Altimmune Inc (ALT) 2024 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to Altimmune fourth quarter and full year 2024 financial results conference call. As a reminder, this call is being recorded. (Operator Instructions)

I would now like to introduce your host for today's conference call, Lee Roth, President of President, Burns Mcclellan Investor Relations, advisor to Altimmune. Lee, you may begin.

Thanks Gigi. Good morning everyone, and once again thank you all for joining us for Altimmune fourth quarter and full year 2024 financial results and business update conference call.

On today's call, you'll hear from Dr. Vipin Garg, our Chief Executive Officer, Dr. Scot Harris, our Chief Medical Officer, and Greg Weaver, our Chief Financial Officer. Dr. Scott Roberts, our Chief Scientific Officer, and Ray Jordt, our Chief Business Officer, will join us for the Q&A session.

Press release covering our fourth quarter and full year 2024 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 harbour provisions under the Private Securities Litigation Reform Act of 1995.

Ultimately 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. 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, February 27, 2025, and the company takes 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 All Commune website. With that, it's now my pleasure to turn the call over to Dr. Vipin Garg, Chief Executive Officer.

Thank you, Lee. Good morning everyone and thank you for joining us for our 4th quarter full and full year corporate update. 2024 was a year of significant progress for autoimmune. The milestones we have achieved over the past 12 months have positioned us for transformative catalysts in 2025 and beyond.

Following the third quarter of 2024 completion of enrolment 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 24 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 MASH in early 2026. With a positive impact readout, pemvidutide would be the first in cretin-based agent to achieve fibrosis improvement at 24 weeks. And the first therapeutic candidate in any class to achieve both significant fibrosis improvement and meaningful weight loss in a 24-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 24 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 in creating-based agents.

In addition to our progress in MASH, I'm thrilled to share that we submitted IND's for family duty in two additional indications in the fourth quarter of 2024. Both of these IND's have been cleared by the FDA, and this positions us to start phase two efficacy trials in mid-2025. We believe. That each of these indications represents an attractive and compelling commercial opportunity for which pamidutide will be ideally suited.

As we announced this morning in our earnings press release, we will be holding a virtual R&D Day on March 13th, at which time we will disclose the additional indications and provide detailed overview of these new opportunities. The R&D event will feature presentations by key opinion leaders specializing in mash, obesity, and the additional indications. We're extremely excited about this event and look forward to sharing our plans on the future of Pena.

From an organizational perspective, we are excited to by the recent edition of Terry Lauer and Jerry Durso to our board of directors. 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 autoimmune, 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 6 years, recently informed me that he plans to retire a year from now at the end of February 2026. Scott has been a valued and trusted colleague whose leadership has been instrumental in advancing pamidutide to the cusp of an important data readout.

If successful, this could position, this read out good position can be decide as the foundational therapy inthe treatment of mash and 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 MASH, 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 not turn the call over to Scott Harris. Scott.

Thank you, Vipin, As Vipin mentioned, after 25 years in drug development, including the past 6 years at Altimmune, I've decided to plan for my departure in early 2026. I want to emphasize that I will remain with the company through all Important milestones over the next 12 months and then 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 and MASH, as well as the initiation of the phase 2 trials in additional indications. You'll be seeing a lot of me throughout the next 12 months. I want to thank Vipin and Altimmune for letting me shepherd [Pen the dotide] from a pre-clinical 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 24 week efficacy data for the impact trial. Unlike current agents approved or in development for MASH, pamidutide has the potential to drive both fibrosis reduction and significant weight loss.

Essentially, pamidutide has combined the weight loss effects of the [inertins] with the liver-directed effects of agents like the FGF 21s into a single molecule that we believe will provide a complete solution for the treatment of mesh. Our key metric for the success in the impact trial will be the ability to achieve statistical significance on the fibrosis improvement endpoint at 24 weeks.

If successful, peptide will be the first [Eerton]-based agent to achieve fibrosis improvement at 24 weeks, and the first therapeutic candidate in any class to achieve fibrosis improvement. And meaningful weight loss in a 24 week period. Liver fat reduction is the key driver of fibrosis improvement. But in addition, we also have pre-clinical data showing that pamidutide has direct antifibrotic effects. Most importantly, we have greater liver fat reduction at 24 weeks than any of the mash agents currently in development, regardless of when the reduction was measured.

With respect to study power, the two primary treatment arms IMPAPACT pempedeutide 1.8 mg and placebo are larger in comparison to the number of subjects in the in the successful FGF 21 trials but also read out successfully at 24 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 24 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 3 readers and using the mode technique of scoring.

Second, we will be re-reading 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 two Pegazofirmin trial, which achieved the placebo response rate for fibrosis improvement of only 7%.

