Altimmune Q4 2024 Earnings Call Transcript

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February 27, 2025

There are 10 speakers on the call.

Operator

Good day, ladies and gentlemen, and welcome to the Altimmune Fourth Quarter and Full Year twenty twenty four Financial Results Conference Call. As a reminder, this call is being recorded. After the speakers' presentation, there will be a question and answer session. I would now like to introduce your host for today's conference call, Lee Roth, President of Burns McClellan, Investor Relations Advisor to Altimmune. Lee, you may begin.

Speaker 1

Thanks, Gigi. Good morning, everyone, and once again, thank you all for joining us for Altimmune's fourth quarter and full year twenty twenty four financial results and business update conference call. On today's call, you'll hear from Doctor. Vipin Garg, our Chief Executive Officer Doctor. Scott Harris, our Chief Medical Officer and Greg Weaver, our Chief Financial Officer.

Speaker 1

Doctor. Scott Roberts, our Chief Scientific Officer and Ray Jort, our Chief Business Officer will join us for the Q and A session. Press release covering our fourth quarter and full year '20 '20 '4 financial results and corporate update was issued earlier this morning and can be found on the Investor Relations section of the Altimmune website. But before we begin, I'd like to remind everyone that remarks made about future expectations, plans and prospects constitute forward looking statements for purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995. AltaMed cautions you that these forward looking statements are subject to risks and uncertainties that could cause our actual results to differ materially from those expressed today.

Speaker 1

For a review of the risk factors that could affect our future results and operations, we refer you to the company's filings with the SEC. I direct you to read the forward looking statements disclaimer in our press release issued this morning, which is also available on our website. Any statements made on this conference call speak only as of today's date, 02/27/2025, and the company undertakes no obligation to update any of these forward looking statements to reflect events or circumstances that may occur on or after today's date. As a reminder, this call is being recorded and will be available for replay on the Altimmune website. With that, it's now my pleasure to turn the call over to Doctor.

Speaker 1

Bipin Garg, Chief Executive Officer

Speaker 2

of Altimmune. Bipin? Thank you, Lee. Good morning, everyone, and thank you for joining us for our fourth quarter and full year corporate update. 2024 was a year of significant progress for Altimmune.

Speaker 2

The milestones we have achieved over the past twelve months have positioned us for transformative catalyst in 2025 and beyond. Following the third quarter twenty twenty four completion of enrollment in IMPACT, our Phase 2b biopsy based trial of pamidutide in MASH, our top line data readout remains on track for the second quarter of this year. The dual primary endpoints of the study will be MASH resolution and fibrosis improvement at twenty four weeks. Pending these results, we will request an end of Phase two meeting with the FDA to align on a registration of Phase three program. While the timing of that meeting will be determined by the agency, we expect that it will take place before the end of this year, which would position us to initiate a Phase three program in NASH in early twenty twenty six.

Speaker 2

With a positive impact readout, pamidutide would be the first incretin based agent to achieve fibrosis improvement at twenty four weeks and the first therapeutic candidate in any class to achieve both significant fibrosis improvement and meaningful weight loss in a twenty four week treatment period. We believe that this unique combination of pemidutide's direct action on the liver together with clinically meaningful weight loss will position pamidutide to become the treatment of choice in NASH. The ability to reduce fibrosis in only twenty four weeks is important because it signals both the potency of pamidutide and the promise of even greater response rates over the longer treatment durations used by other incretin based agents. In addition to our progress in NASH, I am thrilled to share that we submitted INDs for pemidutide in two additional indications in the fourth quarter of twenty twenty four. Both of these INDs have been cleared by the FDA and this positions us to start Phase II efficacy trials in mid-twenty twenty five.

Speaker 2

We believe that each of these indications represents an attractive and compelling commercial opportunity for which pemidjiutide will be ideally suited. As we announced this morning in our earnings press release, we will be holding a virtual R and D day on March 13, at which time we will disclose the additional indications and provide detailed overview of these new opportunities. The R and D event will feature presentations by key opinion leaders specializing in MASH, obesity and the additional indications. We are extremely excited about this event and look forward to sharing our plans on the future of pamidutide. From an organizational perspective, we are excited by the recent addition of Terry Lower and Jerry Durso to our Board of Directors.

