Altimmune, Inc. Common Stock 0 Earnings Call

Good morning, ladies and gentlemen, and welcome to the Altimmune RECLAIM phase II Trial in AUD Top-Line Results Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one one on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press star one one again. As a reminder, this call is being recorded. I'll now introduce your host for today's conference call, Luis Sanay, Vice President of Investor Relations. Luis, you may begin. Thank you, operator.

As a reminder, a press release summarizing the top-line results of the RECLAIM trial and an accompanying presentation can be found on the investor relations section of the Altimmune website. Following some prepared remarks, we will open the call to your questions. Before we begin, I'd like to remind everyone that remarks 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. Altimmune 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 review of the risk factors that could affect the company's future results and operations, we refer you to our SEC filings.

I would also direct you to read the forward-looking statements disclaimer in our press release issued this morning and on slide two of the presentation. Any statements made on this conference call speak only as of today's date, July 28, 2026, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. With that, I'll now turn the call over to Jerry Durso, Chairman and CEO of Altimmune.

Good morning, everyone, and thank you for joining today's call to review the top-line data from the RECLAIM phase II trial of pemvidutide and alcohol use disorder, or AUD. We were very pleased to issue the press release you saw this morning reporting what we believe are outstanding top-line results. Pemvidutide delivered a very strong, statistically significant, and clinically meaningful reduction in heavy drinking days, which was the primary endpoint of the study. Additionally, the trial also met important secondary endpoints, including a two-level reduction in WHO Risk Drinking Levels and zero heavy drinking days. Either of these two measures are currently accepted as FDA registrational endpoints. Therefore, the efficacy package seen with pemvidutide in the top-line readout bolsters our conviction in its potential in AUD. We also saw a generally favorable tolerability profile in a challenging moderate to severe AUD population.

These compelling data represent yet another important milestone for Altimmune and further highlight the potential of pemvidutide as a differentiated therapy across serious liver diseases. While we have obvious focus on the specific and unique patient needs on the individual conditions of MASH, AUD, and ALD, it is important to note that there is also an overlap across these serious liver conditions. The top-line results from RECLAIM are meaningful for the AUD patient community, where there remains a significant unmet need, with approximately 12 million adults in the U.S. with moderate or severe forms of AUD. This AUD population is more likely to ultimately suffer from the consequences of liver disease. The dual mechanism of pemvidutide may importantly have an effect on both reducing alcohol cravings and provide a direct effect on the liver, a potential key differentiator from other molecules in development for AUD.

As I said, this is important and exciting data both for Altimmune and for the field. I will now turn the call over to our Chief Medical Officer, Christophe Arbet-Engels, to walk you through the details of the top-line data set. Christophe? Thank you, Jerry, and good morning, everyone.

I am very excited to share the strongly positive top-line data readouts from our RECLAIM trial in AUD. Starting with slide three, as a reminder, pemvi is a novel peptide with balanced one-to-one glucagon GLP-1 dual receptor agonist that has an effect on reducing liver fat, inflammation, and fibrosis. The activation of glucagon receptors has been shown to have direct effect on the liver, while GLP-1 receptors mediate metabolic effects such as appetite suppression, weight loss, and are involved in pathways related to craving and rewards. Moving to slide four, the RECLAIM trial evaluated the safety and efficacy of pemvidutide in patients with AUD. 100 patients were randomized one-to-one to receive either 2.4 milligram pemvidutide or placebo once weekly for 24 weeks.

Patients on the pemvidutide treatment arm followed a simple monthly dose titration from 1.2 milligram to 1.8 milligram to 2.4 milligram. The primary endpoint of the RECLAIM trial was the change from baseline in the average number of heavy drinking days per week with additional secondary endpoint, including the proportion of patients achieving a 2-level reduction in the World Health Organization Risk Drinking Levels, or WHO-RDL, zero heavy drinking days and the absolute change from baseline in levels of PEth, the serum biomarker of alcohol intake over a two- to four-week period. Slide five shows the patient's disposition, where 80% of patients receiving pemvidutide and 78% of patients in the placebo arm completed treatment. Overall, our retention rate was excellent, with 91% of patients completing the study.

