Altimmune (ALT) Q2 2026 earnings call transcript

I'm going to introduce your host for today's conference call, Luis Zane, Vice President of Investillations. Luis, you may begin.

Thank you, operator, and good morning, everyone. Thank you for joining us for Altimmune's second quarter 2026 financial results and business update call. On today's call, you will hear from Jerry Durso, our Chairman and Chief Executive Officer, Dr. Christoph Arvid-Angels, Chief Medical Officer, Linda Richardson, Chief Commercial Officer, and Greg Weaver, Chief Financial Officer. Following management's prepared remarks will open the line for questions. Our second quarter 2026 earnings release was issued this morning and can be found in the investor relations section of our website. Before we begin, I would like to remind everyone that remarks made about future expectations, plans, and prospects constitute forward-looking statements for the purpose of-of safe Harvard 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 files. I also direct you to read the forward-looking statements disclaimer in our press release issued this morning. Any statements made on this call speak only as of today's date, August 12, 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.

As a reminder, this call is being recorded and will be available for audio replay on our website. With that, I'll now turn the call over to Jerry.

Good morning, everyone. Thank you for joining us today for our second quarter, 2026 financial results and business update call.

2026 is proving to be a year of significant progress as Altimmune evolves into a late-stage company dedicated to serious liver diseases. We've been laser-focused on execution since the beginning of the year and believe we're well-positioned to advance our strategy and deliver on our mission. Hemadutide is our foundation, and our confidence and conviction in its potential continues to We're strengthened with the growing body of clinical evidence. We're building momentum across our Pemidutide franchise and are excited for the future. Let me take a minute to highlight our recent progress. Starting with MASH, last week we announced the initiation of the Performa Phase 3 trial as we began enrolling patients in the global program. We worked with urgency to get the trial started quickly, just three months after securing the financial resources to fund the study through the 52-week readout.

We're very encouraged by the start of the trial. Sites are being activated quickly, and we're seeing great engagement by the medical community about what performa may mean for the MASH treatment landscape. There remains a significant unmet need in MASH. We believe PEMV, with its balanced one-to-one glucagon and GLP agonism in a single molecule, has the potential to offer a differentiated profile for MASH patients. Moving now to alcohol use disorder, or AUD, we were pleased to report positive top line data from the RECLAIM Phase II trial last month. Pemba Dutai delivered a very strong, statistically significant, and clinically meaningful reduction in heavy drinking days, which was the trial's primary endpoint. The study also met important secondary endpoints, including a two-level reduction in WHO risk drinking levels and zero heavy drinking days.

It's important to note that either of these two measures are currently accepted as FDA registrational endpoints. The totality of the top-line data from Reclaims strengthens our conviction in PEBBY's potential in AUD. We're moving quickly to gather the full data from the trial, then prepare the data package to request an end of Phase II meeting with the FDA to discuss next steps. These compelling data, which to our knowledge are the most robust presented in AUD, further strengthens the potential of Pembidutide as a differentiated therapy across serious liver diseases. The results from this trial are also meaningful for the AUD patient community, where Pembidutide could represent an important advancement in an area that has lacked innovation for the past two decades.

And again, where a significant unmet need remains. There are approximately 12 million adults in the US with moderate to severe AUD. It's well accepted that this AUD population is more likely to develop liver disease. We believe hemidutide is uniquely positioned to benefit these higher risk patients, as its dual mechanism can address the totality of disease by reducing alcohol cravings, while also providing a direct effect on the liver. This population could serve as a key commercial opportunity with substantial future sales potential. Pembidutide has the potential to help address the continual liver diseases we're targeting, MASH, AUD, and ALD. We've now delivered strong phase two data in yet another indication, and we're well on our way towards building our Pembidutide liver franchise.

We're committed to executing our strategy with speed and efficiency, and the significant progress we've made this year reflects that commitment. We remain laser-focused on executing on our goal of bringing Pembidutide to patients who may benefit from its promising and differentiated therapeutic profile and creating value for our shareholders.

With that, I'll turn the call over to Christoph for a clinical update.

