Awesome. Thank you very much for joining us today. My name is Mohit Bansal. I am one of the biotech and pharma analysts at Wells Fargo, and I am very happy to have Altimmune management team with us today. We are joined by Jerome Durso, the Chief Executive Officer, Greg Weaver, the CFO of the company, and Christophe, the Chief Medical Officer of the company. Thank you very much for joining us today.
Thanks for having us, Mohit.
Awesome. Why don't we start with those who are new to the story. There have been some changes in the story since last year. Talk a little bit about your journey as a CEO and the story for those who are not familiar.
Thanks. At Altimmune, we are a company focused on liver disease. I have been the CEO since the beginning of 2016. The main focus of our efforts is around pemvidutide, which is a balanced glucagon GLP agonist. We think is well-positioned for liver diseases based on the overall clinical profile that's evolved. We have spent quite a bit of time this year, as we have transitioned to a late-stage development company. Really happy last month to announce that our phase III MASH is enrolling after a lot of work to deliver the phase II data and to raise appropriately to transform the balance sheet in order to support execution of the phase III trial in MASH, which is called PERFORMA. Also importantly, recently we announced very positive phase II data from our AUD trial, alcohol use disorder.
Again, another opportunity with a high unmet need in the market and real important differentiation that we're beginning to see with pemvidutide. We think we're positioned well as we, again, continue to really focus on the execution now. Maybe Greg can touch a minute on the balance sheet, which is an
Yeah
important part of where we are. Then hopefully through the conversation, we can talk about why we're excited about pemvidutide and again, the important differentiation that we think pemvidutide can bring. We've had, I think, a great amount of progress to date as we think about the year. It's been a busy year, but we're clear on the work to do ahead.
Got it. Very interesting. Talk a little bit about, this is where for MASH market, the question is because as of now, there are two different agents out there. Obviously you have approaches which do not lower weight, and then you have GLP-1 approaches as well. What your agent brings to the table and how differentiated it is from what is out there?
Mohit, as you know, we've been talking for a long time in MASH about the complexity of the disease. It's a multifactorial disease, and for a long time now, the KOLs, the investigators have talked about the importance of potentially bringing combination therapy to the table. Why? Because the disease is complex. You have different manifestations ultimately leading to liver complications. A combination approach like pemvidutide is where you're bringing, again, the direct action on the liver, and Christophe can go into some detail, perhaps, along with the benefits of GLP, the metabolic benefits. We know that we're driving weight loss. We see good indicators in phase II of the impact on fibrosis and MASH resolution, and also importantly, when you think about chronic therapy, the real need to keep patients on the drug at the right dose.
We think we saw in our phase II MASH trial that the profile of pemvidutide probably is well-suited to the real world, where we know patients have difficulty staying on some of the existing therapies. As the MASH market evolves, we think that drugs like pemvi that can bring multiple benefits to the table, but do it in a balanced and patient-friendly way, are going to be important. Again, we think that the phase II data that we've generated thus far starts to talk about that differentiation. I've always believed that the MASH market treatment will end up maturing like every other big chronic class where you have multiple mechanisms at play as patients progress in severity of diseases.
We always think about the opportunity for pemvi for a robust segment of patients where we think the benefit of pemvi is different than some of the other options that are out there.
Got it.
But the importance to bring the benefits of both the direct liver effects and the metabolic effects in GLP, we think is one of the important dimensions of pemvidutide.
Just basically GLP plus.
Glucagon plus.
Okay, glucagon plus. Sorry.
Yeah. The importance of glucagon. First we know that GLP takes a long time-
to have the effect because it's an indirect effect. The direct effect of glucagon on the liver is important in these patients early on, so that they can see the benefits of this. Then the GLP-1, it's also treating the cause for what's driving that MASH. When you suppress the cause and you treat directly the liver impairment aspect, either the steatosis, the inflammation, or clearly the fibrosis, now you see the full benefits of what you can bring for these patients. In addition, again, the adherence, as Jerry was highlighting, is critical because it's a chronic disease. If the patients cannot, because the titration is difficult, cannot reach an efficacious dose, or these patients drop out after six months, fibrosis is not something that you get rid of in just a few weeks. It takes a long time.
