Good morning, ladies and gentlemen, and welcome to the Altamune Third Quarter 2026 Financial Results Conference Call. At this time, all participants are on 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 will need to press Star 1-1 on your telephone. You will then hear an automated message advising your hand is raised. To withdraw your question, please press Star 1-1 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. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations.

Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Investor Relations. Luis Sanay, Vice President of Invest Chief Commercial Officer, and Greg Weaver, Chief Financial Officer. Following management's prepared remarks, we'll open the line for questions. Our third quarter 2026 earnings release was issued this morning and can be found on 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 purposes of safe hardware 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 review of the risk factors that could affect the company's future results and operations, we refer you to our SEC filings. 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, November 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, and thank you for joining us today. We enter the final months of the year with strong confidence in Pembedutide and the strategy we're laser focused on executing. Over the course of this year, we significantly advanced our programs across the board in MASH, AUD, and ALD, further strengthening our belief that Pembedutide's differentiated clinical profile can support a broad liver franchise with multiple indications in serious liver diseases. We're now focused on carrying that momentum forward through disciplined execution. We continue to see a growing understanding and scientific support for the potential therapeutic role of Pembe and its ability to provide meaningful benefit to people affected by serious liver diseases. Our conviction in Pembedutide is stronger than ever, coming out of ASLD's The Liver Meeting, where the data presented further validates the potential of Pembedutide and our overall development strategy. MASH data presented at several podium talks at the meeting reinforced the potential of the dual glucagon GLP-1 mechanism in MASH and underscored the differentiation of Pembidutide. We presented new NIT data from our 48-week impact study that highlighted the strong anti-fibrotic activity of Pembi that continues to compare favorably to data across other trials. We believe Pembidutide's balanced one-to-one glucagon to GLP-1 ratio when coupled with our proprietary U-port domain matters and results in a molecule that balances metabolic and liver-directed activity with generally favorable tolerability. Despite new products entering the MASH field and others in various stages of development, there remains a significant unmet need for patients, and we believe that Pembidutide could represent a well-differentiated MASH therapy. We see a major commercial opportunity across the indications we're targeting as we build our liver franchise. In addition to the unmet need in MASH, we view AUD and ALD as part of a patient continuum as AUD patients often progress to liver impairment. In fact, data referenced at the liver meeting estimates that 55% to 94% of ALD patients also meet the criteria for AUD. The reclaimed data highlighted that Pembi has the potential to help address both alcohol consumption and the liver damage that can result from it. Finally, one of the recurring themes at the liver meeting was about the overlap of mash and alcohol use. We believe Pembidutide's differentiated profile positions it well across a multitude of patients. Moving now on to execution, which is a critical focus for Altimmune. First, our global PERFORMA Phase III trial is ramping up, and we're very encouraged by the progress to date. Clinical trial sites continue to come online according to our plan, and we're actively enrolling patients. The engagement we see from the PERFORMA investigators and the broader MASH community is strong. This excitement was quite evident at the liver meeting, and Christophe will touch on the positive feedback and engagement from KOLs on PERFORMA and pembidutide overall. We're also pleased that the IMPACT Phase 2b 48-week efficacy and safety data was published in the Lancet this week. In AUD, the positive reclaimed Phase 2 data were highlighted in a late-breaking oral presentation. We believe this is the most robust AUD data presented to date. The strong results we saw significantly de-risked this program. Importantly, our end of Phase 2 meeting with the FDA is scheduled for next month. representing a key step towards advancing Pembidutide in AUD. We look forward to engaging with the agency and continuing our progress of Pembi in this indication. As part of our continued evolution as a late-stage biotech company, we're also thrilled to recently have added Peter Greenleaf and Alex Harworth to our board of directors. Peter and Alex are accomplished industry leaders that bring a breadth of experience across drug development, commercialization, and corporate development. Their experience and strategic perspectives will be valuable to Altimmune as we continue to advance. So in summary, we're committed to executing our strategy with speed and efficiency reflected in the significant progress we've made across the Pembidutide franchise this year. We're laser focused on delivering on our goals of bringing a differentiated therapy in Pembi to patients and creating value for our shareholders. Our conviction in Pembidutide is stronger than ever and we look forward to sharing our continued progress. I'll now turn the call over to Christophe for a clinical update.