Thank you, Jerry. I am very excited to share that we continue to advance our clinical programs across MASH, AUD, and ALD. Beginning with our program in MASH, last week we announced the initiation of the global PERFORMA phase 3 trial of pemvidutide in MASH and begin enrolling patients. Over the last few months, we've moved very rapidly to set up a strong and experienced global infrastructure to initiate the trial. The trial will be conducted across approximately 300 sites, with one-third in the U. S. and two-thirds ex-U. S. We're working closely with our CRO on site activation in multiple countries and ensuring a smooth start to the trial for an efficient enrollment. The initiation of PERFORMA is an important milestone for Altimmune and for the advancement of MASH treatment.

We also see a growing interest and excitement for pembegutide in MASH from the scientific community. Our increased presence and engagement with the scientific community at the EASOL and solar medical conferences this year is driving awareness and has helped build momentum as we begin enrolling Based on the strong Phase II data we reported last year and the design of the PERFORMA trial, we are looking forward to studying Pemvidetide in a registrational setting.

Moving to AUD. In July, we were very happy to report the strongly positive top-line data from the reclaimed Phase II trial in AUD. The data readout was based on the 90T analysis as it would be for a pivotal study. The trial met its primary endpoint where Pemidutai 2.4 milligrams 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 per week. PEMVDutide also met two critical secondary endpoints, both of which are registrational endpoints recognized by the FDA.

On the first endpoint, we saw a highly statistically significant response in a two-level reduction in WHORDL versus placebo. Roughly two-thirds of PEMV patients achieved a two-level reduction in WHORDL versus only one-third on placebo. On the other FDA registrational endpoint of zero heavy drinking days, one that has historically been challenging to achieve, pemvisitide, again, showed a highly statistically significant improvement in percentage of patients with zero heavy drinking days.

In this data, more than twice the number of the pemvisitide patients achieved zero heavy drinking days versus placebo patients. The trial also saw a highly statistically significant change in the percentage of days with drinking abstinence and pest levels, which is an objective blood-based measure of recent alcohol intake over the last two to four weeks. PEMV also showed a meaningful and statistically significant reduction in body weight from baseline with a 9.1% reduction with PEMV-D type versus placebo.

The totality of the data, including patients' reported measures such as the decrease in heavy drinking days, WHORDL reduction, and the increase in zero heavy drinking days, as well as the past objective measure of alcohol intake, shows strong and consistent evidence in PEMVD-type's potential to address the excessive alcohol usage in AUD patients. Considering the landscape of clinical studies in AUD, including looking at other available GLP-1 AUD trials, the totality of the Reclaim data is, to our knowledge, the most robust to date. While Reclaim was focused on drinking behavior, we evaluated in an exploratory manner whether patients with elevated FIP4 above the threshold of 1.3 at baseline were seeing any improvements. FIP4 is an established biomarker correlated with risk for developing liver fibrosis.

Given PEMV's direct glucagon effect on the liver, the observed data with 50% of PEMV-dutide patients with a FIP4 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 expect to further evaluate the potential liver benefit in a Phase III study in AUD. In terms of safety and tolerability, FEMS-E-DECIDE continues to demonstrate a generally consistent safety and tolerability profile. Let me share a few thoughts as we look ahead to a potential Phase III study in AUD, which of course will be subject to our dialogue with U. S. and European regulators. We would plan a Phase III study in the moderate to severe AUD population.

It is important to note that approximately 50% of AUD patients also have ALD. Therefore, we would expect to study a portion of ALD patients in the AUD Phase III trial. We would look to broaden the study population to also include patients with a BMI under 25 and could explore a lower dosage option. We look forward to engaging with the FDA at a Nano Phase II meeting and discussing a path forward for AUD. In addition, we also plan to engage with European agencies such as EMA. In ALD, we are pleased to report that we completed patient enrollment in the RESTORE trial and expect top-line data in the second half of 2027. The trial enrolled approximately 120 patients with ALD and a history of chronic and heavy drinking at baseline.