Of note, six patients in the placebo arm discontinued treatment due to lack of efficacy, when none did in the pemvi treatment. Turning now to slide six. The RECLAIM study was a multi-center study across 12 trial sites with a diverse population similar to the real world in the U.S. The baseline demographics were balanced across treatment group. Patients were on average 50 years of age, with 52% of the patient population being female. The average body weight was 96 kg and 92 kg for the placebo and pemvi arms, respectively. The heavy drinking days were 5.6 in the placebo and 5.9 in the pemvidutide arm. The population had moderate or severe AUD, including 20%-30% of patients with greater risk of developing cirrhosis, as reflected by the FIB-4 greater than 1.3 at baseline. Moving to the efficacy results, starting with slide seven.

The trial met its primary endpoint, where pemvidutide showed a highly statistically significant reduction in the average number of heavy drinking days versus placebo at week 24, with a treatment difference of 1.45 heavy drinking days reductions, and a P value of 0.0014. In the chart, you can see the rapid effect of pemvidutide at just four weeks and a further reduction through the treatment period. Notably, the clinical relevance of this large difference in heavy drinking days with pemvi versus placebo may lead to important improvements in the social and risk behaviors of patients with AUD. Turning to slide eight. The reductions of WHO-RDL is particularly important, as this is a registrational endpoint recognized by the FDA. On the secondary endpoint, we saw a highly statistically significant response in the 2-level reduction in WHO-RDL versus placebo with a P value of 0.0049.

Roughly 2/3 or 64.4% of pemvi patients achieve a 2-level reduction in WHO-RDL versus only 34.8% on placebo. Moving now to slide nine. On the other FDA registrational endpoint of zero heavy drinking days, a historically more challenging endpoint to achieve, pemvidutide again showed a highly statistically significant improvement in percentage of patients with zero heavy drinking days, with a P value of 0.0066. In this data, more than twice of the pemvi patients achieved zero heavy drinking days versus placebo patients. Both the WHO-RDL and zero heavy drinking days are also relevant endpoints for EMA. Turning to slide 10. In another measure of alcohol usage, the percentage of days with drinking abstinence, pemvidutide showed a highly statistically significant improvement over placebo in the percentage of abstinent days. This improvement occurs early in the pemvi treatment arm and does not plateau after 24 weeks. Moving now to slide 11.

PEth, or phosphatidylethanol, is an objective blood-based measure of recent alcohol intake over the last two to four weeks. The secondary endpoint also showed a highly statistically significant reduction in patients treated with pemvidutide, whereas the PEth level in placebo patients remained unchanged. The treatment difference from placebo at week 24 was 175.3 nanograms per milliliter with a P value of 0.0001, where patients started with approximately 380 nanograms per mL at baseline. The totality of the data, including patients' reported measures such as the decrease in heavy drinking days, WHO-RDL reduction, and the increase in zero drinking days, as well as this PEth objective measure of alcohol intake, showed the strong and consistent effect of pemvidutide in potentially addressing the excessive alcohol usage in AUD patients. Turning now to slide 12.

Given pemvidutide's mechanism of action, we also report here a meaningful and statistically significant reduction in body weight from baseline with vidutide versus placebo, with a 9.1% reduction at week 24. Moving to slide 13. As mentioned earlier, pemvidutide is a balanced one-to-one dual glucagon GLP-1 agonist with a direct effect on the liver. Given the negative impact of alcohol on the liver, we believe that this direct liver effect of glucagon could be an important component of treatment for AUD patients, and we will look to explore this potential differentiator more fully in the future. On slide 14, nonetheless, while we know that RECLAIM was focused on drinking, we wanted to evaluate in an exploratory manner whether patients with elevated FIB-4 at baseline were seeing any improvement over the duration of the study.

As a reminder, FIB-4 is usually used in clinical practice as a prognosis test for patients to assess the risk of developing fibrosis or liver-related events, with values greater than 1.3 indicating an increased risk for liver fibrosis. Given pemvi's direct effect on the liver, the observed data with 50% of pemvi patients with a FIB-4 index above 1.3 at baseline achieving less than 1.3 after only 24 weeks, versus only 17% in placebo, is very encouraging, especially at such an early time point. We would expect to further evaluate the potential liver effect in future studies in this AUD population. Looking at safety and tolerability shown on Slide 15, pemvidutide continues to demonstrate a consistent safety profile across several populations, including AUD, and was generally well-tolerated. The majority of AEs were mild to moderate in severity. There were two SAEs, one patient with breast cancer and another with hyponatremia.

