Altimmune at The Citizens JMP Life Sciences Conference: Pembidutide’s Promise

On Wednesday, 07 May 2025, Altimmune Inc. (NASDAQ:ALT) presented at The Citizens JMP Life Sciences Conference 2025, detailing its strategic focus on pembidutide, a GLP-1/glucagon dual agonist. The company highlighted its potential in treating non-alcoholic steatohepatitis (NASH) while acknowledging the competitive landscape and challenges in the metabolic disease market.

Key Takeaways

• Altimmune’s pembidutide shows promise in NASH treatment, with significant results in Phase II trials.
• The IMPACT trial design aims to minimize bias and ensure robust data.
• Pembidutide offers a unique value proposition by combining GLP-1 and glucagon benefits.
• Altimmune is exploring future indications, including alcohol-related liver disease (ALD).
• The company maintains a strong cash position to support ongoing research and development.

IMPACT Trial Design and Endpoints

• The trial involves 190 subjects, focusing on a 1.8 mg dose compared to a placebo.
• Measures to reduce bias include rereading and scrambling biopsy samples.
• Primary endpoints are NASH resolution or fibrosis improvement, with secondary endpoints including weight loss and liver fat changes.
• The trial includes a 1.2 mg and a 1.8 mg arm, with dose adjustments based on patient tolerability.

Previous Clinical Trial Data

• Pembidutide has a well-established safety profile, confirmed by the FDA, with no increase in major adverse cardiovascular events.
• A Phase II obesity study showed a 15.6% weight loss at 48 weeks, with promising LDL cholesterol reduction.
• MAZL D studies demonstrated a 76% reduction in liver fat at 24 weeks, leading in class for NASH drugs.

Market Considerations and Future Indications

• Pembidutide addresses a gap in the NASH market by providing direct liver effects, unlike GLP-1 alone.
• Altimmune is targeting ALD as a future indication, leveraging pembidutide’s potential to reduce alcohol cravings and heal liver inflammation.

Cash Position and Upcoming Announcements

• Altimmune reports a robust cash position, sufficient to advance two new indications into the next year.
• A detailed update on the IMPACT trial data is anticipated during the upcoming first-quarter earnings call, with a readout expected in the second quarter.

Readers are encouraged to refer to the full transcript for a comprehensive understanding of Altimmune’s strategic insights and future plans.

Full transcript - The Citizens JMP Life Sciences Conference 2025:

John Wallabin: Hopefully, everyone got in who wanted to today. But we’re going to kick off our second session of day one of the Citizens Life Sciences Conference. My name is John Wallabin. Pleased to have Altimmune joining us here, CEO of Vipman Garg and CMO, Scott Roberts. Scott, this is kind of the farewell tour area.

We’re sad to see you go. And what is it, about a year’s time?

Scott Harris: Next February.

John Wallabin: Next February. Okay. So we got you for a little bit

Scott Harris: longer. Right.

John Wallabin: But thanks for joining us, guys.

Vipman Garg, CEO, Altimmune: And Thank you for having us.

John Wallabin: For folks who are not as familiar with the story, can you tell us just at a high level what you’re working on at Ultimmune? And then we’ll dig into the details.

Vipman Garg, CEO, Altimmune: Sure. Well, thank you for having us. So at Ultimmune, are developing a GLP one glucagon dual agonist for multiple indications. Our goal is to leverage the dual mechanism of of pembidutide, our GLP one glucagon dual agonist. The idea is to use the drug where we’re looking for benefit, direct effect in the liver and the benefit of weight loss.

So for instance, we’re developing the drug for NASH. We have phase two b data coming out soon. We’ll talk more about that. And so just really think about NASH as NASH with obesity. Eighty percent of people with NASH have obesity, and they’ll benefit from weight loss.

So you need a drug that’s working directly in the liver, and people are losing weight at the same time. So all of the indications that we are developing are liver focused. So the benefit in the liver, we are taking able to take advantage of glucagon and then combine it with GLP-one. And therefore, we leverage this dual mechanism of action in all of our our indications. We’ll talk more about that.