Thank you, Gerry. I'd like to start by just stating that I am very pleased with the significant progress we are making as we advance our clinical programs across MASH, AUD and ALD. Beginning with MASH, the global PERFORMA phase 3 trial is underway and progressing as planned. We are screening and dosing patients, and clinical site activation continues across the program as we build towards broader global enrollment. We have the majority of planned US sites now active and recruiting patients, and we expect to activate the ex-US sites over the coming months. We will continue to work closely with our CRO partner to support efficient trial execution and enrollment. We remain encouraged by the enthusiasm and engagements we are seeing from investigators and clinical sites for PERFORMA based on the product profile and the efficient trial design. As a reminder, we anticipated the PERFORMA 52-week data readout in 2029. Altimmune had a strong presence at the recent liver meeting in Denver, where we had the opportunity to highlight the potential of pemvigutide in serious liver diseases. We saw a growing interest and excitement for Pembidutide from the scientific community and the role it may play in treating the liver damage that characterizes the overlapping metabolic and alcohol-associated diseases of MASH, AUD, and ALD. During the liver meeting, we presented two analysis from the IMPACT Phase IIb trial, including compelling data showing concurrent improvement across multiple non-invasive measures of liver fat, inflammation, and fibrosis compared to patients receiving placebo. The new data further illustrate the strong and consistent anti-fibrotic activity and a generally favorable tolerability profile in the absence of those titrations. Our data, along with emerging data from other Glucagon GLT1 programs, reinforced the importance of glucagon in treating NASH. The totality of our learning during the liver meeting further support our Phase III study design. We also hosted the well-attended disease state product theater where Dr. Mazen Noureddin, Dr. Rohit Lumba, and Dr. Jessica Millinger discussed the advanced liver disease continuum. They noted the prognostic importance of fibrosis on outcomes and how various factors, including alcohol consumption or metabolic dysfunction, impact the progression of serious liver disease. The product theater further underscored the overlap between excessive alcohol consumption and metabolic causes of serious liver disease and the high unmet needs for a therapy that can chronically address both causes and their liver damage consequences. We believe that the data presented on pemvidutite during the liver meeting strongly support the potential of pemvidutite to address that unmet need with a generally well-tolerated approach that is particularly suitable for chronic diseases such as MASH, AUD, and ALD. In addition, Dr. Henry Krentzler, the lead investigator for our RECLAIM Phase II trial, presented the very robust and positive study results in the late breaking oral presentation at the liver meeting. To our knowledge, the reclaimed data is the strongest data in AUD to date. The trial showed statistically significant improvements with pemvidetide across the primary endpoint of heavy drinking days, as well as key secondary measures, including WHO risk drinking level and achievements of zero heavy drinking days both of which are FDA registrational endpoints. Importantly, we also demonstrated that PEST, an objective serum-based measure of alcohol consumption, corroborated the self-reported reduction in alcohol intake in PEMV-treated patients. Pemvibetide also increased abstinence in patients with AUD. And while Reclaim was focused on drinking behaviors, The trial demonstrated in an exploratory analysis that PEMVI decreased the proportion of patients with elevated risk for developing advanced liver fibrosis as measured by FIT4. These data point towards potential liver improvement in this patient population. Given PEMVI's direct glucagonal effect on the liver, the observed data is very encouraging, and we expect to further evaluate the potential liver benefits in the registrational Phase III study in AUD with inclusion of a subpopulation of AUD patients with advanced liver impairment. Importantly, reclaim was conducted in patients with moderate to severe AUD The population we believe may have the greatest need for more effective and safe treatment options and who are at risk of alcohol-related liver disease. The overall strong positive results, including the generally favorable safety profile observed in the trial, positions us well to engaging with regulatory agencies to align on the next steps for the program. To that end, Our end of Phase II meeting with the FDA is scheduled for December, where we expect to discuss the study design and regulatory paths for a Phase III AUD program. Typically, meeting minutes follow within 30 days. In our registrational program, we will focus on moderate to severe patients, including a subpopulation of patients with advanced liver impairments such as ALD. This approach not only aligns with FDA guidance, where patients with hepatic impairment should be enrolled in AUD registration programs but also may address a current unmet need as therapies for AUD are not specifically indicated in the hepatically impaired subpopulation. In terms of trial design, we expect the primary endpoint to be the WHO RDL with no heavy drinking days as a key secondary endpoint both of which reached statistical significance in the Reclaim Phase 2 trial. We expect other secondary exploratory endpoints to include additional self-reported drinking endpoints, PET, body weight, and liver endpoints including liver fat content, liver stiffness, measurements, and health. We would look to include both 1.8 mg and 2.4 mg doses with a simple one to two step titration. The proposed trial would have a primary efficacy rate of 26 weeks and continue up to one year for additional safety and efficacy data. The final program design will of course be subject to our dialogue with regulators. Moving now to ALD. The RESTORE trial enrolled 121 patients with ALD and a history of chronic and heavy drinking at baseline. The 48-week trial is designed to demonstrate the liver benefits over a period of 48 weeks and includes additional evaluations at 24 weeks. Given the significant overlap between the ALD and AUD patient population, demonstrating liver benefits in the RESTORE trial could further support a unique role for Pembrolizutide in decreasing both Chronic alcohol consumption and the liver damage it causes. We also believe that the ALD restore trial will further strengthen our filing package and discussion with regulators when seeking an AUD indication. We expect the top line data for restore in the second half of 2027. In summary, The significant progress achieved during 2026 across all our clinical program positions ultimately well heading into 2027. I echo Jerry's sentiment that our conviction in PEMVG-Tide is stronger than ever. We look forward to executing against the key clinical and regulatory milestones ahead, moving us closer to bringing PEMVG-Tide to patients. And with that, I will turn the call over to Linda.

