Altimmune Sets Pemvidutide’s Phase 3 MASH Playbook as AUD Data Near

Key Points

• Altimmune is positioning pemvidutide as a Phase 3 MASH candidate, emphasizing its GLP-1/glucagon dual mechanism, tolerability, and potential differentiation in liver disease. Management said the company is financially prepared for late-stage development after raising nearly $500 million over the past 18 months.
• The planned Phase 3 MASH trial will test 1.8 mg and 2.4 mg doses, use a 52-week interim histology readout that could support accelerated approval, and enroll biopsy-proven and NIT-screened F2/F3 patients. Altimmune expects enrollment to start in the second half of the year, with results anticipated in 2029.
• Altimmune also expects Phase 2 data in alcohol use disorder next quarter, with a focus on reducing heavy drinking days and assessing liver-related outcomes. Management said AUD and alcohol-associated liver disease could become additional development paths if the data are supportive, potentially with non-dilutive financing or a partner.

Altimmune NASDAQ: ALT management used an appearance at the Goldman Sachs Global Healthcare Conference to outline the company’s focus on pemvidutide, its lead metabolic and liver disease drug candidate, and to discuss the planned Phase 3 program in metabolic dysfunction-associated steatohepatitis, or MASH.

Jerry Durso, Altimmune’s president, CEO and chairman, said pemvidutide was the primary reason he joined the company, first as a board member last year and then as CEO at the beginning of this year. Durso said the drug’s combination of GLP-1 activity and glucagon activity made it “uniquely suited for liver disease,” with the GLP component targeting metabolic factors such as weight loss and the glucagon component providing what he described as direct activity on the liver.

Durso also highlighted pemvidutide’s proprietary EuPort domain, which he said could be an important contributor to tolerability. He said Altimmune’s current strategy emphasizes liver disease as the primary focus for the asset.

Management Highlights Strategic Priorities

Durso said Altimmune’s priorities over the past year have included strengthening the company’s management team, preparing for late-stage development, refining how it communicates pemvidutide’s potential differentiation and positioning the company financially for a Phase 3 program.

Greg Weaver, Altimmune’s CFO, said the company has raised “approaching $500 million” over the past 18 months. He noted that MASH trials can cost in the range of $400 million and said Altimmune is now “well-positioned” with additional optionality if needed.

Weaver also said investor engagement and clearer messaging around Altimmune’s focus on MASH and liver disease have been important as the company prepares for its next stage of development.

Pemvidutide’s Role in a Developing MASH Market

Durso said the MASH treatment market is maturing, with the first approved therapies now available and more mechanisms expected to enter the market. He said the disease’s complexity likely means multiple mechanisms and combinations will be needed over time.

Durso said Altimmune is thinking about where pemvidutide could fit in a future market with more treatment options, rather than only the current market. He pointed to potential patient segments including those who may have difficulty tolerating other therapies, patients at risk of sarcopenia and patients who may benefit from a simpler titration schedule.

He also said pemvidutide could become a potential combination partner because of what the company believes could be a favorable safety and tolerability profile, along with a simple titration approach.

Phase 2 Data and Differentiation

Durso reviewed prior Phase 2 MASH results, saying pemvidutide showed early activity on MASH resolution at 24 weeks. While the company did not see statistical significance on fibrosis by biopsy at 24 weeks, Durso said non-invasive tests suggested antifibrotic activity was already emerging.

At 48 weeks, he said Altimmune saw improvement across non-invasive tests, including FibroScan and ELF, and that the company believes 52 weeks is the appropriate time point for a biopsy-based fibrosis readout in Phase 3. Durso noted there was no biopsy at 48 weeks in the Phase 2 program.

Durso also highlighted adherence and tolerability, saying pemvidutide had an “extremely low discontinuation rate” in the 48-week data and that more patients stayed on the 1.8 milligram dose than on placebo. He compared that with Phase 2 MASH data for survodutide, saying that program had a discontinuation rate above 20%.

Durso said pemvidutide has a one-to-one ratio of glucagon and GLP-1 agonism, while survodutide is more weighted toward GLP-1 activity. He said the ratio, the molecule itself and the EuPort domain may all be relevant to tolerability and differentiation within the glucagon/GLP-1 class.

Phase 3 MASH Trial Plans

Altimmune’s planned Phase 3 MASH program will include a 52-week interim histology readout that Durso said could support an accelerated approval filing, along with a longer-term outcomes component. The study will evaluate two doses of pemvidutide: 1.8 milligrams and 2.4 milligrams.

Durso said the 1.8 milligram dose is supported by the Phase 2 data, while the 2.4 milligram dose offers potential upside on efficacy and in certain subpopulations. The Phase 3 trial will include a simple one- or two-step titration over four or eight weeks, depending on dose.

The study will include biopsy-proven F2 and F3 MASH patients, as well as a separate cohort of NIT-screened F2 and F3 patients. Durso said the biopsy cohort will support the 52-week efficacy analysis, while both cohorts together will contribute to the safety database and longer-term outcomes analysis.

Durso said the trial will be the first Phase 3 program to use the AIM-MASH AI Assist tool, which is intended to support pathologists in histology reads and reduce variability. He said Altimmune continues to guide for patient enrollment to begin in the second half of the year, with a readout anticipated in 2029. He said MASH trials typically take 18 to 24 months to enroll, and Altimmune is targeting the lower end of that range.

Alcohol Use Disorder and Alcohol-Associated Liver Disease

Durso also discussed pemvidutide’s development in alcohol use disorder, or AUD, and alcohol-associated liver disease, or ALD. He said Altimmune sees a rationale for the drug in these areas because it may address both drinking behavior through GLP-1-related effects on craving and liver-related effects through its glucagon activity.

The company expects Phase 2 data in AUD next quarter. Durso said the primary endpoint is a reduction in the number of heavy drinking days, with additional measures including liver enzymes, weight and secondary endpoints such as World Health Organization classification.

Durso said there are about 12 million people with AUD and roughly half that number with ALD, with no approved drugs in ALD and only older options in AUD. Weaver said that if Phase 3 development in AUD or ALD is supported by the data, Altimmune would likely prefer non-dilutive financing options, which could include a partner, strategic transaction or regional arrangement.

About Altimmune NASDAQ: ALT

Altimmune, Inc is a clinical-stage biopharmaceutical company headquartered in Gaithersburg, Maryland, dedicated to the development of vaccines and immunotherapeutics. The company leverages proprietary technology platforms to create intranasal vaccine candidates and novel therapies targeting liver diseases and metabolic disorders. Altimmune's approach emphasizes the stimulation of both systemic and mucosal immune responses to address unmet medical needs in infectious and chronic conditions.

Among its lead programs, NasoVAX is an investigational intranasal influenza vaccine designed to provide broad, long-lasting protection through a single, non-invasive dose.

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