Altimmune, Inc.

Good morning, ladies and gentlemen, and welcome to the Altamune First Quarter 2025 Financial Results Conference Call. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you will need to press star 11 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star 11 again. As a reminder, this call is being recorded. I'll now introduce your host for today's conference call, Lee Roth, President of Burns McClellan, Investor Relations Advisor to Altamune. Lee, you may begin.

Thanks, Gigi, and good morning, everyone. Once again, thank you all for joining us for Altamune's first quarter 2025 Financial Results and Business Update conference call. On today's call, you'll hear from Dr. Vipengar, our Chief Executive Officer, Dr. Scott Harris, our Chief Medical Officer, and Greg Weaver, our Chief Financial Officer. Dr. Scott Roberts, our chief scientific officer, and Ray George, our chief business officer, are with us for the Q&A session. Our first quarter 2025 results and corporate update press release was issued earlier this morning and can be found on the investor relations section of the Altimmune website. 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. Altamune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For a full review of the risk factors that could affect the company's future results and operations, we refer you to the company's filings with the Securities and Exchange Commission. I'd also direct you to read the forward-looking statement disclaimer in our press release issued this morning, which is now available on the website. Any statements made on this conference call speak only as of today's date, May 13th, 2025. and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that may occur on or after today. As a reminder, this call is being recorded and will be available for audio replay on the Altimmune website. With that said, it's now my pleasure to turn the call over to Dr. Vipin Garg, President and Chief Executive Officer of Altimmune. Vipin.

Thank you, Lee. Good morning, everyone, and thank you for joining us today for our first quarter financial results and corporate update. As you can imagine, we are very excited about the upcoming readout of our IMPACT Phase IIb MASH trial, which we expect to announce this quarter. Based on the class-leading liver fat reduction of pembidutide and the use of biopsy rereads to minimize placebo response, we are confident of achieving the trial's key efficacy and safety objectives. If successful, Pembidutide would become the only improtant to achieve statistical significance on MASH endpoints at only 24 weeks of treatment. Furthermore, it will be the first therapy of any kind to combine these effects with clinically meaningful weight loss at this early time point. If approved, we believe that Pembidutide could provide a complete solution for the treatment of MASH. We announced today that we have entered into a credit facility with Hercules Capital for up to $100 million. This is strategically important as we build upon our balance sheet strength and provide flexibility to support our continued development of Pembidutide. Greg will speak further on our financing later on the call. Our recent R&D day event marked an important milestone in pursuing our vision of pembidutide becoming the treatment of choice in liver and cardiomyocardial diseases. We unveiled our plans for phase two trials in alcohol use disorder, or AUD, and alcohol liver disease, or ALD. Both AUD and ALD are areas of significant unmet medical need with limited treatment options. Pembidutide has the potential to disrupt the treatment paradigm in both these conditions if we are able to demonstrate a reduction in alcohol consumption in combination with an amelioration of fat-induced liver inflammation and fibrosis. This profile of clinical benefits was enthusiastically received by various physician groups and patients. which adds to our conviction for developing pembidutide in these indications. The expansion into these indications demonstrates our commitment to establish pembidutide as a potential foundational treatment across multiple fibrotic liver diseases and their primary causes. With that, I'll now turn the call over to Dr. Scott Harris, our Chief Medical Officer, to provide a clinical development update. Scott? Thank you, Vipin.