Thanks, Christophe. Good morning, everyone, and thank you for joining us today. Following the conclusion of the 2026 LIVR meeting, I'd like to reflect on why we believe pembidutide remains well-positioned to the MASH and AUD markets as a differentiated potential future therapy. First, new data presented at the LIVR meeting clearly supports the validity of the dual glucagon GLP-1 mechanism of action in the treatment of MASH. That said, The molecule matters as we see different profiles emerging within the glucagon GLP-1 class. Pembidutide's balanced one-to-one glucagon GLP-1 ratio has already shown significant early improvements in MASH resolution in our Phase IIb impact study and strong data on fibrosis improvements based on 24- and 48-week NIT analyses. In addition to the strong profile of the 1.8 milligram dose we saw in Phase II, The 2.4 mg dose now being studied in our 52-week Performa Phase III MASH trial may offer additional upside in terms of weight loss and efficacy. Our generally favorable tolerability profile, seen now across multiple Pembidutide trials and lack of significant drug-drug interactions, are important product features that should help patients remain on Pembi therapy as well as continue medications they may be taking for comorbid conditions. These two specific features, in addition to our dual mechanism of action, suggest that PEMBI may play an important future role as a potential combination therapy for MASH patients who do not reach therapeutic goals or cannot tolerate their current therapy. Second, despite the availability of approved therapies in MASH, one thing remains clear. A significant unmet need remains. While encouraged by the growth seen to date in the MASH market, Diagnosis and treatment rates remain low, but we expect this dynamic to evolve. We also believe that evaluating MASH treatment options for patients will move beyond focusing primarily on diabetes and obesity comorbidities to also address additional needs. For example, patients diagnosed with MASH who also drink, those who are at risk for sarcopenia and need to preserve lean muscle mass, and postmenopausal women facing decreases in bone mineral density may be important patient segments for Pembidutide in the future. Third, with Pembi, we have a significant opportunity to potentially redefine what to expect from drug therapy and alcohol use disorder based on our specific profile of reducing alcohol consumption and perhaps demonstrating direct improvements on the liver given our glucagon activity. This could subsequently help activate one of the largest underserved markets in the U.S. As a reminder, approximately 27 million Americans meet the criteria for AUD, and 12 million of these patients are believed to have moderate to severe AUD. This more advanced segment has the highest risk of progressing to severe liver damage and is where pembidutide's dual mechanism of action may be most compelling. Christophe highlighted our AUD data from Reclaim earlier in the call. but I would like to also note that our early mover status in AUD is a competitive advantage for PEMBIE as we are generating important new data in this field. PEMBIE's balanced 1 to 1 glucagon GLP-1 ratio providing both metabolic and direct liver benefits, generally favorable tolerability profile, lack of significant drug-drug interactions, and simple patient-friendly dosing drive significant differentiation versus other therapies in development across MASH, AUD, and ALD. We are excited about PEMBIE's potential, confident in our existing data, and look forward to sharing additional insights on future calls. Greg, you'll now share our financials for the third quarter.