To support future regulatory discussion, we have amended the trial protocol to be able to fully demonstrate the liver benefits in the ALD population that PEMVD-Dutide may provide at one year. The primary endpoint of the trial, the change from baseline in liver stiffness measurements, or LSM, will now be assessed in a hierarchical manner at week 48 and then at week 24, allowing for both time points to be assessed. The RESTORE trial is now designed to show a liver benefit over a long period of time, and this is consistent with our development strategy of focusing on higher risk patients. Demonstrating a liver benefit over a long period of time could be a key differentiator for PEMV versus other AUD therapies in development because AUD patients are often already presenting some level of liver impairment.

In summary, we are very encouraged by the progress we are making as we move closer to delivering on our mission of helping the millions of patients with serious liver disease. And with that, I will turn the call to Linda.

Linda Linder- Thanks, Christoph, and good morning, everyone. In recent quarters, I've shared insights from our market research describing how PEMB's target product profile positions us well for future competitiveness, in the MASH market. Today, I will focus on how we view the current alcohol use disorder market landscape, how we believe this will evolve in the future, and the potential role of Pembidutide in driving this evolution for patients and healthcare providers. First the AUD market has considerable untapped potential Alcohol use disorder is one of the largest under markets in the U Approximately 27 million adults meet the criteria for AUD 12 million of whom are considered to have moderate or severe AUD It's this group that has the highest risk of progressing to subsequent liver damage, and we believe Pembidutide potentially would bring the most benefit.

Overall, only 10% of AUD patients are diagnosed, and of those, only one in four receives drug therapy. It's well known that excessive drinking has direct negative impacts on the liver, including cirrhosis, liver failure, and even death. In fact, excessive alcohol consumption is one of the leading causes of preventable liver injury worldwide. The low diagnosis and treatment rates for AUD seem to represent a bit of a disconnect, given these health consequences. Why is this? Patient concerns about being stigmatized, low awareness of available drug therapies, less than ideal treatment options with poor compliance that limit prescribing, and no recent therapeutic innovations all contribute to the low diagnosis and treatment rates. There is a clear opportunity for future therapies with new mechanisms and better efficacy and tolerability to help address this dynamic.

In fact, there has not been a new drug approved to address AUD in 20 years. Better solutions often bring renewed interest and growth to therapeutic categories that have been relatively stagnant, as was the case with obesity. We believe strongly that PENVY may bring exactly this type of innovation to the AUD market, particularly for moderate and severe patients.

The unmet need in the AUD market demands new treatment solutions. The reclaimed Phase II efficacy and tolerability data show PEMB's balanced 1-to-1 glucagon GLP-1 activity significantly improved multiple measures of excess drinking and may show positive effects on underlying or subclinical liver impairment in future studies. The potential direct liver benefits that PEMBi may demonstrate in AUD would provide a strong impetus to prescribe in the moderate and severe patient segments, beyond the decrease in drinking levels and behavior.

Other products in development may not demonstrate this liver benefit, concentrating more on the cravings and behaviors associated with AUD. Additionally, current AASLD treatment guidelines for MASH strongly encourage alcohol screening, as alcohol consumption accelerates the progression of metabolic dysfunction and increases the risk of liver decompensation, negatively impacting patient outcomes. We see a potential dynamic emerging where increased alcohol screening and routine PEP testing among liver specialists could substantially increase the diagnosis of AUD, even while assessing MASH patients.

Recent market research we conducted shows that 44% of hepatologists and 27% of gastroenterologists reported they already used PEP testing in their MASH patients. There is considerable overlap among MASH, AUD, and ALD populations, highlighting the increasing role that the hepatology and gastro communities may play in managing these patients who have or are at risk for serious liver diseases.

In summary, the AUD market of today will not be the AUD market of the future. We believe PENV is well positioned to potentially disrupt this category, providing a catalyst that sets new expectations for what drug therapy can accomplish in the moderate or severe AUD patients who are most at risk for liver damage. We look forward to generating additional clinical data to support these beliefs and to share insights from our pre-commercial work along the way.

