Altimmune, Inc. (ALT) Earnings Call Transcript & Summary

Good morning, ladies and gentlemen, and welcome to the Altimmune RECLAIM Phase II Trial in AUD Topline Results Conference Call. [Operator Instructions] As a reminder, this call is being recorded. I'll now introduce your host for today's conference call, Luis Sanay, Vice President of Investor Relations. Luis, you may begin.

Thank you, operator. As a reminder, a press release summarizing the topline results of the RECLAIM trial and an accompanying presentation can be found on the Investor Relations section of the Altimmune website. Following some prepared remarks, we will open the call to your questions. Before we begin, I'd like to remind everyone that remarks about future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. Altimmune cautions that these forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those indicated. For a review of the risk factors that could affect the company's future results and operations, we refer you to our SEC filings. I would also direct you to read the forward-looking statements disclaimer in our press release issued this morning and on Slide 2 of the presentation. Any statements made on this conference call speak only as of today's date, July 28, 2026, and the company does not undertake any obligation to update any of these forward-looking statements to reflect events or circumstances that occur on or after today's date. With that, I'll now turn the call over to Jerry Durso, Chairman and CEO of Altimmune.

Good morning, everyone, and thank you for joining today's call to review the topline data from the RECLAIM Phase II trial of pemvidutide in alcohol use disorder, or AUD. We were very pleased to issue the press release you saw this morning, reporting what we believe are outstanding topline results. Pemvidutide delivered a very strong statistically significant and clinically meaningful reduction in heavy drinking days, which was the primary endpoint of the study. Additionally, the trial also met important secondary endpoints, including a 2-level reduction in WHO Risk Drinking Levels and zero Heavy Drinking Days. Either of these 2 measures are currently accepted as FDA registrational endpoints. Therefore, the efficacy package seen with pemvidutide in the topline readout bolsters our conviction in its potential in AUD. We also saw a generally favorable tolerability profile in a challenging moderate to severe AUD population. These compelling data represent yet another important milestone for Altimmune and further highlight the potential of pemvidutide as a differentiated therapy across serious liver diseases. While we have obvious focus on the specific and unique patient needs on the individual conditions of MASH, AUD and ALD, it's important to note that there is also an overlap across these serious liver conditions. The topline results from RECLAIM are meaningful for the AUD patient community, where there remains a significant unmet need with approximately 12 million adults in the U.S. with moderate or severe forms of AUD. This AUD population is more likely to ultimately suffer from the consequences of liver disease. The dual mechanism of pemvidutide may importantly have an effect on both reducing alcohol cravings and provide a direct effect on the liver, a potential key differentiator from other molecules in development for AUD. So as I said, this is important and exciting data, both for Altimmune and for the field. And I'll now turn the call over to our Chief Medical Officer, Christophe Arbet-Engels, to walk you through the details of the topline data set. Christophe?

