Welcome, everyone, to Jeffrey 2026 Global Healthcare Conference. My name is Roger Song, senior at this cover of SMICAP Biotech. It is my pleasure to have the five-side chat with the company from Automune. So we have a CEO, Jerry, Greg, CFO, and then Christophe, CMO. Welcome, gentlemen.
Glad to be here, Roger.
So, Jerry, why not you give us a state of honor of Automune? And we have a lot going on in terms of mash and then some of the disease. And then a lot of exciting things ahead of you.
Yeah, it is an exciting year for Altimmune. Obviously coming off, and I'm sure we'll have a chance during the discussion, an exciting meeting at Easel last week, but really continuing to stay focused and make progress in the areas that we've talked about throughout the last couple of quarters. Importantly, we're continuing to move forward in the startup phase of our Phase 3 MASH program for Pemba Dewtide, where we anticipate we'll be enrolling patients in the second half of the year. Continuing to deepen our understanding of what Pemba can bring to the MASH population, so definitely enhanced data from the recent EASL meeting I'm sure we have a chance to touch on, but really getting a good, deep understanding of really the potential for differentiation of PEMB for the MASH population, which, as we all know, as that market continues to grow up and get more competitive, differentiation is going to be key. We have two additional phase two trials that are ongoing. Exciting to read the fact that we'll read out on our AUD trial next quarter. So it comes quickly, and that we anticipate being fully enrolled in our ALD, our second phase two ALD, also in the third quarter of this year. So a lot going on, and importantly, as we do all of the deep work towards phase three, the fact that we've made a lot of progress, importantly, on our balance sheet and felt it was important to get the balance sheet in a strong position prior to initiating the phase three. So the financing that we did throughout the first part of the year, again, I think gives us a clarity and strength of the work ahead.
Excellent. All right. I think we just right off the press from ESO. And then I think you presented a couple of interesting new data points there, including the AI-generated imaging review and then also some of the metabolic endpoint. Maybe just give us some highlights of why those can increase your confidence about the phase three.
Yeah, Christoph. So, no, we were really happy with EASOL. We had a pretty big presence with our booth, with our team there, met a lot of the KOL. We had receptions as well. And we got the best of EASOL abstract with the oral presentations on our 48-week data. We were also presenting additional data on cardiovascular risk. and the benefit that pemviditide can bring to the patients with cardiovascular risk. We had some data as well on our non-invasive testing and a different presentation, more comprehensive approach to those non-invasive tests. And finally, to your point, we had the skewed fibrosis, which is a different way to analyze our data from the 24-week biopsy. And as you know, we showed during the 24-week already some trend in the fibrosis, anti-fibrotic effect of pemvidutide. We looked at this different ways. The biological marker, ProC3CTX, that were clearly showing a fibrolytic effect there. We looked at also AI generated. The first was the liver explore that gave us a sort of a continuous demonstration that we had that antifibrotic effect already at week 24. And the Q-fibrosis, which is a second harmonization generation approach, that demonstrated this as well. And we were really happy with this data. As you all probably know, this is a new way of looking at those biopsies. And all these different approaches, we're consistently showing that anti-fibrotic effect of Pembidotide.
I know, I think maybe, Christoph, if you can give us a little bit more detail around Q-fibrosis, because that can be interesting. Remember, the phase two, your 24-week MASH resolution is statistically significant, which is very good already. it's fast. The fibrosis part is, you know, too narrowly missed a little bit, but on the, I believe you have some early AI analysis also suggesting it's positive, but this acute fibrosis may be more correlated with the fibrosis you're expecting to read out for the histology.
So I'll start with just saying that the histological reading of biopsies is in general very variable between different pathologists it's a little muddy sometimes they all have different approaches that they like to focus on so that leads to placebo responses there can be fairly variable and also 24 weeks is fairly early so there is more variability and I could explain some of those differences. Q-fibrosis is a way that subtracts the steatosis and calculates without any staining the amount of collagen in those biopsies. So it's a fairly more accurate, maybe, perceptions of exactly what the level of fibrosis is in there and it's a different approach that Parthia is using with the liver explorer approach, but they're all complementary. So, for example, Madrigal with Resmiteron has been using also and has recently presented such data. So we had the opportunity to look at this. I would take all this in the more general consistency of the data. We think that's why we design our phase 3 at 52 weeks because 24 weeks is probably we are in the zone of viability there for the biopsy and that will be that will be the case probably if we had chosen that again so we're putting ourselves in the phase three with some evidence that we have early anti-fibrotic effect we're going to wait later and we've demonstrated that at 48 week in our phase two we have very strong anti-fibrotic effect And in the phase three, we'll have these at week 52. So that's all putting the story together there on the role of the direct role of glucagon and pemvidutide on the liver.
