Hello everyone, and welcome to the first annual H.C. Wainwright Virtual Liver Disease Conference. My name is Patrick Trucchio. I'm a Senior Health Care Analyst at HC Wainwright. This year, for the first time, we've combined our viral hepatitis and MASH conferences, expanding the scope to also include liver cancer. Today, with my colleagues at HC Wainwright, we are pleased to be hosting some of the most innovative biotechnology companies in the world, alongside leading key opinion leaders in areas of HBV, HDV treatments, as well as MASH treatments and hepatocellular carcinoma or liver cancer. It's my pleasure to introduce our next management team, Chief Executive Officer Vipin Garg, Chief Medical Officer Christophe Arbet-Engels, and Senior Strategic Advisor and former Chief Medical Officer Scott Harris from Altimmune, a clinical-stage biotechnology company advancing pemvidutide, a dual GLP-1/glucagon receptor agonist, as a potential best-in-class treatment for metabolic dysfunction-associated steatohepatitis or MASH. Pemvidutide has demonstrated robust weight loss, reduction in liver fat, and improvements in key biomarkers of metabolic health, positioning it as a differentiated therapy in the evolving MASH treatment landscape. Maybe to begin, if you could introduce us to pemvidutide, its dual GLP-1/glucagon mechanism, and why you believe it's well-suited to address MASH. Yeah, good morning, Patrick, and thank you for hosting us. It's a pleasure to be here. As you mentioned, we are developing a GLP-1/glucagon dual agonist, and the key benefit of pemvidutide is really this dual mechanism of action. We believe that the best way to treat MASH is to really treat multiple components of the disease, having a direct effect in the liver through our glucagon mechanism, combined with metabolic effects through weight loss, improvement in serum lipids, blood pressure, et cetera. That's really the best way to treat MASH. Pemvidutide combines both of these mechanisms of action, so it's really a complete treatment for MASH. We've had exciting data readout from our 24-week study that we announced in June. We are looking forward to our 48-week data readout coming up here in the fourth quarter and preparing for an end of phase II meeting with the FDA also in the fourth quarter. Looking forward to moving this program into phase III in 2026 and really excited about the overall profile of pemvidutide in treating patients with MASH. Perhaps, Scott Harris, you can take from here and talk more about the pemvidutide and what we have learned about the data. Sure. Let me walk you a bit through the design and the top-line results of the phase IIb IMPACT trial and highlight what I think are the most clinically meaningful findings. First of all, this was designed as a 48-week trial, although we did read out on the primary endpoint of the trial based on the biopsies at week 24. With that, we achieved class-leading MASH resolution. The effects in MASH resolution that we were seeing were comparable or greater than results that we're seeing with compounds reading out to 48 - 72 weeks. Not only robust effects, but also rapid effects. We also saw effects in non-invasive markers of fibrosis that were as good or better than compounds reading out at later time points. In addition to that, we also saw very meaningful improvements on AI-based reading of the biopsies, showing ongoing and potent resolution of fibrosis. As you're aware, the European Medicines Agency, EMA, has actually approved AI-based methodologies for biopsy analyses in phase II and phase III trials, and the FDA is reviewing that approval right now. We're very hopeful to be able to use this going forward, but I'll let Christophe talk more about our phase III program. In addition to potent readouts on MASH resolution and very significant findings on non-invasive tests and computer readout of fibrosis, we also saw weight loss of greater than 6% at the 1.8 mg dose, recognizing that the 2.4 mg dose, which we've used in our obesity trials, gives even 40% greater weight loss than that. We're very excited about what we would see at week 48. We also saw approximately 50% of subjects normalizing their liver fat, and we saw changes in a CT modality called CT1, which measures liver inflammation and fibrosis. The results that we saw at week 24 alone were best in class compared to other MASH compounds, meaning that pemvidutide is very anti-inflammatory, and this would be predicted to result in potent changes in liver fibrosis over the course of treatment. Finally, we saw class-leading reductions in serum ALT levels. All in all, this was a very positive readout. We think it stands well for the likelihood of success in phase III and also at later time points of biopsy readouts. Right, that's really helpful. On the primary endpoint, IMPACT achieved MASH resolution of around 59% of patients at 24 weeks. I'm wondering how that compared to your expectations going into that readout and how you would expect that rate to evolve at 48 weeks. As I mentioned before, that 59% improvement was as good or better than compounds reading out at 48 - 72 weeks. We expect it, but we're also elated with the results. It means that this compound has very significant effects on MASH and MASH inflammation and sets the stage for success going forward. Yeah, and Scott, maybe just to frame this discussion around the non-invasive tests a bit. You've talked about, I think, over time how the FDA's view on the NITs has evolved. I'm wondering, you mentioned CT1. Maybe you can talk to us about CT1, ELF, VCTE. Which of these stood out to you, and what should investors be focusing on? What is the ultimately, what will we learn from these NITs at 48 weeks? Right. I'll let Christophe talk about our expectations at 48 weeks. Regarding what we saw at 24 weeks, as I mentioned before, CT1, which is corrected T1 imaging, is an MR-based modality which