Speaker 2

Notably, they have decades of experience across the pharmaceutical industry, including late stage clinical development and commercialization of therapeutics in the MASH and metabolic disease space. These areas are highly relevant to Altimmune, and I believe that their expertise and guidance will be invaluable as we embark on our next phase of pamidutide development. I'm excited to work with them and look forward to their respective contributions. Lastly, I wanted to share with you that Scott Harris, who has served alongside me as our Chief Medical Officer for the last six years, recently informed me that he plans to retire a year from now at the February 2026. Scott has been a valued and trusted colleague whose leadership has been instrumental in advancing pemidutide to the cusp of an important data readout.

Speaker 2

If successful, this could position this readout could position pamidutide as the foundational therapy in the treatment of MASH and other metabolic diseases. I am grateful that he will remain with us through the impact data readout and the end of Phase two FDA meeting for NASH and that he has given us ample time to find his successor and to ensure a smooth transition. We plan to initiate a search for his successor in the near future. With that, I'll now turn the call over to Scott Harris. Scott?

Speaker 3

Thank you, Vipin. As Vipin mentioned, after twenty five years in drug development, including the past six years at Altimmune, I've decided to plan for my departure in early twenty twenty six. I want to emphasize that I will remain with the company through all important milestones over the next twelve months and that I'm not going anywhere anytime soon. I'm excited about the upcoming impact readout and the opportunity to lead the medical team through Phase three readiness in MASH, as well as the initiation of the Phase two trials in two additional indications. You'll be seeing a lot of me throughout the next twelve months.

Speaker 3

Want to thank Vipin and Ultramoon for letting me shepherd pemvodutide from a preclinical molecule to a Phase three ready asset in multiple exciting indications. With that, let me turn to our significant progress in MASH. As noted, we are rapidly approaching top line readout of the twenty four week efficacy data for the IMPACT trial. Unlike current agents approved or in development for MASH, pemvadutide has the potential to drive both fibrosis reduction and significant weight loss. Essentially pemvadutide has combined the weight loss effects of the Incretins with the liver directed effects of agents like the FGF21s into a single molecule that we believe will provide a complete solution for the treatment of MASH.

Speaker 3

Our key metric for the success in the IMPACT trial will be the ability to achieve statistical significance on the fibrosis improvement endpoint at twenty four weeks. If successful, pempedeutide will be the first incretin based agent to achieve fibrosis improvement at twenty four weeks and the first therapeutic candidate in any class to achieve fibrosis improvement and meaningful weight loss in the twenty four week period. Liver fat reduction is the key driver of fibrosis improvement. But in addition, we also have preclinical data showing that pembidutide has direct anti fibrotic effects. Most importantly, we have greater liver fat reduction at twenty four weeks than any of the MASH agents currently in development regardless of when the reduction was measured.

Speaker 3

With respect to study POWER, the two primary treatment arms in IMPAPACT, pempedeutide one point eight milligram and placebo are larger in comparison to the number of subjects in the successful FGF21 trials, but also read out successfully at twenty four weeks, albeit without meaningful weight loss. Together with our greater liver fat reduction, we believe the study has more than adequate power to achieve statistical significance on the fibrosis improvement endpoint at twenty four weeks. Controlling the placebo response rate will also assure a higher likelihood of achieving statistical significance at data readout. We've learned a great deal about how to reduce the placebo effect in biopsy based MASH clinical trials. First, we will be employing three readers and using the mode technique of scoring.

Speaker 3

Second, we will be rereading all the biopsies in a blinded manner prior to the trial readout, eliminating any bias introduced when pathologists know the biopsy is a pre or post treatment sample as a result of when the biopsy is being read. Both of these approaches are similar to those used in the Phase II Pegazofirmin trial, which achieved the placebo response rate for fibrosis improvement of only seven percent. Finally, our pathologists have agreed upon a set of rules by which to align the reading of the biopsies, including for example, how to read controversial findings like atypical balloon cells. We believe the advantages of pempedeutide do not end there. We have consistently shown that pempedutide has robust lipid lowering effects.