With that, I'll turn it over to Greg for the financial review.

Thank you, Linda, and good morning. Starting with our financial results for the quarter, which were in line with our expectations. R&D expense in Q2 26 was $18.7 million, compared to $17.2 million for the same period prior year. The increase in R&D spend was driven by investment into our ALD trial, as well as startup costs for the Phase III trial in MASH, offset by a decrease in expenses related to the completion of the Phase II trial in MASH, which was ongoing in 2025. Q2-2026 R&D spend included $11.6 million of direct costs related to PEMVA-Dutai development, of which $3.8 million was for MASH, $5.3 million for the Phase II AUD and ALD trials, and $2.5 million in CMC-related expenses.

Q2-2026 R&D also included $1.1 million in non-cash stock compensation. G&A expenses in Q2-26 were $7.6 million compared to $5.7 million for the same period prior year. The increase in G&A was driven by an increase in professional fees and compensation expenses, and the Q2-26 G&A included $1.7 million in noncash. com. Net loss for the second quarter, 26, with $22.8 million, or $0.12 a share, compared to a net loss of $22.1 million, or $0.27 a share in the second quarter of 2025.

Now, moving to the balance sheet, since the beginning of the year, we strengthened our financial position, having raised approximately $310 million year-to-date, including the $225 million follow-on offering in April. June 30, 2026 total cash was $519 million. This cash position provides us with the operating cash runway through the Performa Phase III MASH 52-week data readout, which is expected in 2029.

While our cash runway forecast fully funds the company through the MASH Phase III 52-week readout, it does not include a potential Phase III trial in AUD. As we previously noted, our plan and preference is to use non-dilutive means to fund that trial when needed. And on the strength of this data, we believe we'll have the options to fund that trial, which could include royalty, debt, and or strategic partnerships.

With feedback from regulatory authorities, we'll determine the scope and level of investment required for a Phase III trial in AUD, and we'll provide the street with an update as appropriate. Thank you very much. That concludes our prepared remarks, and we'll now turn the call back to the operator for the Q&A session.

Good morning. On the Phase 3 Performa study, I appreciate the comments on the regional targeting for the trial sites. I just wanted to ask about your sense of the competitive landscape for mass trials, since there are a number of competing Phase 3 programs at various stages of enrollment. And I was hoping you could provide a bit more detail on how you're targeting study sites with respect to competing programs. How much overlap is there with some of these ongoing pivotal programs?

And maybe if you could talk about your expectations on patient enrollment relative to some of the other Phase III programs or SEMA or Cervodotide or the FGF21s. And then I have a follow-up if I could.

Okay. Thanks, Thomas. First of all, as we said in the prepared remarks, we're really encouraged by the speed at which we've been able to initiate and the work happening on the ground that Christoph can give you a little color on. We are operating in an environment where there are some other studies going on, which I think we've been able to work through and take advantage of, frankly, some of the experience out there, both on the CRO side and on the site side, as we think about the speed at which we want to enroll.

Christoph? Yeah, so we plan to have a number of sites, as we said, in the range of 290, 300 sites around the world. We are well aware of the competitive nature of such trials, and what we've built on is a number of factors that are attractive for our study, including the MASH, the design where we can reduce the screen failures, and also our relationship with the sites, either through our experience in the Phase 2, or through our CRO right now. We also have not expanded the number of patients that we are asking each of those sites to a reasonable number so that they are able to do additional study as well. So this is really, those different features in our consideration for enrollments are really pleasing, I should say, to PIs and the investigators to this point.

So we were able to get a really good response on this. Our enrollment is around for studies in that nature between 18 to 24 months. We are, because of this, different aspects that we heard they are very attractive for the PIs. We are aiming at the lower end of this, and that fits well with what we are hearing right now.

Sure. So, it doesn't impact any, there's no change at all on the protocol for deaths. It's the statistical features from the AUD data and what we've seen and the benefits we expect from pemvidutide on the lever. For future filing and regulatory filing, we are interested in better characterizing this aspect into the ALD study. So what we're going to be doing is reading at 48 weeks. There is no alpha spending or anything like this with that high article. We were collecting those data anyway. What we're just doing is now being able to analyze both aspects at week 48 and at week 24 in a powered manner using that statistical approach. So it's strengthened, if you wish, the role of this study in our differentiation on the liver benefits.