measures liver inflammation and fibrosis. The results that we saw were better than any other compound at any point of development, whether 24 to 48 weeks. It means that pemvidutide is very anti-inflammatory towards MASH inflammatory activity. We also saw changes in ELF and VCTE that were not only statistically significant, but also were comparable to what other compounds were seeing at later time points. Compounds would actually achieve the fibrosis improvement endpoint by biopsy at those later time points. We think we're in an excellent position reading out to week 48. Right, terrific. Christophe, if you could just frame for us what you would consider to be sort of a quote unquote home run bar for the 48-week IMPACT data. What combination across NITs, weight loss, fibrosis, and safety would you consider most compelling? Right. As Scott said, I think the week 24 data were very encouraging and very supportive of moving rapidly into an end of phase II meeting with the FDA and developing the phase III program as we move forward. The week 48 data, I'm expecting to see even greater improvements and confirming that this will support and give us a high confidence on the probability of success of the phase III program. We see a lot of convergence of all these elements from the liver fat to the inflammations to the fibrosis components, and all three are moving in that direction, making us very confident about moving into the phase III program. Right, terrific. How do you expect the 48-week data package to influence your phase III design, particularly around powering, duration, 48 versus 72 weeks, and patient enrichment? We have already at week 24 very comparative efficacy to what other compounds have shown, and that's how we've been powering our study, and that's how we're going to be discussing this study with the FDA. Obviously, any additional improvement will give us additional power, including due to the increased effect size that we might see in the large phase III. The other aspect is, as you discussed before, as the regulatory agencies are moving towards using the NITs as potential surrogates for the biopsy and the histology improvement, we've designed the study in a flexible manner to be able to adapt if the regulatory agencies are changing from the biopsy reading to the NITs. Right, great. Can you outline your objectives for the upcoming end of phase II meeting with the FDA? What feedback would give you greatest clarity heading into phase III? We are looking at confirming that our design will be supporting the registration and the approval of pemvidutide for MASH. We are going to be looking at discussing the safety database, and we are trying to get more insight as well on where the FDA is regarding the NITs versus the biopsy reading, and hopefully this will be something that they will consider. These are three aspects that we are going to look for at the end of phase II. Right. Yeah, to be clear, Patrick, our goal is to go in with a very flexible trial design. It doesn't matter when that change takes effect. There is no question that there is serious consideration at the FDA to not continue with the biopsies and really use NITs as a replacement for biopsies. We are designing our phase III program in such a way that when that change occurs, we can easily pivot and incorporate that new endpoint into our final analysis of the phase III program. We certainly would like to have that discussion and that agreement with the FDA as we go there. Right, terrific. You know tolerability is often a challenge with incretins. I'm wondering, what did IMPACT show about pemvidutide's tolerability profile, and how might this differentiate the drug in MASH? Patrick, we had the lowest rates of adverse event discontinuations of any drug, not only in MASH development, but for any incretin, for any indication. This highlights the pharmacokinetics of pemvidutide, where the drug, because of the modifications to the compound, specifically the albumin domain, results in slower entry into the bloodstream with lower peak concentrations, with the peak concentration driving the intolerability. The ability to achieve 1% overall dose adverse event discontinuations among pemvidutide groups in the face of no dose titration is really remarkable. This is extremely important to compliance with therapy. We all know there's a very high rate of discontinuation of incretins over the course of one year. Drugs that are well tolerated are going to be taken with greater compliance, and that's going to result in much greater effects. We think that the tolerability of the compound, combined with the ease of use, meaning the absence of dose titration, the prescription of the active dose with the first prescription, is extremely important, not only for tolerability, ease of administration, and compliance with therapy. Right. How do you see pemvidutide's dual mechanism, GLP-1 for metabolic effects, glucagon for direct hepatic effects, comparing against other mechanisms in late-stage MASH development? I'm happy to try to answer, being new to this, but the way I look at this is there is a unique opportunity here with pemvidutide because the ratio 1:1 is unique to it. As you mentioned, the glucagon is working directly on the liver. There's no GLP-1 receptor at the liver level. GLP-1 agonists are indirectly working on the MASH situation at the liver levels. We have that opportunity. There is really an importance to have that ratio and balance both effects on the appetite, on the delayed gastric emptying from the GLP-1s, as well as the metabolism of fatty acids in the liver. Pemvidutide has a unique position there. In addition to the tolerability for a chronic disease that will help on the compliance, I think it's a very unique opportunity to move forward with both agonism on the GLP-1 and on the glucagon side. Right. Patrick, as you know, the discussion about treating MASH is shifting