The patient with the AE of hyponatremia was deemed possibly related to the study medication by the principal investigator. Treatment discontinuation for GI AEs represented most of the drug-related discontinuation in this population. Turning to Slide 16, we believe that the simple two-step titration may improve the general tolerability profile of pemvidutide at 2.4 milligram. For example, the nausea rate at 2.4 milligram was only 44% in RECLAIM versus 52% in the obesity trial with the same dose. Finally, I would like to take a moment to express my thanks and deepest gratitude to all the participants, clinical investigators, and everyone involved in the RECLAIM trial. We completed the trial several months ahead of schedule, signaling strong enthusiasm from both patients and physicians to explore new treatment options for AUD. In conclusion, I am very excited about the strong positive data we shared today.

We believe these data highlight the potential of pemvidutide to meaningfully help AUD patients on their alcohol use disorder, and potentially the often related liver disease. As a reminder, the FDA granted Fast Track designation to pemvidutide for the treatment of AUD. We now look forward to engaging with the FDA on the path forward towards registration. I will now turn the call back over to Jerry.

Thanks a lot, Christophe. In summary, from our standpoint, the RECLAIM top line trial results are quite compelling. Pemvidutide met the primary and important secondary endpoints, including the two registrational endpoints recognized by the FDA. In fact, to our knowledge, these are the most robust results that have been reported in AUD. We look forward to reviewing the full data set and requesting an end of phase II meeting with the FDA to discuss the path forward for pemvidutide in this indication. We also intend to present further data at upcoming medical meetings and publish the full data. On a corporate level, Altimmune remains laser focused on execution and continuing to advance our key pemvi programs. In addition to the great news on AUD we shared this morning, we're advancing our MASH and ALD programs.

Regarding MASH, all is going well in the startup phase of the PERFORMA phase III trial, and we now expect to initiate the trial this quarter. In ALD, consistent with our guidance, we expect to announce the completion of patient enrollment in the RESTORE phase II trial in the third quarter. Altimmune is well positioned to execute our strategy and create shareholder value. Today's results add to the growing body of evidence, further building our confidence in the potential of pemvidutide. We now have delivered strong phase II data in another indication, and in doing so, move us one step closer to fulfilling our mission of helping the millions of patients with serious liver diseases. We're excited with the continued progress we're making as a company and enter the second half of the year with momentum. This now concludes our prepared remarks. I'll open the call for Q&A. Operator? As a reminder, if you'd like to ask a question at this time, please press star one one on your touchtone phone and wait for your name to be announced.

To withdraw your question, please press star one one again. Our first question comes from Thomas Smith with Leerink Partners.

Hey, guys. Good morning. Congrats on these excellent results. Thanks for taking our questions. Just wondering, relative to the randomized phase II study with semaglutide, it looks like you may have had a more severe patient population looking at WHO Risk Drinking Levels and total alcohol consumption at baseline. Can you just help maybe put these results and the treatment effect in context versus the phase 2 sema experience? What do you think the glucagon is adding to the results and the treatment effect here?

Thomas, thanks a lot for the question. As we said in the prepared remarks, really exciting data for us to report. To our knowledge, it's the most robust trial results we've seen in AUD. I think Christophe can give some highlights on what we see in terms of some of the cross-trial comparisons with the recent data you saw on sema.

Right. We looked at the compare. It's always difficult to compare the two different trials because these are not head-to-head. We looked at the different ways, and in general, sema looked a little less effective. Our methodology looked at less than a day versus a day and a half reductions in heavy drinking days. Our population is also different, as you just mentioned. Our population is a little more severe. That population, it's unclear whether a population that is drinking more alcohol is actually having a harder time to reduce alcohol. The last part on the glucagon, we know that there is a large amount of glucagon receptor in the CNS, and that component is something that is yet to be further explored.

Altogether, I think as Jerry said, our data are very strong, allow us to think about moving further, especially with regard to the liver components and the benefit that it could bring for those patients.

