Altimmune, Inc. Q1 FY2026 Earnings Call

Good morning, ladies and gentlemen, and welcome to the Altimmune First Quarter 2026 Financial Results Conference Call. Operator instructions were provided. 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, and good morning, everyone. Thank you for joining us for Altimmune's First Quarter 2026 Financial Results and Business Update Call. On today's call, you will hear from Jerry Durso, our President and Chief Executive Officer; Dr. Christophe Arbet-Engels, Chief Medical Officer; Linda Richardson, Chief Commercial Officer; and Greg Weaver, Chief Financial Officer. Following management's prepared remarks, we'll open the line for the Q&A session. Our first 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 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 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, May 13, 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 Durso.

Good morning, everyone, and thank you for joining us today for our first quarter 2026 financial results and business update call. During our last earnings call, I discussed that one of my first priorities as CEO was to strengthen Altimmune's foundation to equip us for the continued successful advancement of pemvidutide and support our evolution into a late-stage development company. Since the start of the year, we've made significant progress across multiple fronts and are excited about the opportunities ahead of us. Let me take a moment to highlight our recent progress. First, we have continued to enhance and build our team strategically to ensure we are best positioned to deliver on our vision as we enter a new phase for Altimmune. We've also remained focused on strengthening our financial foundation. Importantly, in April, we completed an oversubscribed public offering resulting in $225 million in gross proceeds. The proceeds from the April offering, along with our existing funds resulted in a cash balance of approximately $535 million as of April 30. We now have the financial resources to fully fund the company through our Phase III MASH 52-week data readout, which is expected in 2029. This financing highlights the confidence and the conviction of participating top-tier biotech investors in the potential of pemvidutide and represents another key step towards bringing pemvidutide to patients. We're entering a new phase for the company with the right team in place and a very strong balance sheet, and we're now focused on execution and believe we're well positioned to successfully execute our strategy. We believe that pemvidutide has the potential to bring meaningful benefit to people affected by a variety of hepatic diseases. The balanced 1:1 glucagon and GLP-1 activity in a single molecule achieved with pemvidutide makes it potentially well suited for the liver conditions we're targeting. Additionally, pemvidutide incorporates our proprietary UPORT structure, which slows absorption and is believed to drive improved tolerability, potentially reducing GI and other side effects. This can lead to greater treatment adherence. Importantly, keeping patients on therapy at the right dose is crucial to the management of chronic diseases such as MASH. Recent market research we've conducted points to attributes that would drive prescribing in MASH, including the highly favorable tolerability profile that does not sacrifice efficacy and quality weight loss. These are two of the potentially differentiating characteristics of pemvidutide based on our clinical trials to date. As the MASH market continues to evolve, there remains a significant unmet need, and we believe pemvidutide has the potential to offer a differentiated profile for patients. Furthermore, the potential of pemvidutide has been recognized with breakthrough therapy designation in MASH by the FDA. We're continuing to advance our efforts and expect to initiate our global Phase III study in MASH in the second half of this year. The MASH Phase III trial will be called the PERFORMA trial. We've now finalized the study protocol and submitted that to the FDA as part of the standard process. We've also completed the scientific advice process in Europe, and the final study protocol is aligned with the feedback we've received from the EMA. So Altimmune is fully focused on the start-up phase for a large global Phase III trial. We're moving quickly, partnering with a CRO who brings deep experience in the MASH Phase III space. The Altimmune team is working closely with them, and we're progressing to activate the most experienced trial sites, and then we look forward to initiating patient screening. While we have significant focus on our lead MASH program and initiating the PERFORMA study, we're also progressing on two additional indications. First, in alcohol use disorder, an area of high unmet need, we remain on track to report topline data from our Phase II trial next quarter. We remain encouraged by the strong scientific interest in this indication and look forward to the data readout. In alcohol-associated liver disease (ALD), we now expect to complete enrollment of the RESTORE trial in the third quarter of this year. Pemvidutide represents a unique and compelling opportunity to improve the lives of people with MASH and other liver conditions. It has the potential to become an important tool for physicians as they look to improve upon the current treatment paradigm and meet the needs of their patients. With a stronger team in place and cash runway through the topline readout of our pro forma Phase III MASH trial, we're now laser-focused on execution. We're moving with urgency on bringing pemvidutide to patients who may benefit from its promising therapeutic profile and creating long-term value for our shareholders. With that, I'll turn the call over to Christophe for a clinical update.