John Wallabin: Can you talk a little bit about the history of this class? Because you guys were early to the game with GLP and glucagon at least in the SpitCap biotech space. And, you know, pharma looked at it years ago, kind of fell out of favor and now coming back. And now we’re seeing Lilly had great data from their triple agonist with we can talk about the importance of glucagon to that. Novo just licensed a triple agonist.

We’re going to have data from you guys, Merck this year. Why is there a resurgence? What have we learned over the past, call it, five years about importance of having glucagon as an ingredient component?

Vipman Garg, CEO, Altimmune: Yeah. I mean, if you look at the history of obesity metabolic space, people are realizing that it’s not just about weight loss, how much weight loss you’re getting. You know, it’s all it’s going to be more about comorbidities in addition to weight loss. And that’s really where multiagonism comes into play because you you’re trying to have influence dual mechanisms or multiple mechanisms at the same time. So I think it’s a validation of the glucagon mechanism that multiple companies are now looking at it.

There’s no question. For instance, GLP one receptor there are no GLP one receptors in the liver. So if you wanna have direct effect in the liver, you need you need glucagon. Liver is loaded with glucagon receptors. So it’s really validation of that fact.

More and more data that’s coming out about glucagon has showed the benefit of glucagon, not only in the liver but serum lipids, for instance. So it’s really more of a cardiometabolic drug that produces weight loss and improves the overall health of these patients. And that’s really going to be important going forward. The whole obesity space, just the weight loss space, is really going to be one segment, but there will be significant need for additional mechanisms to really treat the patient holistically.

John Wallabin: And it seems counterintuitive to have a glucagon agonist to help with weight loss in people who may have, you know, diabetes, prediabetes. Can you talk a little bit about how you walk that fine line?

Vipman Garg, CEO, Altimmune: Sure. Scott, you wanna take that?

Scott Harris: Yeah, just a first comment, Jonathan. We have two Scotts in the C Suite

John Wallabin: of You got Aaron, sorry.

Scott Harris: It’s okay. I didn’t want anyone to think that Scott Roberts, our Chief Scientific Officer, was leaving. Glucagon itself had been vilified for many years because GLP-one makes glucose go down and glucagon acutely go up. What we learned from a number of studies is chronically you get glucagon in these animals and probably in humans as well the glucose goes down. So, now we’re seeing a shift in the paradigm here where type two diabetes is no longer recognized as an endocrine disease but a disease of obesity.

And insulin is now recognized as being bad for diabetics. Type two diabetics increases fat deposition, weight gain, insulin resistance and leads to a vicious cycle whereas you break that with glucagon. There’s been a lot of focus on treating blood sugar in diabetics. That’s because the GLP-one space grew up in diabetes but it’s recognized also that diabetics do not die of their blood sugar. They die of their lipids, they die of their liver fat, they die of cardiovascular disease.

Penpadutide is designed to be glucose neutral and that it has an even balance of GLP-one and glucagon. And we see we’ve maintained glucose homeostasis across all of our studies. We had an extensive end of phase two meeting for obesity with FDA in November of last year and they agreed that we maintain glycemic control. So we’re accomplishing exactly what we sent out to do maximize the effects of glucagon as Vipin described, yet do that while maintaining glucose control and that’s exactly what we’ve done here. So we think that the way we’ve designed the molecule to maximize the glucose of the glucagon effect while maintaining glycemic control is optimal.

It has class leading effects in liver fat reduction and also excellent reduction in serum lipids things that you don’t see with GLP-1s and GIPs.

John Wallabin: And before we jump into the ongoing study and the next steps, can you talk about the data you’ve generated today? Because for Phase II asset, you’ve been in a lot of patients. So what have you seen so far? Just give an overview about the attributes that look attractive for pemvadutide.

Scott Harris: Sure. Well, when we went to the FDA, had over 500 subjects. That’s quite a lot of subjects in Phase II. And now that is exposed to pemvadutide. And now with the completion of the IMPACT trial, we’ll have over 700.