We are approaching an important milestone in our MASH program, the top-line data from the IMPACT Phase 2b trial, which are expected in the second quarter. We are pleased to report that the trial enrolled a total of 212 participants with biopsy-confirmed F2, F3 MASH, which increased the study power over the original target. As a reminder, the dual primary endpoints of our MASH resolution or fibrosis improvement at 24 weeks. We also plan to provide data on key secondary endpoints, including weight loss, non-invasive tests of fibrosis, such as FibroScan and ELF, liver fat reduction, and serum lipids. We also look forward to reporting an adverse event profile that confirms the safety and tolerability of Penvidutide. As Vipin mentioned, if successful, Penvidutide would become the only incretin to achieve statistical significance on match endpoints at only 24 weeks of treatment. Further, it will be the first therapy of any kind to combine these effects with clinically meaningful weight loss at this early time point. While the top-line efficacy data readout will be at 24 weeks of treatment, we are continuing to treat patients for a total of 48 weeks. This will allow us to estimate the effect of pembidutide on MASH biopsy endpoints using noninvasive tests and determine the additional weight loss achieved by these patients at this time point. We are now on the final stages of rereading the biopsies. The baseline patient demographics and characteristics, including age, sex, body weight, BMI, diabetes status, ratio of F2 to F3, liver fat content, noninvasive measures of fibrosis, and liver function, are consistent with our expectations and closely approximate other studies in MASH. To maximize the integrity and robustness of a histology readout, both baseline and endotreatment biopsies for all subjects are being reread in a blinded fashion using independent reads from three pathologists and a modal approach to scoring, similar to recent successful studies in this indication. Precedent has shown that rereading both the baseline and endotreatment biopsies significantly reduces the placebo response rate in mass trials, and implementing this procedure will add to the likelihood of trial success. Finally, the most compelling reason we are confident heading into the impact readout is that our Phase 1B Masl-D study demonstrated a dose-dependent liver fat reduction of up to 76.4% which is greater than that associated with other successful trials, and is class-leading for MASH therapeutics. Recall that liver fat reduction has been shown to be the principal driver of MASH resolution and fibrosis improvement in MASH clinical trials. Given our confidence in the upcoming data, we are preparing for the initiation of a Phase III trial in MASH and intend to hold the end of Phase II meeting with the FDA in the fourth quarter of this year for this indication. This timeline would allow us to initiate a registrational program in early 2026. Turning now to two additional indications that we unveiled at our March R&D Day event, Alcohol Use Disorder, or AUD, and Alcohol Liver Disease, or ALD, We are progressing towards phase two trial initiations in these indications in Q2 and Q3, respectively. The phase two trial in AUD will evaluate pembidutide versus placebo in approximately 100 patients over a 24-week period. Patients in the pembidutide arm will receive the 2.4 milligram dose titrated over eight weeks to maximize tolerability in this patient population. The primary efficacy endpoint is the patient-reported change in heavy drinking days with the timeline follow-back method as established by FDA guidance, with key secondary endpoints of changes in alcohol consumption by PATH and weight loss. Similar to our AUD trial, the Phase II ALD trial will evaluate penvidutide versus placebo in approximately 100 patients, but over a 48-week treatment period. We will employ a 2.4 milligram dose of pembidutide with the same dose titration method as in AUD. The key endpoint, change in liver stiffness measurement by FibroScan, will be assessed at 24 and 48 weeks, along with key secondary endpoints of change in alcohol consumption and weight loss. Both AUD and ALD are large patient populations with treatment options that either have proven ineffective in clinical practice in the case of AUD or don't exist in the case of ALD. Our market research suggests that a drug with the target profile of pembidutide, one that reduces alcohol consumption, liver inflammation, and body weight, would be well received by patients and physicians. Furthermore, obesity is recognized to be a key risk factor for poor outcomes in both AUD and ALD, and not unexpectedly, patients with these conditions have a high incidence of metabolic abnormalities, including hypertension and hyperlipidemia. If these efficacy trials are successful in AUD and ALD, We believe that pemfidutide has the potential to redefine the approach to the treatment of these serious conditions. MASH and ALD are the two most frequent conditions leading to liver transplantation in the United States. So the long-term potential benefits of pemfidutide, if positive, are significant. We are excited to initiate the trials and look forward to sharing our progress along the way. With that, I'll now turn it over to Greg Weaver, our Chief Financial Officer, to review our financial results for the first quarter. Greg?

Thank you, Scott, and good morning, everyone. Let me begin with adding some color around our cash position, our recent use of the ATM, and today's announcement of the credit facility with Hercules Capital. I'm quite happy with the progress we've made over the recent months in building the cash runway and required to support the Pemba-Dutai clinical development program in MASH, ALD, and AUD. I'm confident that the cash position we construct will support the needs of the Pemba-Dutai program over time. Briefly about the ATM facility, this is one of several financing tools available to us. We've raised $35 million net off the facility in the first quarter of 2025, an additional $16 million since April 1st. The $100 million credit facility announced this morning is another important piece of the financing strategy, and Hercules is a high-quality partner. The facility provides tranche funding that is optional, flexible, and significantly extends our cash runway. There's a $15 million funding at closing up front and an additional $25 million available in 2025, subject to milestones that align with our business plans. The remaining $60 million on the facility is available beginning in 2026 and subject to milestones and conditions. Terms of the facility include interest only for 24 months, which can be extended up to 42 months. The duration of the facility is 48 months. Terms are at market rates, and no warrants are included in the facility. We view Hercules as a long-term partner with the ability to grow alongside us as we continue to advance PIMBA due time. Now to briefly comment on the Q1 financial results. We ended the first quarter of 2025 with $150 million in cash, cash equivalents, and short-term investments, as compared to $132 million at year-end 2024. The increase in our cash balance is related to equity sales off the ATM facility, totaling the $35 million during the first quarter. R&D expenses were $15.8 million for the three months ended March 31st, 25, compared to $21.5 million same period of 2024. R&D expenses in the first quarter included $9.2 million of direct costs related to the development of Pemba-Dutide, specifically to upfront CRO costs for the impact trials. G&E expenses were $6 million for the quarter ended March 31st, 25, compared to $5.3 million in the same period of 2014. The increase is primarily related to a $500,000 increase in non-cash stock count and other labor-related expense. Net loss for the first quarter of 25 was $19.6 million, 26 cents a share, compared to a net loss of $24.4 million, or 34 cents a share, for the first quarter of the prior year, 2024. With that, I'll now turn the call back to Vipin for closing remarks.