Thank you, Jerry. The start-up activities for the PERFORMA Phase III MASH trial continue to progress as planned, and we are well on our way towards initiating the study in the second half of the year. In the last few weeks, we have finalized and submitted the study protocol to the FDA, and the Altimmune team is working closely with our CRO partner. We are ensuring the global infrastructure, vendors, labs and clinical supply chains are in place to support a successful trial. These activities will allow us to initiate screening and start enrolling patients in the second half of the year. We are also pleased to report alignment on the Phase III trial design with both FDA and EMA. As we expected, feedback received from EMA validated our planned trial design and represented the final regulatory step in our Phase III preparation. This is an important milestone in our global development strategy as the data from the PERFORMA Phase III trial will form the basis for regulatory submissions in multiple regions. Importantly, we achieved strong efficacy results at both 24 and 48 weeks in the Phase II IMPACT trial, particularly at 1.8 milligrams. We will introduce the 2.4 milligram pemvidutide dose in Phase III, which has achieved additional weight loss in the previous obesity study and could potentially show increased liver efficacy beyond what was observed at the 1.8-milligram dose in Phase II. We also observed improved adherence to treatment and a low discontinuation rate lower than placebo, which is critical to addressing a serious chronic liver disease such as MASH. Based on the strong Phase II data and based on the design and the powering of the pivotal Phase III study, we are looking forward to pemvidutide continuing to show benefits for large groups of patients. We have announced this morning the 48-week results from the Phase II IMPACT trial will be the subject of an oral presentation by Dr. Mazen Noureddin at the EASL conference later this month in Barcelona. This abstract for the oral presentation has been selected as a Best of EASL abstract, which highlights the most noteworthy contribution to the scientific program at EASL. In addition, our presence at EASL this year will increase with another three posters about cardiovascular risk factors, including weight loss, noninvasive testing and qFibrosis. We believe that the oral presentation and the interest from the scientific community through these activities speaks to the excitement around pemvidutide. We will also have a medical affairs booth and participate in many interactions with key opinion leaders and potential investigators for the PERFORMA Phase III trial. We look forward to engaging with the liver community and supporting their excitement on pemvidutide. While our near-term focus is now the execution of the PERFORMA Phase III MASH pivotal trial, we have another milestone approaching this year with the topline data from the Phase II RECLAIM trial of pemvidutide in alcohol use disorder expected in the third quarter. We believe the AUD population, which has a high unmet need, is particularly suited for pemvidutide therapy because of the expected GLP-1 actions on alcohol cravings, the direct glucagon activity on early liver disease including steatosis, inflammation and early fibrosis, and the excellent tolerability which we have observed to date and is critical in this population. As a reminder, the RECLAIM trial is evaluating the 2.4 milligram dose of pemvidutide with a simple two-step mostly titration scheme versus placebo in 100 subjects with moderate to severe AUD. Subjects are dosed once weekly for 24 weeks, and the primary efficacy endpoint is the change from baseline in heavy drinking days, which are defined as five or more drinks for men and four or more drinks for women in a 24-hour period. Key secondary endpoints include zero heavy drinking days, a two-level reduction in the WHO risk drinking level, change in measures of alcohol consumption and change in body weight and BMI. An important exploratory endpoint is the change in phosphatidylethanol, or PEth, which is a more objective blood-based biomarker of alcohol consumption that represents alcohol intake over the most recent four to eight weeks. We look forward to sharing the topline data next quarter. In addition, the RESTORE trial in ALD evaluating pemvidutide's effect on liver-related noninvasive tests, markers of alcohol consumption and body weight is continuing to enroll, and we now expect to complete enrollment in the third quarter of this year. In summary, with a heavy focus on the execution of the PERFORMA Phase III trial, we continue advancing our clinical development program for pemvidutide with important milestones expected throughout the rest of this year. These efforts are integral to our long-term value creation strategy which centers on optimizing the therapeutic potential of our balanced 1:1 glucagon:GLP-1 dual agonist, pemvidutide, in serious liver diseases. And with that, I will turn the call to Linda.

