AUD program. Let's cover each one this morning.

So maybe focus on the MASH first. You mentioned say you will read out a Phase II 48-week biomarker-driven endpoint and then weight loss. So what you expect to see? And then what would be considered as a good outcome giving you more confidence in this program moving into Phase III?

Christophe, do you want to take that?

Sure. No. So we've had already very strong. I just want to remind you, our 24-week data, we were able to show very strong data on the MASH resolution. We were able to show numbers in the 60% of patients that were responding to the drug, which is in par with what other programs have seen after even all the way to 72 weeks. So it was very exciting to see this already at week 24.

And then we saw also very strong data on the fibrosis side, where at 24 weeks, it's quite remarkable in my mind to see such strong fibrosis. We were able to show this into confirming this with AI with all the noninvasive tests. And that was the basis for going to the FDA and being able to go only with very early data to the FDA and the FDA accepted this and granted us the meeting.

On the 48-week data, so I just want to remind you that we are not doing the biopsies at that time. So we had determined to do the baseline and then week 24 biopsies. On the 48 week, we will look at noninvasive tests. These will be moving as you may understand, some of them move very early in the progression of the -- with the treatment, some move a little later. For example, we had great MASH resolution. So the noninvasive tests related to the fat in the liver, fat content, et cetera, will be continuing -- hopefully continue to improve because we had seen a weight loss that was quite substantial, but was not plateauing yet. So the patients should be continuing to have -- to see the benefits of the metabolic effect.

And then some others, we're hoping to see, for example, on the liver stiffness on the fibrosis with the FibroScan, some continuous improvement there. And so we're excited. We can't wait to see the data and see how this will be just confirming the strong information we had at week 24.

Excellent. Chris, as you mentioned, this is not biopsy endpoint because I'm still clarifying with investors, this is not biopsy -- another biopsy endpoint. With that being said, you say the NIT, the noninvasive testing can be very indicative for the biopsy endpoint, how this will continue to evolve to show even greater treatment. Just can you remind us what type of the NITs you are really looking for can kind of keep modeling the correlation with the biopsy readout, particularly for the fibrosis part?

So this is -- the questions between the NITs and the biopsy is a place where the scientific and the clinical community is ahead of the regulatory agencies. Biopsies have risk, they have the bias of the histopathologist treating. There's a lot of aspects there that are making it more difficult to interpret, et cetera. So -- and it's obviously the part of the burden for the patient is substantial. So the clinical community has been pushing regulatory agencies towards using noninvasive testing.

And among those, they are different -- there are 2 sets of noninvasive testing. There's the blood-based like the ELF or some of the other, the FIB-4, et cetera, type of blood testing. And then you have the imaging part, which is more like the FibroScan and that kind of test. So we believe that the FDA is -- there was a recent discussions at the AASLD meeting in Washington, D.C. We believe that the regulatory agencies are clearly looking into those. They haven't yet planned to our understanding really how to -- they will be probably a combination of blood-based testing and imaging. That's what we understand. But when we meet with them, we will have that more of this information.

One important point is that in our Phase III design and the Phase III program that we're having, we're going to be prepared for both alternative. So establishing the accelerated approval based on biopsies but as well, we will collect all the noninvasive tests that will allow us if the FDA were to move during the time of the execution of the trial towards clearly using this as an endpoint, and that could become an upside for what we are doing with pemvidutide.

Got it.

I just wanted to clarify that in our 24-week as well as the 48-week trial, we're looking at a whole series of NITs. It's not just -- it's really -- so half of them are more markers of inflammation and the others are markers of fibrosis. As you know, when you defect the liver, the first thing that happens is the inflammation goes down. So the early markers, the early changes you detect. And so we're already maxing out in terms of the improvement in those markers early on. The fibrosis markers improve after the inflammation is taken care of.

So we're seeing -- if you look at the totality of the data, we're seeing across the board, all of the NITs improving, moving in the same direction. And that's what tells us that the inflammation is improving and the fibrosis improvement has begun as well.

Excellent. That's a great point. And then my specific question is exactly this one is which NIT endpoint can be more correlated with the fibrosis, any specific number you want to see, okay, 24 week is this, and 48 week is getting better and then this will correlate even greater fibrosis, the treatment effect.

Sure. So I'm not going to give you a specific number. We are actually working on trying to see from our 24-week data and what we're going to see on the 48 weeks, what is the predictability of this. The NITs have been already well established to correlate with the improvements in fibrosis. We do expect to see, for example, the liver stiffness, it's directly correlated to fibrosis. We do expect to see some benefits. We have seen and we presented this at AASLD, some clear biomarkers that are looking at the balance between the fibrogenic and the fibrinolytic and pemvidutide, PRO-C3 and CTX. And when you look at this ratio, we have a very strong fibrinolytic benefits that we can bring with pemvidutide. So we'll continue to look at those markers.

And they will be translating into the things like liver stiffness, et cetera. So these are -- and even on the histopathology now with AI, we have very strong data suggesting already at week 24, suggesting the benefits of pemvidutide on the fibrosis in these patients.

Yes, excellent. And as you read out those data, it will be very helpful for us to know those modeling and then how this correlate with the biopsy because we don't have the biopsy data but you have those endpoint potentially can predict the biopsy. So that will be very helpful. Obviously, you will prepare that for FDA as well.

Another component of the readout is also weight loss, right? So I think just to set the stage, say, you absolutely see the weight loss benefit. It's not plateauing. At the 48 week, what should we expect to see because it is not obesity trial, right? So we should not benchmark you to obesity, number one. Number two is it is also -- relatively not the highest dose you have, right? So it's not like you have to be semi-like kind of weight loss? Or what is your expectation for the weight loss?

So the weight loss is a very important aspect of pemvidutide. We have had prior studies all the way to 48 weeks when we show clearly obesity type weight loss. that was in the range of other compounds. And interestingly, this weight loss never reached a full plateau. There was still possibility for improvement. In our MASH program, we don't even use the top dose, as you mentioned, and we don't see a plateau at week 24.

The weight loss, however, so we hope to see a continuation of that improvement, potentially, they may not be even a plateau at week 48, giving additional benefits on the chronic treatment for the patients with MASH. The very important aspect of the weight loss is not just weight loss with pemvidutide. What we see is a weight loss, and we've shown this in our obesity trials is a weight loss that we call it with quality weight loss, which preserve the lean mass.

Why is that important is because most patients with MASH or the patients as we are studying other steatotic liver disease like AUD or ALD, most of those patients are aging. They are postmenopausal women, they are andropausal men. They are in their 50s, 60s. You don't want these patients to lose their muscle mass. And to a great extent, our weight loss basically is very similar on the preservation of the lean mass of what you would see with diet and exercise. So this is very comparable to that. And we believe that this is a very important attribute of pemvidutide, the benefits for this population. It will avoid the risk of sarcopenia in some patients and all the complications you can see with lean mass that would be lost too much of an extent.

So really, that's something that we have benefits on the week-48 data, we will see some additional weight loss, and we hope to see again that very important lean mass preservation that's unique to our compound.

Got it. Okay. Great. And then moving forward, right, so this is the 48-week. And also simultaneously, I think, Vipin, you said you are preparing in-person meeting with the FDA for the end of Phase II meeting, and then to design the Phase III, what will be the ideal outcome out of that meeting for the Phase III design, particularly when we talk about the unique feature of pemvidutide, many different aspects and then how you incorporate those novel endpoints to the Phase III maybe increase the [ likelihood], of success?

So we always seek with FDA and regulatory agencies, and we're going to meet with the FDA and then after with the EMA. We always seek to find alignments on the design of our program. We try to design our program to the most efficient way. We'll have a more specific question on some details of the design. Clearly, we would like to have a good understanding of where they will be going with the NITs. That's something they have not disclosed completely. There's still some debate, but how close are they? We know on the AI for the biopsy reading that they are pretty close to accept this since the Europeans have already accepted that.

But I think on the NITs side, it will be important for us. So it will be -- we will be able to better understand which of those NITs they're going to be really focusing on, what combination potentially of NITs they would be focusing on and then helping us to maybe gain even more efficiencies in our Phase III design and build upon that.

Yes. I just want to emphasize that our goal is to have a flexible design so we can incorporate all of the measurements, all of the NITs that we are talking about, the AI-based reading of the biopsies. So initially, there may be both a pathologist read as well as an AI-based read. If FDA changes to AI, then we will be ready to switch at that point. Same thing with NIT. So we'll collect all of the data. If along the way, FDA takes away the requirement for biopsies and goes to NIT-based endpoint, we'll be ready to incorporate that in our design of our Phase III program. So we want to maintain that flexibility when FDA changes those requirements, we'll be right there. And really, that's the agreement we want from the FDA as well.

Got it. A couple of quick specifics. So one is the, would you try to increase or incorporate the high dose into this Phase III?

That is up for discussion.

Yes. We are looking at the best approach there in order to be -- to gain the maximum efficacy. Just one point on this that is very important, I believe, because the tolerability, as Vipin was -- that's intrinsic to the molecule itself that you port that delayed Tmax, that decreased Cmax leads to very good tolerability. We have -- in our Phase II, the 24 weeks, we have low nausea rate. We have a discontinuation rate that is really at the low dose, basically it's 0. And at the highest dose without titration, we had a discontinuation rate that's half what we've seen with the placebo.

This is not just by chance. I believe that just the molecule, the way it is designed and what makes it really important. Other products, we have seen -- it was reported at AASLD vary between discontinuation rate between 6% to 20% or more percent. This will be some aspect that is really, really important in defining the dose and how we use to -- we can push a little further. There may be some subpopulation that could benefit from a little higher dose. How we do this, these are some of the discussions we'll have with regulatory agencies, and we'll finalize all these design at the end.

And going forward, tolerability is going to be very important at AASLD. There was a lot more discussion about tolerability than there has been in the past. because this -- NASH is a chronic disease. And if you -- people don't stay on therapy, then you really can't help them. So you want -- as we've seen with GLP-1s, for instance, 60% of people don't -- are not on drug after 6 months. So very significant dropoff. That's not going to help. It takes that long to really even get the efficacy. So it's really important to have tolerability profile so patients stay on medication in the chronic setting.

Got it. Okay. We definitely want to talk a little bit about your pipeline, the ALD, EASD as well. So -- but before we do that is just lastly for MASH. So we know MASH space is evolving along with the incretin, right? So we have semaglutide got approval. And then -- but you also have other mechanism is developing in this indication. How do you think pemvlutide can fit into this? Because you have the component of incretin. Maybe people will think, okay, you are another tirzepatide or semaglutide or even Retatrutide. And then on the other side, you also have very much kind of the liver component like FGFR, et cetera. So 2 questions. One is which target population you think is best fit for the pemvidutide? The other one is maybe the pricing power, how you will lean towards which angle of the pemvidutide?

You take the first part.

Yes. So on the population, and we like to say we're not GLP-1s. We're not the different GLP-1s. GLP-1s don't have a -- there's no receptor for GLP-1 on the liver. So it treats indirectly NASH and it takes time and then there's all the associated tolerability issues in the chronic disease, things like this makes it much more difficult.

With the glucagon, we are a liver targeted product that helps with the really focused impact on the liver, the defatting and the fibrosis as we've shown very rapidly already at week 24. So this is the specificity here that we can bring and that separates us from the. We are having not only a direct impact on the liver but by adding that metabolic aspect that complements the underlying kind of cause of the disease. So imagine you defat your liver, now you have your impact, you decrease the fibrosis you don't want the factors that are contributing to the inflammation to the fibrosis to be still present.

So by treating the metabolic part of the disease, we are able to do that. So that helps us position the product in a very favorable place where in one compound, you have those 2 mechanisms and you have a complete answer to your problem for the patients with NASH, vis-a-vis FGF21, again, they have a direct impact on the fibrosis, but they do not directly impact the metabolic aspect, and in addition, they do have issues with the agonism of the FGF21 and the potential impact on osteoporosis, which is something, when you look at the demographic, these populations are in their 50s, in their 60s, et cetera. And this is not something you would like to have.

So there's clearly a positioning where we could be a first-line therapy for patients with NASH. And then because of the tolerability profile, if some subpopulation need additional impact on some or an additional, for example, an FGF21 because you have a very advanced fibrosis in your liver, you might be able to combine it because you're not going to increase or add multiple side effect to your patients, actually, with the tolerability we have, you're just going to take a little more risk for more advanced patients based on this. On the pricing, I will let Vipin more focused on that.

Yes. So as you laid out the different mechanisms, Roger, there are 2 different classes. There are the mechanisms that produce weight loss and indirectly work on MASH takes a lot longer to get there than their direct acting mechanisms. What we like about pemvidutide is it provides a very broad spectrum because we have both weight loss and fibrosis improvement and very fast-acting drug within 24 weeks, as we have shown, 60% MASH resolution already fibrosis improvement taking place and weight loss, all happening in just 24 weeks. And it's only going to get better with 48 weeks and beyond as you're treating -- keep treating these patients.

So really, the value proposition here is to have 2 synergistic mechanisms that are showing multiple benefits, MASH resolution, fibrosis improvement, weight loss and tolerability. You combine all of that together, that's a very compelling, very differentiated profile from any of these other drugs. So we can start with, as Christophe mentioned, as a first-line therapy for F2, F3 because of both weight loss and MASH resolution and fibrosis improvement, and we go all the way to F4. We can also combine it with other mechanisms because of the tolerability profile.

So I think all of the possibilities are out there. As you know, there have been a number of recent transactions done around FGF21s. But every single one of the companies that have acquired those assets, they're looking to add a metabolic component. And that's exactly what we have done. So we fit really well within the paradigm of treating the whole disease, not just the liver, but also the weight loss component, which 60 -- 80% of the patients with MASH would benefit from losing weight. So really, it's the synergistic effect of both of these mechanisms that we think would be highly attractive to patients, to physicians as well as to payers.

Got it. Yes. Great. We're running out of time. But I think I still want to touch maybe a minute on the ALD, EASD, AUD part because this is very -- also another unique opportunity and then leads to the potential partnership opportunity because this is a real full kind of liver portfolio. Can you just spend a minute on that? So we'll be wrapping up.

I mean on the AUD, ALD, we are very excited because we just completed the enrollment of our AUD study. We have our ALD study that is continuing to be on track. And these are diseases that are very similar. I mean, the AUD patients have fatty liver. They have also the direct impact on the liver. The ALD do have some fibrosis. And then with the GLP-1 side, we clearly target the reward system and the craving. So it's also timely because the post-COVID era, there are a lot of patients that are interested in increasing their alcohol consumptions. They're also happy with a little bit of added weight loss and the right type of weight loss with the preservation of their lean mass.

And so -- and most importantly, in a population like this, these patients or these people are pretty healthy otherwise. And in general, they want a drug that's going to be very well tolerated. So our AUD had a lot of enthusiasm. The trial went on really fast and the ALD is continuing. So we think that we have here an opportunity to more than just targeting the MASH population but targeting additional indications that will be very complementary to our entire portfolio.

And the key is that for both of these indications, again, we are taking advantage of the dual mechanism of action. It's the synergy that helps us because these patients will benefit once again, not just by reducing cravings for alcohol intake, but also improving their liver health. And the patients are actually worried about their liver. Well, that's one of the things they think of. So if you tell them that you have a drug that will improve their liver health, that's very attractive. And you might lose some weight on top of that. So that's a complete package again.

Excellent. Okay. Great. Thank you for the time with us this morning, and thank you, everyone, for listening.

Thank you.

Thank you.

Good morning, ladies and gentlemen, and welcome to the Altimmune Third Quarter 2025 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded.

I'll now introduce your host for today's conference call, Lee Roth, President of Burns McClellan Investor Relations Adviser to Altimmune. Thank you, and over to you.

Thank you, operator, and good morning, everyone. Thank you for joining us for Altimmune's Third Quarter 2025 Financial Results and Business Update Conference Call. On today's call, you'll hear from Dr. Vipin Garg, our Chief Executive Officer; Dr. Christophe Arbet-Engels, our Chief Medical Officer; Linda Richardson, our Chief Commercial Officer; and Greg Weaver, our Chief Financial Officer.