You need to keep your patients at an efficacious dose, suppressing the cause, treating the liver, and pemvidutide is really designed to be able to do that.
Makes sense. The other question is that with the PERFORMA study, what should investors be looking at when the data read out? Obviously, MASH resolution and all those things are there, but are there particular attributes you would ask us to focus on from this study when the data read out?
Right. We have designed the study in a fairly conservative manner because that's a study that's using biopsy as an endpoint. We will look at MASH resolution and fibrosis improvement both for FDA and European regulators. But what we've built in this study is a number of aspects that are unique that we believe, one, will facilitate the enrollment. For example, we have the two cohorts, so for PIs, that helps because they can recycle their patients in the second cohorts, and it's a very attractive feature. Now for the efficacy of the trials, we are the first phase III registrational trials in that PERFORMA study that uses the AIM-MASH AI Assist, which is an AI-generated approach to reading the biopsy-
Right
which should decrease the variability. We also compare to our phase II data, where we had already a very strong efficacy at 1.8 milligram. We added the 2.4-milligram dose because our titration scheme is very simple, one or two steps, and the drug is very well-tolerated. That allows us to do this. The weight loss didn't plateau at 48-week. This combination of things gave us an approach that is conservative in its nature, but also gave us the upside to read the trials and the full potential of pemvidutide on the fibrosis biopsies.
We'll look at the classic efficacy markers, as you mentioned. Importantly, the adherence rate. We anticipate a low discontinuation. Christophe, I think, has underscored how important that is in the context of chronic therapy. We'll look at the 2.4-milligram dose.
which will be important. That was not part of the phase II trial, so we'll get a sense of a higher dose in a MASH population. I guess the other thing which is interesting, we know from our obesity experience that in phase II, pemvidutide seemed to do a good job in the obesity population, sparing lean muscle mass loss. We'll look at that in a MASH population in the phase III study, which again could be another important element as we look about treating these patients over time. So it'll be a really robust data set. Again, for us, the good signal that we were able to start the trial quickly and now heavy focus on the execution and enrollment, and I'm sure over the coming months and quarters, we'll be talking more about the progress of the study as we execute.
Very helpful. In terms of muscle loss, is there a scientific reason why glucagon could be better in terms of muscle preservation versus a GLP, GIP, amylin, all those approaches which newer approach had promised, but they did not deliver on the muscle preservation part of things?
The quality, this is a topic that's evolving in a scientific clinical community, that's of great interest because MASH patients are at risk. The population itself, as we've shown in our phase II, is actually a population that's on average 55. These are patients that are at risk, and in the AUD or ALD, it's even more critical there. We have observed in our obesity study some beneficial effect that seems to suggest that we are preserving this lean mass. That's a combination that's important to keep in mind. We will be studying this in our phase III. We are planning to have a much more rigorous approach in studying this in order to be able to, at the end of the 52 weeks, for example, look at what kind of weight loss happens on pemvidutide.
But this is something that seems to, that quality weight loss, that could be a really positive aspect that pemvidutide is bringing.
Got it. And you're using DEXA scans or MRI?
We're going to use MRI.
Okay.
There is a number of aspects because it's great to look at just some biomarkers, et cetera, or MRI, but it's also the functional aspect of what that means for the patients. I think that's an important factor, too.
Makes sense. Thank you. What are the timelines for PERFORMA study at this point? Timelines for PERFORMA data readout?
The timelines for the data readout? Yes. It's a five-year study. For the accelerated approval, it's going to be 52 weeks.
We've shared that in 2029, we're expecting the data to read out.
Got it. Very helpful. Thank you. You also shared results from the RECLAIM study, the alcohol use disorder study. Talk a little bit about the data you have seen and also how much comfort it gives you in the MASH from that data readout. Like what-
Yeah, I guess first, and Christophe can go into the data, but we were really encouraged by what we saw. We think it's the most robust data set in AUD based on the consistency of the effect on drinking across all of the endpoints, including the two potentially registrational endpoints. I think it gives us a good indicator of what we could be doing in an AUD population. I think it also is a different population than MASH, and so I wouldn't say it's necessarily the transferrable read over.
However, there is some consistency on what we see in terms of what the drug is doing, that as we look more and more, and this is again the third phase II that we've read out, we do see, again, every reason to believe that pemvidutide can have a broad effect across a multitude of liver diseases, which is why you hear us talk about now of a franchise opportunity that we have in liver disease as we get more phase II data.
