All right. Good afternoon, everybody. Welcome to day one of the Citizens Life Sciences Conference. My name is John Wolleben , Senior Analyst here, and we're pleased to have Altimmune joining us, and we got most of the C-suite here. We got Jerry Durso, sorry, CEO, Linda Richardson, Chief Commercial, and Greg Weaver, Chief Financial Officer, all joining us today. Guys, thanks for freeing up the time.
Great to see you again, John. Thanks for having us.
This is a story we've been tracking for quite some time, one of our favorite stories in the MASH space. Jerry, tell us a little bit about pemvidutide, your lead molecule, and what you guys are trying to do.
Yeah, we're excited about the potential we see with pemvidutide, potentially for multiple liver indications. As you mentioned, the lead indication is MASH. We had a couple of different readouts from our phase II trial last year, including the 48-week results right at the end of the year. We feel good about the potential for differentiation here. We're in the process of doing all of the deep preparation. Anticipate to initiate our phase III trial in 2026. At the same time, two other phase IIs that are ongoing in alcohol use disorder and alcohol-related liver disease.
Again, we think the potential differentiation with the mechanism, with the ratio of glucagon to GLP here and the data that's starting to emerge, I think has been what has allowed us now to pivot the company coming on as the CEO in the first of the year with pretty much a new leadership team along with me, folks that have joined, like Linda and Greg and others over the past, let's say, handful of quarters. Really a focus on moving pemvidutide to patients as soon as we can. Of course, doing the right things along the way strategically to build shareholder value here.
You guys actually have quite a bit of data, but if we could focus on maybe the 24-week readout you guys had, the biopsy data in MASH, and then maybe the 48-week follow-up. What did you guys learn, and how does it fit into what we know about, you know, the MASH pipeline?
Yeah. An interesting couple of readouts last year. The study, phase II, was designed with the biopsy read at 24 weeks. You know, as I started to think about getting involved with Altimmune last year, first joining the board and then at the end of the year, transitioning to the CEO role, one of the questions I had. I like the molecule. I like the potential in liver indications, including MASH. Thought that perhaps the 24-week timeframe to read out on the biopsies for this mechanism might have been a little early, a little optimistic. Nonetheless, we saw some great things at 24 weeks. A strong impact on the MASH resolution endpoint with a significant delta. Great tolerability, patients staying on therapy.
The weight loss was progressing well at 24 weeks. Good trends on fibrosis, but we didn't hit the fibrosis endpoint. Again, you know, I think one of the elements in that, we saw a high placebo response rate. Clearly from my standpoint, the way the mechanism works, probably a little longer window might be required, which is why we were interested, excited to see the 48-week readout, which we announced the top line for in December. Again, 48 weeks for the two doses that we tested.
We did see, importantly, although we didn't have biopsies in that window, we saw an improvement from 24 to 48 weeks on the main non-invasive tests that are associated with anti-fibrotic activity, specifically the liver stiffness measurement on FibroScan and ELF. It really allowed us, while we continued to see, you know, good tolerability, weight loss that was continuing and didn't plateau for the 1.8 target. At a discussion with the FDA at the end of a phase II meeting, which happened right at the end of the year, a 52-week endpoint in our phase III and some of the other learnings that we'll bring forward, and we can talk in detail about how we position phase III.
I think if we summarize what we saw in phase II, the drug is reducing liver fat quickly, stopping that inflammatory process, leading to a 48-week impact on non-invasives that look substantial and competitive when you look at where some of the other drugs were on those same NITs at a comparable period. And again, I think this 1-to-1 glucagon to GLP ratio is working to provide a tolerability profile that looks like it can be differentiated. I think the last point maybe on phase II, we didn't have a titration scheme. So all patients started on the target dose, which is definitely-
Unheard of.
Unlike any of the other injectable therapies. Nonetheless, we saw good tolerability, and again, more patients actually stayed on the active dose than stayed on placebo in the study. There's something here that's keeping patients on therapy, which we think is critically important when you consider all of the challenges around chronic therapy in the real world. There are some GI events. They tend to happen, as you would expect, early in the first four or six weeks. We think that introducing a simple one or two-step titration scheme in phase III makes sense. It's still differentiated from the four or five or six steps that some of the other injectable therapies have. We think maybe gives us an opportunity to even improve on the tolerability profile we saw in phase II.
