Executive Summary / Key Takeaways

• Altimmune is a clinical-stage biopharmaceutical company focused on leveraging its lead asset, pemvidutide, a differentiated GLP-1/glucagon dual receptor agonist, across large and growing markets in liver and cardiometabolic diseases.
• Pemvidutide demonstrates potentially class-leading differentiation through its balanced mechanism, showing robust liver fat reduction, significant weight loss with superior lean mass preservation, favorable lipid improvements, and a promising tolerability and safety profile compared to existing and emerging therapies.
• Upcoming catalysts, including the top-line data readout from the Phase 2b IMPACT trial in MASH (expected Q2 2025) and the initiation of Phase 2 trials in Alcohol Use Disorder (AUD) and Alcohol Liver Disease (ALD) in Q2/Q3 2025, represent significant potential value inflection points.
• The company has achieved regulatory alignment with the FDA on a comprehensive four-pivotal study Phase 3 program for obesity, de-risking the path forward in this indication and positively impacting other development efforts.
• Recent financing activities, including ATM proceeds and a new credit facility providing access to up to $100 million, are intended to provide runway to fund operations through key near-term clinical milestones and support the planned initiation of the MASH Phase 3 program in early 2026.

Altimmune's Dual-Action Strategy in a Crowded Landscape

Altimmune, Inc. is a late clinical-stage biopharmaceutical company strategically focused on developing novel peptide-based therapeutics for significant unmet needs in liver and cardiometabolic diseases. At the core of its pipeline is pemvidutide, a GLP-1/glucagon dual receptor agonist. This focus solidified following the 2019 acquisition of Spitfire Pharma, which brought pemvidutide into the fold and pivoted Altimmune towards its current therapeutic areas. The company's journey has been marked by a consistent emphasis on R&D and capital raising, typical of a biotech advancing promising clinical candidates.

The landscape for metabolic and liver diseases is vast and increasingly competitive. Obesity is a global health crisis driving numerous comorbidities, while Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a leading cause of liver transplantation. Emerging areas like Alcohol Use Disorder (AUD) and Alcohol Liver Disease (ALD) also represent large patient populations with limited effective treatments, where obesity is often a complicating factor. Altimmune's strategy is to position pemvidutide not just as another entrant, but as a potentially differentiated, foundational therapy across these interconnected conditions, leveraging its unique mechanism of action.

Pemvidutide's key differentiator lies in its balanced 1:1 agonism of both the GLP-1 and glucagon receptors. While GLP-1 agonism is well-established for appetite suppression and weight loss, glucagon agonism is believed to enhance energy expenditure and, critically, exert direct effects on hepatic fat metabolism. This dual action is designed to mimic the complementary benefits of diet and exercise. The company highlights several quantifiable benefits stemming from this mechanism observed in clinical trials to date.

In the Phase 1b MASLD study, pemvidutide demonstrated class-leading liver fat reduction of up to 76.4% at 24 weeks. This figure is notably higher than the approximately 65% seen with FGF21 agonists and 58-62% reported for survodutide, and is considered a principal driver of MASH resolution and fibrosis improvement. Furthermore, in the MOMENTUM Phase 2 obesity trial, pemvidutide showed class-leading preservation of lean mass, with only 21.9% of total weight loss attributed to lean mass over 48 weeks, significantly better than the approximately 40% lean mass loss reported with semaglutide. This lean mass preservation is crucial for maintaining function, particularly in elderly or sarcopenic individuals, and may impact bone health.

Beyond weight and liver fat, pemvidutide has demonstrated robust reductions in serum lipids. In subjects with elevated lipids, a 21% reduction in LDL cholesterol was observed, comparable to the effects of statins and exceeding the more modest 3-5% LDL/total cholesterol reduction seen with semaglutide in the SELECT trial. This lipid-lowering effect, combined with weight loss, is particularly relevant given that cardiovascular events are the primary cause of mortality in F2 and F3 MASH patients. The company also emphasizes pemvidutide's favorable tolerability profile, noting the ability to administer the drug without dose titration, unlike many other incretins, and reporting low adverse event discontinuation rates (<1% in the IMPACT trial). Importantly, the FDA's review of Altimmune's safety database identified no safety signals, allowing the company to plan its obesity Phase 3 program without a committed cardiovascular outcomes trial, a point of differentiation compared to survodutide.

Altimmune's strategic positioning against competitors like Novo Nordisk (NVO), Eli Lilly (LLY), Viking Therapeutics (VKTX), and others hinges on these quantifiable advantages. While NVO and LLY dominate the current obesity market with established GLP-1s and possess vast scale and financial resources (NVO with ~26% annual revenue growth, 35% operating margins; LLY with ~25% revenue growth, 25% operating margins), Altimmune aims to carve out market share by offering a differentiated profile that addresses specific patient needs, such as better body composition and direct liver benefits. FGF21 agonists like RezDiffra target liver endpoints but lack significant weight loss, creating a potential opportunity for pemvidutide as a single agent addressing both. Viking Therapeutics is an earlier-stage competitor also developing metabolic therapies, but pemvidutide appears to show superior lean mass outcomes. Altimmune's high cash burn and negative margins are typical of a clinical-stage biotech and represent a vulnerability compared to the profitability of large pharma, necessitating continued financing efforts.

Performance and Financial Foundation

As a clinical-stage company, Altimmune's financial performance reflects its significant investment in research and development rather than product revenue. For the three months ended March 31, 2025, the company reported negligible revenue of $5 thousand. Research and development expenses were $15.8 million, a decrease of 26% from $21.5 million in the same period of 2024. This reduction was primarily driven by decreased costs related to the IMPACT MASH trial, other clinical activities, and manufacturing, partially offset by increased spending on the startup of the new AUD and ALD trials. General and administrative expenses increased by 13% to $6.0 million, mainly due to higher labor and professional fees. The net loss for the quarter was $19.6 million, an improvement from the $24.4 million net loss in Q1 2024, partly aided by a $0.7 million discrete tax benefit.