Following management's prepared remarks, we'll open the line for the Q&A session. Our third quarter 2025 financial results and corporate update press release was issued this morning and can be found on the Investor Relations section of the Altimmune website.

Before we begin, I would like to remind everyone that remarks made about future expectations, plans and prospects constitute forward-looking statements for purposes of safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause our actual results to differ materially from those indicated. For a review of the risk factors that could affect the company's future results and operations, we refer you to the company's filings with the SEC.

I also direct you to read the forward-looking statements disclaimer in our press release issued this morning, which is now available on our website. Any statements made on this call speak only as of today's date, November 6, 2025, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this call is being recorded and will be available for audio replay on the Altimmune website.

With that, it's now my pleasure to turn the call over to Dr. Vipin Garg, President and Chief Executive Officer of Altimmune. Vipin?

Good morning, everyone, and thank you for joining us today for our third quarter financial results and corporate update. This is a very exciting time for Altimmune. We are on the brink of a major inflection point with our clinical programs. Pemvidutide, the foundation of our pipeline is ripe with opportunity to redefine treatment for those with serious liver diseases like MASH, alcohol use disorder, or AUD, and alcohol-associated liver disease or ALD.

On today's call, we will emphasize a few key points: the upcoming Q4 milestone of the 48-week IMPACT data readout, the in-person end of Phase II meeting with the FDA in Q4 that was recently granted, the continued strengthening of company's balance sheet and the recent talent additions to the executive team.

The 24-week data from our IMPACT trial shared earlier this year established rapid efficacy of pemvidutide for those with MASH, providing potential best-in-class MASH resolution shortly after initiating treatment and compelling antifibrotic activity and weight loss. The convincing nature of these data has allowed us to move into preparations for Phase III and to receive confirmation of an in-person end of Phase II meeting scheduled with the FDA before year-end to gain agreement on the design for our Phase III program.

We also look forward to the 48-week data from the IMPACT trial, which we expect to share before the end of the year. Beyond MASH, we announced that we have successfully completed enrollment in the RECLAIM Phase II trial of pemvidutide in AUD. The rapid enrollment of RECLAIM which was completed ahead of schedule, is a testament to our team's continued ability to execute and the significant interest from patients and physicians in pemvidutide as a potential new therapy.

In addition, we began enrolling the ALD Phase II trial in the third quarter. As our clinical programs progress, we are ensuring we have the necessary financial resources and executive talent in place to support the next phase of our growth. This includes the recent expansion of our leadership team with the appointment of Dr. Christophe Arbet-Engels, as Chief Medical Officer; Linda Richardson as Chief Commercial Officer; and Robin Abrahams as Chief Legal Officer.

With that, I'll turn the call over to Christophe to speak further to our promising pemvidutide programs. Christophe?

Thank you, Vipin. I am very pleased to be here today and to be joining the Altimmune team at such an exciting juncture. From my perspective, I recognize the significant potential of pemvidutide for the treatment of patients with MASH, AUD and ALD. Given its 1:1 glucagon GLP-1 ratio, pemvidutide is uniquely designed to maximize the contribution of each mechanism. In effect, pemvidutide is a combination therapy in a single molecule.

Early data from the IMPACT trial demonstrated the potential of this dual mechanism of action with rapid and robust MASH resolution achieving statistical significance at just 24 weeks. I want to reinforce how meaningful the observed efficacy is at this early time point as most other MASH program achieved this level of response only after treating for 48 weeks or more.

The 24-week results demonstrated significant and very encouraging anti-inflammatory activity based on biopsies and a range of noninvasive tests, which are becoming increasingly important in clinical practice and in the ongoing regulatory conversation. The statistical significance achieved across a panel of NIT we are assessing in the IMPACT trial provides strong support for pemvidutide antifibrotic effects, which we will look to continue to assess in the upcoming 48-week readout.

Speaking of the 48-week readout, we look forward to assessing the data and the potential of a longer treatment duration on NIT measurement, as well as further weight loss. Recall, we had early and significant MASH resolution in our 24-week biopsy data and strong evidence of antifibrotic activity supported by the NIT analysis, along with the continuing weight loss and excellent tolerability.

The emerging recognition that improvements in certain NITs are likely to translate to clinical improvement has led regulatory agencies to consider allowing the use of NIT data as a measure of efficacy in MASH clinical trial. In clinical practice, MASH patients are often diagnosed and courses of treatment determined based on these noninvasive tests and the possibility of the regulatory agencies more closely aligning with clinical practice bodes particularly well for pemvidutide given the strength of our NIT data.

Dr. Mazen Noureddin, lead investigator on the IMPACT trial will deliver a late-breaking oral presentation on the 24-week IMPACT results at the upcoming annual AASLD Liver Meeting. The acceptance of this abstract reinforces the significance of the data from the IMPACT trial and pemvidutide's opportunity in the broader MASH landscape.

Our confidence in pemvidutide is underscored by the collective data surrounding the molecule from the 7 trials completed to date. We are now preparing for a scheduled face-to-face end of Phase II meeting with the FDA before year-end to review our proposed Phase III MASH program. The Phase III trial will include the flexibility of using NITs and AI reads as an approvable endpoint in our registrational program if regulatory process moves in that direction.

Beyond MASH, we believe that the balanced glucagon and GLP-1 agonism that is the hallmark of pemvidutide makes it a promising therapeutic candidate in both alcohol use disorder and alcohol-associated liver disease. In AUD, we have completed recruitment and randomization in the RECLAIM trial that we were able to fully enroll this trial ahead of schedule is a strong indicator of the significant interest and major unmet need in this indication. We look forward to reporting results next year.

Our ALD trial, RESTORE, was initiated in the third quarter and enrollment is ongoing. Importantly, patients with ALD currently lack any approved therapies, and we believe pemvidutide's dual mechanism of action may make a difference for these patients. We look forward to these results of these trials and further understanding the potential of pemvidutide in the additional large patient population of unmet need.

I am excited to be at Altimmune and to lead these programs forward.

And with that, I will turn the call to our Chief Commercial Officer, Linda Richardson, to discuss how we are preparing for Phase III success in MASH. Linda?

Thanks, Christophe, and good morning, everyone. It's great to be here at Altimmune at this exciting time, and I echo Christophe's enthusiasm for joining this team and helping to shape the future of this significant therapeutic candidate. A quick background on me. I've been involved in all facets of commercialization for over 30 years at organizations of all sizes. I have experience in MASH, rare hepatic diseases, cardiometabolic diseases, including diabetes and dyslipidemia and addiction medicine.

We have a great opportunity in front of us with pemvidutide in MASH as well as AUD and ALD, and I look forward to helping prepare for potential commercialization in each of these areas of high unmet need. My decision to join Altimmune was driven by the opportunity to bring real therapeutic advances to patients and the providers that care for them.

Pemvidutide has this potential. Why do I believe this? With pemvidutide, we have one therapy that provides 2 important mechanisms of action, delivering improvements on 3 critical elements of MASH management. The single therapy is clear. The 2 mechanisms of action, glucagon and GLP-1 agonism in a balanced 1:1 ratio provide both direct liver effects and metabolic improvements, resulting in 3 important benefits for patients: one, rapid MASH resolution in as soon as 24 weeks; two, anti-inflammatory and antifibrotic effects in the liver as demonstrated in multiple NIT assessments; and three, quality weight loss, including lean muscle sparing effects.

Additionally, pemvidutide has demonstrated a potential best-in-class tolerability profile with low discontinuation rates in the IMPACT trial. This could be another differentiating feature compared with other MASH therapies. My enthusiasm aside, I would like to highlight some feedback from recent market research we did in Europe. Health care professionals in a small group of payers were provided with a projected blinded product profile of pemvi along with other blinded profiles of current and future potential MASH therapies.

First, 70% to 80% of the physicians surveyed indicated a high or very high likelihood to prescribe pemvidutide based on the blinded product profile in both F2 and F3 patients. Here are some representative qualitative comments from hepatologists on pemvi's differentiating features. It's quite impressive, the fibrosis and the weight loss seems to be a class leader and the side effect profile is good.

And another quote, "For overweight and obese patients, it would be my go-to substance, my first-line approach, more powerful than other dual agonists with strong fibrosis data. Lean mass preservation would be a meaningful differentiator, very important in MASH and chronic liver disease. This is very encouraging early feedback. In particular, the significance of demonstrating lean muscle mass preservation is potentially very differentiating. There is growing interest in the prevalence and effects of sarcopenia in patients with MASLD. A 2024 meta-analysis found that sarcopenia was associated not only with progression, but also correlated with MASLD-associated mortality.

Other publications project that the prevalence of sarcopenia may be as high as 1 in 4 patients. Initial payer feedback was also encouraging. Payers provided us with a positive reimbursement outlook across the EU with broad coverage expected given payers' positive perception of the pemvi value proposition. We will continue to identify aspects of pemvidutide therapy that may be important to payers, particularly as more therapies enter the MASH field.

Patients and prescriber receptivity is critical, but reimbursement and access are equally important elements of a successful product launch. I've had the opportunity to work closely with our clinical team to incorporate specific endpoints that we believe will be important drivers of market uptake and support a successful launch following potential regulatory approval. It's an optimal time to ensure that commercial considerations are designed into the Phase III MASH program to accentuate the differentiators of pemvidutide from current approved therapies and those to come.

Alongside MASH, the AUD and ALD programs are very exciting and could expand substantially the addressable market for pemvidutide. The rapid recruitment of our AUD trial that we discussed earlier is evidence of interest in this space and the patient need for new therapeutic options as well.

In closing, I'm very excited to be here at Altimmune at such a crucial time. I look forward to continuing to update all of you on our commercial vision, plans and expectations for pemvidutide.

I'll now turn it over to Greg to review our financial results for the third quarter.

Thank you, Linda, and hello. Beginning with our balance sheet at September 30, total cash was $211 million, representing an increase of 60% over our cash position at the start of the year. We've made measurable strides as we source capital through a combination of available options, having raised $127 million through the first 9 months of the year, building the cash position required to support our key development milestones.

Another step we've taken to add to our financial flexibility was to amend our Hercules debt agreement, where we increased the overall facility size to $125 million and funded $20 million on executing that amendment today. The amendment improved several of the key terms extending the interest-only period, for example. You'll see that we're filing a $400 million shelf registration today, along with a new $200 million ATM facility. Consider these filings as part of our ongoing effort to assure the financial tools are in place to meet our needs going forward.

Our cash position continued to strengthen through Q3 and into Q4. I'm happy with the trajectory and confident in the ability to build the balance sheet required to meet our development needs and position pemvi for success.

Now to comment on the Q3 and year-to-date financial results. R&D expenses were $15 million for the 3 months ended September 30, '25, compared to $19.8 million in the same period of 2024. The 3-month variance in R&D spend was related to the timing of CRO development cost year-over-year. The Q3 2025 spend included $9.2 million of direct costs related to pemvidutide development, including roughly $3.7 million for the IMPACT Phase IIb trial, $3.4 million for AUD and ALD start-up costs and $1.3 million for CMC.

G&A expenses were $5.9 million and $5 million for the quarter ended September 30, 2025 and 2024, respectively. This increase was driven by professional fees and noncash stock-based compensation. To note, the total noncash stock-based comp was $3.6 million in Q3 and $11.1 million year-to-date. No surprises there.

Net loss for the third quarter of 2025 was $19 million or $0.21 of share compared to $22.8 million or $0.32 per share in the third quarter of last year. So, in summary, we are well positioned in terms of our financial footing.

And with that, I'll turn the call back to Vipin for some closing remarks.

Thank you, Greg. As highlighted today, we look forward to sharing the 48-week IMPACT data in Q4 and to discussing our progression into Phase III clinical development at our end of Phase II meeting with the FDA. As always, we thank you for your continued support and look forward to sharing further details of our progress.

This concludes our formal remarks, and we would now like to take questions. Operator?

[Operator Instructions] We have the first question from the line of Roger Song from Jefferies.

Congrats for all the progress. Maybe a couple of question. First is on the upcoming 48-week data from the Phase II IMPACT MASH. So how much of the data will inform your conversation with the FDA and then also the Phase III design? And then what's the current thinking about the Phase III in terms of the 24 versus the 48-week time point and then the NIT and AI biopsy-driven AI-based biopsy endpoints?

Yes. Roger, thank you for the question. So as far as the end of Phase II meeting with the FDA is concerned, as you know, the end of Phase II meeting was requested on the basis of the 24-week data. So really, there would not be any 48-week data that would be part of that discussion at this point. Obviously, we will submit 48-week data when that's available. But we believe and apparently, the FDA agrees with us that we have sufficient data at 24-week to request and now FDA has granted a meeting to us on the basis of that data.

So, I think we're in a good shape. Christophe, did you want to add anything to that?

No, I think that's correct. The 24-week data were strong enough to grant the submissions and grant the meeting, and we are in good shape with those discussions by the end of the year.

And about the 48-week data, I think, Roger, did you want to repeat your question, please?

Yes, sure. So just the 48-week data, how -- what's the current thinking about the Phase III design based on the 48-week data?

So the 48-week data, we expect to continue confirming what we've seen in the 24-week data and the strength of this with the added weight loss and hopefully as well on the needs. We are in discussions. We will be discussing with the FDA this current regulatory environment with the potential change from those biopsy readings to the needs, and we will have more clarity when we meet at the end of Phase II meeting.

Yes. And our goal, Roger, is to design a very flexible trial, Phase III program, so we can take advantage of any of the changes that take place whenever they take place. So, we'll go in with a very comprehensive, flexible design in terms of the Phase III program and should changes take place over the course of next months and year, we can certainly incorporate them and pivot to those and appropriately change our endpoints when that happens.

We have the next question from the line of Yasmeen Rahimi from Piper Sandler.

And congrats on the RECLAIM enrollment completion. I guess the first question is based on sort of discussion with the key opinion leaders in the space, do you have any idea in like, I guess, the probability of the different scenarios of potentially using NITs or AI-based histological reading. If you could just maybe help us understand based on the 3 scenarios, which one they think has a high probability of being able to get a sign-off. That's question one. And then question two is, help us understand, I guess, the advantages of using AI-based biopsy reading versus traditional histology reading and especially when it comes to Phase III studies and if any other sponsors have implemented that? And then the third question is on RECLAIM, maybe help us conceptualize what would be considered a clinically meaningful endpoint in the primary endpoint there. And I'll jump back in the queue.

All right. So, I will start with the NITs. The NITs, there are a lot of different discussions ongoing at this point in time. We're going to -- we are aware that some of these discussions will occur with the AASLD meeting coming up at the end of this week, and we will learn more around that. We know the FDA is looking through the -- at this very closely. And there is -- from our understanding, there is an increasing interest to look at those NITs. So as Vipin shared, we are designing our Phase III in order to really have the flexibility to adapt to any changes on the regulatory landscape.

On the AI, there are differences. The histopathologist in general, look at a narrow part of the slides and estimate the level of fibrosis based on a number of criteria, but that introduces quite a large amount of variability and the AI on the other aspect look at the total area of fibrosis and doesn't quantify the stages only, but allows just a gradual and more comprehensive evaluations of the slides.

So, this is something that allows for rapid evaluations with less variability. And we know that this has been already approved by the EMA as an approach to look at the biopsies. And the last -- the third point was, I'm not sure I fully heard the questions on the primary endpoint if you, that was…

The RECLAIM trial.

That's right.

Yes. The RECLAIM trial. So, the primary endpoint of the RECLAIM trial is the number of heavy drinking days that we are going to be looking at and those change from baseline.

Yes. It's the number of heavy drinking days per week that's...

Per week, correct

That's the endpoint that we'll be looking at. And Yasmeen, we're really excited about the fact that this trial enrolled almost 5 months earlier than we were expecting. So, it really shows the critical unmet need out there and the fact that physicians and patients really like the drug. And so, we're really excited about that.

Do you have any follow-up questions?

Thank you. I'm good.

We have the next question from the line of Patrick Trucchio from H.C. Wainwright & Company.

At 24 weeks, you reported statistically significant antifibrotic activity across multiple NITs. And I'm wondering what magnitude of change of 48 weeks would reinforce this confidence in fibrosis improvement as a key Phase III endpoint? And then separately, I think you've referenced expectation of continued weight loss through 48 weeks. What level of incremental loss or lean mass preservation would confirm pemvidutide's quality weight loss advantage and support differentiation?

