Altimmune Details Pemvidutide’s Path Toward a Liver-Disease Franchise

Key Points

• Altimmune is building a liver-disease franchise around pemvidutide, a dual glucagon/GLP-1 agonist targeting MASH, alcohol use disorder (AUD) and alcohol-related liver disease (ALD).
• The company is advancing the Phase 3 PERFORMA trial in F2/F3 MASH, testing 1.8 mg and 2.4 mg doses over 52 weeks with AI-assisted biopsy analysis and monthly titration designed to improve fibrosis assessment, tolerability and adherence.
• Altimmune plans to align with regulators on a Phase 3 AUD program and believes pemvidutide’s tolerability, weight-loss profile and potential liver benefits could differentiate it from competing incretin therapies; its $519 million cash balance is expected to fund the MASH trial through completion.

Altimmune NASDAQ: ALT executives outlined the company’s strategy to build a liver-disease franchise around pemvidutide, a dual glucagon/GLP-1 agonist being developed for metabolic dysfunction-associated steatohepatitis, or MASH, alcohol use disorder, or AUD, and alcohol-related liver disease, or ALD.

Speaking at a Stifel session, Chief Executive Officer Jerome Durso said pemvidutide’s potential across several liver-related conditions was a primary reason he joined the company. He described the drug’s balanced dual mechanism, clinical tolerability and ability to keep patients on therapy as central elements of its development strategy.

“What we continue to see evidence of as the data emerges is a differentiated opportunity across MASH,” Durso said, adding that Phase 2 AUD data released in July created an additional opportunity for the company’s liver-focused portfolio.

MASH Program and PERFORMA Trial

Altimmune is advancing pemvidutide in the Phase 3 PERFORMA trial in patients with F2 and F3 MASH. Chief Medical Officer Christophe Arbet-Engels said the trial includes placebo, 1.8-milligram and 2.4-milligram treatment arms. The company’s statistical powering is based on results observed with the 1.8-milligram dose in Phase 2, while the 2.4-milligram arm is intended to assess potential additional benefit.

Arbet-Engels said Phase 2 findings showed improvements in noninvasive tests and biological markers consistent with an anti-fibrotic effect, including continued improvement between 24 and 48 weeks. He noted that the company did not see an early fibrosis outcome at 24 weeks, which he said had been anticipated.

The Phase 3 trial will use a three-pathologist biopsy-reading process, supported by AIM-MASH Assist, an artificial intelligence-assisted tool intended to reduce variability in pathology assessments. Altimmune said it has trained pathologists and tested the approach ahead of the trial.

Key features of PERFORMA include a 52-week assessment period and simplified monthly titration. The company expects the longer study duration to better assess fibrosis improvement and said the titration approach could further reduce early gastrointestinal events and support treatment adherence.

Arbet-Engels characterized success as a positive trial demonstrating MASH resolution and fibrosis improvement, while also assessing effect size, patient subgroups, weight loss, discontinuations and adherence. The company will additionally evaluate the quality of weight loss, including measures related to lean mass preservation, using MRI-PDFF, blood biomarkers and functional testing.

Positioning Against Other Incretin-Based Therapies

Altimmune executives emphasized what they view as pemvidutide’s differentiated molecular design. Arbet-Engels said pemvidutide has a 1:1 glucagon-to-GLP-1 ratio and strong affinity for both receptors. In contrast, he described survodutide as having a 7:1 glucagon-to-GLP-1 ratio and retatrutide as having substantially different receptor affinities.

The company also highlighted tolerability as a potential commercial and clinical differentiator. Arbet-Engels said pemvidutide’s EuPort domain is designed to slow delivery of the drug, reducing peak concentration and delaying the time to peak concentration. He said this profile supported favorable tolerability in Altimmune’s MASH trials.

Chief Commercial Officer Linda Richardson said the company believes pemvidutide could be relevant for patients who cannot tolerate GLP-1 therapy over time, who do not achieve desired efficacy with available options, or who may be at risk of sarcopenia. She also said the company sees potential opportunities both as a first-line treatment and as an add-on option in areas where other therapies may have limitations.

AUD and ALD Development Plans

Durso said Altimmune’s Phase 2 RECLAIM results in AUD were encouraging, citing consistency across drinking-related endpoints, including two endpoints he said are approvable by the FDA. He also pointed to weight loss, safety and tolerability findings, as well as results from PEth testing, which is used to assess alcohol consumption.

Arbet-Engels added that exploratory FIB-4 findings provided indications of potential liver-related benefits, which the company plans to assess more rigorously in later-stage development.

Altimmune plans to hold an end-of-Phase-2 meeting with regulatory agencies to align on a Phase 3 AUD program. Durso said the company sees an opportunity to study a broad moderate-to-severe AUD population, including patients with active liver disease.

Arbet-Engels said AUD and ALD populations appear to overlap substantially, including through patterns of heavy drinking and obesity. While the company collected more extensive liver measurements in its ALD trial than in the Phase 2 AUD study, it expects future AUD studies to more comprehensively evaluate potential liver benefits.

Funding and Enrollment

Chief Financial Officer Greg Weaver said Altimmune had $519 million as of June 30 and that the balance sheet was sufficient to fund the MASH trial through completion. For a potential Phase 3 AUD program, he said the company is focused on non-dilutive funding options, which could include strategic partnerships, clinical-trial financing or royalty-based structures.

The company also reported early enthusiasm from investigators for the PERFORMA study. Arbet-Engels said Altimmune moved from financing to dosing its first patient in about 90 days and cited the study’s weight-loss component, AI-assisted pathology process and ability for investigators to recycle screened patients between biopsy and noninvasive-test cohorts as attractive design elements.

About Altimmune (NASDAQ:ALT)

Altimmune, Inc is a clinical-stage biotechnology company focused on developing treatments for obesity and liver diseases. The company's lead product candidate is pemvidutide, a dual GLP-1/glucagon receptor agonist being studied for chronic weight management and metabolic dysfunction-associated steatohepatitis (MASH), a form of liver disease associated with metabolic disorders.

Altimmune's research programs are designed to address diseases with significant unmet medical needs, including obesity-related complications and conditions involving liver inflammation and fibrosis.

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