Thank you, Linda, and good morning. Beginning with our financial results for the quarter, R&D expense in Q3 2026 totaled $27 million, compared to $15 million for the same period prior year. The year-over-year increase in R&D spend is primarily driven by the initiation of the Phase III trial in MASH and the ongoing Phase II trial in ALD. Q3 2026 R&D spend included $20.3 million of direct costs related to Pemba-Dutai development, of which $10.7 million was for MASH, $4.3 million for the Phase II ALD and AUD trials, and 5.4 million in CMC-related expenses. Q3 2026 R&D also included 1.1 million in non-cash stock compensation. G&A expenses in Q3 2026 were 8.7 million compared to 5.9 million for the same period prior year as we added additional talent to the company. The increase in G&A was driven by the increase in compensation expenses and professional fees. Q3 2026 GNA included $1.8 million in noncash.com. The net loss for the third quarter of 2026 was $31.6 million or $0.15 a share compared to a net loss of $19 million or $0.21 a share in the third quarter of 2025. Moving to the balance sheet, we ended the quarter with $480 million in cash, cash equivalents and investments. Our year-to-date cash burn tracks in line with plan and is expected to provide operating runway through the performance phase three match 52-week data readout expected in 2029. In addition, following upcoming regulatory feedback in AUD, we expect to have a greater clarity on the scope and investment required for a phase three program in AUD. Our preference remains to pursue non-dilutive funding for the program, including potential royalty debt or strategic partnership opportunities. Thank you very much. That concludes prepared remarks. I now turn the call back to the operator for the Q&A session. Operator? Thank you, sir.

As a reminder, to ask a question, you need to press stall 1-1 on your telephone. To withdraw your question, please press stall 1-1 again. Please stand by while we compile the Q&A roster. And I assure our first question comes from the line of Thomas Smith from LearRink Partners. Please go ahead.

Hey guys, good morning. Congrats on all the progress and thanks for taking our questions. On PERFORMA, I know you've talked about enrollment timelines in sort of the 18 to 24 month ballpark. Just wondering if you could provide an update on how you're tracking here in the early days relative to that timeline and what aspects of the trial design you think will drive preferential enrollment over some of the competing phase two or phase three programs?

Okay, thanks for the question, Tom. Good to speak to you. I'll start and then Christophe can can add in. So as a reminder, our current guidance calls for a readout of PERFORMA in 2029. And as you mentioned, we've been discussing this 18 to 24 month range in terms of the time we think enrollment will take. We are really encouraged on what we're seeing in the early ramp up as we really focus on site activation. At this point in the study, it is the lead indicator. while we also begin to enroll end-dose patients. Christophe mentioned in the prepared remarks that the initial focus, as is typical, has been on the U.S. sites. We already have over 70 U.S. sites activated and we now anticipate in the next period that we'll also commence on the ex-U.S. sites, which take a little bit of time for some of the work that has to happen country by country. So we'll look to communicate on-site activations periodically as we progress, and then we'll provide other appropriate updates as the study matures. The second part of your question, Thomas, was around some of the elements happening to make enrollment happen in a strong way, and I think we already have some good insight from the state's sites, maybe, Christophe, that you can talk about a little bit.

Yeah, absolutely. So we are early into the study, but we are very encouraged by what we're seeing, the enthusiasm from the sites, the study design, how it is set up, how we plan the interactions with sites, is making it very attractive for those PI to enroll their patients. So as Jerry said, activation of sites is With our more than 70 sites in the U.S. is happening, and we're really happy it's on plan, tracking on plan. And then in the next few weeks or months, we're going to start getting the ex-U.S. As you know, these are taking time a little more. But the enthusiasm that we've seen, whether in investigator meetings or at ASLD, was substantial and really encouraging.

That's great. Super helpful. And just a follow-up, if I could. I know at the liver meeting, Merck also presented some Phase IIb MASH data for their GLP-1 glucagon agonists that included some histology data at 52 weeks, also included a semaglutide active comparator arm. Just wondering if you could comment on that data set and what you saw in the profile there relative to PENV and any potential learnings or read-throughs from that study as it relates to Performa. Thanks so much.