So at -- yes, at 24 weeks, we saw very strong data on our fibrosis and we continued to see the weight loss that was not plateauing. As you know, some of the NITs can evolve at different time of the improvement for each of those patient. So, we continue to believe based on this, that we will see added improvements at the patients on the study at 48 weeks after our 24 weeks. And we will see which one. We expect, for example, maybe lever stiffness to be something that should be improved, and we will have those data very soon. So, we're really excited about this. And again, with what we've seen on the 24-week, that bodes well for what hopefully we should see on the 48-week.

Yes. And the weight loss, we -- as you said, Patrick, we expect to continue to have additional weight loss, just like we saw with our MOMENTUM trial. And just to remind everybody, this wasn't even our best dose in terms of weight loss. It was 1.2 and 1.8. So, the 2.4 milligram, we get even higher weight loss. So clearly, there's plenty of runway there in terms of achieving additional weight loss as well. And just to clarify, as far as the NITs are concerned, they don't all move in tandem. Some of them move early, some move later. So, what we need to show at 48 week is continued maintenance of many of these NITs because we've already achieved such high levels and then additional improvement in some of them.

Just to bring the weight -- this is Scott Roberts. Just to bring the weight loss back home, recall that of the direct-acting MASH agents that work directly in the liver, for example, the FGF21s, the thyroid beta agonist, there is no weight loss associated with that. So, we're already ahead of the game with respect to direct-acting agents. And so any additional weight loss and the shape of the curve with a not plateauing certainly bodes well for realizing more weight loss is really just icing on the cake.

Yes, I think I'll touch on -- this is Linda. Thanks for the question. I touched on a little bit this concept of lean muscle mass sparing. When you look at various agents and you look at the studies, most of this has been seen in weight loss studies. So, we look at pemvidutide and the MOMENTUM trial, and we had the -- really a study duration of 48 weeks where our lean loss ratio was about 22% compared to other agents that were in the 39%, 26%, 37% range across the board.

This matches more closely what natural weight loss would look like if you were doing traditional diet and exercise. You're always going to see some impact on lean muscle, but this matches what you would see kind of in the routine weight loss field. When we look at that and we see our weight loss, building this promise into studying in Phase III further, what happens in a longer trial when we have our 52-week study data from a Phase III, if we see continuing loss of weight but muscle mass preservation, this would be extremely interesting to the field. And when we're looking at a forward testing product profile, this is one of the advantages that we very well may have.

So, when I talked about working closely with the team, putting in these markers and preparing to evaluate them fully in a Phase III trial is exactly the kind of thing that I need to have that can resonate with payers and physicians and patients down the line. So that's kind of bringing all of what we know about our product together and ensuring we have the best shot on goal in Phase III.

We have the next question from the line of Jon Wolleben from Citizens.

I was hoping you could talk a little bit about alcoholic use disorder and alcoholic liver disease as distinct opportunities. It just seems like there's going to be significant overlap in the advantages or disadvantages of running one program versus both.

Yes, that's a great question, Jonathan. So, I mean, that's the reason we decided to expand the program into AUD and ALD because we believe there is significant opportunity in both of those, and we could be sort of the frontrunner in terms of driving value proposition, additional value proposition for pemvidutide. So, it's not just MASH, AUD and ALD. These are very similar product profile that we are looking for in terms of having this dual mechanism of action working directly in the liver, as well as in case of AUD having reduction of cravings. So, bringing these multiple features together is really important. AUD typically leads to ALD. So, AUD and ALD go hand-in-hand. So, the idea here is that if we can get -- if we can show success in AUD chances that will also be successful in ALD. We've actually already shown the endpoint that we used in MASH one of the NITs is what would be the endpoint for ALD. So, we already have some idea that the drug is working on these endpoints. So, we're very excited about these additional that can be developed independent of MASH beyond MASH.

We have the next question from the line of Annabel Samimy from Stifel.

Just going back to the product profile and pricing and payer discussions, maybe for Linda. I mean, how -- I understand the potential differentiation, how exciting that could be for MASH. I guess the landscape is shifting a little bit now with obviously, with semaglutide possibly having MASH some combinations that are in development or seeking development with FGF21. So, I guess maybe you can talk about how you think about MASH pricing when we have some of these other alternatives that could potentially help on the liver side, but indirectly and longer term. I just want to think about that because some physicians are really starting to think about payer pushback and cost. So how should we think about that?

Absolutely. Perfect question related to the payer landscape. Reimbursement is largely -- you're looking at what is the value proposition of the drug for, I would say, physicians, patients and the payers. You want to have something that's actually doing what it says it's going to do. And the value proposition is based on the data. So, when you test a product that has the activity that we do, we have in 1 drug, 2 mechanisms of action that provide a host of benefits and excellent tolerability to date.

Then you look at some of the carving off, what kind of quality weight loss, what are the lipid impacts? What are other things downstream that you're seeing? The total package of the value proposition leads into assessing what it's worth. Instead of someone having to take 2 drugs, and have 2 sets of side effects, 2 co-pays or wait for a development program to bring that together or face tolerability issues that don't allow them to stay on. We see that with some of the GLP-1s currently.

We see other products downstream coming together with their combinations, but let's see what their tolerability profiles look like. Let's see not having this 1:1 ratio, what they look like. So, the package of what you can get in a product and the early onset of action, I believe as this is going to become a very crowded marketplace, payers are not going to want to necessarily pay for something that takes 72 weeks to see if it's working, how long do they have to be on this? Is the tolerability there? When you show the MASH resolution that we saw at 24 weeks, which was outstanding.

And then you look at the evidence that we provided in antifibrotic activity with via NITs at 24 weeks, we are pretty much pushing up on what everyone else can do in one molecule with all these benefits. So, my plan will be to focus on what we bring to the table, communicating the value of early activity that you can monitor. You don't have to wait 72 weeks to see some sort of improvement.

Look at that, look at the total benefits and then see where you fit in the spectrum of what the pricing brackets will be. You're bringing more than a generic, even paying for a generic and another product that you might want to use together is still a different activity than having it all in one. And that's where the value proposition will come as we build additional data as we have other data coming out in the Phase III program that we currently don't even have access to in our 24-week data.

So, my plan is to be positioned for the future and drive the very best deliverable assets that we can from this molecule.

Great. That's great context. Just a couple more for me. Just going into AASLD, I know that raising awareness of pemvi is very important. So, can you just give us some color around how you're going to be doing that at the upcoming meeting and how you're going to raise awareness among KOLs? And just on one other quick question, RECLAIM, obviously, enrolled very quickly. How is the ALD enrollment going?

All right. So, on the -- on our presence at AASLD, we have a number of activities that we have planned, a lot of engagements with KOL, one-on-one discussions with all of them, with patients advocacy group as well, and we're going to be continuing. I want to remind you that we have also 2 presentations, one oral and one posters that were accepted as late breaker and that will be there at this time. And we also have a receptions where we have a lot of our clinical investigators, principal investigators from our studies and a lot of interest there where we're going to meet as well.

So, we're going to have a large presence at AASLD with some very exciting data that will be presented through those late-breaking presentation.

And I would just add that having been in the MASH space previously, I do know a lot of the folks who are working with us at Intercept and in hepatology and gastroenterology. And I look forward to rekindling through some of the meetings that we've had set up, relationships with them as well as seeing old friends in the patient advocacy group. So, we are well -- there's -- the company may not have had as many contacts before and Christophe and I being new to the organization, but we will leverage the one from the investigators that we've been working with. And I think really having the podium presentation close at late-breaker is a great way to end that meeting for us.

Yes, we'll have a very large presence. So, we are really looking forward to it. It will be very exciting to bring pemvi out in the open.

And regarding the ALD enrollment, we are moving forward as planned. We're happy where we are right now with this enrollment. Obviously, the AUD was even more exciting by getting this study enrolled much earlier, which doesn't happen too often, but it's a testament to what the team can do and the interest in this area from patients and physicians. So, we're excited, and we continue to move forward as we anticipated.

We have the next question from the line of Mayank Mamtani from B. Riley Securities.

This is William on for Mayank. Congratulations on a very nice quarter. Looking forward to seeing the upcoming AASLD presentation. Two for us. In terms of your Phase II 24-week biopsy results, I was curious if you could talk to any new or incremental analysis that you may have performed that we may get. And specifically, do you know if there's, by any chance, any F2 or F3 analysis that you did on the study? And in regards to F4 patients, by chance upon sort of reevaluation of the biopsies were any included in the study and how the data from your F3 patients might inform how pemvi may perform in the F4 population? And then I have a follow-up.

Yes. No, we continue to analyze our data. We're -- there's a large amount of informations we can gather that will help us drive some of the Phase III. With regard to those different stages, I want to remind you the design included only Phase II and -- sorry, only F2 and F3 patients. There was no F4 patients. We did some post-hoc exploratory analysis. The sample size are small because the study was designed with a small number of patients. So I'm cautious there. But we are very encouraged by what we're seeing. So, in particular, with these Phase II -- F2, F3 patients. So, we continue to have supportive data to move into the Phase III in this population and look forward to the design of this and discussing this with the FDA.

Got it. And then in terms of RECLAIM, as it's been said, it's obviously enrolled pretty far ahead of plan. I was curious if there's been any type of baseline analysis that's been compiled. And if so, could you touch on how those baseline characteristics may compare to the original plan? And then also how that informs to your interest in your RESTORE ALD trial, where you're also looking at these liver-specific endpoints such as VCT and ELF? And maybe what's the broader data package that you're looking for to collect that would help qualify as Phase III enabling?

So with regard to the RECLAIM data, we haven't -- we just finished the enrollment. We haven't done a baseline analysis at this point in time of all this information. Obviously, AUD and ALD are kind of a continuum with the patients in AVD being less severe than the patients in ALD. But there's a clear unmet need in this population, and we are looking at the evolution in those both the most severe and the more -- the less severe populations. This is -- we're going to be looking at different parameters. Clearly, we just mentioned the days of heavy drinking, but as well liver parameters. We know that those population have fatty livers and increase liver stiffness, and we're going to be looking at this as our primary endpoint for ALD. And that's where we are at this point in time. But again, there's -- we hear a lot of enthusiasm around this area.

Well, and I think the timing of this, just with the interest in no alcohol drinks, mocktails, dry January. Every week, there's something coming out on alcohol use. And here, again, we have a product that is designed to help on 2 fronts. You can look at the glucagon direct-acting liver effects. I'm thinking if somebody is drinking that much that they want to cut back, they've probably have done a little damage, just may not know it, but they're thinking about their drinking. And then you look at what you would get with the GLP-1 side, which may be helping with cravings. And again, it is one product bringing together 2 activities that do more benefit for patients with a tolerability profile.

So, this is really the way we're looking at how can this drug best infiltrate indications that make the most sense, whether it's MASH, whether it's AUD, ALD, you look for where are your strengths and play to your strengths.

We have the next question from the line of Michael DiFiore from Evercore ISI.

I have 3. The first one, since you said that Europe has approved AI biopsy reads and that you intend to propose the PathAI platform to the FDA later this quarter, what are the practical steps -- next steps once the clearance comes? Like for example, are your imaging and workflow systems already validated for PathAI? Or would there be a ramp-up period before you could implement the AI read in Phase III? And then I have 2 follow-ups.

Yes. The way that the AI works is they digitize the slides. And so as long as they have good slides, and we've learned how to do that, that was part of our Phase IIb study. We have excellent specimens and how to handle those. As long as they have good specimens to work with, they have their own proprietary digitalization technique. So, it will be a seamless introduction of that technology into the readout.

Okay. And relatedly, how will NIT tracking actually be implemented operationally in Phase III in terms of frequency, imaging cadence, data interpretation? Any color you could offer on that?

So we're going to -- I mean, there's different visits over the 52 weeks with clearly imaging happening at on quarters and 6 months, week 24 and week 48, and then they will be continuing examinations towards clinical outcome for this -- for the patients. And the NITs, we can -- it's much more -- it's much easier to do this more frequently. So, we have different visit schedule that can be even on a monthly basis, especially early on, where we can look at some of the blood-based need and get this information very early. So, we'll get some very nice reads on how those NITs are moving rapidly in the treatment algorithm here.

Got it. And my final question is regards to Lilly's Retatrutide. I know it's very early and a lot needs to happen between now and then. But any thoughts on pemvi's competitive positioning? Should pemvi and Retatrutide compete against each other in the MASH space?

Yes. So as you know, Mike, Retatrutide is a triple agonist. And it's really the benefit here is the same as with dual agonist, we believe the 1:1 ratio is more important here because we are balancing both GLP-1 and glucagon activity in the same molecule. So, we are getting full benefit. Glucagon is working directly in the liver, whereas GLP-1 is working indirectly through metabolic effects through weight loss. So really adding GIP on top of that is not relevant for the MASH space. It may be more relevant for the obesity field. So, we think we are very well positioned versus the Retatrutide in the MASH as well as AUD and ALD space.

We know and we'll have some new data at AASLD around the anti-inflammatory aspects on the liver level, which is also really important, and we're excited to have really that 1:1 ratio is really important for the direct activity on the liver.

We have the next question from the line of Andy Hsieh from William Blair.

This is [ Kelsey Lucerne ] on for Andy. We had a question around the preclinical development program for the oral formulation of pemvidutide. Just curious if you could share next steps and time lines for advancing this candidate and any sort of thoughts around positioning relative to the injectable? Will it also be progressing in MASH as an alternative to the injectable form and who you might see as your competitors for this program?

Sure. Happy to take that question. So, recall that our last earnings call, I expressed a lot of excitement and enthusiasm for what was characterized as appropriately as a breakthrough in our oral formulation program. So, we're continuing to push that forward. Obviously, next steps have to do with an IND in the clinical trial, the timing of that will be more clear on as time progresses here. But as far as how does it fit into the landscape, I think there's 2 important features here that should be appreciated. The first is unlike an oral pill, a small molecule, this is still pemvidutide. It's unaltered. Once it enters the bloodstream following the oral administration, it acts just like pemvi. So we get the long half-life. We get the excellent tolerability profile that we've seen so far.

So, we have the best of both worlds, will. We have the specificity and potency of the peptide that is pemvidutide as opposed to a small molecule. And yet, we have the oral formulation. So we're really excited about that potential. And we think that as it stacks up against the others, which the vast majority, as you know, are small molecules, we have a real advantage there. So we're excited about the program. We've made, as I mentioned last time, real headway. We're continuing to progress that, and we'll share more data as appropriate.

Ladies and gentlemen, this concludes our question-and-answer session. I will now hand over the conference to Dr. Garg for closing comments.

Well, thank you, everyone, again for joining us. The coming weeks will be incredibly exciting. We look forward to sharing updates on the 48-week data and the end of Phase II meeting with the FDA and hope to see some of you at AASLD. Thank you.

Thank you. The conference has now concluded. Thank you for attending today's presentation. You may now disconnect.

Hi, everyone. Thank you for joining us today at the fireside chat for Altimmune. I'm very pleased to welcome the President and CEO, Vipin Garg, along with the Chief Medical Officer, Scott Harris. Before we get into the questions, a reminder of our research disclosure. For important disclosures, please see Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative.

With that, we begin the Altimmune fireside chat, and we are excited to have you here. So for those who do not know the story of Altimmune, can you give us a brief background of yourselves and a brief background of the company at a higher level and what you're currently focused on?

Absolutely. Well, thank you for having us. We appreciate it. I'm Vipin Garg, President and CEO of Altimmune; and my colleague, Dr. Scott Harris, our Chief Medical Officer. Happy, excited to tell you about Altimmune. So we are developing a GLP-1 glucagon dual receptor agonist for the treatment of serious liver diseases such as MASH. We'll talk more about that. But really, the idea is this -- the drug is called pemvidutide is rationally designed to have both direct effects in the liver as well as have metabolic benefits of the drug.