Thank you, Jerry, and good morning, everyone. I am very excited to share the strongly positive topline data readout from our RECLAIM trial in AUD. Starting with Slide 3. As a reminder, pemvi is a novel peptide with balanced 1-to-1 glucagon/GLP-1 dual receptor agonist, that has an effect on reducing liver fat, inflammation and fibrosis. The activation of glucagon receptors has been shown to have direct effect on the liver, while GLP-1 receptors mediate metabolic effects such as appetite suppression, weight loss, and are involved in pathways related to craving and rewards. Moving to Slide 4. The RECLAIM trial evaluated the safety and efficacy of pemvidutide in patients with AUD. 100 patients were randomized 1:1 to receive either 2.4 milligram pemvidutide or placebo once weekly for 24 weeks. Patients on the pemvidutide treatment arm followed a simple monthly dose titration from 1.2 milligram to 1.8 milligram to 2.4 milligram. The primary endpoint of the RECLAIM trial was the change from baseline in the average number of heavy drinking days per week with additional secondary endpoints, including the proportion of patients achieving a 2-level reduction in the World Health Organization Risk Drinking Levels or WHO-RDL, zero heavy drinking days and the absolute change from baseline in levels of PEth, a serum biomarker of alcohol intake over a 2- to 4-week period. Slide 5 shows the patient disposition where 80% of patients receiving pemvidutide and 78% of patients in the placebo arm completed treatment. Overall, our retention rate was excellent with 91% of patients completing the study. Of note, 6 patients in the placebo arm discontinued treatment due to lack of efficacy, when none did in the pemvi treatment. Turning now to Slide 6. The RECLAIM study was a multicenter study across 12 trial sites with a diverse population similar to the real world in the U.S. The baseline demographics were balanced across treatment group. Patients were on average 50 years of age with 52% of the patient population being female. The average body weight was 96-kilogram and 92-kilogram for the placebo and pemvi arms, respectively. The heavy drinking days were 5.6 in the placebo and 5.9 in the pemvidutide arm. The population had moderate or severe AUD, including 20% to 30% of patients with greater risk of developing fibrosis as reflected by the FIB-4 greater than 1.3 at baseline. Moving to the efficacy results, starting with Slide 7. The trial met its primary endpoint where pemvidutide showed a highly statistically significant reduction in the average number of heavy drinking days versus placebo at week 24 with a treatment difference of 1.45 heavy drinking days reductions and a p-value of 0.0014. In the chart, you can see the rapid effect of pemvidutide at just 4 weeks and a further reduction through the treatment period. Notably, the clinical relevance of this large difference in heavy drinking days with pemvi versus placebo may lead to important improvement in the social and risk behaviors of patients with AUD. Turning to Slide 8. The reduction of WHO-RDL is particularly important as this is a registrational endpoint recognized by the FDA. On the secondary endpoint, we saw a highly statistically significant response in the 2-level reduction in WHO-RDL versus placebo with a p-value of 0.0049. Roughly 2/3 or 64.4% of pemvi patients achieved a 2-level reduction in WHO-RDL versus only 34.8% on placebo. Moving now to Slide 9. On the other FDA registrational endpoint of zero heavy drinking days, a historically more challenging endpoint to achieve, pemvidutide again showed a highly statistically significant improvement in percentage of patients with zero heavy drinking days with a p-value of 0.0066. In these data, more than twice of the pemvi patients achieved zero heavy drinking days versus placebo patients, both the WHO-RDL and zero heavy drinking days are also relevant endpoints for EMA. Turning to Slide 10. In another measure of alcohol usage, the percentage of days with drinking abstinence, pemvidutide showed a highly statistically significant improvement over placebo in the percentage of abstinence days. This improvement occurs early in the pemvi treatment arm and does not plateau after 24 weeks. Moving now to Slide 11. PEth, phosphatidylethanol, is an objective blood-based measure of recent alcohol intake over the last 2 to 4 weeks. The secondary endpoint also showed a highly statistically significant reduction in patients treated with pemvidutide, whereas the test level in placebo patients remained unchanged. The treatment difference from placebo at week 24 was 175.3 nanogram per milliliter with a p-value of 0.0001, where patients started with approximately 380 nanograms per ml at baseline. The totality of the data, including patients reported measures such as the decrease in heavy drinking days, WHO-RDL reduction and the increase in zero drinking days as well as this PEth objective measure of alcohol intake showed the strong and consistent effect of pemvidutide in potentially addressing the excessive alcohol usage in AUD patients. Turning now to Slide 12. Given pemvidutide's mechanism of action, we also report here a meaningful and statistically significant reduction in body weight from baseline with pemvidutide versus placebo with a 9.1% reduction at week 24. Moving to Slide 13. As mentioned earlier, pemvidutide is a balanced 1-to-1 dual glucagon/GLP-1 agonist with a direct effect on the liver. Given the negative impact of alcohol on the liver, we believe that this direct liver effect of glucagon could be an important component of treatment for AUD patients, and we will look to explore this potential differentiator more fully in the future. On Slide 14, nonetheless, while we know that RECLAIM was focused on drinking, we wanted to evaluate in an exploratory manner whether patients with elevated FIB-4 at baseline were seeing any improvement over the duration of the study. As a reminder, FIB-4 is usually used in clinical practice as a prognosis test for patients to assess the risk of developing fibrosis or liver-related events with values greater than 1.3 indicating an increased risk for liver fibrosis. Given pemvi's direct effect on the liver, the observed data with 50% of pemvi patients with the FIB-4 index above 1.3 at baseline, achieving less than 1.3 after only 24 weeks versus only 17% in placebo is very encouraging, especially at such an early time point. We would expect to further evaluate the potential liver effect in future studies in this AUD population. Looking at safety and tolerability shown on Slide 15, pemvidutide continues to demonstrate a consistent safety profile across several populations, including AUD and was generally well tolerated. The majority of AEs were mild to moderate in severity. There were 2 SAEs, one patient with breast cancer and another with hyponatremia. The patients with the AE of hyponatremia was deemed possibly related to the study medication by the principal investigator. Treatment discontinuation for GI AE represented most of the drug-related discontinuation in this population. Turning to Slide 16. We believe that the simple 2-step titration may improve the general tolerability profile of pemvidutide at 2.4 milligram. For example, the nausea rate at 2.4 milligram was only 44% in RECLAIM versus 52% in the obesity trial with the same dose. Finally, I would like to take a moment to express my thanks and deepest gratitude to all the participants, clinical investigators and everyone involved in the RECLAIM trial. We completed the trial several months ahead of schedule, signaling strong enthusiasm from both patients and physicians to explore new treatment options for AUD. In conclusion, I am very excited about the strong positive data we shared today. We believe this data highlights the potential of pemvidutide to meaningfully help AUD patients on their alcohol use disorder and potentially the often-related liver disease. As a reminder, the FDA granted Fast Track designation to pemvidutide for the treatment of AUD. We now look forward to engaging with the FDA on the path forward towards registration. I will now turn the call back over to Jerry.