Speaker 3

In this context, it is important to note that F2 and F3 patients cardiovascular events are still the primary cause of mortality. So the reductions in LDL cholesterol and liver fat that we have demonstrated with pemvadutide combined with the expected effects in MASH and body weight may further reduce the risk of both cardiovascular disease and liver disease. As we've shared previously, the ENDITU Phase two meeting for obesity has implications not only for the Phase three VELOCITY trials, but for the entire pemdegutide program. During those interactions, FDA identified no safety signals related to pemvitutide in its review of over 500 subjects that have been treated with pemvitutide in our prior studies. To date, close to 700 subjects have been treated with pempitutide across all of our completed and ongoing trials.

Speaker 3

Turning our attention to the two additional indications, we believe these are areas of significant unmet medical need for which the balanced GLP-one glucagon dual receptor agonism, pempedeutide, provides a highly compelling scientific rationale. The recent FDA clearance of our two IND applications has us on track to initiate Phase II trials in these indications in the middle of this year. We will be providing detailed and comprehensive information on these indications, including our development plans at our R and D Day on March 13. You will be hearing from two of the foremost experts in the treatment of these conditions who have been instrumental in the formation of our strategy and who share our enthusiasm for the development of pemvadutide in these indications. With that, I'll now hand the call over to our Chief Financial Officer, Greg Weaver, to review our financial results for the fourth quarter and full year.

Speaker 3

Greg?

Speaker 4

Thank you, Scott. I'll be providing a brief overview of Altimmune's fourth quarter and full year 2024 financial results with more detailed information to be available in our 10 K, which we we'll file later this afternoon. We reported our year end 2024 total cash and investments of $132,000,000 This current cash position is expected to fund operations well into the second half of twenty twenty six. Through our key catalyst of the Phase 2b MATCH readout next quarter and also includes funding of the Phase two trials for our additional indications. Moving to the details of the fourth quarter results.

Speaker 4

R and D expenses were $19,800,000 in the fourth quarter of 'twenty four compared to $16,900,000 in the same period in 2023. Our R and D expenses in the quarter included $13,600,000 in direct costs related to the clinical development activities for pempedutide, including preparation for the upcoming Phase II trials in the additional indications. Non cash stock compensation included in the R and D expenses was $1,600,000 in Q4. G and A expenses was $5,100,000 in the fourth quarter of 'twenty four versus $4,300,000 in the same period of 2023 with a noncash stock comp included in G and A of 1,800,000 in Q4 to an increase of roughly $500,000 over the same quarter last year. Net loss for the three months ended 12/31/2024 was $23,200,000 compared to a net loss of $31,600,000 in the fourth quarter of twenty twenty three.

Speaker 4

That prior year net loss included a one time non cash impairment charge of $12,400,000 related to a discontinuation of the HEPA cell development program. To summarize our full year results, R and D expenses were $82,200,000 in 2024 as compared to $65,800,000 in 2023. Our R and D expenses included $53,000,000 in direct costs related to development activities for pepidutide. G and A expenses were 21,000,000 for the full year 2024 compared to $18,100,000 in 2023. The increase due primarily to a $2,700,000 increase in stock compensation and labor related expenses.

Speaker 4

The total noncash stock compensation expense for 'twenty four was approximately $14,400,000 as compared to $10,600,000 in 2023. Net loss for the year 2024 was $95,000,000 compared to a net loss of $88,000,000 in 2023. The net loss reported for the prior year included the aforementioned non cash impairment charge of $12,000,000 I'll close the remarks by highlighting our cash position, which provides runway into the second half well into the second half of twenty twenty six based on our OpEx forecast, which includes the cost of launching PEMV trials in two additional indications, funding through the key MASH clinical milestones of both 2025 and 2026 as we anticipate advancing into the Phase III pivotal program next year. I'll now turn the call back to Vivid. Vivid?

Speaker 2

Thank you, Greg. We accomplished a great deal in 2024 and have entered 2025 with multiple major inflection points in the near term. As each of these important milestones is achieved, we expect that they'll open the door for new and larger opportunities with us for us, which I strongly believe we are well equipped to capture. I look forward to sharing our next set of updates at the R and D Day on March 13. The combination of Phase 2b readout in MASH and the launch of Phase two efficacy trials in two additional indications as is poised for an incredible 2025.

Speaker 2

That concludes our formal remarks and we would now like to open the lines to take questions. Operator?

Operator

Our first question comes from the line of Roger Song from Jefferies.