I understand, you know, from an investor's perspective, when you show data and then they have to take the phase value and say, OK, phase two, you didn't hit that. But we have a lot of evidence to support. Even 24 weeks, your fibrosis is very close. and then the 48-week, probably even better, right? I think that's an understood, and obviously you need to show us in phase three. And then in terms of the Q-fibrosis versus, I believe you're using another AM-MASH in your phase three as well. How are those two colorated? I think you also use Q-fibrosis in your phase three.
That's correct. So AMASH is a little different. The liver explorer we've used, So the Q-fibrosis are analysis of the biopsies themselves and quantifying the fibrose into the liver. AMASH is actually a tool to assist the pathologist on how to read the biopsies. So we're going to use this. We're the first phase three registration trial that is using AMASH. Basically, in a nutshell, you have the digitalized image in front of you. It points to the features, and then it clearly scores, and then the pathologist has the final say whether they agree or disagree with the scoring at the end. So it's a very good tool. Hopefully it decreases the variability, and it will help us in that phase three to read this. The Q-fibrosis, we're using this as well in the phase three, not as a post hoc analysis as we've done in the phase two, but we include this as a secondary endpoint. As you know, many in the field are, it's not an approved tool first for primary endpoint, clearly at this point in time. But many of the people in the field are looking at this as an evidence of DLT Fibrotech and will complement our primary endpoints reading on the biopsy with the Q-fibrosis.
Got it. And then you did get the alignment with the FDA using all the AI tool, including AMMASH, which will be supporting the histology read.
So we have alignment with the FDA, also with the Europeans. and at this point in time they have the protocol enhanced and we're all good to go with the Phase 3.
Excellent. Okay. And then on the other part I believe your Phase 3 is a pretty comprehensive, very soft design. You also have an arm or cohort is using the NIT as the primary endpoint or at least part of the endpoint and then with the potential, right, if FDA change mind or they feel involved and then maybe the the NIT become an approvable endpoint, at least for the Accelerator approval. So tell us a little bit more NIT, and then also your phase two, how the data support the potential kind of positive on the NIT endpoint.
Sure. So I'll start with the phase two. Our data on the phase two, we're really convincing around our non-invasive test results. And when we looked at either the ELFs or the VCT results, And we have combined even these that could become potentially an alternative to biopsy read. And we show clear dose response, very strong difference versus placebo at our 1.8 milligram dose. So very encouraging in the phase two. In the phase three, so as you know, this is, we have to, it's an event-driven study with the final approval that is based on liver-related events. Our interim analysis serves to support the accelerated approval. For this, we need to read on biopsy, and that's where the AMH assist will be very helpful. So we have a cohort that is supporting that efficacy assessment. We also need to have a safety database to support the accelerated approval. this is the second cohort that this time between both cohorts will have the total amount of patients that's required for that safety database. And these cohorts is more on the NITs. The good news is that for sites, they have two opportunities basically to include their patients. Their patient could be included on the biopsies. And if they fail the biopsies, but they meet the NITs, They are having that opportunity to bring the patients. It's quite exciting with the feedback we receive from the PIs. It's quite positive, and we hope that it will help us with the enrollment.
And then the enrollment criteria is slightly different between the histology versus the net. I believe you all enroll stage 2 and 3 for fibrosis.
So, correct. We're focusing right now on our F2, F3 populations. And the cohort one is going to be F2, F3 biopsy proven. The cohort two will be either the biopsy they have failed, for example, on ballooning, but they are matching the NITs on the F2, F3 and the criteria that we've determined with our academic experts that are representative and high probability of being F2, F3 patients.
And Roger, as you reference, we're capturing all the NITs for all the patients. So should something evolve on the regulatory side, we would be in a good position to have all of the appropriate information to pivot should that be an opportunity during the execution of phase three.
