Good afternoon, everyone. Welcome to our second day of our Piper Sandler Healthcare Conference. My name is Yaz Rahimi. I'm a senior biotech analyst at Piper, and I'm a long-term supporter of Altimmune, actually one of the first analysts to cover the company for many years and really have seen a tremendous amount of progress. So we have lots to cover, but maybe the first place is Vipin. It's been a pleasure working with you. And Jerry, I've had the pleasure of working with you through my coverage of Intercept.
Great to see you again, Yaz.
It's great to see you and work with you. I guess Vipin, obviously, you're going to be still active with the company as a consultant. Help us understand why was it important, the transition of maybe Jerry coming on. And Jerry, obviously, your tremendous expertise at Intercept through the launch of Ocaliva and in the MASH space and getting the company ready for commercialization there. Help us sort of the learnings from your experience with Intercept and the reasons for joining Altimmune at this time as well.
Yeah, well, yeah, thank you very much. As you said, you've been covering the company for a long time. In fact, I did my first fireside chat for Altimmune with you, so I remember that. That was in 2019. So thank you for all your support, and it's an exciting time for the company. We think this is the right time to transition to a new leadership. Jerry has been on our board for about nine months now, so I've worked very closely with Jerry. I've gotten to know him. He's gotten to know me. This is a very smooth, very orderly transition. He brings very different experience, and I brought the company to the doorsteps of phase III. Now we need to embark on a very large phase III program and bring commercial expertise, so he's the right person to take the ship forward. So I'm really excited about Jerry joining the company and looking forward to the future here. Jerry?
Yeah, and obviously from my standpoint, really excited about what the next phase may hold. A lot of appreciation for all the great work that Vipin has done over the years to get the company to where it is now, really on the doorstep of some exciting opportunity ahead. As Vipin mentioned, I did have a chance to join the board earlier this year, get an understanding of what the company has been doing, where the opportunities are. And it's really that view that gives me the excitement about what's ahead. And first and foremost, as always, part of the excitement and assessment is around pemvi and what it could really bring to the market. And I think you look for products that can be differentiated in an important marketplace. It's clear that the profile of pemvi is uniquely suited for liver disease.
The fact that it brings potential impact both on weight, on metabolic parameters, and directly on the liver, we think has a lot of potential not only in MASH, where we're waiting on this end of phase II meeting to come, but also in the other indications we're pursuing in AUD and ALD. It's been a pleasure to get to know Vipin. I think we have a unique opportunity here. We've been working together for a period of time. We have between now and the first of the year to continue this transition, as I'll take the reins officially at the first of the year, and then Vipin will be available to us for the first half of next year as an advisor. So it really sets the table nice for us to be able to pivot to the next stage of the company and take advantage of all the strength that has led Altimmune to this point.
Wonderful. Lots happening in this quarter. One, that investors are following, obviously, is the end of phase II meeting with the agency. I don't know if I can ask, but has the meeting been granted? Has it occurred? Sort of the cadence of the disclosure around it, let's maybe.
Yeah, so we have two important catalysts coming up by the end of this month, really. We are at the end of fourth quarter. We have a scheduled end of phase II meeting with the FDA. The meeting has been scheduled. It's an in-person meeting. We're very excited about that. We are also expecting our 48-week data during the month of December. So both of these events will take place over the next few weeks. And we're hoping to learn, reach alignment with the FDA in terms of our phase III program. As we have said before, our goal is to have a very flexible design because there's so much that could change over the coming months and years in terms of the endpoints, the whole discussion about doing away with the biopsies and going to an NIT-based endpoint, as well as the discussion around AI-based reading of the biopsies.
So depending upon which direction the FDA goes, our goal is to be able to pivot, have a phase III design that would allow us to pivot to either one of those two scenarios, either AI-based reading or NIT-based endpoint. So that's our goal, is to really reach alignment with the FDA that we'll be able to design that into our protocol upfront and be able to flip at the point that that change occurs.
And maybe for investors who haven't followed this new development, and Jerry, what a big move it would be to being able to get one of these two outcomes. Maybe help us understand the advantage of if you did AI-based reading, so what is the advantage of doing that? And then if you do move to an NIT-based endpoint, what type of NIT would you propose or what would be a compliance proposal that you would have in mind? So maybe help us understand that.
Yeah, so we looked at both NITs and the AI-based reading from our 24-week data, and it was very clear that everything is moving in the same direction. So it's the totality of the data that's important. To your point, in terms of what would be the endpoint, it's probably going to be a composite of a couple of things, both looking at liver stiffness, which is an important measure of fibrosis, as well as a blood-based test called ELF. So really, potentially a combination of the two. But again, it's going to be looking at multiple endpoints and showing that everything is moving in the same direction.