Speaker 5

Hi. This is Fiona for Roger. Congrats on the year and a lot of new developments exciting for this year. Just questions on the new indications. I was wondering if you're going to announce the details like the preclinical data at the R and D day and whether if you're going to start the two Phase II trials simultaneously midyear?

Speaker 2

Yes. So we will provide a very comprehensive picture of the two indications at the R and D day that's coming up. As we mentioned, we have two KOLs that will make presentations about both of these indications and we will share our plans in terms of when we would start the Phase II programs as well. So stay tuned and we're looking forward to providing all that detail.

Speaker 5

Thank you. Yes, looking forward to the R and D Day and congrats on the year.

Speaker 2

Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Yasmeen Rahimi from Piper Sandler.

Speaker 5

Good morning, team. Thank you for the great updates. And, come on, I can't believe you're retiring. You have another twenty years in you, if not more. So, but I'm happy to know that I get to work with you for another year.

Speaker 5

So when I want to say that. And it's been a pleasure working with you honestly. I think one of the questions that we would love to understand is post the Phase 2b data as you guys are going to be engaging with the agency, is there anything is there an opportunity to think about given the profound de fatting of the liver and a lot of data supporting MRI PDFF as a histological response? Should we be thinking about the Phase III design very like the typical studies we have seen based on histology or is there going to be some flexibility on some innovative NIT incorporation into the study? And then also if you're thinking about would you be concurrently starting a cirrhosis study in conjunction?

Speaker 5

Just want to love to understand how you're thinking about on sort of the Phase III development and what sort of strategy you want to implement? And I'll jump back in the queue.

Speaker 3

Scott? Yes. Thanks, Yasmin, and thanks for the complement. I hope I make it twenty years. I will look forward to the prospect.

Speaker 3

So as you know, we're really on the forefront of the nits with our MRI PDFF. And this is a potential of great interest to the FDA. At this point in time, we don't really know what the FDA is going to do with the nits. We think we're right there at the forefront of this discussion when that happens. But there's been a lot of discussion about these nits, but I don't have any new information about what the FDA will do.

Speaker 3

Regarding a cirrhosis study, we have a great deal of interest in that kind of study. We've talked a lot about it internally. We don't have anything that we can guide you on at this time. But certainly, as we get toward our Phase III program announcement, we will make such a disclosure probably around the time of the end of Phase two meeting. I want to say though that we feel very strongly we're going to have success in the cirrhosis population.

Speaker 3

We believe that we have we'll have best in class fibrosis improvement on the F2 and F3 population. And we believe that like the recent Afrexofirmin readout based on our reduction in liver fat and our anti fibrotic effects that we have a very high likelihood of success in cirrhosis or F4 as well. We view cirrhosis in its early stage as simply an extension of F3, and that's as long as patients don't have extensive scarring resulting in clinically significant portal hypertension, the complications of cirrhosis such as encephalopathy, ascites, variceal bleeding that this is reversible. And this is the study population that Achero took it in their trial. We simply see that as an extension of F3 and we think our chances of success in cirrhosis are quite high.

Operator

Our next question comes from the line of Annabel Samimy from Stifel.

Speaker 5

I guess, could you going into this EMPACT trial, can you talk about what your expectations are to consider this not just a clinical success, but a competitive success? And just to follow on from that, we've heard a lot about how the obesity market might evolve, but maybe you can talk about how you expect the MASH market to evolve with thimegutide's essence data and ROSIFRA and FGF21. So can you just talk about how you think all those programs as well as pemidutide will play in

Operator

with each other? Thank you.

Speaker 2

Absolutely. Maybe I'll get started and Scott you can take from there. In terms of we've always said that MASH and obesity are linked to each other. People need to lose weight in order to treat their MASH successfully and we are seeing that even the latest data is showing that many people who are taking Residifra for instance are also taking GLP-1s. That's really what we have.

Speaker 2

We have a combination of both a drug that's for obesity as well as for having a direct effect on the liver. So really it's a complete solution for treating MASH. We view MASH with obesity as really the patient population that we will be treating in the long run. Eighty percent of subjects with MASH have obesity or would benefit from losing weight. So ideal drug would do both.