Vipin? Thank you, Greg. We are entering a truly exciting time for Altimmune. With the upcoming MASH data and the initiation of our AED and ALD Phase II trials, we expect 2025 to be a transformative year for the company. This concludes our formal remarks, and we would now like to open the line to take questions. Operator?

As a reminder, to ask a question, please press star 11 on your telephone. and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Yasmine Rahimi from Piper Sandler.

Good morning, team. Thank you so much for all the great updates. I'm very much looking forward to the impact that you're reading out here in 2Q. Two questions. The first one is, Scott, you mentioned that you guys are analyzing the baseline biopsies. Again, is there, have you had a chance to maybe provide some commentary around what the distribution F2 and F3 are and sort of how representative this phase 2b population baseline characteristics are versus maybe some of the other phase 2b, successful phase 2b's that we have seen? That's question one. Question two is directed to VPEN. I think speaking with investors, we always find that they're excited about pavumetide, but may need help to think about post impact. What is the ideal population within MASH obese that would be ideal for PEMB? If you could provide color there, that would be really helpful. And then the third one is obviously upon positive data from the impact study, you do have the opportunity to think about partnering this asset. If you could provide also, we've been in teams, some commentary around how you're thinking about partnership opportunities. So appreciate if you could tackle these three-part questions. And I'll jump back in the queue.

Absolutely. Thanks for your questions, Yaz. Scott, do you want to take the first question?

Yeah. Well, Yaz, we're... in the absolute final stages of rereading the biopsies and what we're going to present are the demographics of that final qualifying population. So, you know, based on that, we can't give you precise numbers. We would say in confidence, if you look at the other studies in terms of the age of the patients, the average proportion of women the F2, F3 distribution, the distribution of diabetics, the fiber skin scores, the ELF, the liver fat at baseline, the ALT levels. If you look at what we're seeing in the population that will be evaluated, as that data comes to us, it looks very, very similar to other studies. So I think that investors can look at this and say that this will be very meaningful in terms of its comparability to other studies.

In terms of your question about the patient population, yes. What we are doing is we're really leveraging the unique features of pembidutide, which really combines direct effect in the liver with weight loss. So really, the way we look at MASH is it's MASH with obesity. As you know, 80% of the patients, 80 to 90% of patients with the MASH have obesity. So we're treating both the root cause of MASH, which is obesity, as well as the serious condition that results from obesity, which is liver fibrosis. So by combining these two effects, we're really bringing these two features to the table. And really, we believe that's added value proposition for MASH and even the other indication that we are pursuing. So everything we are doing has a common element here where we are looking at obesity as this important secondary endpoint. So we think that really gives us an advantage in terms of identifying the patient population that would be most benefited from pembidutide. With regards to your second question, as far as partnering is concerned, as we have stated, our goal is to move forward into phase three development of pembidutide as quickly as possible. We are putting all of the pieces in place to make that happen. Along the way, we are open to discussions, and if a compelling partnership comes together, we'll certainly look at it. But that's not going to be the gating factor in terms of our ability to move forward with Phase 3 in MASH as well as in AUD and ALD.

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

Hi there. Thanks for taking the questions, and congratulations on the progress. Can you talk a little bit about what you're seeing in terms of discontinuations, how you're handling the discontinuations in terms of the data, and how should we think about any loss from the rereads and things like that? I'm curious.