Thanks, Christophe, and good morning, everyone. The MASH market is evolving as approved drugs and a number of others in late-stage development represent a range of modalities that aim to address various segments of the broader MASH patient population. This reinforces our belief that as the market continues to evolve, distinct patient segments with unique needs will begin to emerge, and satisfying those needs will be a key driver of success. As Christophe mentioned, our PERFORMA Phase III trial design has factored in key learnings from our Phase II data sets, and we believe this positions pemvidutide well for future competitiveness in the market. The potential target product profile for pemvidutide in MASH includes strong early metabolic benefits, significant improvements in inflammation and fibrosis, and quality weight loss that also helps preserve lean muscle mass, combined with the patient-friendly simple titration that leads to a low rate of discontinuation due to GI side effects. This combination of features and resulting potential benefits resonates with healthcare professionals and leads us to believe pemvidutide may provide real advantages to patients facing serious liver disease. During our last two earnings calls, I shared key data points from market research studies we commissioned engaging healthcare professionals in both the U.S. and Europe. The feedback collected from these exercises highlighted the importance of potential key differentiating attributes for pemvidutide that would influence future prescribing decisions in MASH: a highly favorable tolerability profile that does not sacrifice efficacy and quality weight loss. First, let's discuss the highly favorable tolerability profile we've seen to date in our IMPACT trial, which did not include any dose titration. Results showed that both the 1.2 and 1.8 milligram doses of pemvidutide were efficacious, showing early evidence of MASH resolution and noninvasive test-based antifibrotic effects while being well tolerated. In fact, there were fewer adverse event-related discontinuations in the two pemvidutide arms than in the placebo group. To potentially further enhance efficacy and optimize tolerability, our PERFORMA trial design includes a simple titration schedule that begins with an active starting dose of 1.2 milligrams and escalates to either 1.8 or 2.4 milligrams after only one or two titration steps of four weeks. In a real-world setting, this patient-friendly simple and quick titration could readily translate to patients remaining on treatment longer, allowing for a greater likelihood of achieving therapeutic benefit especially in a chronic condition like MASH. Now let's compare this combination of simple titration and favorable tolerability to other therapies on the market or being evaluated for use in MASH. GLP-1-based therapies, in particular, have been associated with GI side effects that lead to discontinuations in both clinical trials and real-world settings. One competitor's Phase II trial included a titration schedule that used 12 different strengths over 20 weeks to get to the maximum dose and at least seven steps to get to the lowest effective dose, all with a proactive attempt to manage GI-related side effects. And still approximately one in four patients discontinued therapy due to GI side effects. In clinical practice, dropout rates are typically even higher than those in clinical trials, where patients are actively managed and encouraged to stay on treatment. From our own market research, we know that physicians are now indicating that there is an emerging unmet need for new options for patients who could not tolerate semaglutide. How can patients get the efficacy they need when tolerability is a real barrier? Turning now to the quality of weight loss as an additional potential differentiator for pemvidutide, we saw steady weight loss with our 1.8-milligram dose in our Phase II MASH trial, with no evidence of plateauing over 48 weeks. This pattern also occurred in our obesity trial, where pemvidutide demonstrated less of an impact on lean muscle mass than has been reported in other GLP-1 trials. Rapid drops in weight loss have been associated with a greater negative impact on lean muscle mass. Current projected average age of diagnosis for MASH patients in the U.S. is between 55 and 60. This represents a high degree of overlap with the ages where preservation of lean muscle mass becomes a concern. Patients diagnosed with MASH and sarcopenia are at a significantly higher risk for adverse outcomes. Therefore, the importance of preserving lean muscle mass in the MASH population should not be underestimated. We naturally begin to lose lean muscle mass as we age, with an acceleration of loss around age 60. By age 70, many people have lost 25% to 30% of the muscle mass they possessed in their prime. Over time, loss of lean muscle mass and muscle weakness can lead to metabolic dysfunction, reduced mobility, difficulty performing activities of daily living and falls and fractures. Clearly, therapies that help reduce the impact of lean muscle loss in patients with MASH are needed for this at-risk population, and we will be evaluating this in our Phase III MASH program. We continue to believe very strongly in the potential of pemvidutide to offer meaningful benefits to patients with MASH and that its potentially unique attributes position it well to stand out in a commercial setting. We look forward to generating additional clinical data to support these benefits in our Phase III MASH program and to sharing additional insights from our pre-commercial work along the way. With that, I'll turn it over to Greg for the financial review.