So glucagon works directly in the liver, has direct effect in the liver, whereas GLP-1 provides metabolic components such as weight loss, mainly through weight loss. The best way to treat MASH is really to go to treat the liver, have a direct acting agent in the liver as well as lose weight at the same time. About 80% -- over 80% of patients with MASH have -- are either overweight or have obesity. And really, MASH is a disease of obesity. So the best way to treat MASH is to not only treat the liver, but also to remove the original insult or the injury that actually caused the disease to begin with. So you'll see that everything we are working on relates to serious liver diseases where it would be beneficial to [ defect ] the liver.

Pemvidutide has very profound reduction in liver fat, liver inflammation, liver fibrosis and on top of that has weight loss. Pemvidutide also has a highly differentiated PK profile that improves tolerability, and we'll talk more about that. We are in the middle of our 48-week Phase IIb trial for MASH. We recently read out a 24-week endpoint in that. That's really the primary endpoint of the study, and we'll talk more about that. I'm very excited to now have 48-week data coming out in the fourth quarter of this year. We're also preparing for an end of Phase II meeting with the FDA in the fourth quarter of this year and then prepare for our Phase III trials in MASH in 2026.

Thank you. With that, we can expand on the MASH discussion for pemvi. So you recently reported a 24-week result from the IMPACT Phase IIb trial. What are the key learnings? And how did this reinforce your conviction about pemvi's potential to disrupt the MASH treatment landscape?

Well, thanks, and thanks for having us here. So let me just go over the basic design of the trial. So it's a 48-week trial. We had 212 patients enrolled. We had 3 treatment arms, placebo, 1.2 milligrams of pemvidutide and 1.8 milligrams of pemvidutide. The treatment is for 48 weeks. We're following patients out to that time point to monitor their noninvasive tests, which, as you know, from recent discussions with the FDA have really risen to prominence there. So we're following noninvasive test through week 48 and also body weight and weight loss.

And the primary endpoint of the study is based on the biopsy, which is done at week 24. We would note also that the 1.2 and the 1.8 milligrams of pemvidutide were administered without any dose titration, which is unique among incretin class agents, and we'll talk about the importance of that in a minute. So at the biopsy endpoint at week 24, we saw class-leading MASH resolution. The anti-inflammatory aspects of this compound were really robust and were really amazing. That MASH resolution we saw was exceeding MASH resolution seen by other compounds at 48 and 72 weeks. All of the activity is built upfront.

There were a lot of other readouts of anti-inflammatory activity such as ALT levels MRI-PDFF, which is a measure of liver fat content and also an MRI-based imaging technique called corrected T1 or CT1, which measures liver inflammation. And in all of these noninvasive tests of inflammation and MASH activity, we were class-leading. And this MASH resolution drives fibrosis improvement. And we also saw great changes in fibrotic activity, whereas we didn't meet the endpoint read manually by the pathologists, we did by the computer AI-based algorithms.

I think everyone would agree, the computer is more accurate than the pathologist reading. Europe has already accepted the standard. There's an application from the company that has produced this technique in front of the FDA. We're hopeful that the FDA is going to act on that in the fourth quarter. And if that's the case, we'll have met the approvability for fibrosis improvement in the United States as well at week 48. But the noninvasive test results that we saw were also class-leading at just 24 weeks. So this supported the very robust anti-inflammatory and antifibrotic activity of the molecule, and we're going to continue to follow those to week 48, where we expect these to grow.

So there's been a lot of discussion at the FDA recently about the use of noninvasive tests for evaluating patients with MASH, something very important happened about a week ago where the FDA accepted the application of a company called Echosens, which produces FibroScan, which is a measure of transient elastography or VCTE, and they accepted a letter of intent [indiscernible] surrogate endpoint. This has not happened before. And it shows that the FDA is extremely interested in moving ahead with noninvasive tests and that the level of evidence has also risen to that level. Now that process could be as long as 6 to 16 months. We really don't know.

But when we look at the prospect of being able to go into Phase III using noninvasive tests, I think that based on noninvasive tests, we'll probably have the most antifibrotic molecule that's out there with a high probability of success and using these noninvasive tests would allow us to conduct much smaller trials, trials that would execute faster and also get us to NDA faster and also cost considerably less. So we're really excited about the readout, as Vipin mentioned, we have another readout coming up as a catalyst in the fourth quarter.

We're meeting with the FDA in the fourth quarter to discuss the Phase III program. Part of that will be a discussion about taking our study and designing it in such a way that we can flip it from biopsy-based endpoints to noninvasive test-based endpoints in the trial. We get agreement from the FDA that we can do that and make that switch over during the course of the trial if FDA approves these knits.

That's great. Are there any specific areas that you'd like to seek alignment on with the FDA during the end of Phase II meeting as it relates to dose regimen and endpoints?

Right. So taking the last one first. As I mentioned before, we want to get agreement on the FDA that we can move -- that we can design a trial such that we have all the noninvasive tests that they need and that we can flip that switch in the middle of the trial if that conversion to take place. Dose-wise, we achieved really remarkable dose with only 1.8 milligrams of pemvidutide, which is not the highest dose we've employed in clinical trials. At the 2.4 milligram dose in the prior trial, the weight loss at 2.4 milligrams is 40% more than 1.8.

That means that we had employed the 2.4 milligram dose in our trial, we would have seen weight losses of about 8% and then you can hypothesize what that result would be at the end of 1 year of treatment, very competitive as good as other compounds in development. So one thing about pemvidutide is that it combines the direct effects in the liver, which are potent with very, very good weight loss. And the combination is very important for MASH patients because they die of cardiovascular complications up until the point they develop cirrhosis, they die of the cardiovascular complications before they die of the MASH complications.

So the agreement will be to align on the endpoints to align on the doses. In addition, we want to get alignment on the size of the Phase III program. Typically, match programs have been about 1,800 patients. We recognize that we're coming into this discussion with 600 patients in obesity. So we hope to have a discussion with the FDA to reduce the size of the study, and we also have some innovative design features that I can't talk about until the FDA gives us a go-ahead on it, but that would also shrink the time required to conduct the trial.

Sounds good. And for the 24-week results that you reported, are there any key learnings that is likely to inform the Phase III trial design as a whole?

Yes. I mean one thing I didn't mention was that we had essentially no adverse event discontinuations, which is unique among all drugs for MASH and also recognize that we accomplished that without dose titration. And hepatologists are now facing the approval of semaglutide that was approved last week or about 2 weeks ago, and they're facing the use of this compound or adding into their clinical practice. But they'll tell you when they see patients on semaglutide, they're not seeing them on the 2.4 milligram dose. Obesity specialists are used to titrating very slowly over the course of a year, 1.5 years to get up to that level and many patients stop before the 2.4 milligram dose.

Hepatologists are really not interested in titrating. So what you're going to see here is a lot of patients taking semaglutide who because of titration are not getting up to that 2.4 milligram dose, which is the only dose that we know works in MASH. In contrast to the 1.2 milligram and 1.8 milligram doses we have here, because they're so well tolerated, it can -- we can give them the dose needed for the treatment of MASH starting on day 1. So the tolerability of the compound here, the impressive tolerability was really a tremendous learning from the study. We learned about the very, very potent anti-inflammatory effects and the fibrotic effects were very potent as well.

Yes. Looking back at the 24-week readout, there are really 4 key messages that came out of that. We are clearly showing direct effect in the liver. We're showing significant weight loss, excellent tolerability, actually class-leading tolerability for any MASH treatment out there and no dose titration. You put that together, that really makes a very compelling story for MASH. It's really a complete solution for the treatment of MASH.

And on that, for the ongoing 48-week trial, is there anything we can extrapolate from the 24-week data to the 48?

Absolutely. Scott, do you want to?

Yes. Well, Nano will be able to project the noninvasive test at week 48, and we'll see the growth of that. I remind you that if this is the basis of approval in the future for MASH resolution and fibrosis improvement that we will have some of the most potent knits that are out there. We'll also be able to see the weight loss at week 48, which will grow over the course of time. And then just the continued tolerability of the compound.

The dropout rate in our trial was very low in the first 24 weeks. That's typically where dropouts occur. This is one of the fastest enrolling MASH trials to date. Patients really like this drug. Docs like prescribing it. So we had no problem getting people who wanted to come into the study. We think that says a lot about the uptake of the drug once it's on the marketplace.

Excellent. And on the study, the participant that enrolled for the Phase IIb that were in biopsy stage F2 and F3.

Exactly.

What are the plans to include the F4 stage participant in future studies?

Yes. We'll have that discussion with the FDA. That's a program that we are very interested in. And we think that we would have a very high probability of success in F4 based on all of the data that we've seen so far.

Got it. Are there any key questions that still need to play out in the MASH arena?

Well, it's just the beginning of drug approvals in the MASH space. We just have a second -- we now have 2 drugs. We have Rezdiffra, which is a direct acting agent in the liver. We've got semaglutide recently approved, which is more working through the metabolic component through weight loss. So I think the key question is that if you combine these 2 effects, both effect in the liver and the metabolic components, what is the benefit of that? And that's really what we need to -- what we would like to emphasize that really the ideal treatment is the combination of these 2 approaches, and that's what needs to be played out.

Our discussions with KOLs and prescribers, it clearly show that doctors want their patients to lose weight in addition to improving their liver health. So they really are interested in that. And that makes sense because the large proportion of patients with MASH have -- would benefit from losing weight. So really, that's the unique advantage of pemvidutide. It's combining these 2 mechanisms in a single molecule.

Got it. And still in that space, we've seen strong data from the FGF21 analog class. And what can we learn from the success of those drugs? And how can the mechanism of [ pemvi ] be differentiated?

And once again, they're emphasizing the need for direct effect in the liver. FGF21 works very effectively in the liver. So that's there. And that's what we are delivering as well through the glucagon component. But again, FGF21s have no weight loss. So there's already a lot of discussion about combination therapies, combining FGF21 with GLP-1, so you can have both of these benefits.

But why would you want to use 2 drugs if you can have a single drug do the same thing. It's very complicated to do combination therapy, 2 different PK profiles, 2 different tolerabilities, could be even 2 different administration -- mode of administration. So we think it's a much better solution to have a single drug doing both of these -- delivering both of these mechanisms.

Got it. And with that, we can actually talk about the obesity program. And you recently had a successful end of Phase II meeting with the FDA and agreed on the design of the Phase III registrational program for pemvi. What would you highlight about the Phase III trial design and the expected benchmark for success?

Okay.

Well, let me quickly review the results of the Phase II study because they're important. The drug was well tolerated. The weight loss that was achieved at the 2.4 milligram dose at 48 weeks of 15.6%. But if you look at the trajectory of the curve, there was a lot more weight loss to be there. And if you take it out to the -- excuse me, the tirzepatide time point at week 68 or the semaglutide time point at week 72, the weight loss would have been extremely competitive. We maintained glycemic control.

There were no cardiac adverse events of any note. We certainly didn't see any arrhythmias, which has been a problem with some other programs. The overall increase in heart rate was [ meanial ], no more than what's seen with any other GLP-1. So we came out of that study with 600 exposures, and we had a meeting with the FDA where they agreed that there were no safety signals in the program. There was no need, for example, for cardiac outcomes trial, which has been placed on other sponsors in the obesity space as well.

So a great deliverable from that program in addition to efficacy with tolerability and safety, which we carry forward now into our MASH program as well as our program in alcohol liver disease and AUD. So I think we established very clearly in discussion with the FDA in November of last year that pemvidutide was safe and it would be safe across the indications for which it's being pursued. Now we had a robust meeting with the agency. We announced 4 different trials. One of them was in lean mass preservation. Another important feature of pemvidutide is that when weight loss occurs, the amount of loss that comes from lean mass is lower than other incretins.

So that's very important because of the high rates of bone fractures and falls in people over the age of 60, particularly postmenopausal women. And in fact, in the semaglutide program, they saw a higher rate of bone fractures. Their -- what we call lean loss ratio, which is the amount of lean mass loss divided by the amount of total weight loss was about 40%. That's been seen in several other studies, and it's not really been fully explained, but it's a real concern. And they have a warning in their prescribing information about the higher rate of bone fractures in elderly and the women. Even retatrutide, which has gotten a lot of attention was 38%.

When you lose weight naturally, if all of us here went in the diet, the amount of lean loss is the ratio of the total weight loss will be about 25%. So that gives you a perspective. Now pemvidutide was 21.9%. So there's been a lot of attention given to the fact that this compound through glucagon preserves lean mass. Now that's very important in our MASH program because patients with advanced liver disease have sarcopenia. They have low muscle mass. And if you give them a GLP-1 like semaglutide, that could be -- have a very critical effect on their health. So we immediately come into a program like F4 with really good safety just based on the compound itself, plus the fact that we don't inflict damage on their metabolic balance, their muscle mass, and that's very important as well. But we actually created 4 studies. We call them VELOCITY.

One of them looked at the reduction of LDL cholesterol in people with elevated levels at baseline. FDA was very excited about that because they saw a synergy between pemvidutide and statins because we got very good LDL lowering effects greater than 20% in people with elevated levels, and we saw it even in patients taking statin therapy. So there's been a real problem with statins and the ability to reach LDL goals with statins in compliance with it. But FDA saw the possibility of driving compliance through the desire of people to get weight loss and then taking the 2 compounds together to get to their goals.

And I would just add that internally, we are focusing on really treating serious conditions that result from obesity rather than going after pure obesity. As you can see, we have lots of data that pemvidutide produces very significant weight loss, and we have a lot of data on safety profile of the drug. So the question is how do we take that and how do we create maximum value from that. We think the way to do it is to go after serious liver diseases rather than pure obesity marketplace. And that's really what we are doing.

We're bringing in the weight loss benefit to liver diseases across MASH, AUD, ALD, people with overweight and obesity have poor outcomes. So they will all benefit from losing weight. So all of these trials, we have a Phase II trial going on in AUD, one in ALD. Across all of these trials would be reporting on weight loss as well. So for instance, in MASH, even though our main indication or our primary indication would be treatment of MASH, weight loss would be an important secondary endpoint, and we hope to have that on the label.

Yes, that's very excellent. Thanks for touching on the AUD and ALD programs. We would like to understand how pemvi fits in the treatment landscape for that, those 2 major disease areas.

Absolutely, Scott.

Well, AUD, alcohol use disorder and ALD, alcoholic liver disease are both areas of huge unmet need. Alcoholism is an all-time high in the United States. Alcohol related obesity is actually -- excuse me, related comorbidities has actually doubled because obesity worsens the outcome in alcohol use disorder and alcoholic liver disease. So with the epidemic of obesity, we're seeing more complications in AUD and ALD. So it makes a lot of sense to have a drug that treats both AUD and obesity, ALD and obesity. So the literature on GLP-1 effects on alcohol craving intake is well established. We have our own data in animal model showing a very dramatic reduction in the intake of alcohol -- free intake of alcohol by animals given pemvidutide.

We're now conducting a Phase II study in alcohol use disorder. The study kicked off in May of this year, and we hope to read out in the second half of 2026. But that IND passed, and we're conducting that study and we're very happy with the way it's going. So that reduction in alcohol intake is probably driven predominantly, at least as far as we know by GLP-1s. But what glucagon gives you is the potential to heal any injury in the liver due to fat because the pathology of alcohol liver disease is almost identical to that of MASH. It's basically fat-driven inflammation going to fibrosis and cirrhosis. And we know the effects of pemvidutide on that sequence, liver fat, liver inflammation and fibrosis.

So it's very attractive to think that the GLP-1 in alcohol liver disease would reduce the craving whereas the glucagon would heal the liver damage that occurred. So that trial was kicked off in July of this year and is also enrolling. We haven't updated the Street yet and what we think the completion date of that trial is as the enrollment is a bit too early to know at this point in time. But it's key to note that we've got agreement from the FDA to assess the liver damage in ALD with a knit. And that knit is VCTE, vibration controlled transient elastography or FibroScan, which is the same knit that was in the headlines a week ago because of the letter of intent in MASH. So it means that there's an endpoint here that's being recognized across 2 indications.

There's a lot of data to show that VCTE is the primary assessment for liver damage and fibrosis in alcohol liver disease, and we have agreement to use it as the primary endpoint in the ALD trial and to read out on that. And we'll do that after the trial itself is 48 weeks. But like the IMPACT trial, we'll read that out at 24 weeks based on the knit. And I think based on the NIT results, the VCTE results that we saw in the IMPACT trial, we're very optimistic about a positive readout in ALD as well.