Thanks. Yeah, Lisa, let me answer that question. I can't give you absolute numbers and study discontinuations, but what I can say is looking across the trial, the discontinuations that we're seeing, and also those due to adverse events, we're very, very happy with the data that we're seeing so far. The trial has been going very well, especially with regards to discontinuations. Obviously, we'll have that data at the time of the readout. The discontinuations are handled in different ways in trials. As you know, some compounds have looked at completer analyses. Others have done what's called the full intention to treat, where all discontinuations are treated as non-responders. And then there's the midway, which is an imputation method which has been used in other trials as well. Our goal is to have all that information available at the time of the readout. I can't give you finite information on the rereads at this point, but what we're seeing is in line with what we had projected for patients who qualify.

Okay, great. And then just one more question. I've been getting some questions on the importance of weight loss in this study because it really is obviously a MASH first study and weight loss is sort of secondary. So I guess how do you see the importance and how do we think about benchmarking weight loss in this study. I know you said to expect something like semaglutide, but what does that actually really mean? And I know this study will have, you know, a combination of patients with MASH, diabetics, you know, they won't be encouraged necessarily on lifestyle and other factors. So, you know, taking that all together, how should we think about how much weight loss to expect in a study like this? Thank you.

Yeah, great question, Lisa. Weight loss is extremely important. You know, if you look at the patient population up through F3, they're predominantly of the comorbidities of obesity and the cardiovascular risk. And if you don't achieve meaningful weight loss in the treatment of MASH patients, you're really pigeonholing the product into a late F3, F4 type population to treat fibrosis. And the goal is to be holistic. and treat all the patients from the least severe to the most severe, and we think we have that in our product. As Vipin mentioned before in his comments, and I repeated that, first of all, we'll be the only incretin reading out at 24 weeks. And that will differentiate us from the other compound because speed is effectiveness. And when you're treating people with F3, they may not have a lot of time before they get into F4. Once they get into F3, they start progressing very quickly, as little as two years. You really wonder if you want to have a slow-acting drug, one that works indirectly by weight loss as being your factor. You need to have direct action within the liver, and our ability to read out in 24 weeks is really going to differentiate us from the incretins because we'll have both the weight loss and the direct acting effects. and compared to the other compounds reading out at 24 weeks, particularly the FGF21s, will have meaningful weight loss. So we will be a complete solution for MASH. We think that with successful readout, both in the MASH endpoints and the weight loss, we will be highly differentiated, not only against the incretins, but all compounds. Now, regarding your question about the weight loss that we expect, as you know, In the semaglutide trial, they had a weight loss of about 10% at 72 weeks. That has to be scaled back to what you would expect at 24 weeks, you know, going one-third of the amount of time. So our position is that any clinically significant, clinically meaningful weight loss that we see will be highly differentiating. But I think that we can roughly project that it would be very similar to semaglutide, as you mentioned, lifestyle interventions like diet and exercise are not used in MASH trials. That compares against weight loss trials where it is, so you tend to have lower placebo response rates. So all in all, I think that comparing this to the semaglutide trial at 24 weeks, something that's meaningful and clinically significant will be very similar to semaglutide in its weight loss but then clearly differentiate from the FGF21s by providing significant weight loss, which these compounds don't have. Now, one other point is, as I mentioned in my comments, although we're reading out now this quarter at 24 weeks, we're also reading out by the end of the year at 48 weeks, so that we will have a lot of information, another catalyst in the second half of the year, we're going to have 48-week weight loss, We're also going to have non-invasive testing that will allow us to predict what the biopsy results would have been at week 48 had we done a biopsy at that point. As you know from other studies, the biopsy response grows with time. So anything we see at 24 weeks will be magnified and even greater in the 48-week readout.

Very helpful. Thank you. And then just final question from me. As you think about phase 3, and I know you'll be pending all this data, meeting with FDA towards the end of the year, is taking the higher dose into phase three a consideration? And also, I know you're really focused on kind of how rapid the response is and how are you thinking about a potentially earlier six-month endpoint? Thank you.

Well, those are great questions, Lisa. So we're strongly considering taking the 2.4 milligram dose into phase three. And it's not because we expect better MASH effects, it's that we expect to get better weight loss. Reminding you that the 1.8 milligram dose that we have in this trial is not the optimal dose for achieving weight loss pertinent to your prior question. That has to be understood in looking at the data that we will get higher weight loss if we employ the 2.4 milligram dose in phase three as we intend. Regarding the more rapid response, the FDA and their guidance does not provide a time course for these trials. One possibility here, as you mentioned, would be to do readouts at not only the end of a year, 48 or 52 weeks, but also at six months. That's something we're strongly considering for two reasons. The first is that it would then also put a stake in the ground for earlier, more rapid MASH effects. But second, it would also allow us to read out the trial results six months earlier. So both of those elements, adding the 2.4 milligram dose and doing an earlier readout, are something that's strongly being considered. We are writing that program as we speak. We are well ahead of our timeline for having an end-of-phase to meeting with the FDA in the fourth quarter. And these are things that we'll discuss with them. And I think they'll be very open to that discussion.