That's a lot to chew on. This is a crazy business. Like, the data in phase II I thought looked great. You had a high placebo response on fibrosis, didn't hit stat sig, and gets no credit from the market. Can you give some context to reality around the numbers there? Then the placebo response, if it was some time behind it now, do you think it was just six months was too short? Did you see the NITs improve or the placebo response drop in over 48 weeks, the non-invasive? Just like because your absolute fibrosis response was very good and competitive. Maybe some context because I have very little doubt that phase III should work, but people seem to either not be paying attention or just are hung up on the statistics.
Yeah, look, I think there's a couple of elements in your question here. We did see a good response rate on the active arm, and we did see, as happens in some of the early and smaller trials, happens sometimes on biopsy reads. We know there's variability there. We know that's one of the elements at play. We know that neither of the two approved therapies for MASH hit at phase II, but they did go on to hit at phase III at a later time period. I think that's one of the elements there. We know that larger populations over a longer period of time help. We think on this mechanism, you know, you may have something like semaglutide, which has been effective in phase III at 72 weeks.
You have the FGF21s that have 24-week efficacy. I think when you think about this mechanism, it's probably in the middle, which is why a 52-week endpoint, we think makes all the sense in the world, in the phase III design.
Yeah. Talk to us about the phase III design. What did you guys change, and what are you guys looking to show?
As I mentioned, we had a very productive discussion with the agency at the end of phase II meeting, which happened right at the end of last year. We got the minutes in early January where we confirmed clarity on how we're thinking about the design. We also got the Breakthrough Therapy designation, which we think is important and relevant as we look to bring support for patients in an area of high unmet need here. A couple of things I think are really important. As I mentioned, the 52-week endpoint on biopsy, one of the questions that we got a lot in that time window is, you know, is the agency considering yet moving away from biopsy. We know there's an ongoing process to consider this.
We asked the question at the time. The FDA confirmed it's premature, so you will see a biopsy endpoint on the two common endpoints, fibrosis improvement and MASH resolution at that 52-week window. We have a cohort of patients, a little under 1,000 patients, with that 52-week readout. Two active doses, the 1.8 mg, which was the, let's say, the anchor dose that looked really good, in phase II. We think there's an upside to look at a higher dose. The 2.4 mg dose, which we studied in our obesity program. We have, you know, some good insight. We know it, in that population, brought more weight loss. We think there's an upside to consider that and to put that into the phase III.
We'll power around the 1.8, and that'll be kind of think about that as the anchor dose. One of the important other elements, we did get alignment with FDA in order to utilize the AIM-MASH AI Assist tool, the AI tool that is used in conjunction with the pathologist. There's a consensus read process that we'll deploy. You've been around these studies for a long time, John. You understand that, you know, it takes two to agree, but they will utilize the AIM-MASH AI Assist tool as part of that process, which is intended to, again, further help reduce some of the variability that we know is a part of the biopsy process.
I guess the last piece, I mentioned that group of patients who will be on the primary efficacy at 52 weeks, a little under 1,000 patients. There's a cohort two-
Mm-hmm
which are non-invasively defined patients. Those contribute to safety at 52 weeks, and both of those cohorts go on to form the population that we'll track for the long term and look at liver-related events, as part of the confirmatory approach. 52 weeks on a potential accelerated approval.
Yep.
We'll track the full population over time in the typical way.
The phase II looked really good. 24 weeks, you missed on stats on fibrosis because of a high placebo response. In phase III, you're going to higher dose. You're dosing for longer, which should potentially boost your efficacy, but also allow that placebo to drop over time as well. I think everything's going to move in the right direction here.
Yeah. The other point, as I mentioned before, we'll have the titration scheme in.
Yeah.