Great. Super helpful feedback. Maybe just one other follow-up question, if I could, on the regulatory path. You clearly hit stats on two potentially registrational endpoints. Do you have an early view or a preference on which of these endpoints you'd look to use as the primary in a potential pivotal registrational study? Maybe if you could just elaborate a little bit more in terms of timing on the feedback from FDA and the potential path forward here. Thanks so much. Yeah. Maybe I'll start on timing, and then Christophe can give some color on the endpoints.

Obviously, on the endpoint, great that we hit them both with such strong results. On the timing, we're going to finish the readout. This is top line, as everybody is aware. We'll get a completion of the dataset. We want to move quickly here and thoroughly. We plan to consolidate the data, put the file together, and then request the end of phase II meeting. We'll obviously provide further color on that as we get closer and have a better understanding of the exact timing. One of the key messages is we think the data is outstanding. We know there's a high level of unmet need here. From a company standpoint, we're going to work quickly and thoroughly to the next regulatory steps. Maybe on the endpoints, Christophe?

No, on the endpoints. The 2-level WHO-RDL is one of the endpoints, obviously, that the FDA consider as validated endpoint for a phase III trial. The zero heavy drinking days is often a much harder endpoint to achieve. We are really happy now we have the choice between the two different endpoints. As we're getting the full package of our data, we will prepare to get the briefing document together and make a proposal for the FDA. On the EMA side, we know that the zero heavy drinking days is the endpoint that they're using, they're asking you also to have the WHO, the 2-level reductions from WHO-RDL as a key secondary endpoint. We are in this situation a little bit like we're done from the MASH trial, where we will address both of the regulatory agencies' requirements.

Thanks, Thomas. Makes sense. Congrats, guys.

Thanks. Our next question comes from Roger Song with Jefferies.

Great. Congrats for the data. Fantastic and impressive. Maybe just a follow-up on the baseline. When we look at the heavy drinking day at the baseline, it's pretty high for the phase II. How do you think about the phase III? In particular, as you apply to the broader population you try to address for the AUD, if that baseline a little bit lower, how you think about the effect size will evolve? That's number one. Number two is just to clarify for the primary endpoint for phase III. For FDA, would that be the co-primary endpoint or dual primary endpoint, or that's just one of those two, like MASH? Thank you. Yep. Either is approvable.

Correct. They're not specifying a co-primary endpoint.

Again, we'll have discussion. I think the great thing is that with the strong data we have, we have good options in terms of how we think about design of phase III to take advantage of the unique benefits that PEMB might be able to bring to the table here. We did enroll intentionally a moderate to severe population. We know that that group of patients is most likely to ultimately suffer consequences of liver disease. Christophe, maybe you want to just talk about how you're thinking about this group of moderate to severe as we prepare for an end of phase II.

No. Clinically, this is a group that requires treatment because of some of the social risk behaviors. This is clearly a group that is having a high unmet need that we can address with this. As Jerry said, for our phase III, the good news is that our phase II is looking at a very diverse population, very similar to what the real world is having, which is important for regulators to have in your phase III. Our data, in a certain way, de-risk our phase III trial substantially here. With regard to your point on the baseline characteristic, I would argue that sometimes the patients with the higher alcohol habits or patterns can be very hard to reduce their behaviors on the alcohol. We are happy with what we see.

Again, the glucagon component on those behaviors is yet to be explored, it's unknown, but we know there are glucagon receptor on the CNS. In the meantime, in these patients, obviously, they are more at risk of liver disease, that's going to be a clear aspect for us to look at in our phase III. We're going to set up all these pieces together when we have all the full data and go towards the FDA with a very strong briefing package.

Got it. Thank you. Thanks, Roger.

Our next question comes from Eliana Merle with Barclays.

Thanks for taking the question. Congratulations on the really impressive data here. How are you thinking about the scale and scope of a potential phase III relative to the size and cost of a MASH phase III trial? How are you thinking about the market opportunity for AUD and how the pricing might compare to that in MASH? Given the non-invasive nature of these studies, could this potentially come to market before MASH? Thanks. A lot there to unpack, Ellie.