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. 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 end of phase 2 meaning for obesity has implications not only for the phase 3 velocity trials, but for the entire pamidutide program. During those inter interactions, FDA identified no safety signals related to pamidutide in its review of over 500 subjects that have been treated with pamidutide in our prior studies. To date, close to 700 subjects have been treated with pamidutide across all of our completed and ongoing trials.

Turning our attention to the two additional indications, we believe these are areas of significant unmet medical need for which the balanced GLP-1 glucagon dual receptor agonism pamidutide provides a highly compelling scientific rationale. The recent FDA clearance of our two IND applications has us on track to initiate phase 2 trials in these indications in the middle of this year.

We'll be providing detailed and comprehensive information on these indications, including our development plans at our R&D day on March 13th. You'll 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 pamidutide 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 4th quarter in full year, Greg.

Thank you, Scott. I'll be providing a brief overview of Alterman's fourth quarter and full year 2024 financial results with more detailed information to be available in our 10K which we'll file later this afternoon. We recorded our year-end 2024 total cash and investments of USD132 million. This current cash position is expected to fund operations well into the second half of 2026 through our e-catalyst of the phase 2 MASH 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, R&D expenses were USD19.8 million in the fourth quarter of 24 compared to USD16.9 million in the same period in 2023.

Our R&D expenses in the quarter included USD13.6 million in direct costs related to the clinical development activities for pamidutide, including preparation for the upcoming phase two trials in the additional indications. Non-cash stock compensation included in the R&D expenses was USD1.6 million in Q4.

GNA expenses USD5.1 million in the fourth quarter of 24 versus USD4.3 million in the same period of 2023 with the non-cash stock comp included in GNA of USD1.8 million in Q4 to an increase of roughly USD500,000 over the same quarter last year. Net loss for the three months ended December 31, 24 was USD23.2 million compared to a net loss of USD31.6 million in the fourth quarter of 2023.

That prior year net loss included a one-time non-cash impairment charge of USD12.4 million related to a discontinuation of the HEPA development program. To summarize our full year results, R&D expenses were USD82.2 million in 2024 as compared to USD65.8 million in 2023. Our R&D expenses included USD53 million in direct costs related to development activities for pamidutide.

GNA expenses were USD21 million for the full year 2024 compared to USD18.1 million in 2023. The increase due primarily to a USD2.7 million increase in stock compensation and labour related expenses. The total non-cash stock compensation expense for 24 was approximately USD14.4 million as compared to USD10.6 million in 2023. Net loss for the year 2024 was USD95 million compared to a net loss of USD88 million in 2023. The net loss reported for the prior year included the aforementioned non-cash impairment charge of USD12 million.

I'll close the remarks by highlighting our cash position, which provides runway into the second half, well into the second half of 2026 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 3 pivotal program. Next year. I'll now turn the call back to Vivian.

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, for us, which I strongly believe we are well equipped to capture. I look forward to sharing our next set of updates at at the R&D day on March 13th.

The combination of phase 2 be read out in MASH and the launch of phase 2 efficacy trials in two additional indications has us poised for an incredible 2025. That concludes our formal remarks, and we would now like to open the lines to take questions, operator.

(Operator Instructions). Our first question comes from the line of Roger Song from Jefferies.

Hi, this is Fionaar rager. Congrats on the year and, a lot of new, developments exciting for this year. Just, ques questions on the new indications. I was wondering if you're going to announce the details like the pre-clinical data at the R&D day and whether if you're going to start the two, phase two trials simultaneously, mid-year.

Yes, so we will provide a very comprehensive picture of the two indications that the R&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 two programs as well. So, stay tuned and we're looking forward to providing all that detail.

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

Thank you.

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

Good morning team. Thank you for the great updates and, I can't believe you're retiring. You have another 20 years and you not more so, but I'm happy to know that I get to work with you for another year. So when I when I when I say that, and it's been a pleasure working with you H1stly. I think one of the questions that we would love to understand is post the C2B 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 defatting of the liver and a lot of data supporting MRI PDFF as a histological response? Should we be thinking about the phase three 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, just want to love to understand how you're thinking about on sort of the phase three development and what sort of strategy you want to implement, and I'll jump back in the queue.

Scott, yeah, thanks for Yasmin and thanks for the, compliment. I, hope I make it 20 years, but I look for I will look forward to the prospect so as you know we're really on the forefront of the NIT's with our MRIPDFF, 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. 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 three, 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. 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 Afrexafermin readout based on our reduction in liver fat and 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 is 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, variseal bleeding, that this is reversible, and this is the study population that Achiro 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.

Thank you so much. I'll jump back in the queue.

Thank you. One moment for our next question. Our next question comes from the line of Annabel Samimy from Stifel.