Right? We'll have a simple, but we think important titration scheme where patients in the 1.8 target dose will start at 1.2, and then four weeks later, we'll move to 1.8. The second group will start at 1.2, they'll go to 1.8, and then up to 2.4. Again, think about the 2.4 as an upside population that we're interested in assessing here.
Even if you're not following the space, you've heard GLP-1s on TV every night or seen a lawsuit or something. You guys are GLP-1 glucagon. You mentioned this one-to-one ratio a couple times. What's the benefit of that versus, you know, more glucagon versus GLP-1 or vice versa?
Yeah. The objective of the dual mechanism, right, is to address the broad disease that is MASH. We're bringing glucagon, which is acting directly on the liver. Again, that process of impacting and reducing liver fat happens quickly. We've put out a couple of different pieces of data confirming that ultimately, that direct liver effect, you know, leads to an impact on inflammation and ultimately fibrotic activity and fibrosis. Then the GLP side of the coin, you're addressing, you know, the more the metabolic effects, the weight loss, there's probably an impact ultimately on the anti-inflammatory process as well. We think that this one-to-one ratio is providing, you know, again, impact on both sides of the equation.
We know that there are other compounds out there that are glucagon/GLP combos. We're not aware of any other that are one-to-one. They tend to be much more weighted to the GLP side. Some of those compounds, as they progress through, are bringing higher drop-off rates, higher challenges with tolerability. Again, we think that this ratio is bringing a balanced approach that seems, when we look at the data, to be not sacrificing potentially on efficacy and bringing some benefits on tolerability. Also the quality of the weight loss might also be another factor here that we can talk about. We like the profile, we like the data that's emerging.
We feel good about all the prep happening, and as I said, anticipate to initiate the phase III this year.
Yeah. I think what got lost in the biopsy results is the tolerability that you guys put, I think is best we've seen for an incretin, and that's before even considering the lack of dose titration, where sometimes it's 16-20 weeks titrations.
Yeah.
That's something that I think needs.
Yeah. Look, we're doing a lot of work, and then maybe Linda can comment on where the needs are currently in the market and where the customers, the patients, the physicians, the payers are thinking about MASH evolving over the next handful of years. Yeah.
That'd be super helpful, because I know we've talked before. You know, designing the trial to give you what you need to market and commercialize this.
Yeah.
Like, what is the profile that you want coming out of the phase III trial?
Clearly, we don't want to lose our tolerability. This is a chronic disease where folks are going to have to stay on the meds to get the benefit. We're seeing fall off in the marketplace. In some recent market research we did, the tolerability of GLP-1 therapy and the falloffs for not just tolerability, but for failure of efficacy, are becoming an issue of concern for physicians. Part of that is because if you titrate too low, you're not at a therapeutic dose. Those who are staying on aren't seeing the results that you would like to have them see. The marketplace sees room for really going after those who aren't tolerating that and aren't getting results. There you have also the benefits of our glucagon activity. It's almost like a GLP-1 with more. Why would you even start?
The physicians played back to us that this is the opportunity for first line in F2 and F3. You look at the weight loss. Weight loss is obviously a critical part of managing a MASH patient. Quality of weight loss also matters. The lean muscle mass preservation is important, not only in the MASH population. You've seen as much in a study in MASLD showed that one in four patients was at risk for muscle loss or sarcopenia. What is the consequence? Why does that matter, right? You see that you have muscle loss leads to lack of activity, leads to bone loss, and we know that the FGF21s have had some issues with.
Mm-hmm
Bone mineral density. You're seeing this cascade. It also plays in our AUD and ALD studies in alcoholics who have sarcopenia or are at risk for that. That's really an important differentiator and very, very much is resonating, particularly with endocrinologists who are like, "lean muscle mass preservation." They've seen the weight loss with these, you know, diabetes drugs is key. We see a very nice early low-hanging fruit marketplace for us with, you know, pulling that through. We saw that in the obesity data, and now we're going to be looking at it in MASH patients. That's another area of low-hanging fruit. Then you look at the differentiation on other mechanisms not providing weight loss at all, FGF21s, efinopegdutide, et cetera.