Thank you so much for answering all my questions. Thank you. One moment for our next question. Our next question comes from the line of Roger Song from Jefferies.

Excellent. Thanks, Tim, for the update and then taking our question. I have a couple of questions related to the impact study as well. The first one is understanding the trial is well overpowered for both endpoints. But just curious how you think about which endpoints are a bit harder to hit based on all the historical data. And then that's number one. Number two is your recent ESO data regarding this mass resolution index. the translation to the MASH biopsy. So how you think about that index will correlate with the fibrosis improvement as well? Thank you.

Yeah, Roger. Well, as you mentioned, the trial is extremely well-powered, and by enrolling additional patients, we've even added to the likelihood of trial success. Historically, the fibrosis improvement endpoint has been harder to hit than the MASH resolution endpoint. I think that's a well-established fact. In our trial, we have dual endpoints, which mean that we can hit either MASH resolution or fibrosis improvement to be successful. But that being the case, we believe that we'll be successful in hitting both endpoints based on all the factors that were mentioned. In terms of what was presented at EASL, that was a new index developed by Rohit Lumba at UCSD who also developed the concept of a 30% decrease in liver fat content was also associated with MASH resolution. And he's continued to evolve this to getting an index that's even more sensitive and specific than that. And this MASH resolution index combines liver fat reduction, the change in ALT level, and baseline AST level. And it has an area under the curve in an ROC analysis approaching 0.9, which is very, very predictive with high sensitivity and specificity. Based on that index, applying it to our original data in the 1.8 milligram dose group, our highest dose group over 90% of patients would be hitting MASH resolution. That's extremely important. What it comes down to, Roger, is basically this. Liver fat reduction continues to be the greatest driver of MASH resolution and fibrosis improvement, shown consistently in all trials and pretty much accepted by experts as being the primary driving force for hitting MASH resolution and also fibrosis improvement. And we also have the highest liver fat content reduction of any compound that's right now an active element for MASH. So based on all those factors, the power of the study the readouts that we keep having by applying indices like the mass resolution index or liver fat reduction, what we know about the science, we are very, very confident about the trial's success. I would also add to that, as I did before in my comments, that controlling the placebo response is key to obtaining statistical significance. And the best way to do that is to use a method of taking all the biopsies at the end of the trial, scrambling them so the pathologist is blind as to when the biopsy actually was done, and then rereading them on a blinded basis. We know that biopsy results are upgraded in severity early in the trial and downgraded later in the trial for a variety of reasons that have been shown consistently. Based on that, a placebo patient who biologically has no change will have a response simply based on the sequence of the biopsy reads. So scrambling all the biopsies so the pathologist is unaware of the timing and sequence has been shown in clinical trials to reduce the placebo response rate. So we think that three important factors, first, are magnitude of liver fat reduction, second, the sample size that we're using going into the readout, And third, the rereading of the biopsies all move us towards trial success.

Action. Thank you. Thank you, Scott. Thank you. One moment for our next question. Our next question comes from the line of Annabelle Samimi from Stiefel.

Hi. Thanks for taking my questions. I just wanted to follow on the comments about the phase three program. You know, we all know that the issue, one of the issues that plays mass development is the long development pathway. So if you're successful here in achieving the fibrosis response in six months and realize that you're going to design the phase three program with a six month program, but do you see any avenue to tighten the development timelines or will FDA be still sticking with its typical years long pathway And how do you see this evolving over time, especially as we see additional movement on these biomarkers at the recent conferences? Do you see greater acceptance from the FDA from that? And I guess I have to ask the follow-up question to that. Just generally speaking, how have your interactions with FDA changed with all the movement there? Anything to the positive or negative that you're seeing? Thanks.