And as we indicated in the prepared remarks, Linda went into some detail. You know, we think about the AUD population with the moderate to severe patients. There is, we know, a significant overlap with AUD and ALD in that population.

So having a 12-month view around the liver benefit fits consistently with where we see the differentiation of PEMB in an area of high unmenu.

Yes. So, given the guidance, the recent guidance, the June guidance from the FDA, we expect that one trial will be sufficient. That guidance talks about the weight of evidence and the quality of the biomarkers. We know that, for example, PESH is becoming more important. We have those PRO, the WHO, RDL, and the zero heavy drinking days that are validated. So our approach is to go with one single trial and to be able to use also our additional experience with SpamVD side in other populations for our safety database. So altogether, we believe that one people told phase 3 in AUD and potentially ALD patients as well will be the best approach, and we have some synergies between our different programs.

And of course, we'll have the expected discussions with the regulators, both in the U. S. and in Europe, as we move forward and try to narrow down the assumptions around what Phase III is going to look like.

Thank you. So, I'll start on that one, and then Christoph can take the second one. I think, you know, we've maintained, Michael, as you know, that we're active and open on the front of exploring how best to accelerate and fund the program globally. We continue to maintain the openness and activity on that. We do believe that with this data set in AUD, the potential of PEMB has increased, and so we take that into the discussions appropriately with strategics.

Right. With regard to the discontinuation rates, we are still looking in more details at those data. The discontinuation rate overall was fairly similar between placebo and the active arm. It was more related to GI AEs. In the placebo effect, it was to lack of efficacy, so this is pretty consistent with what is expected. But we have more of the details of every single aspect of this in the weeks to come We still looking into our final programming etc to get those data Great Thanks so much Thank you Thank you.

Thanks, Michael.

Sure. So, on the sub-analysis, yes, we'll be continuing to dig into our data and look at this. We'll present this data at future medical conferences, and so we will have additional information around this. On the phase three, I shared a little bit in the prepared remarks some of our thoughts right now. I think importantly, again, we are gaining more and more information around the benefits on the lever side, so we want to really establish this in our phase three, given the overlap between our AUD, ALD population. So that's going to be a real factor here that we're going to look into, and also broaden the population a little bit on the BMI side, given that our phase two had that limitation.

So we're looking at a study that's probably given the current guidance having a 24-week primary efficacy endpoint, but we want to look also probably further to get all the way to 52 weeks with regard to additional analysis. So we'll give more details as we are building this and as we're getting feedback from the regulators. Yeah, and on the question of timing, look, we're not yet guiding on timing. We do, we're really encouraged by the data. We're going to work quickly and thoroughly on compiling the full data set to answer some of the questions, even that have come across this morning. We'll look to package that in a submission to the agencies for an end of phase two, and we'll update you accordingly, as you would expect, around specific timing.

But importantly, you know, the AUD data really creates the opportunity for a liver franchise here. I think you heard this morning, and you'll continue to hear from us, about where we see the differentiation not only in MASH, but in AUD, and really the dual mechanism and the opportunity to impact drinking and impact the liver kind of helps us focus on a group of higher-risk patients where we think the benefit of PEMB can be unique and different from the other drugs. that are potentially available or the ones you know of in development now.

Thanks, Peter. Thank you.

Okay, great. Yes, on the placebo, we've built some aspects with regard to, for example, the AMASH to decrease variability, to decrease the training of pathologists, et cetera. And we're reading at 52 weeks. So we think that for the MASH study, that analysis for the accelerated approval will give us what we are expecting with regard to the anti-fibrotic effects that we're seeing. The GLP-1 use is accepted in our study, the anti-diabetic doses, and so we will include also diabetic patients in that particular study as long as they are on GLP-1 or other therapies that are limited. to their anti-diabetic doses. And then I think you had a question on the, sorry, I'm blinking.