towards combination therapies. Everybody's talking about the benefit of direct active activity in the liver combined with metabolic benefits. That's exactly what pemvidutide does. It really combines these two complementary mechanisms to address the entire disease, not just the liver, but the metabolic component as well. We think it's really a dual mechanism of action here, which is what is compelling in terms of the value proposition of pemvidutide. Right. That makes a lot of sense. I'm wondering, just given that payer perspectives often emphasize fibrosis improvement, how are you preparing to demonstrate value to both regulators and payers? As you know, payers are focused on value, and ultimately, what is the value, what's the differentiation that you bring to the table? This combination of metabolic effect, as well as anti-fibrotic effect and direct effect in the liver and rapid activity on top of that, is what's highly attractive to patients, to payers, to providers. On top of that, if you add tolerability and the quality of weight loss, for instance, preservation of lean muscle mass, all of those things really add to the value proposition of pemvidutide. We think pemvidutide is very well situated in terms of having those discussions with payers. Our early market research is showing that pemvidutide has a very attractive profile for all of the constituents, for all of the stakeholders who would want to use a drug for treatment of MASH, either patients or physicians or payers. Right, that's really helpful. I'm wondering, commercially, you know, how large is the opportunity you envision for pemvidutide in MASH, and what patient population do you expect to target first? As you know, MASH is a very large opportunity from a commercial perspective. We've got the early MASH, moderate to severe patients, and then severe patients from F2 to F4. It's really a continuum. What's important about having the dual mechanism of action is that because of that, we'll have a broader footprint, or pemvidutide will have a broader footprint in its ability to treat all of these patients. Initially, we are focused on F2, F3 in our phase III program. We will then add F4 to that as well. We believe that pemvidutide will not only work in F2, F3, but will also work in F4. Physicians will not have to guess as to which, what stage of fibrosis that they need to treat, liver cirrhosis that they need to treat. Because of the broader footprint of pemvidutide, we should be able to address all of these markets, hence have a bigger commercial opportunity. Right, that makes a lot of sense. I'd like to ask about the business development environment. We've now seen three major large-cap moves in MASH within six months. We saw GSK and Boston Pharmaceuticals, Roche and 89Bio, and now more recently, Novo and Akero. Do you think this signals the start of a consolidation phase? How does Altimmune plan to position pemvidutide within that context? Yeah, no, absolutely, that's a great question. It is clear that there is a lot of focus on therapeutics for MASH. Large pharma has always been interested in MASH and overall in the liver disease space. I think what is also interesting is that most of the companies that are getting into the MASH space are looking at a portfolio approach. They're not just looking at one mechanism, but they're really looking to combine mechanisms, for instance, FGF21s with GLP-based therapeutics. There are players who are bringing both of these drugs in combination for the treatment. The ultimate goal is to use them in combination for the treatment of MASH. We think we really fit well in that paradigm. As we've been talking about, pemvidutide brings those together in a single molecule. If you can address both liver effects and metabolic effects in a single drug, why would you want to use two separate molecules, two separate PK profiles, two separate tolerability and safety profiles? It's much more complicated. We think the best way to treat MASH would be to combine these two mechanisms in a single molecule. That's really exactly what pemvidutide does. We feel very good about the positioning of pemvidutide versus these other mechanisms of action. Right, that's terrific. I think maybe just as a final question to kind of bring it all together, you know, we have the IMPACT 48-week data upcoming, the end of phase II meeting ahead with the FDA. What is the timing for both of these? Can you frame this for us in the fourth quarter upcoming for these key catalysts? What's the single most important message that you want investors to take away about pemvidutide's differentiation and readiness for phase III in light of these significant catalysts that are upcoming? Yes, I would back up and say we have excellent data, excellent 24-week data from our ongoing IMPACT trial. We are looking forward to presenting the 48-week data in the fourth quarter coming up here and then having an end of phase II meeting with the FDA, which we have already requested. We have already submitted the request for that meeting with the FDA. Really, three important milestones in succession that would really position us to go into 2026 with a lot of momentum. As we mentioned, our trial design, that we're designing it in such a way that we'll maintain all of the flexibilities. Should there be any regulatory changes in the path forward for approval of drugs for MASH, we'll be able to take advantage of that. This is a compelling opportunity for investors ahead of all these milestones and all these data points coming up. Right, terrific. Thank you so much to Vipin, Christophe, and Scott. Always a pleasure to catch up. It's a very exciting time for Altimmune. We're very interested in these next data and updates from the company. Thanks again. Thanks everyone for being with us at the Liver Disease Conference. Have a great rest of your day and conference. Thank you. Thank you. Thanks.