Yeah. So the study was designed, it's a multicentric study. It uses different sites. It's a population that is much more representative of the real-world population than some of the recent study that have been published. In this data, we show a very clear reduction in heavy drinking days per week. We also show the WHO RDL risk decrease by 2.2 levels and zero heavy drinking days improvement in this population. The consistency of these patients' reported outcome is very striking, especially on the abstinence part, which is very difficult to achieve. Then we also have a more objective measure like the PEth that we were able to demonstrate. The PEth is a test that looks at the alcohol intake in the past 4-6 weeks, a little bit like HbA1c represents glucose-
Right
in diabetic patients. The consistency between all these measures was very striking. I think the importance, as Jerry mentions, the AUD and the MASH patients are slightly different. However, we know that there is MetALD in the MASH population. Some of those, there's patients that are drinking also in the MASH populations, and we know that there is advanced liver disease already in the AUD, ALD populations. This overlap between these different causes of advanced liver disease is really critical because pemvidutide, through the direct effect on the liver and through the impact on the causes, either metabolic or alcohol, can really target this population specifically.
Got it. That makes sense. I understand that glucagon could play a role for the liver side of things, but what glucagon adds to the alcohol use disorder per se, does it cause a little bit more inhibition than just the GLP? What does glucagon add to that?
The glucagon impact is currently unknown or very poorly studied.
It's a great question because we are obviously very interested in this. Everybody knows the GLP-1 and how it works through the dopamine repression, et cetera.
Right.
But there are glucagon receptors all over the CNS.
Right.
Even in the regions, the same regions, that the GLP-1 is affecting, whether it is appetite or the alcohol acquiring in the reward system. So it is potential possible that there could be an effect of glucagon. We don't know. In our study, we plan originally to see an effect that was similar to what we saw in this one study with semaglutide around a one-day improvement, for example, and we saw actually more than this.
Right.
Whether it is due to the glucagon, whether it is due to other factors, it is currently unknown, but it is very encouraging. And again, this population is not only having an addictive issue per se, but is having also already some liver disease. It is having liver steatosis or inflammation at minimum, but also sometimes even early fibrosis. So targeting those two aspects are important.
Got it.
We were really encouraged by what we saw with the data set. Again, the population in the study was moderate to severe AUD. We think that, again, that is where we are going to focus on the more moderate to severe population.
Then we know that those patients are at highest likelihood of going on to have liver issues.
Many of them, many of the AUD patients, are already suffering from ALD. When we think about where a drug like pemvi can have the most impact, it is going to be on the more advanced population, again, where the direct liver action, the potential liver benefit, in addition to the impact on drinking, can be most important. When we think about the marketplace that is ultimately out there is about 12 million patients in the U.S. with moderate to severe AUD.
Wow.
6 million with ALD. It is a sizable population. We know the unmet need is high, and again, we know that the importance of impacting both the drinking and the consequences of that on the liver are going to be really important, and that is how we think about ultimately pursuing phase III and starting to think about the value proposition, ultimately in the marketplace for pemvi.
So maybe alcohol companies should start investing in your companies as well, right? 12 million is a big number. You are in the planning phase III. How are you thinking about it right now?
Yeah, we are in the planning of this. We are preparing to interact with regulatory agencies. We are putting the different pieces together for this. Our concept is to try, as Jerry highlighted, not only to get the patients that have what I would call a more typical type of AUD, but also we have the opportunity with pemvidutide to target the patients that have AUD and ALD. We know that it is a sizable group of patients because 50% of these ALD patients have AUD. So pemvidutide will be suited in our phase III approach. We would like to target both of those populations.
Got it. The interesting data from another GLP glucagon came out, survodutide from Zealand earlier this year. Not in MASH yet, but they have some NAFLD data in there. Talk about what did you learn from those trials? Also, there is a phenomena of controlling the placebo nowadays because people do not want to stay on placebo for a long time, especially in your case, it is a long trial.
How do you plan to manage all those aspects of the trial?
Yeah. So, just those different molecules. survodutide, it's a good validation of the dual agonism.
They have different ratio.