ALD expectations on the ALD data. Oh, it would be good on the ALD. Well, we are looking forward to see, and we believe that exactly by now being able to read both at 48-week and 24-weeks, that we will be able to clearly characterize the liver benefit effect of pemvidutide through this longer treatment all the way to one year duration, and this will be very helpful in our discussion with regulators. So, a study that would deliver this would be obviously a very positive study for us. And remember, in that study, we're also capturing all the expected impact of reduced drinking, which I think when we look at the population in that ALD study, we know at baseline, you know, heavy drinking ongoing.

So again, just reinforcing that overlap that exists between AUD and ALD.

Thanks, Ellie. Thank you.

So, we'll try to pick them off here, because you gave us a bunch. I can go back to the questions. First, I was writing quickly, but thanks. First on Performa, we have, as we've said before, we are doing work as part of the overall program, which will allow us to better characterize some of the impact on body composition in the MASH population. And again, we think doing that as part of the Phase III might give us some opportunity on the labeling side if everything goes in the direction. Maybe, Linda, you can comment on some of the concomitancy. I think the question around the overweight and obesity. You did hear, Kripa, Christoph correctly. We do anticipate including patients in a potential Phase III on AUD that were below the 25.

BMI, that will be part of the construction of the trial and the dialogue.

Linda, maybe you want to talk about the concomitancy. Yeah, I think depending on the source, you see upwards to, you know, practically two-thirds of patients having overweight, not necessarily obesity, but a combination of those. So a safe assumption is at least half because we know what the rates are in the general population, and we see that drinking can contribute to excess weight. There's also, obviously, in some of the more severe populations, particularly in ALD, they actually have some lean drinking. They have caloric restriction issues because they're drinking and have other issues. But the benefits that we talked to some preliminary market access payer work, the losing of weight can be helpful to them as a sign.

But really, the reductions in drinking and the impact on the liver and the potential to address that, you know, here you have something that not only is, in PEMV, something that is not only addressing the cause of the issue, but the damage to the liver potentially. And that's what we're really interested in exploring on that back end, hence the discussion on the ALD, you know, timelines and where we're looking at a 48-week readout. All of these things that differentiate us make us highly relevant to the population that needs the most help. And that's really where we're focusing. And that idea, because there's never been something that really is doing both in the AUD population, that is really resonating with, I would say, patients, prescribers, and payers.

And I think that's why we view the AUD data set we just reported out as so robust and de-risking, because we get clarity across all of the endpoints, including the two approvable endpoints. We have a clear impact at 24 weeks on drinking across those, on weight in a population where, again, the two-thirds of them are overweight or obese, and the signals on the liver, which we'll explore more deeply in Phase III. So we think we're in a good position to understand what PENV can really bring in uniquely in this high-risk segment.

Thanks a lot. Thanks, Chris. Thank you.

In terms of, I think, following up on our own study results, I think we haven't had a chance even to do that. I'll defer to Christoph to look at that because I know we haven't looked at all the data sets yet. Exactly, Linda, thanks. The study was not designed to look at a formal assessment of rebound.

We have a follow-up period that we're going to get some information. We'll look into that. I think, again, to the point Linda made, having a drug that people can take chronically, take on the long term, I think even the guidance from the FDA relates to the fact that this is a chronic disease. This is not just a temporary disease, and the treatment needs to be evaluated chronically, but as well with the safety and tolerability that we have seen with pemvigetide. So this is something we'll be able to look a little further in our phase three and over longer duration. With regard to power assumptions for ALD, we will power the study north of 90%. The single trial needs to be powered like this.

We will have, like we discussed, the typical AUD with already some damage in the liver, whether they know it or not, similar to what we've seen in our Phase 2. And we'll have also a LD population, and we'll make sure that this is powered adequately. We'll have those discussions with the regulators, and we'll be able to design the study so that it supports the indication for these populations.