As of March 31, 2025, Altimmune held $149.9 million in cash, cash equivalents, restricted cash, and short-term investments. The company's accumulated deficit stood at $581 million. Management projects that this cash position, combined with expected R&D incentives, is sufficient to fund operations for at least 12 months from the May 13, 2025 financial statement issuance date. Recognizing the need for substantial capital to advance its planned clinical trials, particularly the large Phase 3 obesity and MASH programs, Altimmune has been actively bolstering its liquidity.

During Q1 2025, the company raised approximately $4.6 million net through its new 2025 at-the-market (ATM) offering program and an additional $30.2 million net from the expired 2023 ATM program. Subsequent to the quarter, an additional $16.3 million net was raised through the 2025 ATM in April and early May 2025. Further enhancing its financial flexibility, Altimmune secured a credit facility with Hercules Capital (HTGC) on May 13, 2025, providing access to up to $100 million in term loans. The initial tranche of $15 million was funded at closing, with subsequent tranches contingent on milestone achievements. This facility, maturing in June 2029 with an initial interest-only period, provides optionality and extends the potential cash runway, supporting the company's strategy to advance its programs independently while seeking a strategic partnership, particularly for the obesity indication. Net cash provided by financing activities was $34.1 million in Q1 2025, primarily reflecting the ATM proceeds.

Outlook and Upcoming Catalysts

Altimmune is poised for a potentially transformative period driven by several key catalysts expected in the near term. The most significant is the anticipated top-line data readout from the Phase 2b IMPACT trial of pemvidutide in MASH, expected in the second quarter of 2025. This trial is designed to assess MASH resolution and fibrosis improvement at 24 weeks, and a positive outcome would be a critical validation of pemvidutide's direct liver effects and its potential to be the first incretin to achieve statistical significance on these endpoints at such an early time point, combined with meaningful weight loss.

Building on the expected IMPACT data, Altimmune intends to hold an End of Phase 2 meeting with the FDA for the MASH indication in the fourth quarter of 2025. This meeting is crucial for aligning on the design of a registrational Phase 3 program, which the company plans to initiate in early 2026.

In parallel, Altimmune is expanding pemvidutide's reach into new indications. Following FDA clearance of INDs for Alcohol Use Disorder (AUD) and Alcohol Liver Disease (ALD), the company expects to initiate Phase 2 trials in AUD in Q2 2025 and ALD in Q3 2025. These trials aim to demonstrate pemvidutide's potential to address alcohol consumption, liver damage, and associated metabolic comorbidities in these underserved patient populations. Proof-of-concept data from at least one of these new indication trials is expected in 2026, providing additional potential value drivers. The company is also continuing R&D efforts on an oral formulation of pemvidutide, with the hope of nominating a candidate for development by the end of 2025, which could offer future lifecycle management opportunities and patient convenience.

Management's confidence in this outlook is rooted in the preclinical and clinical data generated to date, particularly the differentiated profile of pemvidutide and the positive interactions with the FDA, including the successful End of Phase 2 meeting for the obesity program which de-risked the regulatory pathway for that indication. The secured financing is intended to provide the necessary resources to execute on these near-term milestones.

Risks and Challenges

Despite the promising outlook, investing in Altimmune carries significant risks inherent to the biotechnology sector. The success of the company is heavily reliant on the outcome of its clinical trials, particularly the upcoming IMPACT readout. Failure to achieve statistical significance on primary or key secondary endpoints, or unexpected safety findings, could severely impact the investment thesis and stock valuation. Regulatory hurdles remain, including successful completion of End of Phase 2 meetings and ultimately gaining marketing approval, which is a lengthy and uncertain process.

Financing risk is also pertinent. While recent funding has extended the cash runway, the planned Phase 3 programs in MASH and obesity will require substantial capital beyond current resources. The company's ability to secure additional funding through equity, debt, or partnerships will be critical. The terms of the new Hercules Capital loan include customary covenants that could restrict operational flexibility, and an event of default could trigger accelerated repayment obligations.

The competitive landscape is intense, with large, well-funded pharmaceutical companies developing and launching competing therapies. Pemvidutide must demonstrate clear and compelling differentiation to capture market share against established players and other emerging therapies. Macroeconomic factors, including inflation and potential supply chain disruptions, could also impact operational costs and timelines. While recent legal challenges have been dismissed, the company remains subject to potential litigation in the ordinary course of business.

Conclusion

Altimmune stands at a pivotal juncture, with its investment story largely centered on the potential of pemvidutide to differentiate itself in the competitive metabolic and liver disease markets. The drug's balanced GLP-1/glucagon agonism has demonstrated promising results across multiple metrics – liver fat reduction, lean mass preservation, lipid improvement, and tolerability – suggesting a profile that could offer a more complete solution for patients with MASH and obesity, and potentially address unmet needs in AUD and ALD.

The upcoming top-line data from the IMPACT trial in Q2 2025 is the most critical near-term catalyst, with the potential to validate pemvidutide's efficacy in MASH at an early time point. Successful execution on the planned Phase 3 programs and the initiation of trials in new indications will be key to realizing the full potential of this asset. While financial resources have been bolstered, the need for future funding remains a significant consideration. For investors, the story is one of potential upside driven by clinical success and differentiation in large markets, balanced against the inherent risks of drug development and the challenges of competing with industry giants. The coming months will be crucial in determining whether pemvidutide can fulfill its promise and establish Altimmune as a significant player in these therapeutic areas.