They're 7 to 1. They have a high discontinuation rate due to the tolerability.
Right
which is extremely different than what we see with pemvidutide. I think that dual mechanism become more and more accepted. Also, there will be differences in molecule that so far from what we've seen favor pemvidutide. With regard to your question more on the placebo side, clearly it is something that we are looking into and working very hard with the site to keep the patients. There is a number of incentivization for patients to stay in our trial. First, they have two chance out of three to get the active drug.
Right
which is already a good point. The second is that there is, in our trials, there are, as mentioned, like this AIM-MASH AI Assist.
The first 52 weeks is probably the one that is the most difficult to keep those patients. After that, it's mostly hard outcome-
Got it.
liver-related outcomes. I think we see a very good response so far from our sites. Extremely high interest in bringing patients in the study. We haven't heard any concerns around placebo retention.
But we'll see throughout. It's also an indirect measure
Right
of efficacy. So if you lose your patients in the placebo more than in your active arm, it shows that you're
Right.
So, this will play as you would see in the real world. But we have clear efforts. Retention is a key aspect, and unlike survodutide that lost one out of four patients
Right
in their study. With pemvidutide, we keep more than 80%, 90% in our study. So we're in good shape so far from what we've observed, and we have experience with 48 weeks in the phase II.
We will see when we see their MASH data.
Right
We feel good at this point about the potential differentiation.
We know that the ratio matters, and you have a balanced ratio with pemvidutide that we think plays in our favor. The molecule matters.
The EuPort domain is probably having an impact on this tolerability and why in the MASH phase II, more patients stayed, less patients discontinued on pemvi due to AEs than did on placebo.
Right
which is a really different picture from what we see in the MASH phase II on survodutide. We will of course learn more, but we think the compounds are very different, and we like what we are seeing thus far in terms of the differentiation, which we know ultimately, when you think of a fast-forward to these drugs in market, the differentiation is going to be critical.
Right. That is fair. That is fair. The other question obviously you get a lot as well is probably retatrutide, right? So retatrutide is a three-drug mechanism combo here. Would love to learn about the differences there versus your molecule. And then also, they are running a very interesting trial. So they are comparing retatrutide to Mounjaro. So that will probably be the most definitive trial to, maybe it will help you as well to show that glucagon is important or not. So talk a little bit about that aspect of things.
retatrutide is a very different molecule. So the affinity, it is mostly focused on the GIP.
The EC50 for the GIP is 0.06. The EC50 for the GLP-1 is 10 times higher, I want to say 0.8. And then the glucagon side is another 10 times, where it is close to 5.6, 5.8. Which means there is 100-fold difference between the GIP and the glucagon affinity. Which means that this is really heavily focused on the GIP side of things, and the glucagon is actually much less-
important. We are really on the glucagon and the GLP-1 directly with a very high affinity upfront. So pemvidutide is different. Whether they are moving forwards and all the effect that they have, I agree that it could help us
in that direction. I think, again, some of the things that we need to look at is the tolerability.
Right.
Clearly there is some differences. There is also those. As clinicians, if you want to treat diabetic patients, but you add dysesthesia and those patients could have diabetic neuropathy, that is an issue that I would be concerned about. So it is a little different. We have not seen this with pemvidutide or experienced anything similar to this. So it is a bit of a different molecule than pemvi that has that one-to-one ratio with very high affinity, both on the GLP-1 and on the glucagon.
Got it. Very helpful. I also want to touch upon the alcohol-related liver disease trial that you are running, the RESTORE trial. Same question, what aspects of RECLAIM trial that make you comfortable about ALD? Some patients already have liver disease there as well. Again, talk us about the timeline and how should we set the stage for the data readout? What should we expect there?
Yeah. We announced last month that we were fully enrolled in the ALD phase II trial. We will read out at 12 months. FibroScan is the primary endpoint, so we'll really be able to assess in this population the impact on FibroScan, both at 12 and at six months. We'll read at 12, but we'll have a chance to look at both time points. Again, those patients are drinking at a considerable rate, so we'll also assess the impact in that more advanced ALD population on the drinking levels, on weight, on tolerability, on all the usual suspects. We think this is going to be a really important incremental learning that will help support a population that we'll also look to include in our AUD trial.