Thanks, Linda, and good morning. Starting with the balance sheet here. A key strategic focus for the company was securing access to the capital required to successfully drive our clinical programs. And to that end, in April, we were pleased to complete an oversubscribed public offering with gross proceeds of $225 million with participation from top-tier biotech investors. As of March 31, we reported total cash of $332 million. And on a pro forma basis, our cash position as of April 30 was $535 million. This very strong cash position now provides us with the operating cash runway through the pro forma Phase III MASH 52-week data readout expected in 2029. Now moving to our financial results for the quarter. R&D expense in Q1 2026 was $16.2 million as compared to $15.8 million for the same period prior year. The increase in R&D spend was driven primarily by the ongoing AUD and ALD trials as well as the start-up costs for the pro forma Phase III trial in MASH, partially offset by a decrease in expenses related to the completion of the IMPACT Phase II trial in MASH, which was ongoing in 2025. The Q1 2026 spend includes $9.5 million of direct costs related to pemvidutide development, of which $3.7 million was for MASH and $4.2 million for the Phase IIs in AUD and ALD and $1.6 million in CMC-related expenses. Q1 also included $1.2 million in total noncash stock-based compensation. G&A in Q1 2026 totaled $8.1 million as compared to $6.0 million for the same period in 2025. The increase in G&A was primarily driven by an increase in severance costs and professional fees. The first quarter 2026 G&A included $2.1 million in total noncash stock-based compensation. The net loss for the first quarter of 2026 was $22.6 million or $0.18 a share compared to a net loss of $19.6 million or $0.26 per share in the first quarter of 2025. Looking ahead, we're looking forward to initiating the pro forma Phase III MASH trial in the second half of the year and topline data readout from the Phase II AUD trial next quarter. With a stronger balance sheet, providing us with the cash runway through Phase III data, we're now really focused on execution and looking forward to continuing to advance pemvidutide. This concludes our prepared remarks, and I'll now turn the call back to the operator for the Q&A session. Operator?

Operator instructions were provided. Our first question comes from Eliana Merle with Barclays.

Congrats on all the progress. So you announced this morning some presentations at EASL. Can you go into some more details on what new information we'll learn from these?

Eliana, thanks for the question. Christophe, can you take that one?

Sure. Yes. So the different presentations we're going to bring at EASL are regarding our qFibrosis analyses. So additional evidence of early fibrosis and antifibrotic effect that we had at 24 weeks on our biopsies. It's a different type of reading from AI-generated assessments. We're going to also have some looks at our weight loss and potential lipid data and cardiovascular risk in that population. And obviously, very importantly, we'll have our 48-week data that we'll be sharing in this oral presentation that was selected as a Best of EASL abstract. So we're really happy with this. It's an important contribution to the scientific program based on their selection, and we believe it is the case as well. So excited about it.

Our next question comes from Jiale Song with Jefferies.

Great. Congrats for the quarter and then all the progress. Since you're finalizing the Phase III MASH trial starting in the second half, I'm just curious any interim analysis has been updated to the design, potential for security or the sample size adjustment. So that's a question for MASH. And then for AUD, can you just elaborate on what will be the decision criteria before you can commit more investment into the pivotal stage?

Sure. So on the MASH, the study is designed as an event-driven study to reach the final clinical outcome for final registration. The interim analysis is the 52-week biopsy analysis that will support accelerated approval and for which we're going to have that readout in 2029. There is no other interim analysis planned beyond these, and we are, again, very well powered in order to reach this outcome.

Yes. Thanks, Roger. We're definitely encouraged by all the interest emerging in the AUD indication overall and definitely look forward to the readout and pleased to say that we expect the readout next quarter. Obviously, we'll assess the data fully once we get it, and we'll look to disclose that to the market. We'll also then undertake the right conversations with the regulators. And so all of that will factor into what we think about as the potential value. If we get to a situation where we believe there's value to move ahead with that indication, then we would definitely have a preference in that scenario to really explore nondilutive options in terms of funding to move that program ahead. So again, next important step for us is to get the Phase II data readout, and that will give us additional insight. Again, an indication where we think pemvidutide can play a unique role potentially not only on the impact on drinking but also on the direct liver benefit, which is such an important part of that disease as it progresses.

Our next question comes from Annabel Samimy with Stifel.