Hi everyone, thanks for taking my question, questions and great progress. I guess could you going into this impact 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 some glut tides essence data and ROSIFRA and FGF 21. So can you just talk about how you think all those Programs as well as some of the dot will play in with each other. Thank you.

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, you need people need to lose weight in order to treat their MASH successfully, and we're 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. 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. 80% of subjects with mash have obesity or would benefit from losing weight, so ideal drug would do both. It will have a direct impact on the liver. And as well as people who 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. Regarding the competitive success, if we have statistical significance at 24 weeks, we'll be the only IncRETin. That has even attempted a readout of 24 weeks, let alone has success at 24 weeks, and that's because unlike semaglutide, which you mentioned or tirzepatide, we have direct effects in the liver. I want to remind you that semaglutide conducted a phase two trial about the same size as impact about 2 years ago, and even going all the way out to 72 weeks failed to show significant statistical significance. We expect to show it at just 24 weeks, so it's a much more potent compound.

If you listen to the experts out there who are treating MASH, they don't really A rely on the fibrotic effect 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 incritins, we think we have a more potent effect and simply reading out in statistical significance at 24 weeks will separate us now.

Regarding the FTF 21s, which have had successful readouts in 24 weeks, and which has guided us to actually make the decision to study the endpoint at 24 weeks. And as I mentioned before, we believe we can be successful because we actually have better liver fat reduction than the FGF 21, so we think our probability of success is even greater is the FGF 21s do not have weight loss, nor does risk differ. So you hear doctors talking about using re differ for advanced mash with F3 fibrosis, but when the patient needs weight loss, they add some glutide. That won't be necessary. With Pembeducide, you get both. You get the weight loss and the potent effects and fibrosis. So we think not only in terms of our upcoming readout, but in terms of our competition in the evolving marketplace, they're going to have a very successful drug.

Great. And if I could just ask one more question, are you going to be releasing any of, any other exploratory or secondary end points, on this top line readout?

Yeah, we're still planning to read out, obviously there's only so much we can do in a top line read out, but we'll TRY to provide as much data as we can. Great thank you so.

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

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

Thank you.

Yes, good morning, Lisa. 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. So it'll be all highlighted in our indications. The additional indications, the phase two 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 on MASH. Our focus will continue to be on MASH and executing the phase 3 program on MASH, which As we're very excited about. We think we have the best in class agent for pursuing that. So when we get to the end of 2026, we could be looking at multiple indications that we could pursue in parallel with MASH by having data, phase two data in these additional indications at the same time.

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

Scott, yes, the readouts of the FTF 21s have had different placebo responses, etc. 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 FF 21s on weight loss.

The other thing I would add to that is that if we get statistical significance at 24 weeks, we know the response is only going to get better with time. So when you go from 24 weeks to 48 weeks to 72 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 seeing statistical significance at 24 weeks really sets us up well.

And how do you think of Served tide and tide as constant at this juncture?

Yes, well, as there's really no indication at this point that reddirutide is being developed for MASH. That data is over 2 years old, and we've not seen motion.

We think that servid tide readout was nice. We think that the effects that were observed were a clear indication of the benefit of of glucagon and its direct effects. We think it really confirmed our mechanism. I would emphasize though that we'll do better. We have more glucagon molecule. That's what drove the additional improvement over the other incretins, and we have greater liver defatting effects. There are defatting effects at 24 weeks is about 62%. Ours is 76%. That's the major driver of mass resolution and fibrosis improvement. I think even more importantly, we differentiate on safety and tolerability. On the tolerability front, we're giving embedducide without dose titration. No other inertin can even approach doing that. And that was done in some of the other programs, the rates of GI side effects were enormous. We're not experiencing that.

With serviotide, even at their lowest dose, they're seeing 20% adverse event discontinuation rates, and that was with 20 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 the titration up to between 24 weeks and 32 weeks. 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 Cerviduy 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 different look at the molecule. And 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. In close to 700, including the ongoing trials, and we've maintained the safety profile of Pembadu tide, and you don't get to play in the space without safety. As you recall with a true tide, they saw a signal of arrhythmias and we know that they have very substantial heart rate increases. We don't have that.

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

Scott Roberts, you want to take that?

Yes, I think that at the R&D Day we'll be focusing on the new indications. I think that that's where everybody's attention is, and so that that'll be the focus of that day. As far as progress on the 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. I think we're closing in on a. On a bioavailability that makes commercial sense, that's always, the consideration when you talk about an oral 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.

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

Hi everyone, this is, Jasmine on for Ellie. Thanks so much for taking your question. So for the additional indications, I just want to get confirmation. So for the two phase 2s starting this year, would these be cases where we can potentially see proof of concept data next year? And then I think you know previously you said you were thinking about up to 3 additional indications so would that potential third one be something we could also see in IND from this year and will we learn more about this or any others of the R&D day? Thanks.