You have a product here that not only has additional efficacy on anti-fibrotic, anti-inflammatory markers, but can give you some of that weight loss. The tolerability helps with that, and also an easy titration schedule. The ability to use our drug potentially with these other products because of the tolerability, because of the lack of drug-drug interactions, is bringing more to the table. If you're looking at it more of a advanced F2, F3 patient, well, there you are. You've covered the spectrum.
With Wegovy now approved for MASH, how do you guys think about comparisons to other GLPs that could be used in MASH?
Well, I think it goes back to the molecule matters. You get back to really what is it in a one-to-one glucagon GLP-1 active product with our special EuPort domain that helps with it. You're never going to take that away from us, right? That tolerability that lowers Tmax, time to Cmax, and we believe that's part and parcel of what you see, the tolerability, the lack of titration, and you're not giving up efficacy. We too believe in phase III, we are going to hit that fibrosis mark with more time. It's designed that way. That is the vision for the product. The product profile is highly competitive on efficacy, early MASH resolution, major fat reductions. We wouldn't expect those to change in a phase III study.
Mm-hmm.
You're putting your package up against other products, and the one-to-one matters. You see a different tolerability profile. One of our competitors has a, you know, one in four dropout rate due to AEs in a clinical trial. How's that going to translate to real life?
This might be the same answer, but you know, when we think about the space, the evolution, we had GLP, then we had GLP-GIP, throw on.
Mm-hmm.
Some more acronyms. GLP-1 glucagon, you guys, and your aforementioned Zealand and Boehringer, who's a little bit more advanced, but I'd say an intolerable product.
Mm-hmm.
for the most part. We have GLP-1, GLP-1/GIP, glucagon coming.
Yep.
Does this class get leapfrogged by the triple agonist?
We don't believe so.
Mm-mm.
You know, again, I think that bringing more mechanisms or even comparing against the same mechanism at the end, the molecule matters. The mechanism, there is some variability in what these mechanisms can provide, but it's also dependent on the molecule itself, which is why we feel good, not just because we're a glucagon GLP combo, but because of the specific ratio, because of the EuPort. Ultimately, it's about what it translates into in terms of clinical impact. We also know that MASH is a complicated disease. There will be room for multiple players in this marketplace. I've always said that I anticipate the MASH market will ultimately evolve like a typical chronic class, where you have different mechanisms at play for different patient segments.
The goal is differentiation in a robust enough group of segments where you have a positive value proposition. We definitely feel like, you know, there's a sustainable differentiation. It's not just being successful in a phase III trial, it's about defining and then realizing the differentiation in the marketplace. We're preparing, again, not for where the market is today, but for where we anticipate it'll be, John, with those new entries coming.
Mm-hmm.
Yeah. I know because of our history that we've always thought MASH as a market and a large market, but with Rezdiffra doing so well, you know, what are you guys learning about that launch, and how is that changing maybe your perception or opportunity set for pemvidutide?
Look, I think that, you know, and again, we've talked a lot historically about there being a big need here. I think they've done a good job with the first entrant into the market. I also can honestly, after having looked at the MASH space for a lot of years, I'm not surprised that physicians are seeing value in therapeutics coming to the marketplace. We know that these patients are at risk, have had few options up to now. It's been good to see that the payers have understood that there's non-invasive tests out there to be able to find the right patients to treat. I do think as more entrants come, that more patients will be identified.
Even if you look at the volume of patients that have driven the early success, we're still just in the very early part of the game here in terms of identifying and bringing appropriate treatment to the large number of patients out there that are at risk with MASH.
Yep.
And-
Go ahead.
We also know from the market research, the lack of weight loss is a concern there for both FGF21s and Rezdiffra. That's clear. We have some pretty strong antifibrotic. You know, if you look at the NIT data, we're not going to, you know, overstate the biopsy stuff, but we clearly have very strong antifibrotic effect. If you look at some of those measures, our measures were higher. We had better results on those versus Rezdiffra. We're prepared to go in and really come in with a solid product with lots of attributes that will have patient play in the marketplace.