With AI, the benefit, obviously, is that it takes away the bias of a pathologist, the human bias, and our 24-week data looks very good in terms of AI-based reading because we can look at the total fibrosis improvement as opposed to just the stage improvement, which is what the pathologist is required to read. So you can really look at whether the drug is working or not. Is it working from day one? It's very clear. We got class-leading MASH resolution without worsening of fibrosis. We also have very strong fibrosis improvement on an absolute basis. Pemvidutide is very comparable to other compounds. It was the placebo that came in higher than expected, so we didn't hit the statistical significance, but we fully expect to do that during our phase III at the 52-week readout.
The flexibility is going to be important. And as Vipin mentioned, we're going to be proposing a flexible design so that if the agency moves, we would be able to seamlessly evolve the study. It's also going to be important as we think about, again, the continued evolution of the capabilities of the company that we're ready to execute on that because it's great to have the flexibility in the design, but you have to also be able to execute flexibly. So getting the team ready, consistent with what we're going to be able to come to alignment with the agency is going to be crucial. It's been nice to see all the momentum here towards NITs. I mean, Yaz, we've been talking about this for a long time. We'll see where the agency gets to, step one, step two, step three. But even coming off the most recent liver meeting, there is really a lot of alignment from the scientific community around this combination of NITs being a really sound way to look at this. So we'll put the discussion forward.
Tim[guess], I assume the cadence would be the meeting is already scheduled. You will have an active discussion. You would wait for the minutes, and probably then in one queue, you could come back and communicate sort of what the outcome of the study would be.
That is a potential scenario. That's a potential scenario. We'll obviously evaluate the outcome of the meeting. Sometimes you can get fairly good clarity just after the meeting itself, but we'll have to make that decision when we have that kind of phase II meeting.
Okay, that's helpful. And I think it's also an important distinction that when you did analyze with your AI, you showed a statistical separation in fibrosis. It's a much more sensitive assessment and takes the bias out, which is also critically important.
Absolutely correct. I think Jerry has his own point of view when he looked at the whole data. It's clear that the drug is working not only for MASH resolution, not only for reversing inflammation, but also reversing fibrosis.
And again, the reminder that the two-week results that we put out earlier in the year, we're at 24 weeks. And so hitting fibrosis benefit on histology at 24 weeks is, frankly, a very aggressive. So the fact that we saw a very strong impact on MASH resolution and all these other indicators that the anti-fibrotic process was underway so quickly for me was a very positive thing. We'll see the NITs at 48 weeks now and then clearly propose a 52-week endpoint in phase III.
Tim, one of the questions we get is to fast forward. Let's say one of the two scenarios play into hand, either AI-based or you get NIT. A lot of investors will ask, what is the time saving, especially if you do get NIT, right? Because then you end up not having to do a baseline biopsy, and maybe the patient would be more inclined to wanting to be. Have you guys gotten a good feel for, as you, let's say, fast forward, you've done the study, you're going to probably give some color on how you're thinking about timelines?
Yeah, I think we're not ready yet to guide on time.
[crosstalk] there's moving forward.
What I would say is that we know it's easier to enroll patients if you don't have to do the biopsy. Obviously, if we enroll by biopsy and it changes, you have some ability then potentially to roll new patients in. But I think first and foremost, the NITs probably give you, to the point you made, a more objective measure. And that's ultimately the most important benefit. And then you probably have other benefits on ease of running the study and things that would come into play, and again, we'll come back if we're in a position with a phase III design to talk about timing expectations next year.
And AI has similar benefits in the sense that, again, it takes away that subjectivity and it becomes a more objective measure. So I think it really increases the probability of success and provides more accurate data.
Perfect. And then Tim, maybe just a few questions. Obviously, the next, another big catalyst is the 48-week data that's going to be presented, which is all NIT-based. And based on what you said, it is on track. It's going to come. I don't know if you have visibility which one is going to come first. I assume the data first.
Given the timeline we are at, they're going to be very close. So we'll just have to see. It's a race between the two of us.
And what do you want?
The scientific team is very busy in the company right now preparing.
Perfect, and then Tim, help us understand what do you hope to gain from that data readout, right? I think investors walk away. Especially the frequently asked question is, what are the NITs of importance that you want to see continued benefit in as we go from 24 weeks to 48? And then the second question also, given that promising weight loss benefit, what do you expect when we transition from 24 to 48?
