Altimmune, Inc. (ALT) Earnings Call Transcript & Summary

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.