To me, it's a no-brainer. When I think about options that would be presented to a patient, you know, you're going to have a drug that will have comparable histology benefit as anything out there, weight loss and better tolerability than any of the other increments and a known safety profile. It seems to be like, why would this not be preferred?
Look, we agree that it's going to be, if the things that happen in phase III as we anticipate, it's going to be a very attractive profile. All of the work that Linda and the team are doing, as you can imagine, we're deep in the commercial strategy planning process, and you know, the feedback we get from the customer side of the house continues to tell us that this target profile resonates.
What do you think is the biggest competitor from a mechanistic standpoint to your class?
Look, I think that you mentioned a couple of the other combos out there, and I think that, you know, we think about a GLP monotherapy as being early. We know that that might be an early on entrant, maybe in a different value proposition. We think that the FGF 21s have shown efficacy in an F4 population.
Mm-hmm.
For instance, you might see them a little later. You might have the middle of the road, where some of the other combos will be considered in the same patient segments as pemvidutide will, and we like our ability to potentially compete with all of those options.
You know, this is just too interesting to talk about to me. We got a few minutes. Alcohol use, alcohol liver disorder, we're going to have a readout this year. Talk to us about how you're thinking about optionality in those two indications and the opportunity.
Yeah. Maybe just quickly, the AUD study, we anticipate the top line for the phase II in quarter III of this year. Really, area again of high unmet need that potentially the profile of pemvidutide can deliver not just an impact on the level of drinking, which is the primary endpoint, but start to get an understanding of the direct impact on the liver and how might that play for some patients. The second study is an ALD, alcohol-associated liver disease, where we anticipate we'll be fully enrolled this year. Linda and the team have started to look at the opportunity there, and maybe you can give us a couple of highlights.
Yeah. I mean, such unmet need really. The drugs that are out there are older, not well, you know, penetrated into the market. Lot of interest in this space, and our trial really will be informative not only for AUD and what else we will learn about the molecule, but our mechanism of action going right after, again, glucagon direct acting in the liver also comes into play both in AUD, because they tease me 'cause I have this phrase, "If you're thinking maybe you're drinking too much, you probably have some liver damage." If that's where you've gotten to, you know, this is something that's going to be able to help patients, help physicians, and hopefully they don't progress into ALD. That glucagon component with the GLP-1 kind of working on cravings, et cetera, should really be a unique proposition.
Well, one of my takeaways from AASLD last year was a ton of sessions on alcohol.
Yeah.
It seems like that's going to be the next focus of the general hepatology community.
No doubt. I think you had the same conclusion we did, which was, wow, what a change really in-
Mm-hmm
from the prior two years prior.
Yeah
Just in terms of the amount of sessions and scientific discussion.
Yeah
on the role of alcohol in hepatology.
In the last minute or so, to make sure Greg's awake.
That's right.
Remind us of the cash position, balance sheet, runway, all the
Yeah
logistics.
Thank you. Yeah, appreciate it, John. Thanks for having us. Yeah, just briefly, cash is still king. We've made great strides in strengthening the balance sheet over the past year. Reported out end of February cash position that reflects runway into 2028 and with more work to do. Reminding you how we got to this point would be raising approaching $300 million over the last year. Combination of a registered direct, our friends here and others helping us out on the ATM, et cetera. Just in a position here in addition to potential for strategic funding to make sure we have the balance sheet to support this program.
Have you guys talked about ex-US partnering? We're always open to whatever, but is this something you guys want to do ex-US or find somebody?
Yeah. Look, as you know, we continue to stay focused on bringing pemvidutide to patients as quickly as we can and building shareholder value, as you would expect, we're active and open on that front.
Mm-hmm.
We'll continue to move forward and ensure that we're in the right position to initiate the phase III.
Well, it's a really interesting asset. I think it speaks for itself, and you guys get this across the goal line, it's going to be a major drug. We're looking forward to tracking the progress, and thanks again for coming today.
All right. We'll continue the updates.
Thank you so much, John.
Thanks, John.
Thank you. Thank you.
Thank you.