Again, because of this important overlap in the two diseases, we think that this is an important differentiator because we think, again, because of the mechanism that pemvi brings, the impact on liver scan measurement at 12 and 6 months could be an important differentiator against other compounds that might be more on the GLP side and won't bring the direct liver.
Yeah, just on the regulatory side, it strengthens our propositions now when we go to have an indications that address AUD, whether you have ALD or not.
I think for the phase III and vis-à-vis the regulator, our current thinking is that having those data enhanced and our phase III in that subpopulation should give us a very strong differentiated package.
Are you measuring biopsy-driven liver disease or not?
We're not measuring biopsies in the current phase II. As you know, ALD PEth regulatory-wise is more complicated. You need an outcome study.
But through the AUD indications, we know that 50% of those patients have AUD, so we want to strengthen that package through our phase II, as Jerry said, at week 24 or at week 48, and in addition, include that subpopulation in our phase III.
Got it. Very helpful. One more on AUD, going back to AUD trials. Do you have to get a buy-in from the FDA before you start the trial at this point?
Yes. It's a registrational pivotal study, so we're going to engage in end of phase II meeting.
We will propose our approach, we'll have the discussions with the FDA, and obviously we'll have also discussions with other European regulatory agencies, like we've done for MASH, basically.
Right.
It's aligning on our approach for registration.
Who treats these patients? Is it primary care for AUD?
I'm sorry?
For AUD, is it primary care or liver doctors?
It's a mix, right?
It's a mix.
As patients get more advanced, the higher the probability they are with GIs or with hepatologists. We know that a considerable number of GPs and psychiatry often for the addiction side of things.
Right
There is a mix of physicians that are out there. As Christophe mentioned, that end of phase II meeting is going to be important for us to finalize size, the scope of what a potential phase III trial may look like in AUD as we do the kind of commercial thinking along the way in terms of the treaters, how to think about it.
Right
Then that input from the end of phase II will be important as we think about potential funding mechanisms for a phase III. Maybe Greg can touch on how we think about that dimension
Yeah
of our AUD approach.
Yeah, thanks, Jerome. Mohit, we've got first of the balance sheet today at the end of June, reported out $519 million in cash. That's a runway that takes us full on through the readout in MASH in 2029.
Right
Importantly, we mentioned the two phase IIs. ALD that's ongoing, AUD that just read out. We're in position for an AUD phase III. That's going to need a requirement for some funding on top of today's balance sheet. We have some prospective look at non-dilutive options there that we're confident we can pull off. I think that's the approach, and I think investors are looking to the solid balance sheet and new leadership team. I should mention our internal team doing just a yeoman's work in execution day in, day out on these trials. Happy about that. As we go into later in the year, we'll give more guidance around what that phase III scope and scale would look like.
Awesome. One last question for all of you. Fast-forward one year, Wells Fargo Healthcare Conference 2027. I hope you are here. I hope I am here. What would make you look back at the year and say, "It was a great year for us?
A lot of work ahead of us.
Right.
I think if we think about a year from now, look, we're going to monitor closely, and we anticipate the execution of the PERFORMA trial. We're going to be progressing well. Those are large studies. The enrollment clip is important, so we'll be anticipating that the fast start that we've had in terms of getting up in the trial is translating to a robust and rapid enrollment, because that's going to be critically important. We anticipate we could be in a position, again if all things progress, where we could be in phase III for a second program. We'll think about timing around that.
Right
We've got to size the trial. We have to work through some of the elements that Greg mentioned. But every reason to believe that there's a really unique opportunity. We'll be in the window of a lot of learning on our ALD readout. Again, when you think about progress in terms of execution on two major indications, as well as more data coming with good, strong execution and clear understanding of how we want to ultimately differentiate pemvidutide in the market, a lot of progress forward to look front of. If we're getting the invitation from you now, we say, "Oh, we'll be back
September 8 to 10 next year
in a year talking about that.
This is your invitation. Awesome. Anything to add?
No, the time moves quickly.
Yeah.
We will be here a year. It will go like this. There is a lot of hard work going on, and very proud of the team and the progress being made here. Pretty impressive.
Awesome. On that high note, thank you very much for coming, and all the best.
Thanks, Mohit.
Thank you very much.
Thank you, Mohit.
Thank you. Really appreciate it.