I just wanted to point out, we recently got fast track status for AUD as well, just a few couple of weeks ago. So we're the only drug in development that has fast track status for AUD.

Yes. On that note, I wanted -- you've been upfront about your intentions to partner pemvi with ahead of the Phase III trial for obesity. Can you discuss your business development plan? Has anything changed?

No. I mean, as far as obesity is concerned, as I've mentioned, our focus is not to go primarily after obesity as the main indication. In our partnership discussion, that's clearly an option that our partner can pursue. But we think we bring much more value by going after serious liver diseases. Also, there's going to be tremendous pricing pressure on obesity drugs as more and more drugs get approved. Already with just 2 drugs, we are seeing a significant price war out there. Whereas if you are going after a serious disease that results from obesity, it's a totally different value proposition.

So we plan to stick with that strategy and really move forward full speed ahead in MASH and then we'll look forward to getting the data from AUD and ALD as well. As Scott lined up earlier with MASH, we are expecting the 48-week data, very important milestone coming up as well as the end of Phase II meeting with the FDA coming up. So looking forward to then really talking about our Phase III program next year.

Thanks, Vipin. Thanks, Scott. Thanks for joining us here at Morgan Stanley for the conference.

Well, thank you very much. Thank you for having us.

Good morning, ladies and gentlemen, and welcome to the Altimmune Second Quarter 2025 Financial Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded.

I'll now introduce your host for today's conference call, Lee Roth, President of Burns McClellan, Investor Relations Adviser to Altimmune. Lee, you may begin.

Thanks, Olivia. Good morning, everyone. Once again, thank you for joining us for the Altimmune Second Quarter 2025 Financial Results and Business Update Conference Call. On today's call, you'll hear from Dr. Vipin Garg, our Chief Executive Officer; Dr. Scott Harris, our Chief Medical Officer; and Greg Weaver, our Chief Financial Officer. Dr. Scott Roberts, our Chief Scientific Officer; and Ray Jordt, our Chief Business Officer, will join us for the Q&A. Our second quarter 2025 financial results and corporate update press release was issued earlier this morning, and it can be found on the Investor Relations section of the Altimmune website.

Before we begin, I'd like to remind everyone that remarks made about future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties, and these could cause our actual results to differ materially from those indicated.

For a full review of the risk factors that could affect the company's future results and operations, we refer you to the company's filings with the SEC. I also direct you to read the forward-looking statement disclaimer in our press release issued this morning, which is available on our website. Any statements made on this call speak only as of today's date, August 12, 2025, and the company does not undertake any obligation to update any forward-looking statements to reflect events or circumstances that occur on or after today's date. As a reminder, this call is being recorded and will be available for audio replay on the Altimmune website.

With that, it's my pleasure to turn the call over to Dr. Vipin Garg, President and Chief Executive Officer of Altimmune. Vipin?

Thank you, Lee. Good morning, everyone, and thank you for joining us today for our second quarter financial results and corporate update. As many of you know, we presented the 24-week top line data from the IMPACT trial at the end of June. As we shared, pemvidutide achieved statistical significance in the primary endpoint of MASH resolution and across multiple objective measures of efficacy at 24 weeks of treatment. These included all noninvasive markers of inflammation and fibrosis, liver fat reduction and weight loss along with best-in-class safety and tolerability without the need for dose titration. These data will serve as the foundation of the package that we take to the FDA for our end of Phase II meeting in the fourth quarter and will inform the design of our Phase III program.

In addition to the advancement of our MASH program, our Phase II trials in AUD and ALD, RECLAIM and RESTORE are now underway. Alcohol use disorder and alcohol-associated liver diseases are two indications with significant unmet needs and few to no treatment options for which we believe pemvidutide may be particularly well suited. As we announced yesterday, our Board has appointed Jerry Durso as Chairman of the Board, succeeding Dr. Mitch Sayer, who has served in this role for the past seven years and will remain with us as a Non-Executive Director. This change reflects our planned advancement to Phase III development of pemvidutide in MASH. Jerry has a wealth of commercial and corporate development experience, including the building of a successful liver franchise as CEO of Intercept prior to its acquisition. We are excited to continue moving forward under Jerry's leadership and look forward to Mitch's ongoing contribution.

With the $183.1 million in cash and cash equivalent, we have considerably strengthened our balance sheet as we work to continue to advance the development of pemvidutide and look forward to reaching additional milestones, including the full 48-week IMPACT data as the year progresses.

With that, I'll now turn the call over to Dr. Scott Harris, our Chief Medical Officer, to provide a clinical development update. Scott?

Thank you, Vipin. Those of you on the call with us are likely familiar with the IMPACT top line data that we reported about six weeks ago. I'd like to expand upon a few of the key highlights of this positive and important data set. First, we achieved MASH resolution up to 59.1% of subjects a highly statistically significant result after 24 weeks of treatment. On the other measure of fibrosis improvement, we did not reach statistical significance, but clear evidence of antifibrotic activity was observed that was supported by additional objective measures of fibrosis improvement.

As Vipin noted, multiple measures of efficacy that were assessed at the 24-week time point achieved statistical significance. We demonstrated impressive results in all of the noninvasive tests of liver fibrosis, including enhanced liver fibrosis and vibration-controlled transient elastography. In addition, the PathAI-based analysis of the biopsies showed a statistically significant improvement in liver fibrosis in a supplemental analysis. We recently completed our analysis of another important noninvasive test of fibroinflammation, corrected T1 imaging, or cT1, where a class-leading effect for pemvidutide was observed at the 24-week time point. cT1 is a reproducible MRI-based liver imaging method that has been correlated with changes in liver inflammation and fibrosis in clinical studies.

Decreases in cT1 relaxation time of 80 milliseconds or greater have been correlated with improvements in liver inflammation and fibrosis in clinical studies. At 24 weeks, mean decreases from baseline and cT1 relaxation time were 145.0 and 147.9 milliseconds in the 1.2 and 1.8 milligram pemvidutide treatment arms, respectively, compared with a decrease of 27.5 milliseconds in placebo, representing a p-value of less than 0.001 for both doses. These new data add additional depth to the data, demonstrating the strong anti-inflammatory and antifibrotic activity of pemvidutide treatment.

In addition to these impressive effects on the liver, pemvidutide was associated with a greater than 6% decrease in body weight at 24 weeks of treatment with a weight loss trajectory indicating that further weight loss was likely. Decreases in body weight are important in MASH patients as they succumb to the complications of obesity at greater rates than the complications of liver disease until cirrhosis actually develops. In the aggregate, the IMPACT top line data compare very favorably to other MASH therapies, including those that have read out at much later time points.

Now moving to safety. Pemvidutide demonstrated potentially class-leading results in that important area. Through 24 weeks, pemvidutide was remarkably well tolerated with only a single adverse event-related discontinuation across the two pemvidutide treatment arms versus two adverse event-related discontinuations in the placebo group. It is worth noting that this excellent tolerability was achieved in the absence of dose titration, which is unique for GLP-1-based agents. The ability to start patients at a dose that is both effective and tolerable will be highly attractive to prescribers and will be another key differentiator for our therapy.

We're continuing to analyze the 24-week data and look forward to providing updates as the results become available. The team is preparing for our fourth quarter and the Phase II meeting with FDA that will further guide our Phase III plans. We will also be reporting the full 48-week data in the fourth quarter. This data will include the noninvasive tests that were reported at the 24-week readout, weight loss and safety. In addition to our MASH program, we've made progress in the development of pemvidutide in two additional indications, AUD and ALD, with the initiation of Phase II trials in these indications in May and July. AUD and ALD are serious and highly prevalent conditions where current treatment approaches are inadequate and innovation has been limited.

RECLAIM our AUD trial is a 24-week trial evaluating weekly 2.4 milligram pemvidutide versus placebo. The primary endpoint is the change in the number of heavy drinking days with key secondary endpoints, including other measures of alcohol intake and weight loss, including the World Health Organization risk drinking level, which has recently been accepted by FDA as an additional basis of approval in this indication.

RESTORE, the Phase II trial in ALD started enrolling in July. It is a 48-week trial evaluating the 2.4 milligram weekly dose of pemvidutide versus placebo with a primary endpoint of change in liver stiffness measurement at 24 weeks. Liver stiffness is a noninvasive measure of liver inflammation and fibrosis that characterizes the prognosis and severity of ALD.

Key secondary endpoints include an assessment of liver stiffness at 48 weeks as well as changes in ELF score alcohol consumption and body weight at both 24 and 48 weeks.

And with that, I'll turn it now over to Greg Weaver, who will review our second quarter financial results. Greg?

Thanks, Scott. Beginning with the balance sheet. We finished the second quarter with total cash of $183.1 million. That's an increase of approximately 40% over our cash position at the start of this year. We've raised $88 million in gross equity capital this year, while adding the flexibility of $100 million Hercules debt facility which we announced in the second quarter and drew down $15 million from that facility at signing.

These strategic financial moves are part of our ongoing efforts to ensure that our balance sheet is able to support the continuing clinical development of pemv. We are committed to staying focused on driving value as we work to position pemv to benefit MASH patients.

Now to briefly comment on the Q2 financial results. First, R&D expenses, which were $17.2 million for the 3 months ended June 30 as compared to $21 million in the same period of 2024. And this amount includes $11.2 million of direct costs related to pemvidutide development, breaking that down further, including approximately $5.5 million for the IMPACT Phase IIb trial, $2.6 million for AUD and ALD start-up Phase II costs, and $1 million for our pemvidutide oral formulation preclinical development.

G&A expenses were consistent period-over-period at $5.7 million and $5.6 million for the quarters ended June 30, '25 and '24. Really nothing not worthy to call out in our G&A. Net loss for the second quarter of 2025 was $22.1 million or $0.27 a share compared to a net loss of $24.6 million or $0.35 a share in the second quarter of the prior year.

With that, I'll turn the call back to Vipin for closing remarks.

Thank you, Greg. The second half of 2025 will be an exciting period for Altimmune as we report the 48-week IMPACT data and prepare for our end of Phase II meeting while continuing to enroll the Phase II trials in AUD and ALD.

This concludes our formal remarks, and we would now like to open the line to take questions. Operator?

Thank you. [Operator Instructions] Our first question coming from the line of Annabel Samimy with Stifel. Your line is now open.

Hi, This is [indiscernible] for Annabel. Thanks for taking our questions. I have 2.

The first one related to the MASH development plan. You've had some time to digest the data, and we did see fibrosis improvement not reach stat sig. But to what extent could you still leverage the other improvements in MIS and the PAF AI analysis at week 24? How does the FDA view these new measures? And could you potentially get into the label by including those endpoints in the Phase 3?

Hi Jed, this is Scott, and thank you for the question. There's more and more emphasis being placed on non-invasive tests and the overall feeling among experts in the area is that we will be moving to a non-invasive test or knit-based improvement at some point in the future. I think the FDA is warmed to that.

We actually haven't seen that happen at this point. I want to remind you that we achieved highly statistically significant effects on ELF and VCTE, sometimes called FibroScan, which are considered the best non-invasive tests for assessing fibrosis. And also, the PATH -- I should remind you that PATH AI analyses have been accepted in Europe as the basis of approval and that FDA is now reviewing that proposal, and we should have some news on that in the near future.

So we think that based on these highly recognized and validated measures of fibrosis improvement that we not only have excellent evidence that fibrosis improvement is occurring, we're actually meeting what could be FDA and EMA expectations for approval in both of these areas. So as we've said before, there is a great deal of evidence that we have very potent antifibrotic effects. We're very confident about our ability to be able to hit these effects in Phase III.

Yes. I just want to add that just to remind everybody that this readout was at 24-week at 48-week or beyond, which is where really the Phase III program will be designed for. We believe that we will hit the statistical significance in the fibrosis endpoint with longer trial and larger trials that would reduce the placebo noise. That's really the reason we didn't hit the endpoint in this 24-week study. So we feel very good about going into a Phase III program. In spite whether the knits are allowed or not, even without that, we should hit the fibrosis endpoint in a longer Phase III trial.

I had one more question. It's related to the AUD-ALD trial. I could be wrong about this, but I do recall you guys mentioning that you would test different doses like 1.2, 1.8, 2.4 with titration. It looks like you're only testing the 2.4 milligrams in these trials. Is there a particular reason for that?

Yes, Jed. I mean we think that for a Phase II trial, it's appropriate to only test one dose. We're testing the most efficacious dose. And then we'll have that conversation with FDA and other regulatory agencies going forward, and there's always the opportunity to expand that and to analyze different doses in a Phase III program. But we think that we're going in with what will be our most efficacious dose, and then we can reexamine other doses as the program unfolds.

Thank you. And our next question coming from the line of Ellie -- more with UBS.

This is Jasmine on for Ellie. So on your end of Phase II meeting, can you talk about what you're hoping to discuss with the FDA and align with them on? Are you planning to discuss the possibility of an knit-based Phase III design with them? And will we get an update after this meeting?

Jasmine, thanks for the question. I think that we really can't provide a lot of details about the meeting and our proposals until we actually have the meeting, and there will be a lot of topics to discuss. And the opinions of the FDA on this are shifting right now, and we're keeping our ears very close to the ground on this. So we expect to be able to have a very rich conversation with the FDA along multiple lines of approaching this and have an update for you after the end of the Phase II meeting.

Thank you. And our next question coming from the line of Yasmeen Rahimi with Piper Sandler.

This is Dominic on for Yasmeen Rahimi. Congrats on a great quarter. So we just had a few questions. The first one, was there any measures on alcoholic consumption in the impact study that could derisk reclaim and restore? And then kind of going with that, what is the timing for those readouts? And what do you need to see to advance in the Phase III?

Right. So we are continuing to analyze the data sets from the IMPACT trial, and we'll have an update on any alcohol measures as we continue to provide data. As you know, we're continuing to analyze the results of the trial and we'll provide on that information as we further analyze the data. We think we have a great deal of evidence for the effects of pemvidutide on AUD and ALD. As you're aware, we have a very impressive animal study showing about an 80% drop in alcohol consumption in animals who were given free choice as well there's a huge literature on the effects of GLP-1 agents and alcohol consumption, both observational trials and at least one randomized trial. And as you know, with ALD, the pathophysiologic basis of that is fat-induced liver inflammation very similar to MASH. So we feel very confident of our ability to hit the endpoints in both the AUD and ALD trial. And in terms of the Phase III development program in those indications, we'll meet with the FDA after the Phase II results and get agreement on what that program looks like.

And our next question coming from the line of Roger Song with Jefferies.

Congrats for the progress. Maybe just also on the end of Phase meeting, how much more work you need to do before you can request the meeting? My understanding you have not requested the meeting. How much data from the 48-week readout is needed to finalize the Phase III design proposal? And then I have a follow-up question.

Yes, Roger, we feel very good about having that meeting by the end of the year, and we'll have the results of that meeting and share it with the Street. Other companies have met with 24 weeks of data. And I want to remind you that we have a lot of information 48 weeks of data and dosing from our obesity MOMENTUM study. So consequently, we don't really -- we feel confident that we'll have the data to go in, and we'll have that meeting. We should have it sometime in the fourth quarter, and we'll inform the Street on what the results of that meeting were.

And then my follow-up question is with the new Chairman appointment, so how will the corporate strategy evolve regarding the partnership for Phase III and the commercialization? It seems you're more focused on the commercialization now.

Yes. That's -- as you can imagine, that's part of the natural evolution. The Board is continuously evaluating the skill set at the Board level, given that we are now moving into Phase III, the Board felt that addition of bringing Jerry as Chairman would be an added advantage for the management team to move forward. So his experience in domain area in building a liver disease company and ultimately, being part of that M&A transaction would be important as we move forward.

Our next question coming from the line of Catherine O'Klakone with Citizens.

This is Catherine on for John. I have a quick question about the T1 responses and how the results from impact compared to other programs? I know that you said kind of best-in-class, but if you could kind of give us some kind of ranges from the other competitor programs.