Yes, let me just first set the stage as to what we saw at 24 weeks. And we really saw four important things. We saw MASH resolution without worsening of fibrosis. Very good results at 24 weeks. Magnitude of the effect, statistically significant, class-leading effects. Very fast activity. We also saw very good defatting of the liver. It all begins with defatting the liver. Inflammation goes down, MASH resolution follows, and so on. Then we saw compelling evidence of fibrosis improvement. We didn't hit stats, but it was clear that the fibrosis improvement was taking place. We saw very profound weight loss, high-quality weight loss because, again, as we have shown before, it's not just weight loss, but it's preserving lean muscle mass, which is very important in MASH patient population and all of the patients that we are trying to treat because sarcopenia is a risk there.
You want to not only lose weight, you have quality weight loss. And finally, something that people haven't talked about as much is tolerability. These are chronic therapies. You need to keep the patient on drug to see the benefit. GLP-1s, as we know, patients on GLP-1s, 60% of them are no longer on treatment after six months. So you're not going to see the benefit if we can't keep these patients on treatment. So really, all those are four things we want to show as we go into 48-week data. As you said, we're not going to have biopsies, but we'll have all of the NITs. Some of the NITs move early. The ones are more driven by liver fat and inflammation, and we've already seen kind of peaking of those. If we just maintain those, we'll be doing really well.
Some of the fibrosis-related NITs, such as FibroScan, should see further improvement, and clearly, weight loss, there was no sign of plateauing of weight loss. The weight loss should continue. On top of that, if we showed the same similar tolerability, which was excellent, better than placebo, we can show the similar tolerability at 48 weeks. That's really the package that we're thinking about.
Yeah, I think we build on what we saw at 24 weeks. I think it's clear the potential opportunity to differentiate pemvidutide is around the multiple benefits, so it would be good if we saw the indicators that the anti-fibrotic effect on the NITs continues to go in the right direction, and just underscoring Vipin's point, this lack of drop-off that we saw in the first readout for me was extremely impressive when you think about chronic therapy. You can't get any of the benefits of chronic therapy unless patients stay on, so I think if that trend holds, that would be also a really positive sign because I see that as one of the, again, in addition to the multiple benefits being a real differentiator downstream when we get to thinking about how to position commercial.
How do you think the 48-week data probably will be also informative on your dose selection, right, for phase III? Are you thinking about multi-doses in phase III, or would you propose a single dose? Or contingently, you got to see this.
We'll probably go with two different doses because there is benefit in having two doses approved in the end. That would be our goal. We haven't disclosed at this point as to, obviously, we have to talk to the FDA and have a discussion about it. But we will probably go with two doses, a lower dose and a higher dose.
But it's clear that the data will help as part of that.
And I think it's also important that I think a lot of investors think of semaglutide, which requires a dose titration, which here you do not need. You have two doses that are introduced, so that's going to be also critically important.
Absolutely. And that goes along with tolerability. I mean, we are getting that kind of tolerability without dose titration. We can further improve tolerability if we were to introduce a short dose titration.
Yeah. No, that's very helpful. Tim, as we look past, obviously, this fourth quarter is critically important, and then you're going to come back and discuss maybe this sort of early next year, the phase III development. But also another big update for 2026 is going to be the phase III data that's on track to readout. So I guess help us understand sort of you finished enrollment ahead of schedule. Significant enthusiasm exists in the AUD population. So maybe help us understand what have you seen? I don't even know if you track alcohol usage in the current MASH study to give. So maybe help us understand what clinical data exists to support pemvidutide to be positive.
So let me first say that we see the benefit of the combination of glucagon and GLP-1, similar to MASH in AUD and ALD as well. Because AUD is not only alcohol consumption, but also liver damage in the background. And many of these patients tend to be obese or overweight or would benefit from losing weight. So all of the three benefits of the drug are still at play for both AUD and ALD. And that's why we think it's ideally suited for treating these diseases. These are very large market, very large indications. There's really no treatment for it. There are three very old drugs for AUD that really don't work well. The only way they work is they make you feel sick if you take alcohol. So this is kind of not a very good way to treat a disease, not a very good way.
It's making you nauseous. Yeah.
That's right. That's right. So the idea here is that the GLP-1 is going to reduce cravings. There is a lot of anecdotal information where people who are taking GLP-1s are drinking less. We have our own data, preclinical data where we have shown in hamster models, which are very well validated, immediate reduction in alcohol intake if we give them pemvidutide. So it's based on that. And on top of that, glucagon for liver improvement in liver and that's the reason we enrolled the trial so fast. Because the clinicians could offer patients, "Hey, not only it's an AUD trial, but you might actually improve your liver health and lose weight." These patients are acutely aware of their liver health. So that's a big motivating factor. And on top of that, weight loss. So we're very excited about these two indications. As you mentioned, we'll have data in 2026. The trial enrolled five months ahead of our expected timeline. Jerry, you may have some comments.