Speaker 2

It will have a direct impact on the liver as well as people will lose weight and that's exactly what pamidutide uniquely does. So we think it's very well positioned for addressing both of those comorbidities together treating MASH as well as people losing weight at the same time. Scott? Yes. Thanks for the question, Annabel.

Speaker 3

Regarding the competitive success, if we have statistical significance at twenty four weeks, we'll be the only IncRETin that has even attempted a readout at twenty four weeks, let alone has success at twenty four weeks. And that's because unlike semaglutide, which you mentioned, or tirzepatide, we have direct effects on the liver. I want to remind you that semaglutide conducted a Phase II trial about the same size as impact about two years ago and even going all the way out to seventy two weeks, failed to show significant statistical significance. We expect to show it at just twenty four weeks. So it's a much more potent compound.

Speaker 3

If you listen to the experts out there who are treating MASH, they don't really rely on the anti fibrotic defect of semaglutide. They see it as being weaker than risdiffra and there's a lot of concern about using it in their advanced patients. We know, for example, that they failed in a cirrhosis study in which the placebo actually did better than the drug. So regarding all of the incretins, we think we have a more potent effect and simply reading out in statistical significance at twenty four weeks will separate us. Now regarding the FTF21s, which have had successful readouts at twenty four weeks and which has guided us to actually make the decision to study the endpoint at twenty four weeks.

Speaker 3

And as I mentioned before, we believe we can be successful because we actually have better liver fat reduction than the FGF21. So we think our probability of success is even greater, is the FGF21s do not have weight loss nor does Risgifera. So you hear doctors talking about using Risgifera for advanced MASH with F3 fibrosis, but when the patient needs weight loss, they add semaglutide. That won't be necessary. With pemidutide, you get both.

Speaker 3

You get the weight loss and the potent effects on fibrosis. So we think not only in terms of our upcoming readout, but in terms of our competition in the EVAMI marketplace, they're going to have a very successful drug.

Speaker 5

Great. And if I could just ask one more question. Are you going to be releasing any other exploratory or secondary endpoints on this top line readout?

Speaker 3

Yes. We are still planning the readout. Obviously, there is only so much we can do in a top line readout, but we will try to provide as much data as we can.

Operator

Great. Thank you so much. Thank you. One moment for our next question. Our next question comes from the line of Lisa Baco from Evercore.

Speaker 5

Hi there. I'm wondering if you could just talk through the overall strategy of pursuing pivotal studies for pemidaldehyde in the MASH population as well as bringing on some new indications. How do you prioritize it and fund all of this stuff from here? Just curious about you're thinking of prioritizing all of that as well with the I know the obesity is kind of lingering in their background waiting for partnership, but just love some clarity and thoughts on prioritization there. Thank you.

Speaker 2

Yes. Good morning, Lisa. Thank you. Thank you for the question. Everything we are doing with pemidutide you'll see when we talk about these indications are really tied to the liver benefits, are tied to the really the mechanism, the dual mechanism of action of pemidutide.

Speaker 2

So it will be all highlighted in our indications. The additional indications, the Phase II program is very inexpensive, relatively speaking. We think that's additional validation of the mechanism and will provide optionality in terms of adding, expanding the indications for pemidutide B on MASH. Our focus will continue to be on MASH and executing the Phase three program on MASH, which as you know we're very excited about. We think we have the best in class agent for pursuing that.

Speaker 2

So

Speaker 6

when

Speaker 2

we get to the end of twenty twenty six, we could be looking at multiple indications that we could pursue in parallel with MASH by having data, Phase II data in these additional indications at the same time.

Speaker 5

Okay. And then for the upcoming Phase IIb data in MASH, can you give us a sense of what you kind of think the bar is to have the competitive profile both on weight loss and fibrosis reversal?

Speaker 2

Scott?

Speaker 3

Yes. The readouts of the FGF21s have had different placebo responses, etcetera, different treatment effects. So it's a bit hard to compare it exactly to that as a percentage. We think the key metric is to achieve statistical significance because we know that's not that's something that the Incretins could never get and then we compete against the FGF21s on weight loss.

Speaker 2

The other thing I would add to that is that if we get statistical significance at twenty four weeks, we know the response is only going to get better with time. So when you go from twenty four to forty eight to seventy two weeks and beyond, we've seen that in other programs that longer treatment, you will see even additional benefit, more patients will respond, the response rate will go will become higher with time. So, achieving statistical significance at twenty four week really sets us up well.