Yes, let me take the second part of the question, and Scott can answer the first part. As far as up to 3, that's precisely what we said that we'll look at up to 3 indications. We've got 2 on the on our plate, which we think is plenty for the time being. We'll continue to evaluate additional indications, but at this point we're very happy having 2 active INDs and pursuing two additional indications beyond mash. So we're in really good shape there, Scott.

Yes, and thanks, Jaz. So yes, both of these studies will be phase 2 proof of concept studies, and for at least one of these indications we expect to have data in 2026. There's the potential 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 from these proof of concept phase 2 studies. In 2026 and we'll have to see about the second whether that makes the cut by the end of the year.

Great, thank you.

Thank you. One moment for our next question. Our next question comes from the line of Mayank Mamtani from B. Riley Securities.

Hi, yes, and thank you for taking our questions. This is William on from Maun. 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 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, 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 have a follow up?

Well thanks William yes, the readout will include readouts in both mass resolution and fibrosis improvement and also the combined endpoint and we expect to hit all of those end points. 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 be have a higher power for chance of success relative to the other FGF 21 studies that are read out in 24 weeks. 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 end points. 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 FTF 21s at 24 weeks.

Okay, thank you. And then just to curious about the two new indications. Is it safe to assume or maybe give us some colour if you could, will these, should we be expecting these indications to be sort of based on or in the obesity subgroup, 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 we, when you actually unveil this.

And the only color I can provide, well, let me just say that we're going to be talking about all of this in 2 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 would be a benefit to in all of these indications. So that's how we're looking at it. One of the The critical component of PAIduide 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 combination of these two features, and you'll see that the develop through these additional indications as well.

Excellent. Thank you and congratulations again on a very nice year and Scott, best of luck for you going forward. Congratulations.

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

Hey, thanks for taking the questions. 2 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. We've seen pretty low discontinuations in phase 3 programs from other inertons, but the real world use not being, sustained long term. How do you think you could buck that trend if there's anything in the data that could suggest, you'll have a different profile in the real world?

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 FGF 21s and to some extent risks differ by offering. Weight loss that also has a meaningful effect on cardiovascular risk.

The actual weight loss that we'll achieve in our trials will be probably greater in phase 3 because we've opted to use the 1.8 mg 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 running aficient trial, we decided to study 1.2 and 1.8 mg 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 2.4 mg dose and back phase three and create a target product profile with not only potent mash effects but the type of weight loss that we saw in the momentum trial.

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 ft, we're very happy with the way that trial is going.

Okay thanks appreciate it.

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

Thanks. Good morning. A few follow ups on mash first on impact, specifically, I was just, 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 mass trials to control placebo effects? Secondly, regarding the phase 3 timing, at the end of phase 2 meeting occurs by year end, when could the registration of phase 3 trial and mash begin? And last on MASH regarding phase 3 planning, will you design the Phase 3 MASH program run in parallel with additional trials and other metabolic indications? How would you prioritize the sequence of development?

Patrick, I'll handle the first two, and then I'll turn to Vi and the answer the third. So, the 3 reader approach that we're using is, identical to the approach used by 889 by Pegga affirmin in their trial. We think they learned a tremendous amount by their predecessors, and this 3-reader approach was advocated by Stephen Harrison. And the way it works is that each reader reads individually.

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. And with that combined with the strict guidance's given to the pathologists for reading the biopsy, they're able to get their placebo response rate down to 7%.

Using a somewhat similar approach in the with differ program although it's different but. Like our study. And the Pegas or Fermin study, re-reading all of the biopsies, scrambling them so the pathologists 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 3D mode approach, 3 reader mode approach. And also the guidance given to the 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 two meeting with the FDA by year end, and that would enable us to commence our phase 3 program in the first quarter of 2026.

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

Yeah, I think it's also important to remind everyone that it's a 4 the impact trial, even though we are our primary endpoint is at 24 weeks. It's really a 48 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 48 weeks. It's a 48 week trial. So that trial is already ongoing all, it's fully enrolled at this point. 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 3 meeting or after that. So that's how that will play out, we're fully focused on executing that phase 3 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're waiting for all of the information on on impact trial, and those are much smaller proof of concept phase two efficacy studies. The goal there, as we've stated all along, is really to create additional expansion of indications for deide 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 3 program for for MASH.

Great. Thanks so much.

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

Thank you everyone for joining our call today. As always, we sincerely appreciate your continued support and interest in autoimmune as we work diligently to advance family duty.

Thank you again for your time today.

This concludes today's conference call.

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