Pemvidutide

What is Pemvidutide*

Pemvidutide is an investigational peptide with balanced 1:1 glucagon/GLP-1 dual receptor agonist activity, in development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), alcohol use disorder (AUD) and alcohol-associated liver disease (ALD). The activation of glucagon receptors results in direct effects on the liver, while GLP-1 receptors mediate metabolic effects such as appetite suppression and weight loss and are involved in pathways related to craving and reward. The proprietary EuPort structure prolongs serum half-life and likely contributes to controlled absorption, allowing for weekly dosing and potentially reduced gastrointestinal side effects.

The U.S. Food and Drug Administration granted Fast Track designations to pemvidutide for the treatment of MASH and AUD, as well as Breakthrough Therapy Designation for MASH.

Pemvidutide was evaluated in the 48-week IMPACT Phase 2b trial in MASH, which demonstrated statistically significant histological MASH resolution without worsening of fibrosis in up to 58% of patients, against 20% in placebo at 24 weeks. Non-invasive tests (NITs) including liver stiffness measurement (FibroScan®); Enhanced Liver Fibrosis score (ELF); cT1; PRO-C3; ALT (Alanine aminotransferase); and MRI-PDFF (Magnetic Resonance Imaging-Proton Density Fat Fraction), as well as measures of combined NITs supported the resolution of MASH and were consistent with reductions in liver fibrosis. These findings were further supported by analyses using HistoIndex qFibrosis® and Liver Explore.

After 48 weeks of treatment, NITs of liver fibrosis were further improved compared to those seen at 24 weeks. Measures of combined NITs showed that the proportion of patients achieving both a ≥0.5 reduction in ELF and a ≥30% reduction in Liver Stiffness Measurement (LSM) at week 48 was 27.8% for pemvidutide 1.2 mg (p<0.001) and 32.4% for pemvidutide 1.8 mg (p<0.0001), compared to 3.2% with placebo. Pemvidutide demonstrated a generally well-tolerated safety and tolerability profile without dose titration leading to improved adherence, with a discontinuation rate of 1%, which was lower than placebo.

In August 2026, the Company initiated the PERFORMA Phase 3 trial, a global, randomized, double-blind, placebo-controlled, parallel-group study of pemvidutide in patients with MASH, which is intended to serve as the registration study for pemvidutide.

Altimmune also continues to advance development of pemvidutide for AUD and ALD. In July 2026, the Company announced positive topline results from the RECLAIM Phase 2 trial in AUD, that showed pemvidutide achieved a statistically significant and clinically meaningful reduction in heavy drinking days, the primary endpoint of the trial. Important secondary endpoints were also met, including a 2-level reduction in World Health Organization risk drinking levels and zero heavy drinking days, both recognized by the FDA as registrational endpoints.

In August 2026, the Company announced that it had completed enrollment of the RESTORE Phase 2 trial in ALD.

Pemvidutide: Balanced 1:1 Glucagon/GLP-1 Dual Receptor Agonist

Pemvidutide Balanced Glucagon GLP1 Dual Receptor Agonist

Pemvidutide Aims to Address Both the Cause and Consequence of Serious Liver Diseases

Pemvidutide Aims to Address Both the Cause and Consequence of Serious Liver Diseases

Pemvidutide Being Studied for the Treatment of MASH

There are an estimated 16-17 million adults (5% of the U.S.) population living with MASH in the U.S. The MASH prevalence is projected to rise to 23.2 million adults (7.9% increase) by 2050. MASH is driven by underlying metabolic dysfunction, which can lead to the accumulation of liver fat, inflammation and progressive fibrosis. Over time, this damage can advance to cirrhosis or other serious liver-related complications. Effective treatments are needed that address both the underlying metabolic drivers of MASH and the resulting liver disease.

The IMPACT Phase 2b MASH trial was a 48-week study of pemvidutide in approximately 190 patients with MASH, with and without diabetes. The trial assessed MASH resolution and fibrosis improvement by biopsy at Week 24, followed by an additional 24 weeks of treatment to evaluate safety and changes in non-invasive measures of liver inflammation and fibrosis. The trial met its primary endpoint of MASH resolution without worsening of fibrosis at Week 24. Additional analyses at Week 24 showed improvements in measures of liver fat, inflammation and fibrosis, including quantitative digital pathology and multiple non-invasive tests. At Week 48, pemvidutide demonstrated continued improvements in non-invasive markers of liver inflammation and fibrosis, together with improvements in metabolic measures and weight loss. Pemvidutide, without dose titration, also maintained a generally favorable tolerability profile, and a lower rate of treatment-related discontinuation than placebo. These findings supported the advancement of pemvidutide into the PERFORMA Phase 3 trial in MASH.

Compelling Phase 2 Data in MASH

Compelling Phase 2 Data in MASH

Pemvidutide for the Treatment of Alcohol Use Disorder (AUD) and Alcohol-Associated Liver Disease (ALD)

Pemvidutide for the Treatment of AUD and ALD

In AUD, the RECLAIM Phase 2 trial met its primary endpoint with a highly statistically significant reduction in heavy drinking days (HDD) versus placebo, with consistent positive results across important secondary endpoints, including the World Health Organization (WHO) Risk Drinking Levels (RDL), zero HDD and phosphatidyl ethanol (PEth) levels. A generally favorable tolerability profile was observed in the trial. Altimmune plans to request an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) based on the results of the trial.

In August 2026, Altimmune announced completion of enrollment of the RESTORE Phase 2 trial in ALD, with topline data expected in the second half of 2027.

Summary

Pemvidutide represents a differentiated approach to the treatment of serious liver diseases like MASH, AUD and ALD. The balanced glucagon and GLP-1 activities of pemvidutide along with the clinical data observed to date support its continued investigation as a potential treatment for MASH, AUD and ALD and their related comorbidities.

*Pemvidutide is investigational and has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory authority. Safety and efficacy have not been established. There is no guarantee that it will successfully complete clinical development or receive regulatory approval.