Speaker 5

And how do you think of servadutide and ritadutide as comps at this juncture?

Speaker 3

Yes. Well, as you know, there's really no indication at this point that retrutide is being developed for NASH. That data is over two years old and we've not seen motion. We think the cerverdeotide readout was nice. We think that the effects that were observed were clear indication of the benefit of glucagon and its direct effects.

Speaker 3

We think it really confirmed our mechanism. I would emphasize though that we'll do better. We have more glucagonmar molecule, that's what drove the additional improvement over the other incretins. And we have greater liver defatting effects. There are defatting effects to twenty four weeks is about sixty two percent, ours is seventy six percent.

Speaker 3

That's the major driver of match resolution and fibrosis improvement. I think even more importantly, we differentiate on safety and tolerability. On the tolerability front, we're giving pemidutide without dose titration. No other incretin can even approach doing that. When that was done in some of the other programs, the rates of GI side effects were enormous.

Speaker 3

We're not experiencing that. With servadutide, even at their lowest dose, they're seeing twenty percent adverse event discontinuation rates, and that was with twenty weeks of dose titration. Remember, we're not doing having dose titration. We believe in the tolerability profile of our compound. And in fact they're now extending their titration up to between twenty four and thirty two weeks.

Speaker 3

So we clearly differentiate on tolerability and I want to also remind everyone that we went to an end of Phase two meeting with the FDA where FDA identified no safety signals in our compound and told us to proceed with four efficacy trials without a committed cardiovascular safety trial. We don't know the details, but that apparently was not the case with Servedutide where they're doing a cardiovascular safety trial. It's not like Select where you show the benefit over placebo for reducing cardiac rates. It's to show that the compound does no harm versus the standard of care. That's a very, very different look at the molecule.

Speaker 3

We don't know a conversation they had with the FDA, but we want to emphasize that's not the conversation that we had with FDA. They saw no signals and they confirmed the safety of the compound and that's an important platform for going forward for all of our trials, not just in obesity, but in MASH and the two indications as well. We've had over 500 subjects in completed trials and close to 700 including the ongoing trials and we've maintained the safety profile of pemidutide. And you don't get to play in the space without safety. As you recall with bradetrotide, they saw signal of arrhythmias and we know that they have very substantial heart rate increases.

Speaker 3

We don't have that.

Speaker 5

And then just should we expect any update at your R and D Day on your oral form of pemvadutide and has there been any progress there? That's my final question. Thanks.

Speaker 2

Scott, Robert, do you want

Speaker 7

to take that? Yes, I think that at the R and D Day, we'll be focusing on the new indications. I think that that's where everybody's attention is and so that will be the focus to that day. As far as progress on oral formulations, we're excited about what we're seeing here. As I've mentioned before, we have a number of parallel tracks that we're investigating.

Speaker 7

I think we're closing in on a bioavailability that makes commercial sense. That's always the consideration when you talk about nor formulation, which will always be less efficient as far as the amount of drug that you have to administer. So just stay tuned on that, but excited about the progress we're making.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Ellie Merle from UBS.

Speaker 8

Hi, everyone. This is Jasmine on for Ellie. Thanks so much for taking our question. So for the additional indications, I just want to get confirmation. So for the two Phase IIs starting this year, would these be cases where we can potentially see proof of concept data next year?

Speaker 8

And then I think previously you said you were thinking about up to three additional indications. So, would that potential third one be something we could also see in IND from this year and will we learn any more about this or any others of the R and D Day? Thanks.

Speaker 2

Yes. Let me take the second part of the question and Scott can answer the first part. As far as up to three, that's precisely what we said that we'll look at up to three indications. We've got two on our plate, which we think is plenty for the time being. We'll continue to evaluate additional indications.

Speaker 2

But at this point, we're very happy having two active INDs and pursuing two additional indications beyond MASH. So we're in really good shape there. Scott? Yes. And thanks, Jaz.

Speaker 2

So yes, both of these studies will be Phase II proof of concept studies. And for at least one of these indications, we expect to have data in 2026. There's the potential

Speaker 3

for a second, but we're not committing to that at this time. So we do expect to have data in at least one of these additional indications, some of these proof of concept Phase II studies in 2026, and we'll have to see about the second whether that makes the cut by the end of the year.