Yes, Catherine. So as you're aware, the results that we have were in the range of a reduction of about 145 to 140 milliseconds. That was seen in this trial, but it was also seen in a prior trial, our Phase Ib trial in patients with fatty liver. And based on the public data, we're seeing readouts of approximately 50 to 60 for resmitteram and up to about 107 for tirzepatide. So you can see that these results that we're getting, 147 versus a range of 50 to 107 are clearly superior to other compounds, at least those that are reported in the public domain and that given the association of cT1 with reduction of both MASH activity and fibrosis that this is one other measure among many measures showing the potent anti-inflammatory and antifibrotic activity of the compound.

Our next question coming from the line of Patrick Trucchio with H.C. Wainwright.

On all the progress. I just have a couple of follow-up questions on expectations around the Phase III program. And then as well, just maybe looking further ahead to potential commercialization and the product profile that's emerging. I guess the first part of the question is just around kind of updated thoughts on dosing strategy, 1.2 milligram, 1.8 milligram and then the higher dose and how you're thinking about the dose selection for the Phase III? And then as well for the primary endpoints, how are you thinking about primary endpoint, co-primary endpoint with MASH resolution as primary with fibrosis improvement? Or would there be a co-primary design? And I guess, how would you power for both? And then just as it relates to just the commercial potential, just based on -- I mean, there's a lot of data, and I think there's a lot of points of differentiation here. So if the Phase III were to reproduce the impact efficacy and tolerability, I guess, how do you see the positioning in MASH if there's an eventual approval?

Patrick, I'll take the first part of the question for the commercial potential. I'll turn it over to Vipin. So as you are aware, we studied the 1.2 and the 1.8 milligram doses and impact. And even at the 1.8 milligram dose, which is not our most potent dose for weight loss, we still achieved 6.2% weight loss at only 24 weeks and the trajectory of the weight loss indicated there was a lot more weight loss to be had. So we think it's going to be very attractive to put the 2.4 milligram dose into Phase III would not only give more weight loss to the extent that it could problem us even more -- provide even more efficacy, we find that very attractive.

Regarding the other 2 doses, that's currently being looked at very critically, and we'll discuss that with the agency and have an update for the Street after we have our end of Phase II meeting. As you're aware, there are 2 endpoints in MASH, MASH resolution and fibrosis improvement.

In the impact study, we had a dual endpoint, meaning that we either had a hit MASH resolution or fibrosis improvement for the trial to be successful and consequently, impact was a successful trial. We could go into Phase three with a similar strategy of dual endpoints. There's also the possibility of co- endpoints when you have to hit both, et cetera. And then in the background, you have endpoints based on noninvasive tests, which we feel are very exciting.

And by the way, EMA has approved the use of a Path AI methodology for actually reading out MASH resolution and fibrosis improvement using computerized algorithms assisted by the pathologists, but driven predominantly by the computer, which we think is going to reduce greatly the noise that we're seeing in the trial and probably help us control the placebo response and really express the antifibrotic potential of the compound. So we think there's a lot of things at play here in terms of the discussion with the FDA. It's going to be a very exciting and important end of Phase II meeting. And as soon as we have further information, we'll update the Street. So with that, I'm going to turn the commercial discussion over to Vipin. Vipin?

Yes. I just want to emphasize one other thing with regards to the FDA discussions. One thing I want to remind everybody is that we have a very large safety database that we have already accumulated on pemvidutide. So part of our discussion would be how do we leverage that? Do we think there is an opportunity to reduce the number of exposures in terms of the safety database. So we'll certainly be having that dialogue with the FDA, as Scott said, among many other things that we'll be discussing with the FDA.

So looking forward to that. Patrick, in terms of commercial potential of pemvidutide, as we have said all along and as you pointed out, there are multiple points of differentiation. First and foremost, we are combining 2 mechanisms, direct action in the liver, a direct-acting agent in the liver, with a metabolic agent with weight loss. So really think of it, we are treating MASH with obesity. And when you look at the MASH landscape, everybody is talking about the benefit of adding weight loss on top of liver-directed effect.

We're bringing that in single molecule. We're combining these 2 mechanisms. So we're treating MASH, but on top of that, people are losing weight. 60% to 80% of patients with NASH are obese or overweight, so they would benefit from losing weight. So that's # 1, which we believe is a very big advantage or differentiating factor for pemvidutide. In our market research, it's clear that physicians are looking for a drug where people will not only improve their liver health, but will also lose weight.

Secondly, safety and tolerability is going to be very, very important. And as you can see from our data, we are seeing class-leading tolerability profile. We think that can be leveraged. Patients like that, doctors like that, lack of dose titration is going to be a major plus when we commercialize pemvidutide. So it's really the benefit of combining the 2 mechanisms and on top of that, having a very clean safety and tolerability profile that we think is going to speak well in terms of the commercial success of the product.

Our next question coming from the line of Mayank Mamtani with B. Riley Securities.

This is William on for Mayank today. Two from us. Maybe I'll start with the first. So now that we know that Lilly has gotten positive FDA buy-in on pursuing high-risk MAL trial for their RETA and tirzepatide, they're using NITs for patient screening and then foregoing biopsies completely for primary efficacy endpoint, and it looks like even in the trial, looking more of an outcomes-type trial. How do you see this as an opportunity for pemvi to execute on a capital-efficient Phase III trial? And is your understanding that this still only biopsies are a way to secure Subpart H accelerated approval? And then I have a follow-up.

Well, thanks, William. Yes, I mean, I think it's really exciting. I think it creates a real opportunity for us in noninvasive tests, and we're taking a very careful look at that. And we think that there's real opportunity for us here, and we'll certainly have that discussion with the FDA.

Yes. And then we will look at every potential opportunity to come up with an innovative trial design and incorporate all of these things that are now becoming clear, that the FDA is reviewing. So we'll certainly have all of those discussions. We can't get into the specifics right now, but we'll definitely talk about it once we've had the end of Phase II meeting.

Yes. Let me add to that, William, that there are a lot of exciting things happening here, the development of knits, the movement toward AI-based reading in Europe, and we think there's a good chance that FDA will pick that up. And you saw that we had very positive results from the AI-based analyses that really reduce the noise from the manual pathologist readout. So there are developments here that are going to increase our probabilities of success in Phase III, and we're very interested in those and share your excitement and plan to have that discussion with the FDA this fourth quarter.

And then also, again, also sort of thinking of crosstown per, Merck has their ainpeutide readout coming out shortly, and they're looking at biopsy results at 48 weeks. Slightly different glucagon ratio here, but what could their data mean in terms of your 48-week data, potentially in Phase III? Or obviously, you just your data coming up at the end of the year? And what may you be specifically looking for to bring you additional confidence in Phase III, sort of going forward? And what will help guide you in sort of development of that Phase III?

Right. Well, as you noted, William, they're reading out at 48 weeks, and another glucagon compound is read out at 48 weeks, and these have lesser ratios of glucagon. And as Vipin mentioned, we read out at only 24 weeks. So we think that our readouts at 48 week had we done the biopsy at week 48 weeks would have been as good, if not better than the other compounds, and that's certainly supported by the very potent noninvasive test results we're seeing at week 24. I want to remind you that there hasn't been an incretin, let alone a glucagon-containing incretin, that is read out at week 24. And at week 24, our MASH resolution was comparable to or superior to other compounds at week 24 and better than compounds reading out at later time points in 48 to 72 weeks. So we think that Efinopegdutide readout will be further confirmation of the efficacy of the compound.

Now, as you know, we don't have a biopsy at week 48, but we have the noninvasive tests. And we expect to be able to use the noninvasive test to model and to predict what we would have seen at week 48 had we done the 48-week biopsy. So we think that data will be very supportive of our mechanism and our efficacy.

Our next question coming from the line of Corinne Johnson with Goldman Sachs.

Maybe just one from us. How should we think about the cadence of research and development spend from here as these AUD and ALD studies get up and further running, and enrollment increases?

Thanks. Appreciate the call. This is Greg. And in terms of the R&D spend investment in AUD and ALD, these are Phase II trials. They're baked into our budget for this year. So they're incorporated in our cash runway. These are relatively modest in size, and we're on it. I don't anticipate anything unusual in our burn rate going forward in the near term as related to AUD-ALD.

Our next question coming from the line of Andy Shah with William Blair.

Just a quick one. Very interested in the oral program that you're advancing. So I'm curious, maybe from a technological perspective, we think about it as a gastric absorption enhancer. And also just curious if you could tell us a little bit more about how you would position this formulation in the grand scheme of things.

Thanks for the question. We've been at this for a little while here, and I'm excited to share that we've had a big breakthrough in the activity. From the very beginning, we focused on 2 elements to really differentiate an oral formulation of the peptide from others that are out there, Rybelsus, for example. The first is to get away from the food restriction. You mentioned gastric absorption. That's exactly what we're trying to get away from. And we've done that from the beginning and focused on that because when it's absorbed in the gut or in the stomach, then it's really about very tight food restrictions that you're aware of for the Rybelsus indication. So that's one of the things we wanted to do.

And the secondary feature was to make sure that it really made sense from a cost-of-goods standpoint. As you know, the oral absorption is always inefficient compared to subcutaneous injection. But to make it work, we had a fairly high threshold for what we would be interested in. And so I think that things are looking very, very good in that respect. I think this breakthrough that we had was mechanism-based and went just the way we expect, and we're looking forward to translating that into a preclinical development and nomination there. So as far as the impact to the commercial situation, I'll let Vipin speak to that.

I mean, our strategy with the oral program is very similar to what you would expect with what's being done with other products, really a life cycle management question. As this field grows, there would be attractiveness to the oral program. As Scott mentioned, oral delivery is never going to be as efficient as subcutaneous injection. So we believe that both of these formulations would be important in terms of developing commercially the value proposition around pemvidutide.

And there are no further questions in the queue at this time. I will now turn the call back over to Dr. Vipin Garg for any closing remarks.

Thank you all for joining our call today. As always, we appreciate your continued support and look forward to keeping you updated in the months ahead. Have a wonderful rest of the day.

This concludes today's conference call. Thank you for your participation, and you may now disconnect.

Good morning, ladies and gentlemen, and welcome to the Altimmune conference call to review the top line data from the Phase IIb IMPACT trial of pemvidutide in MASH.

[Operator Instructions] As a reminder, this call is being recorded. I would now like to introduce your host for today's conference call, Lee Roth, President of Burns McClellan, Investor Relations Adviser to Altimmune.

Sir, please go ahead.

Thanks, Michelle. Good morning, everyone, and once again, thank you for participating in the conference call to discuss top line results of the IMPACT Phase IIb trial of pemvidutide in metabolic dysfunction-associated steatohepatitis, or MASH.

Joining me on the call are Dr. Vipin Garg, Chief Executive Officer; Dr. Scott Harris, Chief Medical Officer; and Dr. Mazen Noureddin, Co-Chairman of the Board for Summit and Pinnacle Clinical Research and Principal Investigator of the IMPACT trial.

A press release summarizing the results of the trial was issued earlier this morning and can be found on the Investor Relations section of the company's website. A copy of the slide set that will be reviewed on today's call has been posted to the IR site as well.

Following prepared remarks from Dr. Garg, Dr. Harris and Dr. Noureddin, Dr. Scott Roberts, Chief Scientific Officer; Greg Weaver, Chief Financial Officer; and Ray Jordt, Chief Business Officer, will join them for the Q&A session.

Before we begin, I'd like to remind everyone that remarks about future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause our actual results to differ materially from those indicated. For a discussion of some of the risks and the factors that could affect our future results and operations, please refer to the risk factors and other cautionary statements contained in the company's filings with the SEC.

I'd also direct you to read the forward-looking statements disclaimer in our press release issued this morning and on Slide 2 of the presentation. Any statements made on this conference call speak only as of today's date, Thursday, June 26, 2025, and the company undertakes no obligation to update any of these forward-looking statements to reflect events or circumstances that may occur on or after today's date. As a reminder, this call is being recorded and will be available for audio replay on the Altimmune website.

With that said, I'd now like to turn the call over to Dr. Vipin Garg, Chief Executive Officer. Vipin?

Thank you, Lee, and good morning, everyone. We appreciate you joining us today for a discussion of the exciting 24-week results from the IMPACT trial of pemvidutide in MASH.

During our call today, we will review the top line data from our successful trial, including the primary endpoints of MASH resolution and fibrosis improvement, led by a team of pathologists as well as AI, and key secondary endpoints, including weight loss, well-established noninvasive tests of liver fibrosis, safety and tolerability. We will conclude with brief remarks from Dr. Noureddin, the principal investigator of the study, before opening the call up to questions -- to your questions.

With that, I'll turn the call over to Dr. Scott Harris, our Chief Medical Officer, to go through the results of the trial. Scott?

Thank you, Vipin, and good morning, everyone. I'm very excited to share with you the top line 24-week results of our IMPACT Phase IIb MASH trial.

Let me start with the design of the IMPACT trial on Slide 3. Total of 212 subjects were enrolled. 3 treatment arms were employed, placebo, pemvidutide 1.2 milligrams and pemvidutide 1.8 milligrams, each administered weekly without dose titration for 48 weeks. Key eligibility criteria included F2, F3 MASH, a liver fat content of at least 8% by MRI-PDFF and a BMI greater than or equal to 27. The dual primary endpoints of the study, MASH resolution or fibrosis improvement were assessed by liver biopsy at week 24, along with noninvasive tests, or NITs, and weight loss. Noninvasive tests and weight loss will also be assessed when subjects complete 48 weeks of treatment, and we expect to present these 48-week results in the fourth quarter of this year.

The next slide is a concert diagram that describes the disposition of subjects during the trial. The randomization was 2:1:2 with 85, 42 and 85 subjects randomized and dosed to the placebo, pemvidutide 1.2 milligrams and 1.8 milligram arms. In the second row, note the very low rates of discontinuations due to adverse events with rates of these events in the pemvidutide 1.2 milligram and 1.8 milligram arms being less than placebo. This speaks to the superior tolerability of the compound. Finally, note that only 9% of subjects discontinued therapy before 24 weeks of treatment. This is impressive given that discontinuation rates of up to 23% have been observed in other 24-week trials.

The baseline demographics and disease characteristics are shown in the next slide. These include mean age of 52 to 54 years, female sex of 55 to 61, body weight of 109 to 112 kilograms, BMI of 38 to 39.8, 42% to 45% diabetics and 40% to 47% F3 fibrosis. The baseline ELF, VCTE liver fat content and ALT levels were also similar to previously conducted trials.

The next slide shows the dual approach to biopsy reading that was employed. In the first approach, 3 pathologists independently scored biopsies using the [ Mode ] method, blinded to subject treatment endpoint time point of sampling. In the second method, AI-based readings, biopsies were scored without knowledge of treatment assignment or time point. AI analyses that will be reported were limited to the quantification of fibrosis, and it should be noted that additional analyses are ongoing. While a rereading of the biopsies was conducted at the end of the trial in an effort to control the placebo response, we discern no real difference between the reread biopsies and the original biopsy data set. And based on this, we decided to readout on the full trial data set. This allowed us to make apples-to-apples comparisons with other trials and to provide for a larger sample size.

In the next slide, we have the first of the 2 primary endpoints, MASH resolution without worsening fibrosis, one of the FDA-defined endpoints. This was performed with an ITT analysis in which subjects with missing biopsies for treatment discontinuation and other reasons were considered nonresponders. We saw highly significant rates of MASH resolution up to 59.1% -- with up to 59.1% of subjects compared to 19.1% for placebo. In the table to the right, the results of a completer analysis and analysis using multiple imputations in which missing biopsy data was imputed are shown. Multiple imputation analyses have been employed for other compounds in previously reported trials. You can see when these latter 2 approaches were employed, the effects of drug were even greater.

On the next slide, we compare these results to the results of other studies using the same ITT approach. The FGF21 trials reading out -- after reading out at 24 weeks of treatment are shown on the left and light background, while the agents reading out after 48 weeks of treatment or longer were shown on the right darker background. Although none of these were head-to-head studies, the results achieved in IMPACT were better than or comparable to the FGF21 compounds at 24 weeks and superior to the results achieved with other compounds at 48 to 72 weeks. These results are even more impressive in consideration in the rate weight loss and tolerability that will be described.