Thanks a lot, Christophe. So in summary, from our standpoint, the RECLAIM topline trial results are quite compelling. Pemvidutide met the primary and important secondary endpoints, including the 2 registrational endpoints recognized by the FDA. In fact, to our knowledge, these are the most robust results that have been reported in AUD. We look forward to reviewing the full data set and requesting an end of Phase II meeting with the FDA to discuss the path forward for pemvidutide in this indication. We also intend to present further data at upcoming medical meetings and publish the full data. On a corporate level, Altimmune remains laser-focused on execution and continuing to advance our key pemvi programs. In addition to the great news on AUD we shared this morning, we're advancing our MASH and ALD programs. Regarding MASH, all is going well in the start-up phase of PERFORMA Phase III trial, and we now expect to initiate the trial this quarter. In ALD, consistent with our guidance, we expect to announce the completion of patient enrollment in the RESTORE Phase II trial in the third quarter. Altimmune is well positioned to execute our strategy and create shareholder value. Today's results add to the growing body of evidence, further building our confidence in the potential of pemvidutide. We now have delivered strong Phase II data in another indication and in doing so, move us one step closer to fulfilling our mission of helping the millions of patients with serious liver diseases. We're excited with the continued progress we're making as a company and enter the second half of the year with momentum. This now concludes our prepared remarks, and I'll open the call for Q&A. Operator?

[Operator Instructions] Our first question comes from Thomas Smith with Leerink Partners.

Congrats on these excellent results. Just wondering, relative to the randomized Phase II study with semaglutide, it looks like you may have had a more severe patient population looking at WHO-RDL and total alcohol consumption at baseline. Can you just help maybe put these results and the treatment effect in context versus the Phase II sema experience? And what do you think the glucagon is adding to the results and the treatment effect here?

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

Right. So we looked at the same comparison, and it's always difficult to compare the 2 different trials because these are not head-to-head. We looked at the different ways. And in general, SEMALCO look a little less effective. Our methodology look at less than a day versus 1.5 days reductions in heavy drinking days. And our population is also different, as you just mentioned, our population is a little more severe. And that population, it's unclear whether a population that is drinking more alcohol is actually harder -- having a harder time to reduce alcohol. And the last part on the glucagon, we know that there is a large amount of glucagon receptors in the CNS and that component is something that is yet to be further explored. Altogether, I think as Jerry said, our data are very strong and allow us to think about moving further and especially with regard to the liver component and the benefit that it could bring for those patients.

Great. Super helpful feedback. And maybe just one other follow-up question, if I could, on the regulatory path. You clearly hit stats on 2 potentially registrational endpoints. Do you have an early view or a preference on which of these endpoints you'd look to use as the primary and a potential pivotal registrational study? And maybe if you could just elaborate a little bit more in terms of timing on the feedback from FDA and the potential path forward here?

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

Now, on the endpoint, so the 2-level WHO-RDL is one of the endpoints, obviously, that the FDA consider as validated endpoint for a Phase III trial. The zero heavy drinking days is often much harder endpoint to achieve. So we are really happy. Now we have the choice between the 2 different endpoints. And as we're getting the full package for the -- the full package of our data, we will prepare to get the briefing document together and make a proposal for the FDA. On the EMA side, we know that the zero heavy drinking days is the endpoint that they are using, but they're asking you also to have the WHO, the 2-level reductions from WHO-RDL as a key secondary endpoint. So we are in this situation, a little bit like, we have done from the MASH trial, where we will address both of the regulatory agencies' requirements.

Our next question comes from Roger Song with Jefferies.

Great. Congrats for the data. Fantastic and impressive. So maybe just a follow-up on the baseline. When we look at the heavy drinking days, the baseline is pretty high for the Phase II. How do you think about the Phase III? And in particular, as you apply to the broader population you try to address for the AUD. If that baseline a little bit lower, how do you think about the effect size will evolve? That's number one. Number two is just to clarify for the primary endpoint for Phase III, for FDA, would that be the co-primary endpoint or dual primary endpoint? Or that's just one of those 2 like a MASH?