I'll try to start and then perhaps Christophe and Linda can chime in. It's a little premature to be very specific on size and scope. As I said, we're going to complete the full readout, review the data, plan to submit it. Importantly, we'll continue to reiterate that the strength of this data set gives us great options when we think about what we will be proposing when we sit down with the agency. Of course, that important dialogue at the end of phase II meeting is going to help a lot define exactly what the size and scope of phase III might be. We do know, though, however, that we would expect the AUD program to be smaller in size and duration than what we're thinking about in MASH.

As we get tighter on that and have more feedback from the FDA, we'll talk more specifically about the range. With this data set, we really have the ability now to plan and position a Pemvi franchise. As I announced this morning, things are progressing well on the MASH side and that we did tighten the guidance and initiation now to be this quarter in phase III, where we'll initiate PERFORMA. We have great data here on AUD, which we'll also be factoring in when we think about the overall value proposition of Pemvi, which will help guide how we think about pricing. We know now that the potential for a benefit to a broader group of liver disease patients is bolstered by the AUD data that we have.

We think about really the value and ultimately pricing for both indications now that we've progressed through phase II on around the impact on both the behavioral or metabolic factors and the direct impact on the liver, that's the value proposition. That's what we're going to work towards. Ellie, we will be thinking about this on a franchise level. Again, a good value here. We'll talk a lot about pricing over time. Again, for us, important movement here. We have a larger group of patients now that we think could benefit as a result of this AUD data set.

Great. Thanks for the color, congrats again on the data.

Thanks, Ellie. Our next question comes from Michael DiFiore with Evercore ISI.

Hi, guys. Thanks so much for taking my question, and congrats on the fantastic data. Two questions from me. To what extent do you think the efficacy results were driven or perhaps confounded by the GI adverse events? In other words, could nausea, vomiting, diarrhea have influenced the desire to drink? My second question is how robust was the primary endpoint to perhaps alternative S demands and missing data assumptions? Thank you. Okay, Christophe? Yeah, I'm happy to.

First, we had 12% of our patients that withdrew in the placebo because of lack of efficacy versus 0% in the pemvidutide arm. I think the GI tolerability is not necessarily a factor. However, as you know, those patients with alcohol use also have nausea, have esophagitis, have GERD, and those kind of things. In that population, these are factors that we also are gathering as we're running these trials. With regard to the estimates and the powering of the study, basically, we powered on the heavy drinking days per week. We powered for a 1-day difference, and we were able to show almost a 1.5-day difference. We are really happy with this data. In addition to this, if we were able to also have highly statistical significance in the WHO, the 2 levels. Often studies are reporting only even 1 level.

We have 2 levels of reductions with highly statistical significance. We have the zero drinking days that we achieved. As you can see on the presentation, the days of abstinence are also highly statistically significant. Overall, not only we are reducing the amount of drinking, but we are reducing the number of days of drinking. That's really the way to think about this. The way I like to put it is basically the patients are drinking all week long, and now they're drinking less and only on the weekend. It's kind of this picture that we are able to approach with pemvidutide for these severe and moderate patients.

Great. Thanks so much. Our next question comes from John Wolleben with Citizens.

Hey, thanks for taking the question. Two from me. Did placebo perform as you expected here? It looked pretty consistent, you have about a twofold effect on most of these endpoints. I'm hoping you could comment a little bit about the titration to the 2.4 mg and read-through on tolerability to MASH. It seems like the event rates were pretty similar to what you saw, at least for the 1.8 mg arm in the obesity patients. Any learnings going into the phase III MASH trial and tweaks you may have there? Thanks, guys. Great, Jonathan. Christophe?

Yeah. On the placebo, the patients' reported outcome are the heavy drinking days, the WHO rDL, the zero drinking days. Those we saw a placebo effect as expected. Our test measures sees no difference in those patients. Remain stable throughout the duration of the study. We are having data that are exactly consistent with what we were expecting with regard to both the patients' reported outcome and the more objective measure as the phosphatidylethanol as shown here. With regard to the titration, the number, as we shared, do seem to show some improvement, especially on nausea and vomiting, especially when we start looking at a placebo-adjusted comparison. For us, it's just an indicator that this titration seems to be working. Again, it's difficult to compare with our other trials.