Just a follow-up on the AUD questions. So thank you for laying out the differentiation on the competitor versus semaglutide. What I'm wondering here is given that they have recently shown some meaningful data in AUD, with the addition of glucagon, are there any measurements that you're looking at for AUD that could show the benefit of the direct liver targeting that you'll have with pemvidutide over a GLP-1 alone? Any other things that you think you should be incorporating into the trial or looking at to further differentiate pemvidutide from semaglutide given that semaglutide might be generic by the time you come to market? And then I guess another question on AUD: in terms of the clinically meaningful endpoint, you have heavy drinking days, clearly, and you also have some other measures. Is it clear what the final endpoint should be for Phase III from a regulatory perspective?

Okay. So maybe, Christophe, we'll take that in order first, the question on the differentiation and how we see that evolving and then second on appropriate endpoints from a regulatory context.

Right. So thank you. We are really excited to see those semaglutide data because this clearly validates the hypothesis that pemvidutide has real potential to show benefits in this population. In addition to this, as you mentioned, the glucagon component is really important. We believe that—and this has been demonstrated in prior scientific presentations—that these patients have early markers of liver disease, including steatosis, inflammation and even early fibrosis. So targeting the liver is a critical aspect for us. That is something that GLP-1 alone will not be able to achieve since there is no GLP-1 receptor in the liver. In our study, we have markers of liver health that we're going to be looking at. And to your last point, we will obviously review all the data we have and see how we can incorporate those differentiation factors into our Phase III and the registration program, as appropriate, because we believe we have a product well suited for this population. The last piece I would remind you about is the adherence to treatment and tolerability in a population that is otherwise fairly healthy. Pemvidutide continues to show what we've seen in our IMPACT Phase II MASH data and should have a clear advantage in that population. That's important. Regarding the endpoints: for Phase III, right now, the FDA has proposed two endpoints—zero heavy drinking days or a change of two levels in the WHO drinking risk category. So we'll explore this and see how our data lead us, and we'll have those discussions with the FDA as we reach the end of Phase II.

Our next question comes from Michael DiFiore with Evercore ISI.

Congrats on the progress. Two questions for me. At your December IMPACT call, you said that there was no obvious path to re-evaluate the 24-week biopsy data in an AIM MASH-like way because LiverExplorer is a different quantitative tool. That said, the EASL poster now says quantitative digital pathology showed fibrosis regression at 24 weeks. So can you clarify what exactly is new in that analysis? And the second question is, given Roche's proposed acquisition of PathAI, does that change anything in how you plan to incorporate the AIM MASH assist into the Phase III biopsy read process?

Yes. Maybe I'll start with the second question first, and then Christophe can clarify the LiverExplorer versus qFibrosis analysis. There are a lot of different AI tools, so it's important to be clear which one is being used. On the question of the proposed acquisition by Roche of PathAI, the teams are working closely between Altimmune and PathAI on the Phase III incorporation of the AIM MASH assist tool. That conversation has continued fully since the announcement, and we don't anticipate any change to the process that's already been mapped and planned around execution for being the first program to incorporate the AIM MASH assist tool to aid the pathologist in the Phase III. Christophe, maybe you can add clarity on the qFibrosis data versus the AIM MASH assist tool.

Again, sharing my enthusiasm, we are moving forward to be the first registration study using the AIM MASH assist, and we are working closely with the PathAI team—no change there. Regarding qFibrosis, it's a slightly different approach that assesses fibrosis by removing confounding steatosis signal to allow a more accurate AI-based read of fibrosis itself. AIM MASH assist can't be applied retroactively in the exact same way because the AIM MASH approach requires specific pathologist reads and workflows. We created internal analyses that have biases if you try to map them back. The qFibrosis approach subtracts the steatosis signal to focus on fibrosis and, in our view, helps detect antifibrotic effects early, even at 24 weeks. We believe our drug, pemvidutide, is decreasing MASH and leading to MASH resolution rapidly, and that can make it harder for pathologists to detect changes in fibrosis because some features change quickly. So qFibrosis is an interesting analysis we'll be presenting, and we're excited to show data that again support an early antifibrotic effect at 24 weeks. Putting these analyses together is very exciting heading into EASL.

Our next question comes from Srikripa Devarakonda with Truist Securities.

Congrats on getting Best of EASL. So a couple of questions on the Phase III trial design. Beyond the 52-week biopsy endpoint, I was wondering if you can provide a bit more details. You're moving from the no-titration Phase II to starting with 1.2 mg and titrating. So can you just remind us of the rationale for the strategy, and then with the inclusion of both the 1.8 mg and the 2.4 mg arms for the primary endpoint, can you talk a little bit about the statistical design there? Does it need to succeed on both doses or how does that work?