So either is approvable. So they're not specifying a co-primary endpoint. Again, we'll have discussion. I think the great thing is that with the strong data we have, we have good options in terms of how we think about design of Phase III to take advantage of the unique benefits that pemvi might be able to bring to the table here. We did enroll intentionally a moderate to severe population. We know that, that group of patients is most likely to ultimately suffer consequences of liver disease. Christophe, maybe you want to just talk about how you're thinking about this group of moderate to severe as we prepare for in a Phase II data.

Yes. So clinically, this is a group that requires treatment because of some of the social risk behaviors. So this is clearly a group that is having a high unmet need that we can address with this. As Jerry said, for our Phase III, the good news is that our Phase II is looking at a very diverse population, very similar to what the real world is having, which is important for regulators to have in your Phase III. So our data in a certain way derisk our Phase III trial substantially here. And with regard to your point on the baseline characteristic, I would argue that sometimes the patients with the higher alcohol habits or patterns can be very hard to reduce their behaviors on the alcohol. So we are happy with what we see. And again, the glucagon component on those behaviors is yet to be explored. It Is unknown, but we know their glucagon receptor on the CNS. And in the meantime, in these patients, obviously, they are more at risk of liver disease. So that's going to be a clear aspect for us to look at in our Phase III. So we're going to set up all these pieces together when we have all the full data and go towards the FDA with a very strong briefing package.

Our next question comes from Ellie Merle with Barclays.

Congratulations on the really impressive data here. How are you thinking about the scale and scope of a potential Phase III relative to the size and cost of a MASH Phase III trial? And then also, how are you thinking about the market opportunity for AUD and how the pricing might compare to that in MASH? And I guess, given the non-invasive nature of these studies, could this potentially come to market before MASH?

Okay. So a lot there to unpack, Ellie. I'll try to start and then perhaps Christophe and Linda can chime in. I think, first of all, look, it's a little premature to be very specific on size and scope. As I said, we're going to complete the full readout, review the data, plan to submit it. I think importantly, we'll continue to reiterate that the strength of this data set gives us great options when we think about what we will be proposing when we sit down with the agency. But of course, that important dialogue at the end of Phase II meeting is going to help a lot define exactly what the size and scope of Phase III might be. We do know, though, however, that we would expect the AUD program to be smaller in size and duration than what we're thinking about in MASH as we get tighter on that and have more feedback from the FDA, we'll talk more specifically about the range. I think with this data set, we really have the ability now to plan and position a pemvi franchise. And so, as I announced this morning, things are progressing well on the MASH side and that we did tighten the guidance and initiation now to be this quarter in Phase III, where we'll initiate PERFORMA. But we have great data here on AUD, which will also be factoring in when we think about the overall value proposition of pemvi, which will help guide how we think about pricing. We know now that the potential for a benefit to a broader group of liver disease patients is bolstered by the AUD data that we have. And so we think about really the value and ultimately, pricing for both indications now that we've progressed through Phase II on around the impact on both the behavioral or metabolic factors and the direct impact on the liver. And that's the value proposition, and that's what we're going to work towards. But Ellie, we will be thinking about this on a franchise level. And again, good value here. We'll talk a lot about pricing over time. And again, for us, important movement here. We have a larger group of patients now that we think could benefit as a result of this AUD data set.

Congrats again on the data.

Our next question comes from Michael DiFiore with Evercore ISI.

Congrats on the fantastic data. Two questions for me. To what extent do you think the efficacy results were driven or perhaps confounded by the GI adverse events? In other words, could nausea, vomiting, diarrhea have influenced the desire to drink? And my second question is, how robust was the primary endpoint to perhaps alternative estimands and missing data assumptions?

Okay. Christophe?

Yes, I'm happy to. So first, I mean, we had 12% of our patients that withdrew in the placebo because of lack of efficacy versus 0% in our -- in the pemvidutide arm. So I think the GI tolerability is not necessarily a factor. However, those -- as you know, those alcohol -- those patients with alcohol use also have nausea, have esophagitis, have GERDs, and those kind of things. So in that population, these are factors that we also are gathering as we are running these trials. With regard to the estimates and the powering of the study, basically, we powered only heavy drinking days per week. We were able -- we account for a 1 day difference, and we were able to show almost 1.5 day difference. So we are really happy with this data. In addition to this, I mean, if we were able to also have highly statistical significance in our heavy -- in the WHO, the 2 levels, often studies are reporting only even 1 level. We have 2-level reductions with highly statistical significance. We have the zero drinking days that we achieved. And as you can see on the presentation, the days of abstinence are also highly statistically significant. So overall, not only we are reducing the amount of drinking, but we are reducing the number of days of drinking. So that's really the way to think about this. And the way I like to put it is basically the patients are drinking all week long. And now they're drinking less and only on the weekend. And it's kind of this picture that we are able to approach with pemvidutide for these severe and moderate patients.

Our next question comes from Jon Wolleben with Citizens.