It's more a directional aspect given that we are giving here because the population are different, the BMIs are different, the timing of those studies are different. We believe from what we are seeing at this point in time, that the monthly titration is probably a good progress for especially the 2.4-milligram dose.

Thanks, guys. Thanks, Jonathan. Thank you.

Our next question comes from Annabel Samimy with Stifel.

Hi, thanks for taking my question. Just going back to the phase III trial and thoughts on the length of trial. Looks like we've seen a few phase III trials, some are 28, some are 56. Is there any thought to consider a longer trial so you can really flesh out the potential benefits of glucagon and its impact maybe on liver enzyme to, I guess, commercially differentiate it from the other incretins? Just one follow-up. Do you have any clues as to whether the hyponatremia is related more to glucagon or if it's related to the GLP-1? Thanks. Maybe first on timing, then you can talk about the timing of the study.

I think, Annabel, you bring up an important dimension, which is that the impact on the liver is an important potential differentiator of Pemby in this population as it is in other populations that we're studying. The timing upon which we consider for phase III, that will be an important dimension. Again, more to come on that in the future. I think we underscore the differentiation element that we think we can bring to the table, and we'll be very thoughtful on the timing of that study because we do want to make sure we're reinforcing the liver benefit. We think the mechanism will have a strong probability to have an impact there.

You get a little sense with the exploratory data on FIB-4 that we showed today, that will be one of the objectives of a potential phase III is to really make sure we understand the liver impact. Christophe, maybe on the SAE that you questioned.

Yeah. With regard to the SAE, to give you more color, I don't think that this is related to either the GLP-1 or the glucagon. It was a complex patient that had several health issues, including malnutrition. Their change in alcohol behaviors led to also some issues with beer potomania. There were also other concomitant medication, including ZOLOFT, that has in their label the hyponatremia. There's a whole picture here. We had an external expert looking at this particular patient, and the expert concluded independently that this was not related to study drug. However, given that the PI insisted on having it at the lowest level as possibly related, we have to report it as such. Now, vomiting and nausea could have partially contributed to this in that particular patient, but that patient had already some issues because this patient was taking Prilosec prior to the trial.

There is too many factors that led to this assessment, and I think it's complicated to just attribute it to GLP-1 or glucagon, as we agree with the independent expert.

Great. Thanks for the color.

Thank you. Our next question comes from Srikripa Devarakonda with Truist Securities.

Hi, this is Alex on for Kripa, congrats on the data. Two from us, one on the potential phase III. This trial only enrolled patients that were obese or BMI above 25. If the phase III maintains that, do you think the FDA could restrict the label to AUD in patients who are overweight or obese, or is there a path to a general AUD indication with that? Number two from us, on the study drug-related AEs that led to discontinuation, did the discontinuations happen throughout the study, or were they more skewed towards the beginning of the trial or immediately following a dose escalation, something like that? Thanks. Yeah, thanks. First, on the question around the population.

When the study was designed, there was a decision taken to put in the BMI ranges that we outlined. It is the majority. The majority of the patients with AUD do fall into that overweight or obese category. Nonetheless, we would anticipate enrolling a phase III that gives us also the opportunity to go for patients that are normal in terms of body weight. We'll assess that in the context.

As Stuart just said, the data, we run those by our KOL, the data do not limit us to this population. We've chosen that population for our phase II now that we have the data and the safety and tolerability profile allows us to go beyond this. We're going to have those discussions with more analysis, but this is clearly under consideration to not limit to a certain BMI. With regard to the study discontinuation, we don't have all the details at this point in time of the timing of all these sub-analysis that we're working on as we speak. We just got this data recently, as you can imagine, in a study like this, we have a lot to still dig in and look into.

Great. Thank you. Great news today.

Thanks, Alex. Thank you. Our next question comes from William Wood with B.

Riley Securities. Yes. Thank you for taking our questions and congratulations on the data.

Just thinking in terms of the sort of digging in potentially to the lack of efficacy denoted on the placebo patients. Was curious actually, if the efficacy was related to weight loss or if it was specifically what that was specifically denoted as. When we think about what we've seen in past trials between your impact and now here, with reductions in VCTE and impact, and then obviously FIB-4 here, how do you feel that that gives you confidence going into your RESTORE trial that would potentially read out next year between those two endpoints?