Yeah, so I think, look, we were interested in the data, of course. We think that that data set further validates the mechanism, probably, and Christophe can talk a little deeper, probably gives us a good indicator that 12 months is a good time to read the biopsy, which is what we deployed in in Performa. And I also think that, again, the totality of the picture we've seen, we believe that PEMB compares favorably and offers some advantages to patients. That'll be a big part of what we continue to speak about and to focus on because the differentiation from the other options is going to be key.

Yep. No, and exactly. So this is What we observed with the FENO data, and again, it's two separate studies, not a head-to-head comparison, but the fact that they demonstrated with that open-label GLP-1 arm added value of the glucagon components from the GLP-1 is for us really important. It's now the third or fourth dual agonist also that validates the mechanism, that class, and we like what we see with pemphigetide, that tolerability, the strong efficacy at our 1.8 milligram dose. We will test also the 2.4 milligram dose in our phase three perform a trial. So this actually comfort us in our assumptions for the phase three trials and the probability of success for it.

Got it. That's helpful. Thank you, guys. Thanks, Tom. Thank you.

Thank you. And I'm sure our next question comes from the line of Michael DeFiore from Evercore. Please go ahead.

Hi, guys. Thanks so much for taking my question. Two for me. One on proforma. Not sure if you disclosed in the past, but what placebo rate and treatment effect did you assume for proforma's fibrosis endpoint? And how does that compare with impact? And separately for AUD, Now that the Phase II reclaim data had been out for a while, I was wondering if the drug-related discontinuations cluster around the step up to 2.4 milligrams, and does that change how you're thinking about titration in Performa? Thank you.

All right. So first on the Performa, the placebo rate, we've taken, as we've shared, we haven't disclosed the whole statistical details, but as we've shared, We have taken a very conservative approach that is based on what other trials have achieved so far for approved drugs. Now, having said this, as you remember, and as the recent article manuscript that has been published on our 48 weeks data, our needs were much stronger than this, but given the size of the study and the way to to develop such a study, we have to take those assumptions into consideration. Regarding the placebo, again, a couple of things. We have probably the most robust approach with regard to the bio series. We've reconfirmed this through ASLD. The part that is important is this AMASH assist as well, the selection of the pathologies. The AMASH assist is something that clearly increase precision, accuracy, and decrease variability on the IOPC reads. So these are important factors, and that will be playing in our favor if this pan out to be really the case here. On the AUD side, could you repeat the questions, I think?

Sure. Full Phase II reclaimed data are out. Did the drug-related discontinuations cluster around the step-up to 2.4 milligrams? And if so, does that change how you're thinking about titration in the Phase III PERFORMA MASH trial?

Thank you. No, so that doesn't change anything on the Phase III PERFORMA MASH trial. Actually, it confers us. These are two different populations, so we have to be very careful. a couple of learnings here. One, the profile of those AE is not unexpected and there's nothing new there. The second is in different population you may see some variability in those AE profile but clearly in our AUD the titration for by monthly of one step or two step because in our phase three we will go also with the 1.8 milligram dose that was extremely well tolerated in the phase two. MASH trials. So putting this together, we're comfortable moving forward and confidence that we can manage and keep the very good tolerability profile that we've seen with Pembidutides throughout different populations. Great.

Thanks so much.

Thank you. Thanks, Michael.

Thank you. Can I share our next question? It comes from the line of Ellie Murrow from Barclays. Please go ahead.

Good morning, Ellie. Hi, this is John.

This is Joseph for LE. Thanks for taking our question. Congrats on the progress. For AUD, could you remind us of the percentage of AUD patients who have obesity, diabetes, and MASH, and if there's any real-world evidence from off-label CLT1 use in AUD?

So the percentage of patients with AUD in MASH is actually... looked at under the umbrella of the MET ALD patients. We know that there is more than 10% of this population. Keep in mind that this is not always screened appropriately, that the test evaluation test is not always done. So it's probably very much underestimated. And actually at the SLD, again, at the liver forum, there was a clear overlap between the patients that do have MASH and the patients that do have alcohol. And these are very much The other things that I wanted to mention is what we know is that on the ALD side, they're close to 55% to 94%, so almost all of them that do have AUD. So there is clearly two aspects to consider. There is the liver damage in itself, which is at the center of these two different pathologies. and there's the different causes and these seem to have more and more overlap as we learn more about these different patients' populations.