So we have quite a bit of a safety database here. As I mentioned, we went in front of FDA and they confirmed the safety profile of the compound. Not only for glycemic control but cardiovascular safety as well. We’ve had no imbalance or increase of arrhythmias. We’ve had no MACE major adverse cardiovascular events.

So the safety profile of the compound has been firmly established in the prior studies that you’ve mentioned. We conducted a phase two obesity study. With that, we achieved fifteen point six percent weight loss at forty eight weeks. However, the trajectory of weight loss was still steep at that forty eight week mark. Had we followed patients out to the seventy two week time mark of tirzepatide, we would have been very comparable.

In patients who had elevated lipids, LDL, at baseline, we saw dramatic reductions, we saw a 20% reduction of LDL cholesterol. The FDA looked at that and said, Wow, you’ve got synergy with statins here. Because the same effect was seen in patients taking statins and we know that only fifty percent of patients who take statins achieve their LDL goals. So the FDA recognized the potential for synergy here. In our MAZL D studies, we’ve seen class leading reduction of liver fat, 76% at twenty four weeks, the highest among any drug that’s now in development for NASH.

And then on top of that, in our obesity population, we also saw class leading preservation of lean body mass, is extremely important in obese individuals. We know that with drugs like semaglutide, we’re seeing as much as a 40% loss of lean mass, or let’s rephrase that, that 40% of the weight loss is lean mass and that’s been associated with morbidities like hip and pelvic fractures in elderly women, elderly men and women. So these are very important attributes that I think we brought out in our current program going into our IMPACT Phase II readout this quarter.

John Wallabin: Can we talk about the IMPACT design because the MASH fields learned a lot with a lot of failures early on about how to find the right patients, how to measure, how to read biopsies. Can you talk a little bit about and then also you guys have talked a lot about dosing titration. So can you talk about patient selection, endpoints and dosing and scheduling and impact?

Scott Harris: Well, as you mentioned, we have learned a lot from the prior studies and this has really helped us be at the top of our game here. So the study was designed to have 190 subjects. The primary comparison is the one point eight milligram dose to placebo. The study has more patients than other Phase II studies that have had successful readouts. And also based on the fact that we think we’re going have a higher treatment effect based on the liver fat reduction, which is the primary driver of the endpoints in NASH, we think we have a very highly powered study.

As you mentioned or inferred, we are rereading all of the biopsies based on the learnings from other studies. It’s been recognized that in studies that if you just simply read biopsies in the beginning of the trial, knowing that they’re baseline biopsies in the beginning, that creates bias. Those biopsies are upgraded in severity. That effect is lost later in the study. It may even be pushed, the readings may even be pushed to less severe grades because pathologists think that they’re reading post treatment biopsies.

A placebo patient with absolutely no biological change can actually have a placebo effect. They can get a response on these endpoints. We’ve seen that in prior trials where we’re seeing placebo response rates between twenty to thirty percent in studies in which the biopsies are not being re read. So what we do is we take all the biopsies at the end of the trial, this is what we’re doing right now, you scramble them and give them back to the pathologist. They have no knowledge of when the biopsy is being done.

That immediately takes away that bias. Based on that, when you look at studies that have done that, we see read out placebo rates of seven to twelve percent. Big difference. You control your placebo response, you increase your chance of statistical significance. So we’re very bullish on the readout.

We think we have a better treatment effect. We have a larger study. We think the study is better powered, and we think we have control of the placebo response.

John Wallabin: Have you guys said what your assumptions are for NASH resolution of fibrosis improvement responses, your powering assumptions?

Scott Harris: Well, key endpoint that people are focusing on here is fibrosis improvement. So as I mentioned before, if you look at the assumptions and study power, our chances of hitting statistical significance on fibrosis improvement are high.

John Wallabin: What are kind of your thresholds for successful or what’s clinically because you guys are reading out earlier than most other trials too. Right. So if

Scott Harris: you look across the studies the numbers are all over the board. And it depends on the placebo response rate. We see fifty percent versus thirty percent. We see twenty seven percent versus seven percent. If you have statistical significance, that’s what’s really meaningful.