No, thank you for the question. First, I want to remind you about the 48-week data that shows that both the 1.2 and 1.8 milligram doses produced efficacy; the 1.2 milligram dose had tolerability similar to placebo and the 1.8 had a bit more GI effect, and that was in a no-titration setting. So we believe we have upside with a single-step titration that will help improve tolerability. We've seen GI adverse events occurring within the first four weeks typically. So we believe that first step will really help because of the placebo-like tolerability for 1.2 mg. That's why we designed it that way. Regarding the dose arms, our anchor dose based on Phase II is 1.8 milligrams; our data support this as an efficacious dose, and tolerability at 48 weeks confirms this. We've seen added weight loss in the obesity program with the 2.4 milligram dose, and based on this, we believe there is potential for added efficacy. That's why we included it. On powering and statistical approach, we've taken a conservative approach and powered the study on the 1.8 milligram dose for the primary efficacy. The 2.4 milligram arm is included as an additional arm where we expect potential upside; it's somewhat exploratory relative to the primary powering, and we'll evaluate both arms at the 52-week endpoint.

Our next question comes from William Wood with B. Riley Securities.

Sort of two from us. Just curious how you're seeing the long-term treatment of patients with MASH on pemvidutide. Has there been any sort of evaluation of dose reductions or what happens when patients reduce dose or take less frequent dosing, and is that expected to be looked at in some of your upcoming trials, maybe possibly even after your Phase III reads out? And then also just a quick add-on or a follow-up to your EASL data: it looks like in the abstract of your cardiovascular presentation that we'll be getting some visceral adipose tissue data or similar. Could you confirm we'll be getting that data and how it might bolster the cardiovascular story?

Right. So on the dose reduction, we've explored this in our Phase II. We've seen very few patients reducing the dose and no significant discontinuation attributable to dose changes. Obviously, we'll be looking at this in our Phase III. We have put in place—up to the 2.4 mg dose—a mechanism where patients can reduce the dose if needed. However, we are designing the study to encourage patients to remain at the most efficacious dose, which is 1.8 mg or up to 2.4 mg. There is a whole system put in place to have those efficacious doses tested and to allow, if there were any GI tolerability issues, for dose reduction. We believe even with the current titration scheme proposed that we'll be able to minimize dose reductions and keep most patients on effective doses. On the lipid and cardiovascular risk assessments, we'll be looking at lipid profiles. We have shown some lipid benefits in previous studies, and we will include those analyses; the poster will include related assessments.

Our next question comes from Arabelle Ng with H.C. Wainwright.

I was just wondering: will PERFORMA use a prefilled autoinjector? And if it is given as an autoinjector, have you secured a partner for that? And then generally, are there any gating items you need to complete before you initiate the trial?

Maybe I'll start on the gating items first. As we said in the prepared remarks, and to stress, we're in the full start-up phase on the trial. It's about establishing the global infrastructure, ensuring the vendors are online and ready, initiation of the trial sites and ensuring that the clinical supply chain is ready to support initiation. All of that activity is ongoing and the start of the trial with initiation in the second half is what we're moving toward. Christophe, can you address the autoinjector?

For the PERFORMA Phase III study, we're not using autoinjectors in the trial itself. We're going to do a separate comparability study to validate autoinjectors ahead of potential launch. That's how we've approached that aspect. We've got good adherence with our current approach in the Phase II trials, so we'll continue using that approach in the pivotal trial and have the autoinjector ready for launch.

Our next question comes from Anupam Damani with Goldman Sachs (on behalf of Colleen Johnson).

Maybe can you just talk about, in terms of digital pathology and fibrosis, how should we think about translating outcomes based on these measures to the fibrosis improvement as it will be evaluated in the Phase III trial?

Yes. So there are two aspects. Obviously, there's the regulatory path that requires the biopsy read and that is how regulatory agencies are looking at this. For digital pathology, there are different tools. One is the AIM MASH assist, which is a tool that assists pathologists in reading and harmonizing features on biopsy slides, which should reduce variability and increase consensus between pathologists. That's one approach. The other approach is the continuous quantitative assessment we used in the Phase II study—LiverExplorer—which demonstrated an impact on fibrosis at 24 weeks. And another approach is qFibrosis, which we are presenting at EASL. We saw that when you decrease liver fat rapidly, as we've seen at 24 weeks, it can make it more challenging for pathologists to read fibrosis changes. Being able to subtract steatosis to focus on fibrosis is very valuable. These will be additional assessments that will confirm the biopsy reads from the pathologists through the AIM MASH assist. But clearly, in our Phase III, the primary endpoint will be based on the biopsy read using the AIM MASH tool. We'll have multiple pieces of evidence to cross-reference at week 52 for any accelerated approval discussions.