Hey, thanks, Annabelle. Let me handle those questions. We believe we have the opportunity here to shorten that development path. For one, we could have a readout at six months. We may combine that, by the way, with having two readouts, one at six months and one at 12 months in different patient populations so that patients only have to go through two biopsies, one at baseline and one at either six months or a separate cohort in 12 months. We have not made final decisions about that. I think Lisa in her prior comments was absolutely correct. There's an opportunity that has to be looked at. But again, we have to look at it with the FDA. So we can't make any firm announcements about that, only the fact that we're looking at that. We're very encouraged by the enrollment rate that we had in the IMPACT trial. We've been told it's the fastest enrolling trial to date. It shows that patients like the drug, and then investigators enjoyed putting their patients in the trial. And one of the big motivating factors was the fact that people could lose weight, but they also liked the tolerability of the drug. We think that will play out in the final results of the trial, the tolerability in adverse events. So we think that combining a faster enrollment ramp, we could also accelerate the timeline. You're absolutely correct that there's a great deal of interest in biomarkers. I think that there's greater and greater acceptance over the course of time. It has to meet the FDA's legal standards. Ultimately, FDA is a body governed by laws and regulations in terms of what they consider to be proof. There's every evidence that they want to move away from the biopsy endpoints, but whether they've met that standard is yet to be seen. We think that going into our program that we're probably going to need biopsy endpoints for efficacy, but those non-invasive tests are very important because holistically showing the entire response, both the biopsy response and the non-invasive test is shown to be important. Now, going back to our impact program, as you are aware, we have a biopsy readout at 24 weeks. We don't have it at week 48 weeks. We didn't want to subject the patients to another biopsy, we didn't think that they would accept that going into a trial. But nonetheless, in getting to your point here, we have the biomarkers both at week 24 and week 48. We could use that to model the response. We saw that in the recent data with resmitorum, where they were able to give a forecast of the response in serotics with their FibroScan results in their open-label study at one and two years. We believe that using that biomarker data for four weeks creates a very important catalyst for us also at the end of the year. Regarding your last question about FDA interactions, we haven't noticed any difference. We're not aware that there's been any meaningful changes in any of the FDA divisions with which we interact. With MASH, that would be liver and nutrition. We've not seen any changes. We've not had any formal interactions with the agency since our last meeting with them. But we will be meeting with them in the fourth quarter of this year, and we don't anticipate there will be any difference from our interactions in the past.

Hey, Annabel, I just wanted to add one more point to the trial size and the efficiency of trial. One thing to keep in mind that we have a very large safety database on pembidutide, unlike other MASH programs. because of our database in obesity, as well as a very successful end of phase two meeting we've already had with the FDA from a safety perspective, safety and tolerability perspective. So that should give us additional reason, you know, in terms of designing the trial for phase three for MASH, where we might be able to get more efficiency. In other words, we may not need as many patients exposed to drug because we already have a very sizable safety database.

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

Hey, this is Jasmine on for Ellie. Thanks so much for taking our question. So when you meet with the FDA for your end of phase two after impact, do you expect to discuss NASH F4 cirrhosis with them at that time? And just what can you say about your latest plans and timelines there? And then second question, can you just confirm for us your cash running with the Hercules facility? And are there any specifics that you can share on what that runway includes? Thanks.

Todd, do you want to take the first question?

Yeah, yeah. Jasmine, I'll take the first question, then I'll hand it over to Greg for the second. So we are extremely interested in F4. We believe that we will be successful in F4. If you look at the populations of F4 that have enrolled in trials to date, it's been an early F4. Patients who are considered child's A by the child's putercot classification, these are people who have good liver synthetic functions who haven't developed the complications of cirrhosis And they also have high liver fat. So consequently, although they're technically F4, they're behaving like they're F3. And we think we're going to be extremely successful on F3. And I think that forecasts we're going to be extremely successful on F4. So yes, we have drawn out an F4 trial. Now, we can't give you details on that until we get confirmation with the agency. But to your question, We intend to discuss F4 with the FDA. I would imagine that we would have a fibrosis improvement trial that we would use for accelerated approval in F4, as well as follow these people to outcome to full approval. So you're absolutely right. We're very interested. This is going to be a big part of our meeting, and I think we're going to have a high probability of success in F4. I want to also remind everyone that our drug has both metabolic and direct effects on MASH, right? So back to my original point and Lisa's point about the importance of weight loss, we will clearly be able to treat the metabolic abnormalities of F0, F1, F2, and even F3, but we have the direct effects that are going to be potent for F3 and F4. So unlike some other drugs, it might be restricted to certain points in MASH development, say the FGF21s to F3, F4, the other incretins, F0, F1, and F2, we have the opportunity to treat all of MASH. In other words, we can be a complete solution for the disease, both F0, well, from F0 to F4. Greg?