Operator

Our next question comes from the line of Mayank Mamtani from B. Riley Securities.

Speaker 9

Hi, yes, and thank you for taking our questions. This is William on for Mayank. Congratulations on a very nice year and definitely looking forward to some of the data and events that are coming up. So I did just want to dig in just a little bit more on the top line data at IMPACT. I know that we'll be expecting sort of the fibrosis and liver fat reduction, and please correct me if I'm wrong there, but I was also curious if we would be if we should be expecting fibrosis improvement and MASH resolution sort of that combined endpoint.

Speaker 9

And then on statistical significance, could you speak to what treatment effect you're thinking that you'll need to hit that STATs Diego and fibrosis endpoint? And then I have a follow-up.

Speaker 3

Well, thanks, William. Yes, the readout will include readouts in both MASH resolution and fibrosis improvement and also the combined endpoint and we expect to hit all of those endpoints. In terms of the treatment effect, what we would say is that our goal is to hit statistical significance. There's been differences between studies and the actual treatment effects. But we would say in terms of the study power that we've actually powered the study to actually be have a higher power for chance of success relative to the other FGF21 studies that are read out at twenty four weeks.

Speaker 3

We have more subjects per treatment arm and we're also going into the trials with greater liver fat reduction, which is the primary driver of these endpoints. So we think both in terms of a better treatment effect and having higher numbers of subjects to show it that we're sufficiently powered, if not more powered to achieve the effects that we're seeing by the FTF21s to twenty four weeks.

Speaker 9

Okay. Thank you. And then, just curious about the two new indications. Is it safe to assume or maybe give us some color if you could? Should we be expecting these indications to be sort of based on or in the obesity subgroup?

Speaker 9

Or could they be something more akin to even a MASH or cardiovascular or something outside of obesity directly that may actually surprise us a little bit when you actually unveil these?

Speaker 2

The only color I can provide well, let me just say that we're going to be talking about all of this in two weeks' time. So please do stay tuned and we look forward to seeing you there. But the color I can provide is that obesity cuts across all of these indications. It's a comorbidity that results into other comorbidities. So people losing weight would there will be a benefit in all of these indications.

Speaker 2

So that's how we're looking at it. One of the critical component of pemidutide is the ability to achieve meaningful weight loss, while also improving liver health. So that's really how we're looking at the molecule and everything we're doing going forward is trying to leverage that differentiation of pemidutide, this combination of these two features. And you'll see that team develop through these additional indications as well.

Speaker 9

Excellent. Thank you. And congratulations again on a very nice year. And Scott best of luck through you going forward. Congratulations.

Speaker 3

Thank

Operator

you. Our next question comes from the line of Jonathan Wollevin from Citizens JMP.

Speaker 6

Hey, thanks for taking the questions. Two for me. In the past, we've talked a little bit about potentially seeing reduced weight loss in MASH patients due to metabolic dysfunction for the same drugs than in a non MASH population. I was wondering your current thinking there if it's evolved since we've seen some more data from other drugs and programs. And then I guess the elephant in the room is real world adherence.

Speaker 6

We've seen pretty low discontinuations of Phase III programs from other incretins, but the real world use not being sustained long term. How do you think you could book that trend if there's anything in the data that could suggest you'll have a different profile in the real world?

Speaker 3

Jonathan, if I understand your first question, I would answer by saying that we're going to distinguish ourselves from the potent drugs which have direct acting effects in the liver, such as the FGF21s and to some extent risk differ by offering weight loss that also has a meaningful effect on cardiovascular risk. The actual weight loss that we will achieve in our trials will be probably greater in Phase III because we've opted to use the one point eight milligram dose in our trial, and that's because the dose response for liver fat reduction and we believe MASH effects is different than weight loss. So to run an efficient trial, we decided to study one point two and one point eight milligrams to study the dose response and to demonstrate that. And by the way, that's not been seen with other compounds, so that would be a success. But we have the optionality to add the two point four milligram dose in back Phase III and create a target product profile with not only potent MASH effects for the type of weight loss that we saw in the MOMENTUM trial.