I want to emphasize the fact that if we have STAT SIG on these endpoints at twenty four weeks, we will be the first incretin to have accomplished that goal. All the other incretins which work more slowly indirectly in the liver through weight loss take forty eight to seventy two weeks to see their effects. We have direct effects in the liver. That’s the glucagon component. Think of it like an FGF-one having direct effects.

So we have sufficient potency, unlike other incretin agents, to be able to read out successfully in these endpoints at week twenty four. But compared to the FGF21s, we bring something they don’t bring, which is extremely important, which is weight loss.

John Wallabin: Yeah, how should we think about weight loss in a mash, metabolically deficient population? Because you did see lower weight loss for our call in your Phase 1b mass hold study and that was the pre supposition along with the Hispanic population. What have we learned since then about what to expect in NASH patients in terms of weight loss for this class?

Vipman Garg, CEO, Altimmune: Yes. It’s not so much about just the magnitude of the weight loss, really combining these two benefits, direct effect in the liver with weight loss. So think of it as NASH with obesity. Now, we know eighty percent to ninety percent of people with NASH well, the reason they have NASH is because of overweight and obesity to begin with. So we’re treating both the cause of the disease, a serious disease, as well as directly we’re treating that disease.

So that’s really the benefit of combining GLP-one and glucagon. So really, eighty percent to ninety percent of the patients will benefit from losing weight. So we will be the only drug in a single molecule will show that benefit combining that benefit of NASH resolution fibrosis improvement and meaningful weight loss. Based on all of the data that we’ve generated today, we’re very confident that we should see meaningful weight loss that would benefit these patients.

John Wallabin: And I haven’t thought about this before. I’d be interested in how you guys think about this. So you’re going to have the you’re hitting the liver hard early, but then you’re also having the benefit of the body weight reduction over The other semaglutide tirzepatide, they see their effects longer because they’re seeing the benefit of the weight loss, which lags. How do you think about hitting glucagon early but then seeing continued weight loss? And we’re never probably going to do a serial biopsy study, but do you think that that would continue to have a compounding effect over time?

Vipman Garg, CEO, Altimmune: And will continue to also see glucagon effect over time. So, yeah, we agree with you because and we’ve seen that in other studies where longer you treat these patients, the better the benefit even without weight loss. So now you combine two of these effects and continue over a period of time, seventy two weeks and beyond, you should see significantly more effects. So that’s what Scott was saying, that if we show statistically significant improvement in fibrosis and meaningful weight loss at twenty four weeks, that effect is only going to grow with time.

John Wallabin: Look, actually, can you talk about your normalization of liver fat? Because can it get better than normal?

Vipman Garg, CEO, Altimmune: Clearly. Well,

Scott Harris: when we talk about 76% relative reduction of liver fat, which is class leading, What’s also class leading about our results is that despite starting with the highest liver fat content of baseline of any study, we had the highest rates of liver fat normalization. So we had a greater burden to carry to get from 23% down to five percent, and we achieved that in over half the subjects. That’s something that other studies haven’t done.

John Wallabin: So perhaps it’s just giving more time for fibrosis to clear and the pathways to, you know, heal themselves.

Scott Harris: Well, you have that effect at twenty four weeks because of the glucagon effect. As Vipin mentioned, we know in other studies that those endpoints improve over time. We know in a recent study comparing twenty four weeks to ninety six weeks, the effects of fibrosis improvement doubled. Now we think we can have an even better growth of our effect than that because not only do we have the continuing glucagon effect, same as the continuing FJF21 effect, but also we add on top of that the benefit of weight loss which continues to grow over time. That weight loss is very important for many reasons in differentiating our product.

First of all, patients see MASH as a silent disease. When they come to get treated, want to lose weight. We saw that in our style study, this study enrolled faster than any other study out there. And the reason is that patients wanted to lose weight and it shows that investigators and patients were happy with the study. But that’s also going to drive the commercial aspect of the compound.