The next slide shows the fibrosis improvement data based on pathologist reads using the ITT method. Although we saw positive trends in fibrosis improvement, statistical significance was not achieved on this endpoint. We'll dig into this further on the next slide.

On the next slide, we compare these fibrosis improvement rates to other studies. The 34.5% absolute fibrosis improvement observed for pemvidutide at 1.8 milligrams was similar to other candidates, but the achievement of statistical significance was impaired by the higher-than-expected placebo response. The magnitude of the treatment effect on a placebo-adjusted basis was not dissimilar to that observed with other compounds. Based on the additional analysis that I'm about to show you, it is our belief that these effects, which were observed at only 24 weeks of treatment have the potential to amplify over time and that statistical significance could potentially have been achieved at week 48.

The next slide shows the results of supplemental AI-based analysis that measures the proportion of liver with pathological fibrosis corrected for reductions in liver fat. As shown, statistical significance was observed for both the 1.2 and 1.8 milligram treatment arms at the 30% level of reduction and nearly 1/3 of the 1.8 milligram patients achieved a 60% reduction in fibrosis compared with 8.2% of placebo patients. It is important to note that in contrast to pathologist-based liver biopsy reads, which state biopsies in the basis of liver architecture, the AI reads evaluated total fibrosis across the biopsy field. It is evident from these results that the antifibrotic engine is up and running and that stage reductions in fibrosis as read by the pathologists could potentially have been achieved with a longer duration of treatment.

The studies on the following slide further support these conclusions. Here, we show the results of established noninvasive test results of ELF and VCTE or FibroScan as well as a more stringent composite of the proportion of subjects achieving both a 0.5 point reduction in ELF and a 25% reduction in VCTE. As shown, there was little to no placebo effect and statistically significant differences were observed that were comparable to or better than compounds achieving fibrosis improvement. The 0.5% reduction in ELF and 25% reduction in VCTE are important because they have been shown to predict favorable MASH outcomes. The reduction in fibrosis in AI-based readings and its corroboration with established noninvasive tests suggests that pemvidutide has antifibrotic activity and that statistical significance on the fibrosis improvement endpoint could be achieved with longer durations of treatment.

The next slide shows the composite endpoint of patients achieving both MASH resolution and fibrosis improvement. As shown, when more stringent endpoints are employed, the placebo response, which appeared are achieving statistical significance on the fibrosis improvement endpoint was minimized. In fact, in this analysis, the pemvidutide response was almost twice that observed with placebo and approached statistical significance with a P value of 0.07 at the 1.8 milligram dose. It is important to note that resmetirom and semaglutide, 2 drugs that are either approved or on the verge of approval for MASH, failed to meet statistical significance on the fibrosis improvement endpoint in Phase II trials, but met them in Phase III.

In the case of resmetirom, success was achieved by extending the duration of treatment from 36 to 48 weeks, allowing the fibrosis improvement response further time to develop. And in the case of semaglutide by the reduction of the placebo response inherent when large number of subjects are studied as when Phase III studies are conducted.

Moving to the next slide. Pemvidutide reduced liver fat content by up to 62%. There were also high proportions of subjects achieving 30% and 50% reductions of liver fat or liver fat normalization, all of which were statistically significant.

The next slide shows significant reductions in alanine aminotransferase, or ALT, a key marker of liver inflammation. Reductions were noted as early as week 4, showing the rapid onset of drug effect. As shown in the next slide, significant weight loss up to 6.2% was observed with the 1.8 milligram dose at 24 weeks of treatment with the trajectory of weight loss showing no evidence of plateauing at that time point. It should be pointed out that pemvidutide 1.8 milligrams is not the most effective dose for weight loss as 40% more weight loss was observed with the pemvidutide 2.4 milligram dose in our Phase III -- excuse me, Phase II MOMENTUM obesity trial. Therefore, inclusion of the 2.4 milligram dose in Phase III would provide even greater weight loss. The weight loss achieved with pemvidutide is a major differentiator with pemvidutide compared to FGF21, which failed to demonstrate a significant weight loss effect compared with placebo in prior trials.

The weight loss is a critical element of MASH therapy as the comorbidities of obesity and MASH account for higher mortality rates than the liver disease up to the advent of cirrhosis. In addition to these significant efficacy results, we also observed a potentially class-leading tolerability profile as shown on the next slide. Although there were a small number of serious adverse events in the trial, these were equally balanced across treatment arms and none were related to study drug.

As mentioned before, virtually no adverse events leading to treatment discontinuation were observed despite the absence of any dose titration. Adverse event discontinuation rates approaching 30% have been observed in other trials even with those titrations out to 24 weeks. There were no adverse events of special interest and importantly, no imbalance of cardiac events compared with placebo and no arrhythmias. While dose reduction for intolerability was allowed in the IMPACT trial, this option was chosen by a small number of patients and the reduction was temporary in the majority of study participants.

Looking at GI tolerability in the next slide, the rates of GI adverse events were comparable to what has been observed in other incretin trials, and this was achieved without dose titration. The majority of AEs were mild in severity and no severe GI adverse events related to study drug were noted.

Turning to the next slide. Hemoglobin A1c was maintained in subjects regardless of diabetic status. These results are similar to the results observed in prior trials of pemvidutide.

On the next slide, changes in blood pressure and heart rate are shown. As noted, significant reductions in systolic blood pressure were observed versus placebo, and minimal increase in heart rates were observed that were not significantly different from placebo.

In summary, as shown in the next slide, pemvidutide was the first therapy to achieve statistically significant MASH effects along with weight loss at 24 weeks. The study demonstrated MASH resolution in up to 59.1% subjects in an ITT analysis in which subjects with missing biopsies for treatment discontinuations and other reasons were considered nonresponders with a high level of statistical significance compared with placebo. A level of mass reduction was achieved at 24 weeks that was not achieved by other compound -- that was not achieved by other compounds at 2 to 3x the treatment duration. It is important to remind you that based on FDA guidance, these effects alone would be sufficient for approval in MASH. We believe these data position pemvidutide well to achieve Phase III success and regulatory approval.

Regarding fibrosis improvement, we demonstrated trends to improvement on pathologists reading of the biopsies, but in AI-based readings of the same biopsies, significant reductions in fibrosis were observed at both pemvidutide doses. This was supported by statistically significant improvements in well-established noninvasive tests of liver fibrosis, including ELF and VCTE. Collectively, these results build our confidence in the antifibrotic activity of pemvidutide and lead us to believe in the potential of meeting that endpoint had the biopsies been performed at 48 weeks.

We also saw robust liver fat reduction of up to 62.8% and achieved weight loss of up to 6.2% at the 1.8 milligram dose with no evidence of plateauing at 24 weeks. In addition to these encouraging data, there were impressive safety results with discontinuation rates due to adverse events approaching 0% in both pemvidutide treatment arms. This was class leading among drugs in development for MASH. Impressively, this effect was observed in the absence of dose titration. There were no heart rate increases or differences in cardiac AEs between pemvidutide and placebo, and we saw that hemoglobin A1c was maintained regardless of diabetic status. Collectively, these data point to best-in-class potential of pemvidutide in the treatment of MASH.

With that, I want to ask Dr. Noureddin for his comments on the data. Dr. Noureddin?

Scott, thank you so much for the great presentation, and good morning, everyone, from Houston, Texas. I was the PI of the study, but also one of the high enrollment in the study. So I had direct experience and observation of the drug in my patients. And Scott, I will start with congratulations to Altimmune of hitting the primary endpoint of the study at this early point, which is 6 months. And as you alluded nicely, the MASH resolution was one of the highest we have ever seen, again, noted at 6 months only of this study. The weight loss is something I look for in my patients. And again, congratulation on this amount of weight loss. And as you said, the 2.4 milligram will even take us probably further.

I think I want to highlight a very, very important point here, which is the safety profile and the discontinuation rate as well as the titration. There was no titration in this study. The discontinuation rate was in 1 patient on the drug and 2 patients on the placebo. And I'm sure like our investor colleagues, they follow the obesity world, and there are many medications now in the obesity world, and what the obesity world is focusing on now which drug is tolerable. And this is the first time we see this in MASH that such a drug has such a low discontinuation rate and the titration is very favorable. So those are things I want to congratulate our patients of having it in this trial.

I think the elephant in the room here, Scott, is the question we'll ask about the likelihood of achieving fibrosis improvement within 48 weeks and in Phase III study. And you said it nicely that just watch what happened with previous drugs with the resmetirom and semaglutide, they did not achieve fibrosis improvement statistical significance at week 36 and 72 weeks. Here, again, we're only at 24 weeks.

Nevertheless, you said it correctly, the antifibrotic engine. I think the AI data, the statistical significant, especially in that 60% reduction is giving me a highly likelihood of achieving fibrosis improvement at week 48, not to mention, we can also have the 2.4 milligram with further fibrosis improvement and further weight loss. The NIT data is very strong, suggesting that it's corroborating with the fibrosis improvement seen in AI. So the totality of data showing me highly likelihood of achieving fibrosis improvement in week 48, especially with the 1.8 and 2.4 milligram.

I guess the other question, I'll finish with a couple of 2 comments, the place of this drug within the MASH therapeutics. I think one thing to note in this trial, we shaved off another 6 months by doing 6 months only trial, and we're going to enter Phase III hopefully soon, and that will put us in a very competitive position with this drug. I think the drug is efficacious. We will hit both MASH resolution and high likelihood of fibrosis improvement at week 48. It has outstanding tolerability. So it has a very strong place as a very highly efficacious drug within the MASH drugs.

The last comment is, Scott, you and I, we are considering and the Altimmune team are considering a unique design that we'll discuss with the FDA that will accelerate our enrollment in Phase III and to deliver this drug to our patients in the market as soon as possible.

So again, congratulations. This is an excellent outcome and outstanding results, and I look forward to the Phase III.

Thank you so much, Dr. Noureddin. With that, I want to thank you for your attention and turn the microphone back over to Vipin. Vipin?

Yes. Thank you, Scott. To summarize, we are very excited by the data we are sharing with you today. The category-leading MASH resolution we achieved in IMPACT positions us well to continue our efforts to bring this potentially transformative therapy to MASH patients. Based on the positive fibrosis improvement trends observed and the highly statistically significant improvement in the noninvasive biomarkers, we believe that statistical significance can be achieved in both MASH resolution and fibrosis improvement in Phase III, which would not only put pemvidutide in position for a regulatory approval, but to become a foundational therapy in the treatment of this highly prevalent disease.

That concludes our formal remarks, and we would like to invite Dr. Noureddin to the microphone as well to join the team as we open the lines to questions. Operator, could you please instruct the audience on the Q&A procedure?

[Operator Instructions] Our first question will come from Roger Song with Jefferies.

Congrats for the data. I have a couple of questions related to data. Maybe just start with the fibrosis. Can you just give us some context why the completer analysis even lower than ITT for fibrosis, while we see some improvement for the MASH resolution, understanding this is tougher to hit endpoint.

Yes, Roger, thanks for the question. It really depends on why patients didn't complete the study. If you look at other studies, completer analyses are better than ITT. And the reason is that more patients on the drug dropout, so that when you censor them and don't consider them, you get better results. I think that's the opposite case here because we have less dropouts with the drug than with the placebo.

Our next question comes from Lisa Bayko with Evercore.

I just wanted to understand a little bit more the placebo rate and your thoughts on the methodology you're using. I mean we've seen some pretty extreme placebo rates with this sort of 3 reads and then using the mode and rereading the biopsies. If we look at that methodology, overall, we've seen placebo rates as low as 7%, which really stand out and then 25% here, which is also a very high number. I'm just curious if you think that's the right approach. I'd be curious for everyone to comment on that? And then if that's something you'd consider for the Phase III?

And then I guess my second question is, how are you thinking now about glucagon adding to the mechanism of action versus GLP-1? And I'm trying to distill out sort of fat exiting the liver and the liver naturally resolving itself from a direct antifibrotic effect, which I think we were hoping to see within the first 6 months as having a profound impact, but it seems like it's a little slower. So I'm just kind of trying to understand the direct antifibrotic effect that you're seeing here versus fat exits from liver.

Thank you, Lisa. Let me answer the questions in the reverse order. I also want to have Dr. Noureddin give his thoughts about the placebo response rate. Glucagon is clearly quite active here. It has very potent effects in liver fat reduction, as you've seen, and that's one of the drivers of the fibrotic response. I think that if you look at the AI and you look at the noninvasive test, glucagon is very active. And what we're seeing here is not a glucagon effect on fibrotic activity, you see the problems with the biopsy reads and not being able to observe it. But the ELFs and the VCET (sic) [ VCTE ] responses that were observed are as good as any compound at any time point.

So based on the noninvasive tests and then the AI-based reads, glucagon is very active here. The problem is overcoming the noise in the biopsy reads. Regarding the placebo rates and the methodology and the [ Mode ] method, you did -- are correct in pointing out placebo rates between 7% and 25% on the slides. But in the semaglutide Phase II study, it was 32%. And quite frankly, we went to great extremes to try to control the placebo response, as you know, and we were not able to control it. I think the jury is still out on what the placebo response is with the biopsy readings and how we better control it. There's a lot of activity going on, much of which is being led by Dr. Noureddin to find alternative methods to the biopsy, such as the noninvasive test and AI reading, which we at Altimmune feel are going to be superior to the biopsy reads. Nonetheless, the pathology biopsy reads are still the point of approval for the FDA.

But I'm going to stop there and ask Dr. Noureddin for his comments. Mazen?

Yes. Thank you, Scott. And I think, Lisa, right, you pointed correctly that the placebo rate was on the higher side. Just to give you an idea about that 7% you mentioned, that has seen -- that was seen in only one trial and most trials are not that. This is point one. Point number two, what you see between Phase II and Phase III studies a consistent story that the placebo response dropped in Phase III studies. And it could be because of the larger sample size, which will happen here. So if we just look at all Phase IIIs, those that failed and those that succeeded, the fibrosis response will drop in the placebo. In terms of the Mode method, you asked if -- what people will do in Phase III. And there's a lot of discussion now with the FDA about that method to do it or not, and we will be discussing that with the FDA. But I feel like if we -- once we conduct the Phase III study, if we are consistent with the other trials that will show better placebo response that has been seen across all other trials in Phase III.

Just one follow-up. What happens with the fibrosis response on drug? I know the placebo response goes down in Phase III. I understand the idea. And what happens with the treatment arm?

Yes, go ahead, Mazen, please.

In general, the delta -- I mean, this has been seen in resmetirom as well as the semaglutide. Overall, the trials, the delta increase between the placebo as well as the effective drugs.

Yes. And I would say that not only would the placebo response go down, the drug effect will go up. I think that we're seeing the engine up and running. And I think that the 35% response rate we saw at the 1.8 milligram dose is only going to grow with time. I think also you would note that going to more stringent endpoints, like the composite endpoint when you control the placebo response, you can clearly show the drug effect. We saw a twofold response rate on that composite of MASH resolution plus fibrosis improvement compared to placebo. And that just barely missed statistical significance with a p-value of 0.07. And we think that this truly represents the drug effect when the placebo response is controlled.

Sorry, just a follow-up [indiscernible] -- sorry, what was the p-value for the fibrosis change in this trial? I know that wasn't...

Yes, it was not significant, but I did mention the fibrosis improvement plus MASH resolution because it did come very close to it. The other values were not significant.

And the AIs, all of them were statistically significant, including the 60% reduction, which -- to me, that is equivalent to one stage fibrosis improvement at that method AI. But I'm not comparing apple-to-apple here, but it's an indication for me that that's a good delta there.

[Operator Instructions] And the next question will come from Yasmeen Rahimi with Piper Sandler.

This is Emma, on for Yas. I guess we're wondering that beyond the larger size in a Phase III and duration, what are some things you can do to mitigate the placebo response in the Phase III? And do you think that there is an opportunity for the regulatory like landscape to shift towards maybe accepting AI-based histological analyses?

Thanks, Emma. Well, obviously, we have one very successful strategy here, which is the placebo response will go down in Phase III. We're also looking for additional methods to control the placebo response given the biopsy reads. Obviously, more stringent endpoints like the one that was shown in the presentation will also improve the treatment effect.