Speaker 3

With regards to real world adherence, we believe that we're going to have very competitive compliance in this program and also discontinuations. I can't give you a preview of the data. We saw in our Maslow D trials and also our diabetes trial very low adverse event discontinuation rates. And we think this is going to also carry over to the IMPACT trial. I can simply say in terms of the way that trial is going from a view of 10,000 feet, we're very happy with the way that trial is going.

Speaker 6

Okay. Thanks, Scott. Appreciate it.

Operator

Thank you. One moment for our next question. Our next question comes from the line of Patrick Trucchio from H. C. Wainwright and Company.

Speaker 9

Thanks. Good morning. A few follow ups on MASH. First on IMPACT, specifically, I was wondering if you could elaborate a little bit more on that triple reader model technique and blinded rereads. How does that compare to approaches used in prior MASH trials to control placebo effects?

Speaker 9

Secondly, regarding the Phase III timing, at the end of Phase II meeting occurs by year end, when could the registrational Phase III trial in MASH begin? And last on MASH, regarding Phase III planning, will you design the Phase three MASH program run-in parallel with additional trials and other metabolic indications? How would you prioritize the sequence of development?

Speaker 3

Patrick, I'll handle the first two and then I'll turn to Vipin to answer the third. So the three reader approach that we're using is identical to the approach used by eighty nine Bio and Pegasofirmin in their trial. We think they learned a tremendous amount by their predecessors. And this three reader approach was advocated by Stephen Harrison. And the way it works is that each reader reads individually.

Speaker 3

And then if there is agreement of all three, fine. If it's two of the three, you take that. And if none of the three agree, then they go to an adjudication. We know that happens very uncommonly. So that's what's called the mode approach.

Speaker 3

And with that, combined with the strict guidances given to the pathologists for reading the biopsy, they are able to get their placebo response rate down to seven percent. Using a somewhat similar approach in the RASDFIR program, although it's different, but like our study and the Pegasarfirman study, rereading all of the biopsies, scrambling them to the pathologist are totally blinded to the time of the biopsy and the sequence and takes out the bias of a higher severity score early on because pathologists are trying to help the sponsor by getting the patients into the trial and a lower score later on when they believe they're reading post treatment biopsies, you can see without any effects of placebo simply because of reader bias, you can get placebo responses. And we know that in the semaglutide program, when they didn't do that, they had a 30% placebo response. So combined with that, the three mode approach, three reader mode approach and also the guidance given to pathologists, we believe that we're going to get very controllable placebo response rates that will aid us in getting statistical significance. Regarding your second question, yes, we do expect to have an end of Phase II meeting with the FDA by year end and that would enable us to commence our Phase III program in the first quarter of twenty twenty six.

Speaker 3

And I'll turn the mic over to Vikram for the third question. Yes.

Speaker 2

I think it's also important remind everyone that it's a forty eight the IMPACT trial even though we are our primary endpoint is at twenty four weeks, it's really a forty eight week trial. So the IMPACT trial, we would still be collecting additional data. So we're actually planning to have our end of Phase two meeting before all of the data is in and we'll submit that data once that becomes available, the safety data as well as biomarker data that we will be collecting all the way through forty eight weeks. So it's a forty eight week trial. So that trial is already ongoing or it's fully enrolled at this point.

Speaker 2

It's simply a matter of collecting all of the data and compiling it and making it available to the FDA around the time of the Phase three meeting or after that. So that's how that will play out. We are fully focused on executing that Phase three program as efficiently and as quickly as possible in 2026. As far as the additional trial, that's happening right now in parallel while we are waiting for the all of the information on IMPACT trial. And those are much smaller proof of concept Phase II efficacy studies.

Speaker 2

The goal there as we've stated all along is really to create additional expansion of indications for pemidutide that sort of take leverage the mechanism that we've been working with. So we think it's easy to sequence them and still have data additional data from these studies while we are initiating a Phase three program for MASH.

Speaker 9

Great. Thanks so much.

Operator

Thank you. At this time, I would now like to turn the conference back over to Vipin Garg for closing remarks.

Speaker 2

Thank you everyone for joining our call today. As always, we sincerely appreciate your continued support and interest in Altimmune as we work diligently to advance pamdeutide. Thank you again for your time today.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.

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Earnings Conference Call
Altimmune Q4 2024
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