That's right. That would be a huge upside because that's what the field want to look like. And then the physician side and the scientific community want to see that. But regulatory seems a bit lagged behind. But I think the conversation is going to be ongoing.
We would need the agency to move their position.
Yeah, that's right. And then the other thing, and now you remind me this, you know, because some of the patients, they qualify histology, some of the patients only qualify the NIT, how should we think about the ultimate outcome in terms of histology result and then the ultimate liver event result? Will it be different, you know, huge difference between those two populations?
So, no, this serves to, so the F2, F3 might have difference, and it's known that on the liver-related events, they have different risks. So the F3s are clearly more advanced. The F2s are less advanced and have a hazard ratio for liver-related events that is usually smaller. So we have the opportunity to adjust. We've determined based on the literature. There is no current study that has demonstrated outcome. So based on our knowledge and the literature and the academic experts, we have a hazard ratio that we feel is reasonable. We're going to monitor that event rate, and we have the options to adapt this in our enrollment based on this. So we'll have that flexibility. Our primary focus, obviously, is to get to accelerated approval, and these are the biopsy-proven patients on the efficacy side.
Got it. And then you have the flexibility to change the ratio between the F2 versus F3. How about the cohort one and the cohort two in terms of the histology validated and then the NET validated?
So for the cohort one and two, those ratios have been determined. So we are going to have 990 or approximately 990 patients in the cohort one. This is based on an effect size that we have determined on our own phase two data, on the prior products that have been approved so far and what was the effect size. We've powered ourself based on mesh resolution, and this one is easy to achieve. So we're well north of even 99% powered. On the fibrosis, this is the most difficult to achieve. So we've taken a rather, I would say, a bit of a conservative approach on our assumptions, but there is a few upside. One, we're having the 2.4 milligram dose that has demonstrated the added weight loss and potentially could demonstrate added benefit on the fibrosis, but that's not been part of the powering. so we powered based on the phase two on the 1.8 milligram so we see that as upside we have as i mentioned the decree the decrease in viability potentially on the a mash assist that could also play in our favor one additional aspect that i think is really important in all of these mash trials is adherence to treatment we've demonstrated with pemvidutide that more patients stay on wrist print, this continuation rate could be lower than, for example, other competitors or GLP ones. And if we do more patients we keep in our study, obviously, the more chances we have to demonstrate strong efficacy. So we're trying to, all these are kind of added upside that have been put in the design of the study, but they are not factored in our sample size.
Got it. And then in terms of the cohort one and cohort two, I believe both of them will serve to the final endpoint, which is an event-driven endpoint. So will those two population difference in terms of natural history and then the reaction or response to the incotent?
No. So the two population will not be different. It's not because you do the biopsy and you fail on the biopsy that you have lesser risk, et cetera, to evolve towards progression to cirrhosis or other liver-related events, and that's part of some of the challenges of the biopsy and where the scientific community is trying to push regulators to understand that the needs could be sufficient to determine the risk of those patients. So they will be extremely similar, and we hope to have the same progression for these. We've built as well a little bit of what we call NIDS-triggered biopsies to follow those patients and identify events. Hopefully that could help us either wrap the study a little faster or figure those things out as they come, given the event rate. So, we build a few things like this that we think can help us and can ultimately be more efficient for the MASH patients.
Got it. Okay, great. You know, it's going to take a while to read out, but I think we have a lot of evidence to support the phase 3 could be positive. And if that's positive, then you can get accelerated approval and then waiting for the final approval. If you get approval at the interim based on histology, how should we think about the market? Because a lot of investor discussion or pushback, I would say, is, you know, Incoturn also should benefit there. And they will go generic pretty soon. The pricing point is different. You as a, now it becomes a more liver specialized kind of a compound, Pemiridotide. How should we think about the dynamic there? why people want to not use the generic incoterm, rather using PEMVU, and then what's the pricing strategy there?