I'll let Mazen comment further on the AI. There's been a lot of movement in that direction. There is the belief that at sometime in the future, the FDA would accept AI-based readings, but I'd like to Mazen to expand on that further. Mazen?

Yes. And I want to also build up on what you said, like the other drugs that they met the fibrosis improvement in their Phase III, they did not change much in their designs or endpoints or anything. They just went for larger sample size, larger -- longer duration in the case of resmetirom, and that happened, the placebo went down. So as Scott said, we have strategy to mitigate the placebo response. In addition, the 2.4 milligram is a strong consideration for Phase III that it's possible that it will need larger fibrosis movement and more weight loss.

I don't know what's in the public in terms of AI. I know what's in the public that PathAI has applied for FDA approval, which I anticipate it's not going to be far away from us. Rather that's in the clinical trials or clinical use, I'm not sure yet. But there is FDA process for PathAI to be approved by the FDA. And my understanding, it's far along in the process.

And our next question will come from Annabel Samimy with Stifel.

I had a question actually about the dose. You mentioned that you are going to be pushing the dose higher to 2.4 in Phase III. I guess one thing I was surprised by in certain of the measurements were -- was the reverse dose response. So I know you're pushing dose for more weight loss. Will you actually achieve any greater mass improvement or fibrosis improvement with a higher dose? And at this point, should we give up on this potential for pemvidutide to have differentiation based on the 24-week fibrosis improvement? Because if that's the case, does it differentiate sufficiently from semaglutide?

Right. Well, thank you, Annabel. So I want to point out that -- while there is potential for achieving higher weight loss and as Mazen mentioned, higher MASH effects with the 2.4 milligram dose, we have not made a firm decision on that at this point, and it has to be discussed with FDA. So it is a vision, but please be aware that there has not been a firm decision made on that point.

Regarding what you're calling the reverse dose response, which you're probably seeing in Slide 8 on the MASH resolution, I'd point out several things. First, the 1.2 milligram dose, which has the appearance of beating the 1.8 milligram dose in that slide is 1/2 the number of subjects and 1 or 2 subjects would have made a big difference there. But also, if you look across the slides, with regards to fibrosis improvement, with the exception of efruxifermin dose response has not been seen on MASH resolution.

And also, if you look ahead to Slide 10 on fibrosis improvement, the same could be made. And in fact, with pemvidutide, there is the appearance of a dose response. So I think this has to be shown with larger trials. This was 80 subjects per trial and Phase III will be considerably larger. No, we would not give up on pemvidutide results at week 24. The AI-based readings are extremely promising. And with larger sample sizes, that effect could come out very clearly in clinical trials, especially with AI-based reading.

But I'd like to have Mazen add his thoughts to that. Mazen?

I'm going to add a few things to what you said, Scott. In terms of the 2.4, we're still making the decision, but I don't want to underestimate the 1.8 milligram. It has a likelihood of meeting fibrosis improvement at week 48 based on the AI data that I'm seeing here as well as the noninvasive testing that you have seen here. If you want to comment on the MASH resolution, along the same page, Scott, but I will say actually, the MASH resolution variation and not having the dose response is actually across all drugs. We're not sure why. It's probably variability on the biopsy. But still, like the MASH resolution, I'm not sure like 53% versus 56% make much difference in a highly variable field of biopsy. So that MASH resolution is across all trials actually.

Annabel, let me just chime in on the question regarding the differentiation. We've actually already established a differentiated profile, MASH resolution at 24-week and significant weight loss. That's a unique combination already that we are bringing to the table. We believe that we'll hit the fibrosis resolution improvement as well at 48 weeks. So if you combine all 3 of them, we would be highly differentiated from any other drug for MASH, where there is a combination of MASH effects and weight loss and the tolerability on top of that. So you put all that together, it's a very highly differentiated product profile that we believe we will have at the end of Phase III.

And our next question will come from Ellie Merle with UBS.

I guess curious for a little bit more color on how you're thinking about a potential Phase III design and what you learned from this data and how you're thinking about that and your base case for what the design would look like in terms of like specific doses and the length of the study? And then just a second one kind of on the design and prioritization, just the timing for when you would potentially start a Phase III and how you would prioritize the development in MASH relative to ALD and AUD programs.

Thanks for the question, Ellie. Well, I'll look over to Mazen, but it's likely that the FDA will, regardless of any data that we see here, ask for 52 weeks in Phase III all the other studies that are being conducted even with the FGF21s, which showed good results at 24 weeks are doing trials of longer duration, even one sponsor is doing 1.5 years. So the design is currently being formulated at this point. We're taking a good look at which doses we want to take forward. As Mazen mentioned, we're working with him to develop some very innovative strategies that will potentially shorten the time to the completion of the program.

As you're aware, the Phase II study was one of the most rapid enrolling studies to date. We think that in the tolerability profile and the low dropout rates in the trial really speak to the great patient experience. And I think the investigators saw that as well when patients rallied to come into the trial. The funnel was very -- was always filled with patients trying to get into the trial. So we think that with innovative design, rapid execution, as Mazen mentioned, we were able to save 6 months by reading out at 24 weeks and still achieved a positive trial that will move us into Phase III that these things will accelerate the program.

The other thing I would mention is that the safety database that we have of almost 700 patients coming into the end of Phase II meeting will help defray the number of patients needed in the overall program. And that by itself will cut down in the cost of the program and speed up enrollment. So we're looking to have the end of Phase II meeting in the last quarter of this year and launch the Phase III program in the first quarter of next year.

Regarding the other indications, as you know, the AUD trial has already been initiated. We press released on that approximately a month ago. And while we are projecting that, that trial will read out in the third quarter of next year, the trial is enrolling rapidly, and we may have to adjust that estimate for the Street. And we'll be making an announcement on the initiation of the ALD trial very shortly. And we think that, that would follow in the tail of the AUD study readout.

And our next question will come from Jon Wolleben with Citizens.

Wondering if you guys had looked at responses based on F2, F3 fibrosis at baseline in diabetics and nondiabetics? If you saw any differential responses between those 2 groups?

Yes, Jon, we haven't been able to get -- to analyze that data to date, and we should be providing further information at a scientific meeting coming up later in the year.

Do you think that any differential response there makes these results better or worse?

We're just going to have to see the results, Jon. And we anticipate we'll present them and make determinations based on that data.

And the next question will come from Patrick Trucchio with H.C. Wainwright.

The first is for Dr. Noureddin. Just curious if you can talk about the learnings that have emerged from this data readout in terms of informing the Phase III program? And what you would hope to learn from the 48-week data? And then separately for the Altimmune team. With weight loss of 6.2% at 24 weeks and no plateauing, how do you see pemvidutide positioning against semaglutide and survodutide as well as tirzepatide?

Yes. I'm happy to answer the first question. So the first question is the 6-month trial in GLP-1s and duals in particular, and the duals with the glucagon are very, very important. As you know, this is the very first trial that does that within 6 months paired biopsy. So I think we are just on track to see what we see in other Phase III trials. So I guess the biggest question for us in this Phase III, should we use the 2.4 milligram or not? So that's one of the questions. At the week 48 data, I look forward to seeing the static and the fibrosis improvement, which I think will be the case. So I still think that the 6-month trials put us an advantage that we will enter Phase III sooner. And I'm very comfortable going to Phase III and with higher likelihood of meeting both.

Thanks, Mazen, Patrick. I'll take the second question. You had asked about the 6.2% weight loss and how that's positioned versus other drugs with weight loss such as semaglutide, survodutide and tirzepatide and the treatment of MASH. The first thing I would point out, as I did in the presentation, that in the MOMENTUM Phase II obesity trial, the 2.4 milligram dose achieved 40% more weight loss at 48 weeks than the 1.8 milligram dose. So you could take the 6.2% here and project what that weight loss would have been had we employed 2.4 milligrams in this trial. But this is very comparable to the weight loss seen with semaglutide.

So we think the drug is well positioned against semaglutide. We think the rates of MASH resolution and fibrosis improvement. Let me start with MASH resolution. We'll be achieving at 24 weeks, better MASH resolution that semaglutide achieved at 72 weeks. We think the fibrosis improvement would follow in the same path showing superior MASH results.

Regarding survodutide, it has to be pointed out that this drug is far superior in tolerability to survodutide. In their MASH Phase II trial, they titrated for 24 weeks and even with that, saw adverse event discontinuation rates between 22% and 30%. Ours were less than placebo, and we achieved that without dose titration. So we think that there is really no comparison between the 2 drugs in terms of the tolerability and the patient experience. And I would also point out that we've been to FDA in an obesity program, and we found the FDA identified no cardiac safety signals in our trial, in our data, in our compound in our program. I think you'd have to look at the survodutide program in question, with that there's a possibility FDA may have identified a signal on their programs.

And finally, with regards to tirzepatide, we think that the same comparisons we made to tirzepatide in terms of the MASH resolution and fibrosis improvement rates that would be seen at 48 weeks. But to the best of our knowledge, the data has been out there for well over 1.5 years, and there's been no indication that the company will take tirzepatide into Phase III MASH trials. So we're not sure that compound should even be included in the spectrum of MASH therapies for comparisons.

I think I just want to add to that, that the key differentiation remains this combination of dual mechanism, direct metabolic effect through weight loss and direct effect in the liver with the glucagon. So that's really what we are bringing to the table, very compelling weight loss, very meaningful weight loss that MASH patients need. 80% to 90% of MASH subjects have obesity would benefit from weight loss. So we're bringing that. And on top of that, there is direct effect on the liver in terms of excellent MASH activity we've already shown and with fibrosis improvement, again, that would put together a very compelling package, highly differentiated from all other programs.

And our next question will come from Mayank Mamtani with B. Riley.

Most of my efficacy questions are being -- have already been addressed. Maybe if I could have you comment on safety and tolerability. What do you guys think drove a very low discontinuation number here? Is it the GI AEs mostly being mild, maybe not being persistent was only observed with initial few doses? Or is it just motivation of getting the weight loss that you get with this drug?

And then one for Dr. Noureddin. With resmetirom uptake going well and sema approval expected shortly, how do you think of allowing for user background therapies? And if you could clarify in this study, was there any background GLP-1 use? I didn't see that information as part of the baseline characteristics?

Mayank, I'll answer the first question, partly answer a little of the second question, and then I'll turn it over to Mazen regarding the color on resmetirom. So we've always contended that pemvidutide is amongst, if not the best tolerated drug in the incretin class. And in fact, hey, based on this data, probably even the best drug in the MASH class, including all the other compounds in development. And we're getting this without dose titration, and that's based on the slow entry of the drug into the bloodstream. And we think that's highly differentiating because titration is a real problem in practice and also getting approval for the different steps of drug titration.

So it's clear that patients who have diseases such as MASH and diabetes have lower adverse event rates and lower rates of adverse event discontinuations than in conditions such as obesity, where there's probably less motivation to get treated and other alternatives they can get without staying in a trial. The adverse event here, the major ones were GI. And as you pointed out, the majority of them were mild. They were transient, and they didn't require pharmacological treatment. And I think there was a great acceptance in the program of patients based on their experience. I think they like the therapies. They stayed in the trial. We got the same feedback from investigators. I'd be interested in Mazen's comment about that.

Regarding the GLP-1s, we did allow low doses of GLP-1s in the program, in the study up to a semaglutide dose of 1 milligram, RYBELSUS 14 milligrams and other GLP-1s except for tirzepatide. Unfortunately, I don't have that data to share with you in terms of the numbers of patients or how these patients did in the trial. As I mentioned before, we did include diabetics. I don't have the response rate on that either. But I'd be interested in hearing Mazen's comments about his experience as an investigator as well as his color, Mayank, on your question on resmetirom. Mazen?

Yes. And just to follow up on that GLP-1 question. I don't -- if I recall correctly, we did not have a lot of patients in the trial with GLP-1, definitely on the lower side. And I think we stopped that at a certain point. This is anecdotally my memory. So I mean, I get this question always about like what do you think is going to happen in the field now you have resmetirom with a great uptick actually and semaglutide coming to the market. And it's just like it shows -- the uptick shows the appetite and how big gap we have in the field and how many patients we have out there that they're needing treatment.

Now I always try to learn lessons from other fields, such as the type 2 diabetes field and the weight loss field. And what you see here is the -- you still have multiple drugs entering in these studies. And what they are trying to do is add effect, show superiority and show a tolerable side effect. And many of them, especially in the type 2 diabetes field, have multiple rooms and large patient population, especially when you add a combination therapy to each other, which we think the case in MASH. I think this drug is going to be great as stand-alone as well as for combination. I think the -- it has -- as a physician, I'm waiting for better drugs, more tolerable drugs, add an efficacy today already on the market drugs.

So I think there's a lot of room for this pipeline of MASH. So I always say it's not competition, it's a harmony between these drugs for the patient's benefit. I will be surprised if patients with F3 in particular, will be on one MASH drug eventually like a MASH drug, F4, I will definitely say that we will see patients on combination dual or even triple sometimes because once I hit cirrhosis, I want to reverse that as soon as I can, as hard as I can. And of note, I would recommend to do the Phase III program, including the cirrhotics, and I'm comfortable that it will show results and higher likelihood there.

That is actually another important question we got like the plans for F4 cirrhotics. Is there anything formalized? Or are you guys still kind of contemplating that? I don't know if Mazen want to take that...

I mean, I just said I would recommend it. I think it's -- I'll leave Scott to answer that question. We did not comment on the design and the unique designs we have already been discussed because we need to discuss it with the FDA. But we're -- we have made very good plans thus far.

Scott, do you want to add additional flavor to this?

Yes, Mayank. Yes, we think that we'd be very effective in phase -- in F4, and this is a population that we really like to study in Phase III, and that will be discussed with the FDA.

And our next question will come from Andy Su with William Blair.

I just have one for Dr. Noureddin. And it's really a follow-up on Emma's question on AI. So we know that there is a very clear and significant delineation between various fibrosis stages and liver outcomes, progression to cirrhosis and death. But do we have any data to suggest that the area of fibrosis is done by the AI in this case also has a strong correlation. And just kind of related to that, I'm curious about how that AI is trained? What are some of the training data sets that they use or you basically just kind of use PathAI kind of what they offered?

Yes. I didn't understand exactly what do you mean by the correlation in particular. But to talk about correlation, there is -- the PathAI studies in general showed that it's plausible that this 60% reduction is equivalent to one-stage fibrosis improvement. It's just done in a more careful and methodological way than the conventional one-stage fibrosis. Again, so in my mind, when I look at that 60% from the data across trials and discussions, that to me is the one-stage fibrosis improvement. The -- I think we have plans also to use Histoindex. I think that has not been finalized. And I think they have also a very solid method out there. As I mentioned, my understanding from PathAI that they are in the FDA sitting down for discussions, and I do predict that they will get FDA approval.

Did I answer your question or I missed part of it?

It's really about kind of the area of fibrosis and outcomes, right? Obviously, from a regulatory perspective, that's what they want to see. And so we have that, and I think the FDA accepted that as a proxy, right, for fibrosis stage and outcomes. I'm just curious about whether you can substitute area of fibrosis as a potential alternative surrogate given some of the supportive data, right? So I'm just wondering whether that there's supportive data on the liver area of fibrosis with outcomes.

Yes. So the first data come to mind, not necessarily from the PathAI from the Histoindex. It was the SNOF score that I worked on with Histoindex and that SNOF score was in people with cirrhosis that we did from the Galectin trial. And that AI methodology, the SNOF score did correlate in particular with reduction in portal hypertension. As you know, there's not a lot of trials that showed outcomes yet. They are still ongoing. So I'm sure the AIs of the world will correlate that eventually with histology. The most data came from -- in cirrhotics, which are closer to outcomes from data from, for instance, the Galectin trial, and we have shown correlation with reduction in portal hypertension in particular. So more data is needed, but there is a hint there that it does correlate with outcomes. But I would love to have more solid data, but that's when we have the outcome studies.

Yes, I think you have to move to the next question.

I'm showing no further questions at this time. I would now like to turn the call back to Vipin Garg for closing remarks.

Thank you, everyone, for participating today. We appreciate the opportunity to share our results and outlook with you, and thank you for your continued interest. Have a wonderful day.

This concludes today's conference call. Thank you for participating. You may now disconnect.