When would you kind of decide to allocate additional funds, and what would you need to see to do that? Okay, maybe Greg, you can jump in. I'm sorry you cut out a little bit on our end, but I believe the question is around how we're thinking about financing on the AUD side. Yeah, thanks. Greg here, and I appreciate the question.

So, yeah, this strength of this Phase II data in AUD presents us with an opportunity for Phase III. So, the next steps, as was teased out earlier in the call, will be feedback from FDA in the Phase II meeting, And that will allow us then to step back and sketch out and design the blueprint for the size and scope of that phase three costing that out Clearly anticipate that will be quite a bit less costly than a MASH Phase 3 would be and with that design would then be in a position to finance that in the new year and anticipate that the preference would continue to be for non funding Those options could include a combination of strategic money and or debt or royalty, et cetera.

So, again, highly confident that that's a program that's fundable. And, again, just to remind, we reported June 30 cash, $519 million. That's runway through the MASH Phase 3 readout top line in 2029. So, again, takeaway message there is a strong balance sheet today. Great opportunities for the second great indication and a second Phase 3 to build out the franchise.

Sure. Yeah. So, to the first point on the titration and the learnings from the AUD trial for the 2.4 milligram, yes, we have learned that in that particular population, the monthly titration is a simple step. That is a couple of steps, and it's favorable with regard to, in particular, nausea and vomiting. So I think the direction is very supportive to move for the 2.4, and we'll have one step for going to the 1.8 milligram and the two steps to go to the 2.4. So very simple, easy titration. So those are consistent learnings from the AUD trials applying into the PERFORMA phase 3. With regard to GLP-1 and, as mentioned, or resmiteron, as mentioned before, the GLP-1 will be tolerated only at antidiabetic levels.

The resmiterone will not be included in the trial in order to not jeopardize our primary endpoint with regard to the 52-weeks readout on the biopsy. We will collect history of patients that do have failure on GLP-1, resmiterone, et cetera, who have not improved, not tolerated this. So we'll be able to kind of characterize the population and understand which were, I would call, treatment failures for those particular therapies.

And with regard to the AMASH Assist, the way it works is basically the slides that are taken from the biopsy are stained, and then they're digitalized. Now, the program on the AMASH Assist will point to the features based on that AI system, propose the score, and the pathologist will be able to look at those and agree or disagree with the scoring or with the evaluation on certain aspects. And given it's a consensus reading, at the end, as per the FDA requirements, the pathologists are responsible for the scoring.

But PATH-AI claims that it improves viability and improves consistency between pathologists. We've already put in place additional aspects to make sure that we have that consistency between training, harmonization, and using charters and alignment on how to read the slides. So all these features, we hope, will decrease any variability, improve consistency in the reading, and help not only in the enrollment phase to decrease the screen-filled patients, but also in the efficacy reading to have less variability around the reading. So put together, this is the first, again, PERFORMA. It's the first phase three trial with DMH Assist, and there's quite a lot of, actually, excitement around this from the sites, as we've heard. And then just on the reclaim, if I can add a few additional follow-ups, just in terms of durability of the AUD effect, do you have any sense of whether the treatment effect was early and durable, and will you eventually have this data?

And then on the Phase III endpoint selection, or would you eventually share that data? And then on the Phase III endpoint selection, I think you noted that two-level World Health Organization risk drinking level reduction, zero heavy drinking days, or the FDA-recognized registrational endpoints. Which one, or is there a preferred primary endpoint, and would heavy drinking days be supportive or primary? And then just lastly, on the AUD phase 3 population, you mentioned broadening the phase 3 AUD population to include BMI below 25 and potentially lower dose options. What's the rationale for those changes, and would the phase 3 trial include both AUD-only and AUD-ALD overlap patients? Thank you. So, on the durability of the AUD, we have some elements in our data that show that there was no plateau of the effect after 24 weeks.

So, clearly, we're going to continue to explore this in the phase three, which will go all the way for 52 weeks and is needed anyway for the safety database. So we'll have that information, but it is expected, for example, even on the weight loss and other aspects, on the past, on the number of abstinent days, for example, to continue improving these patients and the chronic exposure to penviditide is really important to assess.