I think the role of obesity also is you clearly see that as a comorbidity in MASH but you also have calories from drinking, etc. So these patients may also be obese and drinking and have MASH and in ALD sometimes this dynamic changes because you can be, you know, have the Lean Drinking, they're drinking, they're not consuming calories, so there is a spectrum with the weight across both MASH, AUD, and ALD, different concerns, so clearly the lean muscle mass sparing elements potentially of our drug will be important in all the populations.

And one quick follow-up, if I can. When can we expect an update on AUD from your learnings from the end of Phase II meeting with FDA?

So, as we announced, we're going to have that meeting in December. You typically anticipate the minutes coming within 30 days after that, and we would communicate appropriately at that point. As you would expect, we also anticipate dialogue, as Christophe mentioned, with EMA happening in the first quarter.

Thank you. And our next question in the queue comes from the line of Kripa Devarakonda from Truist. Please go ahead.

Hi, this is Alex for Kripa. A question from us. Can you provide an update on how you're thinking about potential partnering or the lack thereof in order to optimize the development of PENDI across all three indications? And if you could provide more detail on how, when, or if you would pursue a partnership and what would ultimately be looking for in a partner if they did choose to go that route?

So as you can imagine, as our program matures, we're active on this front and fully open to approaches that help move PEMBI forward and create value. As Greg said, in the context of the non-dilutive options that we would prefer to fund AUD, that's one of them. So I can't go into any more detail than that, but that's how we think about it strategically. while we ensure that we're driving execution on our program as strongly as possible.

All right, thanks a lot. Progressive on the progress. Thank you.

Thank you. And I'm sure our next question comes from the line of Catherine Okokone from Citizen. Please go ahead.

Hi, this is Catherine on for John Walden. I have a quick question on developmental timelines. So how are you thinking about prioritizing? The meetings clear up a lot of the phase three design AUD, but as far as prioritizing the start of the phase three, what variables are going to determine that? Just any more commentary on how you think about developmental timing?

Thank you.

Yeah, I think as we have been indicating, The next step in this process is that feedback that we'll solicit and discuss with the agency in December. That will allow us to take that important input around sizing and scoping the trial. We will be getting feedback from Europe alongside of that. And of course, as we said, then the opportunity of ensuring that we're building towards the right kind of value-creating funding will be happening. So we're not at a point where we're going to guide specifically on timing, but we think about this in a stepwise approach and getting really prepared for that next important step, which is that discussion with FDA next month.

Perfect. Thank you.

Thank you. And I'm sure our next question comes from the line of Roger Song from Jefferies. Please go ahead.

Hey, good morning. Congrats on the progress and thanks for taking our questions. This is Peter Chen calling in for Roger. Just a quick one for AUD from us. Are you still thinking of including lean patients in the AUD phase three? And if so, have you guys observed a relationship between weight loss and heavy drinking day reduction and reclaim? And did patients with limited weight loss still show an alcohol benefit?

Yeah, so all our data, the totality of our data allows us, and we confirmed this with our KOLs, that if in our phase two we had limited the BMI of the patients to patients above 25, now we will explore this in the phase three. So we will have a cohort of patients that are below 25 or normal into our cohorts, and we'll be looking at this. With regard to our data, we're still looking at all these different aspects, but it's clearly there's a good response throughout the different BMI, and that's what allows us to include these patients below 25 or makes us comfortable and confident we can include them into the Phase III program.

Great. Really appreciate the additional color. Thanks, guys.

Thank you.

Appreciate it.

Thank you. And our next question comes from the line of William Wood from B. Reilly Securities. Please go ahead.

Thanks so much for taking our questions and congrats on the continued progress here. Just to sort of double-click on performer execution, could you comment on how many patients have actually been randomized and In terms of sort of the mix between U.S. and ex-U.S., I believe you said that total sites activation will be around 300. So should we expect, you know, is that 70 sort of maxing out in terms of the U.S. and then the rest should be ex-U.S.? And then I have a follow-up.