Thanks, Scott and Jasmine. Good question. Let me add a little color around our Hercules facility that we announced this morning. and the effect on the runway, positive effect on our runway. The facility is broken into four tranches. The first will be funded this week upon closing. We disclosed that as $15 million. The second tranche available later this year, and then the balance across 2026. I'll break down the runway answer in two steps. First, on today's cash position, gives us runway in the Q3 of 2026. And if you layer on top the optional draws, if we were to draw all of them, it could extend the runway for as much as another year. Now, that's more details to be disclosed in the TANQ to follow later today.

Great. Super helpful. Thanks so much. Thank you. One moment for our next question. Our next question comes from the line of Mayank Mamthani from B. Riley.

Good morning, team. Thanks for taking your questions, and congrats on the recent progress. Scott, you know, I don't know if I heard from you. Could you comment on the range of placebo responses you're expecting on fibrosis and mass resolution endpoints? As you mentioned, we've seen a relatively broad range in prior trials, and And if you're able to comment at all, sorry to push you here on the female-to-male ratio and what baseline weight is relative to your prior Phase 1B MAFL study, if you could maybe comment on that. And then I will follow up.

Mike, I'm sorry. I didn't hear the second part of the question. I heard the first part about the range of placebo response. Could you repeat the second and then I'll address both? Yeah.

Sorry, yeah, the female to male ratio and then the baseline weight relative to your prior phase 1B MAFL study. So both baseline demographics questions.

Yeah. The first question is the range of placebo response has been wide in these trials. In the semaglutide phase 2 trial, it was 32%. And we've seen other readouts in 20%. We've even seen readouts in single digits. We think that the unifying factor here is how you handle the placebo response. And in the trials that have reread their biopsies by scrambling them, we're seeing placebo responses for fibrosis improvement between about 7% and 13%. So we can't be absolute. about what our placebo response is, we think that our trial is very well powered because we have a better treatment effect and a larger sample size than those trials that ran out successfully. But we would hope that we would drive down the placebo response to those ranges. Regarding the baseline characteristics, as I mentioned before, we're in the final stages of rereading the biopsies, so the exact numbers are not available to us, but we think we're very close. And rather than getting into numbers that we're just going to have to re-announce, which could be confusing to people, we think it's better to say that the range of females to males, things like the baseline weight, will be very similar not only to other trials in the space, if you line them up and we've done that, but also is what our targets were. So I think you're going to be very happy when you see that. But until we have the final numbers, we're a little reluctant to put them out there because it could create confusion.

Wonderful. Thank you. And which secondary endpoints you may include as part of your top-line release next month? And obviously, I want to understand which NITs should we focus on at this 24-week time point versus maybe the 48-weeks? You know, the 48-week could be important as you also think about powering the long-term outcomes trial as part of your end-of-phase to FDA discussion. So if you could maybe segment that, that would be helpful.

Right. I want to first start by saying that we don't believe that we need the 48-week data to meet with the FDA. There are sponsors that met with 24-week data. It will be helpful in the discussions, and we can certainly add it in. but you're correct, those non-invasive tests are gonna be extremely helpful for us to predict and model the changes in the liver biopsy results that would have occurred had we done the biopsy week 48. So the primary endpoints that we'll read out will be MASH resolution and fibrosis improvement. By the FDA guideline definitions, the key secondary endpoints will be things such as weight loss, liver fat reduction, changes in non-invasive tests such as FibroScan and ELF. We'll also have liver fat reduction by MRI PDFF, and we'll have adverse events, discontinuations in study demographics. I believe that would be a comprehensive view of what we'll have, and probably we'll also have a week 48 as well.

Understood. And lastly, could you touch on the impact you believe based on PEMB's mechanism would be on bone and muscle health and on muscle health? Thanks for taking the question.

Well, bone health is extremely important. You're seeing accelerated bone loss with other compounds. There was a recent readout at ASLD and it was also published of a 5% bone mineral density loss versus placebo. in cirrhotic patients. You have to also recognize that in a cirrhotic population, placebos are losing bone density. And it could be as much as 5% over the trial duration of 96 weeks based on what we know from other databases. So adding in the natural 5% with the 5% that you lose with FGF21s, that's significant. That's 10%. That has to be looked at very carefully. That's not something that we're seeing with penvidutide. We're not seeing it with the GLP-1s. As you're aware, lean mass preservation is extremely important in this population. We know that in the semaglutide data, where in two trials they lost approximately 40% of their body weight as lean mass, they had a four to seven-fold higher rate of pelvic and hip fractures And this was seen as susceptible populations. That's the key, that you see it in the elderly and you see it in post-menopausal women, which is not an insignificant number or proportion of the patients that are being treated with these drugs. So consequently, these are extremely important features of drugs. As you're saying here, Mayak, it's important not just to look at the MASH effects and the weight loss but holistically at the whole patient. And we believe the fact that we have class-leading effects in lean mass preservation, we lose only 21.9% of our body weight loss as lean mass over 48 weeks. Glucagon appears to preserve muscle and lean mass, and that's going to be extremely important in all populations that are obese and overweight, not just an obesity population, but a MASH population with obesity as well.