Yeah, I mean, I guess the only thing I would add is the indication is the types of indications that you should be pursuing research. And there's a high unmet need. There's a mechanistic hypothesis here that's extremely sound. Why? Because glucagon is going to have a direct effect on the liver, which is a big issue here. And the GLP component hopefully spares the cravings associated with drinking and brings other metabolic benefits. Now, we'll see what the data looks like. But I think the encouragement of how quick it enrolled means we'll know pretty soon whether we have a real prospect in AUD. But for me, this is a real sound bet based on the uniqueness of pemvidutide and what it might bring. And in addition, just this glucagon-GLP combo, the ratio, the one-to-one ratio between the GLP and the glucagon is really important in MASH and we think really important also in these other indications.
What do you need to show in sort of the alcohol average consumption to be considered clinically meaningful?
So our primary endpoint for this study is reduction in heavy drinking days over a four-week period. So you start off the study versus the end of the study. That is the primary endpoint. There are other biomarkers as well that we'll be studying. So it's not just based on the number of drinking days, but actually looking at the biomarkers of alcohol consumption. We'll, of course, be looking at all of the NITs, all of the liver-related NITs that we've done in MASH, as well as weight loss. So there'll be quite a bit of readout from the data, but the primary endpoint really is the reduction in the number of heavy drinking days.
And obviously, a lot of liver parameters are also going to be tracked, right, to look at liver enzyme elevations and potential MRIP and others. And then Tim, fast forward, let's say it's successful across the primary endpoint as well as many of the biomarkers. What would a registrational path look like in this indication?
So it's going to be data-driven. That's why we're collecting all this data. The FDA right now, the endpoint that the FDA has accepted in the past is total abstinence from drinking, but that's probably not realistic going forward. So we will have to have a discussion with the FDA and agree to that. But if our data shows significant reduction in number of heavy drinking days, that'll go a long way to having that conversation with the FDA.
Okay. Helpful. Jerry, obviously, you joined in getting the company also ready to transition from a developmental company to a commercial company. Obviously, you were an integral player during the launch of Ocaliva, which was a tremendous success, and as well building out the launch for MASH. What were some of the lessons learned? And obviously, now we saw Rezdiffra at the launch that you are hoping to implement or build out. What are sort of your things that's key objectives?
Yeah. I think, look, you have to make sure that you're always being extremely externally focused, and that's one of the big changes in a company when you move from a great science with a good focus on your investigators to understanding how the market is evolving, and that's going to be one of the important elements here because the MASH market is growing up as we speak, right? It was a lot different 12 months ago than it is today, so having the right strategic insights on what's happening in the marketplace and how we're feeding that back to our thinking, not only on what data we're going to capture, but that early conversation and planning around what the value proposition is going to be.
Again, all of that work around what the payers may want, not today, but the time that we may be entering into the market is going to be critical. So you have to bring a little bit of that strategic insight into the commercial world. And you've seen we brought Linda Richardson as the Chief Commercial Officer on board, bringing Christophe in as the CMO, who has a lot of experience not only on the development side, but also in market. I think we'll look to supplement that. The payer thinking is usually the first part of the strategic piece. But it is a development of capabilities in the company that has to start with the right understanding and that focus on the marketplace so that your conversation evolves from a scientific one to a scientific and commercial. Science isn't going to go away. We have to build our business on the science, but it is about an evolution of the product strategy first and ultimately then the capabilities that come along with that.
Yeah, the company has already evolved quite a bit over the last six months, and I think it'll continue to evolve under Jerry's leadership. That's really the reason for that transition.
Okay. And Tim, I think a lot of investors will say to me, it's like, "Yeah, I like semaglutide," but then they got the company phase III ready for obesity. They didn't sell the company. Now they're focused on MASH. What do they want to do? I think, Jerry, your appointment joining makes it very clear that the strategy for Altimmune is going to be building and developing semaglutide in MASH. Just help us think about sort of the strategic focus, right? It's not about we want to sell.
Yeah, look, I mean, we're going to reserve the right to come back after the first of the year when I'm actually in. You got a little bit of a sneak preview. If you stay tuned, we'll be talking a little more overtly about where we're going to go as a company. But it's clear we have a really interesting opportunity here with Pemvi that it's our responsibility to create as much strength and enhancement in that program as possible, building it around how are we going to differentiate ultimately. There's capabilities that have to be brought on board. But look, we're here to add value, create value. That will be an extreme focus of the leadership team as we move forward, and stay tuned as we get into the first of the year, and we'll talk more about where we're going to go.
Wonderful. Well, just give a big applause to the team, and thank you so much for being here.
Thank you.
Oh my God, we've been.
Wonderful.