Yeah, so as I said earlier, we're focused on site activation in this phase while we – enroll and start to dose patients. We're not yet at a point where we're going to comment on specific patient numbers. We have talked about that one-third, roughly one-third of the ultimate study sites will be in the U.S., so with 70 in, there's some more to happen in the U.S., and again, that progresses really on a weekly basis in terms of adding those sites, and then the

We are, as you understand, the phasing of those different sites will vary between countries. We have the vast majority of our sites already activated in the U.S. and this is really encouraging. and we are moving step-by-step into the activations of the other countries, Europe, Asia, etc. will come next. So that will bring all these patients, again, to just repeat myself, but we are very encouraging when we see the screening, the number of patients that are coming through the sites right now by the PI's engagement for the study, how they respond and how they were present and The receptions as well as the number of PIs and sites that have come to our booth at the LIVER meeting was also telling on that interest for the performance study. So this is working. We are in the early stages, but this is working exactly as planned, and we see a great engagement to work with us.

And of course, we understand why this is such an important question, and we're thinking about it carefully as we move ahead. And as I said, we'll provide the appropriate updates as the study matures. And I'm sure this will be a source of conversation on each quarterly call.

Got it. And then also for your AUD trial, obviously we'll need to wait post end of phase two and then the obviously appropriate timeline after that. But just in terms of what's your expectations on when we could actually expect the phase three to initiate? Is that something that could happen in the first half of next year? And then also based on your development already in MASH, should we expect a safety database Should we expect the FDA to require a safety database for AUD or ALD? And maybe are you already screening with PEST in your MASH trial? Thank you.

So maybe Christophe, take that question, then I'll come back on how to think about timing.

So we are definitely using PEST in our performer MASH trials. This will be an important evaluation to be done. As we mentioned, PEMVD ties has really the potential to treat both. The appetites and the metabolic causes of the serious liver disease as well as alcohol. So we're looking at this into our free-spree trial. And for the AUD, there's a number of steps that we're taking to move forward. And we will include patients with also liver impairments or ALD in that population that do have AUD. So this is where we are going right now and working with KOLs, with regulatory agencies to put all these aspects together.

So this is a stepwise approach. We talked at the initial top line readout that the next step was to compile the data, submit the data. get the meeting on the books with the FDA. That's the next step now in December. That will allow us, I think, to have a lot of the right inputs to finalize the design of the trial. And then, of course, the funding question is going to be getting the right funding mechanism that we think is in ultimately the best interest of moving the program ahead and in the best interest of the shareholders. So as I said earlier, we're not yet going to guide to timing around this. update as we go through these steps. And underneath that is that kind of dual objective of trying to move as quickly as we can while also ensuring that each step of the process is the right thing for the program long term. So stay tuned on that.

Just want to answer the question on the safety database. Obviously, with the number of patients, we already have exposed more than 750 patients. We expect to have those discussions with the regulators and trying to limit that safety database to its strict minimum on the specific AUD population and being able to use the other trials like the MASH PERFORMA trials or the previous Phase II trials for total exposure to the drug.

Very helpful. I appreciate it.

Thank you very much.

Thanks.

Thank you. And I show our next question comes from the line of Patrick Trucchio from HC Wainwright and Co. Please go ahead.

Thanks. Good morning. Just a couple of questions. The first is I was wondering how consistent was reclaimed drinking benefit across baseline BMI and weight loss subgroups, particularly among patients who maybe lost relatively little weight? and then I'm wondering which AUD patient population offers the clearest initial commercial opportunity for pembidutide based on the product profile that's emerging and how the drug would be positioned among others in the space, particularly in generics.

So the data in the RECLAIM study were remarkably consistent between the different groups with a response not only across different measures as we've seen with the PROs and the more objective PATH measures, but also across subpopulations, gender, BMI, etc. So the consistency is what makes those data extremely robust, and I will let Linda answer the questions on the commercial side.

Certainly. Thanks, Christophe. Thanks for the question. I think we've mentioned that of the 27 million people who meet the criteria in the U.S. for alcohol use disorder. There are roughly 12 million that suffer from or would meet the criteria for moderate to severe and that is where we believe the chronicity of use, the binge drinking potential, etc. that leads to liver damage, they are the most likely to progress or in fact have subclinical underlying Thank you, Patrick. Thank you.