On the phase three endpoint, we are lucky enough in our reclaim study to have a validation of both. Obviously, we're powering, we're going to select one and align with the regulators. Keep in mind that very often the regulators will look at both. So we have also the options to power fully for both, more likely into one primary endpoint, one key secondary endpoint, something in that nature in the way to look at it. But the zero heavy drinking days or the WHO-RDL will be the endpoint that we'll be clearly looking at. And the population with regard to lower dosing or extending to BMI below 25, as Linda said, originally there's two-thirds of the population that are overweight and have AUD.

There's an overlap between these two aspects. But there is also another third that is not overweight. So we believe we can address that population by doing this. These patients may require less exposure or the current 2.4 could be very efficacious, but in some patients a lower dose could be sufficient. So we need to evaluate this during our phase three. We believe a couple of doses will be something, an approach that will allow us to better characterize how to distinguish in this different population and having a broad picture with all the details that we need when we discuss with the regulators at filing.

So I was just curious how we should be thinking about, at least in drinking reduction, The differences that may occur with GIP versus a glucagon component added on. Thanks.

Yep, I'll start on the LSM, on the liver stiffness criteria, inclusion criteria. These are not related at all to the change in reading of primary endpoint at week 48 with the hierarchical procedure. The Hayashi-Cook procedures I mentioned is directly focused on strengthening our understanding of PEMVD-type's beneficial effect on the liver and supporting further discussions with the regulator. The criteria and the amendment that we've had was actually related to a study that we've made as a hepatic impairment study that allowed us to now expand to those patients and broaden that criteria. So as you can imagine, every time we do developments, we have a number of learnings, and we were able to implement the learnings from the hepatic impairment study that didn't show any risk in the population, and we were able to expand and broaden the criteria.

With regard to the AUD and the brain appetite, we're looking forward to see this data. I think what, again, brain appetite is a GLP-1 GIP. It doesn't have the liver effect, so it's probably similar to what you see with GLP-1 semaglutide. I think to that extent may be a little different because of the GIP component, but the direct liver impact we believe is important. We've heard from our KOL that it's really for them what they call a game-changing approach if you're able to treat the patients that have a UD and may not even know they already have liver steatosis, inflammations, or even having fibrosis. So PEM-Vigetide fits really well in that population, and that's what we want to build on.

Yeah, I think they're also looking at earlier patients, the mild segment.

Thanks for the question. Operator, are there any more?

Okay, thanks for squeezing me in. So, maybe one more on the RESTORE study and about liver stiffness. So, the upper end of that range, 10 to 25, the upper range is suggestive of cirrhotic features for these patients. I'm curious, if the data is supportive in that segment, and how would you use that data, Potential read-throughs to other indications, basically generating more data for PEMB in the cirrhotic patient population. Thank you.

Thank you for the question. So on the liver stiffness, as you know, the range, there is a little bit of variability there. So you're correct. We may include a very small or minor population of patients that are a little more advanced, closer to the cirrhotic stage. We know the drug is safe because we've done the hepatic impairment as mentioned before. We know that in this population we're going to be okay. I think we will have the opportunity to include those patients in our phase three and look at the AUD. But in the meantime, it's important, again, one piece that in this population is happening is over a certain period of time, from a regulatory perspective, it will be important to show that even if patients advance, if they're worsening, we can address this population.

So that will be something that the regulator will be looking at, and we'll be happy to provide that information based on those approach or inclusion criteria.

And as of the time we have our Q&A session, I will now turn the call back over to Mr. Jerry Durso for any closing comments.

Thanks, operator, and thanks, everybody, for joining us today. From our standpoint, we feel very positive about the progress we've made, significant progress to date. I think we're clear on the work to do ahead of us and definitely committed to continuing to advance what we believe to be a promising, meaningful, differentiated therapy in PEMB for serious liver conditions.

Moving forward, it's going to be an exciting time. I'll continue to forward to update you on the progress moving forward, and enjoy the rest of the day, and have a great last of your summer. Take care.