Given the choice between a compound that produces weight loss with MATCH effects like we have and one that doesn’t have the weight loss, the patient will choose the drug with weight loss. Also recognize the fact that MAH patients, up until they hit F4, die predominantly of cardiac disease, not liver disease. They die of the lipids. They die of the liver fat. It’s very important to have movement in these areas, a lot of which are driven by weight loss, and really have meaningful effects in the mass population.

John Wallabin: I forgot to ask this. Are you guys including F1 patients in impact? No. To be F2, F3.

Scott Harris: It’s going to be F2, F3. We think we have approximately a fiftyfifty split between F2 and F3.

John Wallabin: Which de risk phase three even more for you guys. Exactly. Can we talk about tolerability for a minute? Because that’s also the big hang up with the GLPs as well as patients, you know, have tolerability issues, can’t stay on long term, probably some mix of, cost, price and tolerability in the real world. But can talk about pembidutide’s tolerability profile and how you think that compares to the field?

Scott Harris: I can tell you specific to this trial, Jonathan, we are watching things like discontinuations, adverse event discontinuations and the like. You know, we have to know about them because they get reported to us and I would just simply say from 10,000 feet that we’re very happy with the way the trial is going. Mesh patients tolerate adverse events better than other populations. Diabetic patients in particular, and you know that MASH patients, fifty percent of them are diabetic. In our diabetes study at twelve weeks, we had no adverse event discontinuations.

And in fact, at the 1.8, which is the key dose that we have in the IMPACT trial, we didn’t have a single patient reporting nausea, zero percent, or vomiting. So it means that going into this trial in patients with NASH, fifty percent of whom will have diabetes, we’re probably going to have a very good tolerability profile manifested by the frequency of GI adverse events, but more importantly, adverse event discontinuations due to that intolerability.

John Wallabin: And, you know, talking about interpreting these data sets, it becomes complicated when you hear about things like dose reduction or dose maintenance. You guys have no titration or slow titration, but is there any flexibility in dosing in your trial like others have shown that might make their profiles look better than they actually would be in a more rigid design?

Scott Harris: If you look at all the other studies, thirty percent of patients are either reducing their dose because they can’t tolerate what they were given, or they didn’t achieve the dose that they were targeted to achieve, thirty percent. Had they been forced rigidly up to those doses, we would have seen very high adverse event discontinuation rates. And by allowing this in these other trials, they’ve gotten their adverse event discontinuations down to low numbers. We made that transition in going from our obesity study to this study. So in this study, patients can dose reduce for intolerability to stay in the trial.

It’s only going to add to that excellent profile that we anticipate. So you have a one point two and a

John Wallabin: one point eight milligram arm?

Scott Harris: And neither are dose titrate.

John Wallabin: Yep. So then if you’re starting at one point eight, can drop to one point two. But if you’re one point two, that’s You go to placebo. Go to placebo. Okay.

And you said blinded discontinuations look very good.

Scott Harris: Yeah, we can’t give you specifics, we can say that from 10,000 feet watching the progress of the Tau Trial, it’s going extremely well. And we’re really happy with what we’re seeing to date. And data coming this quarter, everybody’s asking when, and people are asking, could

John Wallabin: it come today? And I was like, it’s a busy morning, I hope not, but maybe. But you talk about the biopsy reading and, you know, when we look back at trial, so you have everyone you have can you talk about the reading methodology for your biopsy readers? You talked a little bit about dropping that placebo rate, but you know, how difficult is it to be sending biopsies to multiple pathologists and then do they have triplicate reads of baseline and end of treatment biopsy for 100 and some odd people? It seems like that would take quite a long time.

Scott Harris: Well, as we mentioned when we announced the rereading of the biopsies, we pushed the readout back to the second quarter to accommodate that whole process. That’s what led to the shifting of the trial readout from this first to the second quarter. But we have a very good handle on it right now. We’re at or near the completion of the rereads, and we should be moving to, readout this quarter. I think we’re very firm in our belief that we’ll readout this quarter.

John Wallabin: And what data will you be giving us on the top line?