And I share our next question comes from the line of Annabelle Samimi from Stiefel. Please go ahead.

Hi, this is Kyle. I'm from Annabelle. Thank you for taking our questions. Two from us. On the AUD primary, you guys selected who RDO and then the ZOHDD as secondary. Just curious why you chose one over the other and then how receptive that is from that DA. And then separately on AUD, Given that incretins are now 50% cash pay and, you know, semi-generic in the early 2030s, how do you see your ability to price effectively and do you envision cash pay and telehealth as a strong component of the commercial infrastructure? Thank you.

All right. So, just as a reminder, both of those key secondary endpoints in our Phase II study were highly statistically significant. and the No Heavy Drinking Days. We believe that the WHO, so we had the opportunity to choose any of them based on this. And we chose, for right now, we're going to propose the WHO RDL for a couple of reasons. One, the level of drinking and the risk of drinking is very relevant from an addictive aspect. We believe that no heavy drinking in days is a little less relevant from a clinical practice point of view. At least this is what we are hearing from our experts, academic experts or clinicians. So this is a very relevant measure. That risk is really important. It allows us also to look at the partial and full remission potentially for these patients. in the phase three and move in this direction. So this is an important one. And again, the results that we're seeing were very robust and very strong.

So I'll take the second part of that question. Now, recall that only about of all the AUD patients in meeting that criteria, only about 2.5% are receiving any kind of pharmacotherapy presently. Are data... As far as we are aware is the strongest data in reduction of drinking and impact on AUD of any company that's presented to date. And the uniqueness of again going directly to that liver issue and the tolerability of our product. This is something that patients may need to stay on for a while. We don't know. And the tolerability is going to play in. So all the features that we see coming from the inherent molecule matters in our whole presentation of 1 to 1, we believe will play into the value proposition for Pembe Dutide and AUD and we are in conversations, we've had some early work talking to payers and some ad boards and what would it take, how would that look, what would we need to show, what we need to demonstrate and I think we're well aware of how to approach that and the things that will be important but clinically speaking our data is very strong and that's the kind of dual action help that people will need potentially moving forward.

Thank you.

Thank you. And I show our last question in the queue comes from the line of Andy Shea from William Blair. Please go ahead.

Thanks for taking our question. You talked about material overlap between AUD, ALD, and MASH. So regarding the effect size that we can expect to see from Restore, reading out in the second half of next year, Is that 3 to 4 kilopascal demonstrated from the impact study a good metric to look at?

Thanks for the question. I can't guide on the number here for what's happening in the population that we have not yet studied directly. We were really happy with the data we've seen in our mash with the almost 4 kilopascal in the population. That distinction was extremely are strong, and as a reminder, this is only at our middle dose, the 1.8 milligram dose. So for the MASH trial, clearly this is very encouraging. For the ALD trial, again, if the effect is a number of consideration, you would have to assume that the effect is similar in both population, that the timing of this effect is similar as well, all those kind of things. But this is why we think that having that study will be really important when we look at the AUD indications because it will reinforce our filing package with a really good understanding around that ALD population. We already know that this is a population that is heavily drinking, so we'll have the AUD population that is more the regular population, if you wish, but we will also be able to really focus on that lever Impairments or ALD populations. So I think clearly we're looking at the FibroScan, the VCT, the change in kilopascal as you're rightly saying, but so far it sounds like the direct impact of glucagon on the liver in addition to the impact of GLP-1 on the drinking levels is really a big differentiation from the GLP-1 alone. especially in those severe and moderate patients.

All right, that's very helpful. Thank you.

Thank you. Thank you. That concludes our Q&A session. At this time, I'd like to turn the call back over to management for closing remarks.

Thanks a lot, operator, and thanks, everybody, for joining us today. As you heard on the call today, we remain confident in the opportunity ahead for PEMBI and the franchise that we're building around it. We have several important milestones ahead, so we remain focused on executing with speed, with efficiency, and advancing this differentiated therapy for patients with serious liver diseases and creating value for our shareholders. I'll end the call with one overarching sentiment that should be the key takeaway, which is that our conviction in pembidutide and its potential is stronger than ever as we look ahead. So thanks again for joining us, and we look forward to updating you on our continued progress. Have a great day.

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