Yeah, as I mentioned on the front end, the whole opportunity is going to be about differentiation and making sure in market you're identifying the patient segments that can best be served by PEMVidutide. Importantly, the market's going to continue to grow up. It's been great to see since the first couple of approved drugs have come out that the physicians are able to identify the MASH patients at risk non-invasively, the payers have been supportive, and you see the utilization of MASH therapies, which we talked about for a long time. Once some drugs are available, you'll start to see the structure of the market evolve, and it has. Importantly, I think when you look at the potential profile of Pembidutide, we're meeting some of the needs that will be there in spite of the fact that their drugs approved today and that we anticipate more coming so where might pemby play i think first and foremost we continue to get strong feedback that the dual mechanism impacting high quality weight loss along with direct liver activity is one of the key treatment goals it's why from the beginning when the first phase threes were set up for mesh the scientific experts always talked about combination therapy because we know it's a complex disease that's going to bring multiple mechanisms at play PEMB, we believe, is going to bring good solid weight loss, addressing many of the elements on the metabolic side, and bring the direct liver action. I think that the GLP monotherapies, by the time that a drug like PEMB gets to market, will be often a first-on option. You mentioned it might be at a lower price point. We know the access and experience with therapy. But even today, we know that the majority of patients, MASH patients who are put on GLP monotherapy don't stay on the therapy for the long term, right? And chronic therapy, getting patients at the target dose and keeping them at the target dose in the real world, is the whole key to effective treatment. I think that's where the Profile PEMB can play best. We saw in the Phase 2 the dropout discontinuation rate on the 1.8 was lower than placebo. again keeping patients on in the real world I think is going to be one of the opportunities to differentiate from GLP monotherapy we know there are significant portions of the population that have difficulty tolerating GLP monotherapy we know that some of the oral options which aren't bringing weight loss to the table there's a desire for a drug that can bring both and at times avoiding having to take two different drugs uh which they are doing already some of the patients that are starting on uh the oral option that's available and and sam are getting both together again the opportunity here is you bring something to the table that that can do both so roger we continue to see again you know good strong segments of patients we can talk about the group of patients that are at risk of sarcopenia which might be again an ideal candidate for a drug like pembidutide if the phase three data is as we anticipate and again we we believe there's a middle of the treatment cascade here that may not be first on may not be you know there might be some later stage patients f4 patients that where fgf21s are a good option but we think there's a really good solid several segments of patients where pembid is going to be a good option. We're going to continue to focus on the differentiation. Some of the data that came out enhanced that, the way we're setting up some of the elements around phase three, play in that direction. So again, the market will grow, will grow up. And the key to success is going to be not just getting into the market, but getting into the market with clear opportunity to differentiate for important segments. And that's the approach we're going to take.
Got it. Yeah. And I think it's maybe it's a down the road, but I would think that this is also a branding strategy because you want to differentiate yourself from the top is not just another obesity incretion. You are rather it's a more glucagon, liver-targeting agent because a lot of the other, you do have a couple GLP-1, GCG, but their ratio is basically the GLP-1. It's very little kind of a GCG. Rather, you are one-to-one, so it's more on the GCG side. So when you do the branding or the you know pricing this is a more you know more kind of a liver targeted agent yeah
that's a key point roger and it was one of the i think themes uh that we saw at the easel meeting the growing understanding of the importance and the potential of combining glucagon and glp and on top of that the fact that all of these compounds are not the same so the ratio matters we believe that the balance ratio we see in pembedutide is important uh we think that the you port domain uh which is again a core uh component of the connection of the the peptides is important on the tolerability side uh and again i think ultimately yielding a profile that's going to be different not just from other combinations which might be uh you know the the glp gip but also significantly different from the other glucagon glp combos out there these combos are not not all the same. It's about the molecule, it's also about the formulation, it's about how the drug is delivered, and I think all of these are going to be contributing to what we believe is a differentiated profile.
I agree. Okay, Greg, I know you've been busy and successful, right? So you try to finance this kind of major, massive phase three, MASH, and then tell us where is the balance sheet so far, and then how this, you know, the whole program is funded.