Thank you. Look forward to the data update.

Thank you. One moment for our next question. Our next question comes from the line of John Wollobin from Citizens.

Hi, this is Catherine on for John. I have kind of a quick question about the speed that you expect liver fat as well as histologic change with the GLP glucagon agonist. whether you expect any differentiation from some of the others that we've seen. I guess mainly service due tides. Is there any reason to believe that PEMBI due tides should be faster? And also in terms of biomarkers, are there any that you expect to change from the 24-week readout to the 48-week readout in particular? Or is it more of you're expecting to see sustained improvements at the later time point? Thank you.

Yeah, great question, Catherine. So speed is important. Speed, first of all, implies efficacy. The faster you work, the more efficacious you are. And speed is important. F3 patients can progress to cirrhosis and complications within two years. We know that from the data. And the change in liver fat content predicts the histological change 24 weeks so you know speed of liver fat content reduction speed of histologic changes now the 76.4% is at 24 weeks we also have very similar effects at 12 weeks that data has been published in J hepatology and in fact in our own internal data we're even seeing these effects as early as six weeks so We believe that we not only have the most potent drug, but also the fastest acting drug. Now, regarding cervidutide, that molecule has a ratio of GLP-1 to glucagon of 8 to 1. We are 1 to 1. We have a much greater amount of glucagon in our molecule, and it's the glucagon that's driving the change in liver fat reduction. That's what it is. So we believe that what we're seeing at 24 weeks would not be achievable by a compound with lower glucagon content. We believe that it's contributing some to cervidutide, but if you look at their liver fat reduction, it's lower. It's in the range of 58 to 62%. So we believe that we have a molecule with more glucagon, more liver fat reduction, faster liver fat reduction, faster histological change, and that We are an agent that can read out at 24 weeks. In contrast to cervidutide, we don't think that they could do it. So we believe that we'll be differentiated against all of the prior incretins that have read out, not only terzepatide and semaglutide, but also cervidutide as well. So regarding your second question, we believe the biomarker response will grow between 24 and 48 weeks. There's been a lot of talk in this conference call regarding NITs and the fact that they're becoming more and more reliable and predictive of what's going on. We saw a lot of attention being placed on the change in the fiber scan data and the cirrhotic cohorts and the resmiteron trials. So biomarkers are getting there. They're there, in fact. And we think that what we see at 24 weeks, and we'll report out on that will grow over 48 weeks. We think they'll be all of them. They all move in tandem. ELF and FibroScan are felt to be, at this point, the best non-invasive tests. And in fact, there's even talk now of combining the two for prognosis, a combined score of ELF and FibroScan. We think we're going to have meaningful results in both. And we think those results at 24 weeks will be even better at 48 weeks and will be an indicator of how we would have done it 48 weeks with a biopsy at that time point, and that will be in the fourth quarter of this year.

Thank you so much. Thank you. One moment for our next question. Our next question comes from the line of Andy Shea from William Blair.

Great, thanks for taking our questions. One quick one for us. We're just wondering about the overlap between clinical sites that you use for obesity and MASH compared to potential sites for AUD and ALD that you look to activate in the coming quarters. Thank you.

Oh, hi, Andy. Thanks for the question. There is some overlap. I don't have the data in front of me right now. I can't give you percentages, but, you know, the underlying unifying feature of all these patients is obesity. And many sites specialize in this area, as well as they would obesity and liver disease or MASH. So there's obviously going to be some overlap. But offhand, I don't have those numbers in front of me right now. Yeah. So the sites that we picked for AUD and ALD We'll also have some overlap with the mass and obesity populations as well. But again, I don't have that number in front of me to provide for you on this call.

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

Thank you, everybody, for joining our call today. As always, we appreciate your continued support and look forward to keeping you updated in the months ahead. Have a wonderful rest of your day.

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