Our next question comes from Jonathan Wolleben with Citizens.

Two for me. MASH trials are large and take a long time to run but enrollment in incretin trials goes pretty fast. I'm wondering if you think about the pace of enrollment potentially being faster than expected in the MASH trial because of the potential dual benefit. And big picture-wise, you talk a little bit about differentiation. We're seeing more and more triple agonists announced. Do you think down the road dual agonists will be displaced by the triples that are becoming more popular and crowded as well?

On the first question, we expect that the weight loss benefit and the overall profile of pemvidutide will help enrollment. We've seen in other trials that incretin-related enrollment can be faster, and we are building a robust study that targets efficient and effective enrollment. The profile and weight loss is one component that we think will help with that.

Nothing else to add except that the study design is attractive because we have a couple of cohorts, which increases the chances for investigators to include their patients. Overall, the rate of enrollment is much higher in obesity trials where there is a strong weight-loss signal, and the design of PERFORMA should help.

On your question about differentiation versus triple agonists, we see an opportunity with pemvidutide to focus on our attributes of being direct-acting on the liver via glucagon in a 1:1 ratio with GLP-1, and the package of benefits we are seeing is competitive even versus metabolically forward triple agonists. The direct-acting component of pemvidutide hasn't been as clearly defined in some of the other approaches. We also believe our tolerability profile and simple titration could allow pemvidutide to be combined with other agents when appropriate, and our quality of weight loss—less rapid loss with better preservation of lean muscle mass—may be an advantage, especially in older MASH patients. We'll keep an eye on the evolving market, but we're confident in our ability to demonstrate differentiating benefits in Phase III and beyond.

Our next question comes from Tsan-Yu Hsieh with William Blair.

Sorry about the typographical noise earlier. Two questions: first, there are other GLP-1/glucagon assets that will have obesity datasets and muscle data presented at upcoming conferences. How do you interpret their obesity and muscle data without biopsy? Second, you mentioned tolerability a lot during the call. Looking back at the Phase II trials, MOMENTUM and IMPACT, do you have any persistence or adherence data—for example, percentage of patients who persisted through the trials or to the end—that could paint a picture of patients staying on therapy with pemvidutide?

Maybe we'll start with the adherence point because we've talked about that a lot. In the 48-week data, we observe a strong tolerability profile and high adherence: a large percentage of patients on pemvidutide at both doses stayed on therapy, even more so than placebo in some cases. Tolerability is not just avoidance of side effects but also the ability to get to an effective dose and stay on therapy, which is important in real-world physician decision-making.

Yes. In IMPACT and MOMENTUM, we saw a clear dose response in favor of higher doses of pemvidutide, where patients stayed on treatment. This is encouraging for chronic therapy settings where keeping patients on an efficacious dose long term is key. We've also received qualitative feedback from investigators running other GLP-1 and co-agonist studies that pemvidutide is a very different approach in terms of treatment satisfaction. Regarding the other asset you mentioned, survodutide, we've seen comparable weight loss in some settings, but a major challenge appears to be tolerability and the need for a very long and complex titration scheme. In some reports for that drug, discontinuation rates were close to one in four patients. By contrast, pemvidutide's data show a much simpler titration and better tolerability. The ratio of glucagon to GLP-1 differs—survodutide appears more GLP-1–dominant—while our 1:1 ratio may be important for liver targeting. Again, in chronic settings, adherence and the ability to stay on treatment matter a great deal, and we see advantages for pemvidutide in that regard. We'll continue to evaluate these aspects in the Phase III PERFORMA trial.

That concludes today's question-and-answer session. I'd like to turn the call back to Jerry Durso for closing remarks.

Thanks, operator. We've made significant progress as we evolve into a late-stage company. Altimmune is focused on execution, and we're committed to further advancing our promising, meaningfully differentiated liver therapy and creating long-term value for our shareholders. It's an exciting time here, and I look forward to updating you on our progress as we move forward. Thanks a lot for joining today, and everybody, have a great day. Take care.

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