Thanks, Roger. Yeah, let me start with sort of how I think about the financing strategy as we came into the year. We had a pretty good line of sight on what the investment in the match trial was going to take. And so we broke that down and through two different equity offerings, most recently the 225 on top of the 75 raised back in January, bring us to a total balance sheet north of $500 million. and the so what is that that will cover the runway to deliver on the mash results in 2029 so that's three years out and the effort that christophe and his team and uh just end to end the the efforts to uh to take the uh the mash phase three uh through the gauntlet um that were covered there i think we also have a budget for the aud and the ald phase twos so those are also covered and as we go forward we have some flexibility and optionality we think about the use of perhaps some strategic investments also in combination with perhaps our debt facility and or an atm but again going forward we would focus on non-dilutive options as our preferred
go forward plan? I think it was also important in all the work that Greg helped lead that we brought in some real top-tier biotech investors into the story. It had been clearly one of the objectives and an important element as we look at the long-term opportunity with MASH and hopefully
with AUD and ALD also. Yeah. Okay. Let's talk about the AUD and ALD. Honestly, I'm very interested in those two programs. Add the liver, more specialty in the liver. And then the MN need is even more than the MASH, considering how many options are there available to them. So you will have the data pretty soon, I believe, with 3Q. And the AOD a little bit later. That's for AOD first. And then I think at this point, we treat them as the optionality and how excited you are internally in terms of the upcoming phase 2. And then what is the profile can trigger you to tell Greg, say, okay, we're going to fund this even more, and then let's do more.
Yeah, we're excited. We're looking forward to the data. You know, I think that this was a real important expansion of the potential for PEMB-Dutide. We always hope to go into areas where there's large unmet need and where we believe there can be differentiation in what PEMB-D can bring versus what some of the options might be. And it's the context upon we designed the two studies. And maybe, Christophe, you can give a little insight in the data we're anticipating, just what we're going to read out on and how you see the mechanism of PEMV playing in that indication.
Sure. So AUD and ALD are kind of those next indications we're looking into. PEMV-2 Tide fits really well, because through the GLP-1, we address the reward than the cravings on the alcohol aspect through the glucagon we are very uniquely positioned to address the liver aspect in particular obviously in ALD patients but AUD patients also already have liver steatosis inflammation and even at easel some KOLs were telling her that it's underestimated the the level of fibrosis they have in their liver so this is a great opportunity for us. Our AUD study will read on heavy drinking days. We were really encouraged to see the semaglutide data. It was a one single center study. We're multi-centered. There are differences with our study, but it looks like it's validating our approach with the GLP-1, at least, component of pemvidutide. And as you mentioned, I mean, it's going to be helping us moving we'll see with the data but moving to um based on this data what else can we do next and uh starting uh uh planning to engage with the uh the regulators and uh and moving forwards and then i'll i'll be bugging greg to to accelerate more funding efforts um to support it so yeah
roger you can expect in quarter three we'll read out the data a traditional top line release from the company. We'll put the data together. If it's positive, request an interaction with the agency and then, you know, continue to update on our plans there. But we look at that as a good solid bet and excited for the day to come. We'll see what it looks like. How many days reduction on
the heavy drinking days you think will be clinically meaningful also? I believe you power
for one day difference. Is that right? That's correct. So we've been fairly conservative in in the sense that these are PROs, that the placebo effect can be fairly important. Also, we're measuring more objectives assessment through some blood markers like the pest, the photofatidylethanol measurements. So we'll get a good sense of where those things are. And we've assumed only a one-day difference between the effect of the pemvidutide arm versus our placebo. And obviously, we'll get a sense of how that plays out when we read out the data.
And you think the one-day difference is also clinically meaningful in terms of, you know, your advisor or the feedback you're getting from physicians?
Yes, I think it's already clinically meaningful. It's, again, it's an average. So in some patients, it will be more than that. It's what we believe as a starting point can be important. And based on this, we'll look also other endpoints that have been validated and regulators look at it for the phase three, such as zero day of drinking or WHO levels, changes, and these will be aspects altogether clearly will tell us how far and where we can get with this data.
By the way, the time period, one week, within the week, heavy drinking day, and then you reduce by one day.
So it's an average per week, but we're measuring four weeks in a row at the baseline and four weeks in a row at end of study at 24 weeks. So it's not just one week like this. It's an average and we'll get a sense as well as what's happening throughout the study.
Got it. Okay, great. Jerry, any closing comments? No, I
accept just to say that the company stays extremely focused. We are in an era of execution. We're executing towards the readout. We're executing towards getting the MASH trial up and running. Again, I think at the heart of it all is our belief that PEMB is an important potential therapy for patients and can bring elements different to the table than any of the other medicines out there. So a lot of work to do, but good progress, and we'll keep you informed.
Excellent. Thank you, gentlemen. Thank you, everyone.
Thank you.