Scott Harris: Well, obviously the primary endpoints, Jonathan, that’s a dual endpoint of mass resolution or fibrosis improvement. And also important key secondary endpoints like weight loss, changes in liver fat, the non invasive tests such as FibroScan, E. F, the Enhanced Liver Fibrosis Scale. We also have a readout on adverse events, discontinuations, demographics and glycemic control.

John Wallabin: And not to hold you

Scott Harris: to

John Wallabin: anything if you say it today, we also see sometimes NASH and fibrosis improvement or two step fibrosis improvement. Do you guys think you’ll have that available as well?

Scott Harris: We’ll eventually have those tables. Whether we have them for the readout, we’ll have to Okay.

John Wallabin: All right. And then I want to ask like two big picture NASH questions. How are you thinking about what we’re seeing with Resdevra’s launch and what that could mean for pempedutide long term? And then what do we know about incretin use in NASH today? And do you think that semaglutide’s official approval of NASH will change that at all?

Vipman Garg, CEO, Altimmune: Well, there’s no question that losing weight is a beneficial thing for treating NASH. So there will be some of that use. But I think it’s one thing is clear, looking at Residifera, that just GLP-one alone or incretins alone are not going to be able to address this market. So we are going to need a direct effect in the liver. So I think that has, that’s now firmly established, which is good for all of the other agents that are more direct acting in the liver, including pembidutide.

So we think that’s really a very encouraging sign that risdipla is doing well and continues to do well. If, you know, and as you know, Risdipla has no benefit in terms of weight loss. It’s purely working in the liver. Same thing with FGF21. So we think you combine these two effects, you have even better chance of succeeding.

And that’s really put you in a prime position in terms of why would you use two drugs, GLP-one and a direct acting agent in the liver, if you can accomplish that same goal with a single molecule. And that’s really the value proposition here. When physicians hear about this profile, they really get excited about the drug because now they can completely this is really a full complete solution for NASH, not just half of the fixing half of the problem, but even taking away the the cause of disease itself. So we think that really speaks well to the future of pempidutide. And as we’re bumping up on time,

John Wallabin: I wanted to just give you an opportunity to talk a little bit about the two other indications that you’ll be pursuing with pempidutide. Can you talk about you know, those indications, next steps, and the potential opportunity?

Scott Harris: The rationale for the indications are compelling. GLP-one suppress alcohol cravings. With regards to alcohol liver disease, it’s a disease of fatty liver. The histology is indistinguishable from NASH. When I trained as a hepatologist, we used to call this non alcoholic steatohepatitis because these patients we accused of being pocket alcoholics were actually not.

It was clear that when you have excess fat in the liver, drives inflammation and fibrosis. And the histology, the pathological findings look the same. So, for AUD, it’s quite clear that that will progress to ALD. So we have a drug that not only reduces the cravings, but also heals the inflammation, the ALT elevations that’s seen in these patients. With regards to ALD, that’s a fatty liver disease.

Between NASH and ALD, we’ve accounted for the great majority of liver transplantations that have been done in The United States. Our goal, our vision is to own that space. We plan to own the fatty liver space because we have the drug that can do it.

John Wallabin: Okay. And we’ll be getting an update from you guys, your first quarter earnings next Tuesday, I believe. But can you remind us of kind of your year end 2024 cash position? And then historically, you guys have announced data with your earnings calls as well. So maybe what should we look forward to next week?

Vipman Garg, CEO, Altimmune: Well, we’ll give you a full update next week. Again, as Scott mentioned, we’re very comfortable saying that we’ll have data in the second quarter. So we’re not providing any more you know, color than that, but, stay tuned. We’ll provide a full update, next next week.

John Wallabin: And if you remember cash position and runway that gives you, we have the important data coming 2Q. Yeah. You know, how you

Vipman Garg, CEO, Altimmune: So at the end of at the end of 02/02 new indications into the second half of next year. Okay. So we’re in a good position, and we’ll continue to monitor and be prepared for the next steps in development of when we

John Wallabin: do that, particularly as we look forward to the Phase III program. Perfect. Well, as we just ran over time, Vipin, Scott Harris, thank you for joining us. We have

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