Chris, maybe I'll let you start there.

Yeah, I'll start on the lack of efficacy. The lack of efficacy, we know the patients reported that they did believe they were on placebo. It's not because just of weight loss or anything to that extent. That lack of efficacy is probably a combination of those different aspects that we have seen. The impact on our ALD study, as you correctly mentioned, we do expect to have an impact on the liver and having some benefits on these particular patients. We also know that a large number of the ALD population has AUD, the combination of both are very consistent with the data that we've provided today. That's a benefit that we think is very differentiated from pemvidutide.

Got it. Very helpful. Thank you.

Thank you. Thanks, William. Our next question comes from Andy Hsieh with William Blair.

Great. Thanks for taking our question. Just one quick one really about the phosphatidylethanol biomarker. As discussed previously. All the efficacy endpoints, from a patient-reported outcomes perspective, there's a pretty robust placebo effect in the trial, even though the biomarker didn't really show that. I'm curious if you mind explaining the discordance between the biomarker and then the reported outcomes. Thank you. Yes. Patients' reported outcome, when you start including a patient in a study, in general, they underestimate the alcohol intake they are taking, and they start reporting that they have some improvement.

A more objective measure, as you can see with the test measurements, is showing that these patients do not improve their intake. They may just have a different pattern around it or things to that extent, but they clearly are not. It's really important to not only look at the patient's reported outcome and the placebo response that we have seen is very consistent with this.

That's actually reinforcing the fact that those measurements were done appropriately in that population and that the test, when you look at the more objective measure, that the placebo is actually not changing throughout the duration of the study, and only the one that truly decreased their alcohol intake are having the benefits that we have seen, almost a 40% decrease in their alcohol intake.

That's super helpful. Thank you so much.

You're welcome. Our last question comes from Patrick Truchio with H.C.

Wainwright. Hi, good morning, everyone, and congratulations on the data.

This is Luis in for Patrick. Do you have any follow-up data that might indicate improving effects or plateauing effects towards the end of the treatment? Do you plan to disclose this data later on? I have a follow-up. Yeah.

It depends on the measurements that we have seen. We haven't seen in all of them some plateauing of the effect. It's going to be interesting actually to look for longer effects. For example, the weight loss or some of the abstinence do not plateau, so there could be some additional benefits to treat this patient chronically, and the tolerability and safety allows us to do that, as we've shown with pemvidutide.

Great. That's helpful. Yeah. For the phase III, will the take control behavioral intervention that you used here, will you use the same?

Will the FDA ask for a more raw approach to be able to separate the signal that is due to the drug or due to the intervention? Thank you. The intervention we have used is much milder than the Simalco intervention, for example.

That was using a nurse with direct patients to healthcare provider interactions. We just had a computer approach that was pretty mild already. We will evaluate all these data and have the discussions with the FDA, what is the most appropriate for the phase III. Again, we are going to be having those discussions as we have all the full package of our data and putting together the briefing package.

Thank you, congratulations. Thank you.

Thank you. That concludes today's question and answer session.

I'd like to turn the call back to Jerry Durso for closing remarks.

Thanks, all for joining us today. Hopefully, you'll share our excitement as we report out this data. For us, to our knowledge, again, it's the most robust data set that we've seen in AUD and the moderate to severe patients that we assessed in this trial we know are at a high level of unmet need, and we look forward to supporting them and continuing advancing pemvidutide. The data set also bolsters our confidence that we have a potential franchise opportunity here with pemvidutide. In order to make sure we're delivering a maximum amount of value, we're going to stay focused on execution. We're going to move quickly towards requests of an end of phase II meeting with the FDA on AUD. We're also going to continue fully ahead on our MASH and ALD trials.

As I mentioned in the prepared remarks, we now expect initiation of our PERFORMA phase III in MASH to happen this quarter, now in quarter 3. Lots to do, lots to focus, and a lot to review with you at our upcoming earnings call. Stay well till then, and we'll talk soon. Thanks. This concludes today's conference call.

Thank you for participating. You may now disconnect.