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

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.