Pemvidutide

Pemvidutide is a novel, investigational, peptide-based GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and metabolic dysfunction-associated steatohepatitis (MASH). Activation of the GLP-1 and glucagon receptors is believed to mimic the complementary effects of diet and exercise on weight loss, with GLP-1 suppressing appetite and glucagon increasing energy expenditure. Glucagon is also recognized as having direct effects on hepatic fat metabolism, leading to rapid reductions in levels of liver fat and serum lipids. In clinical trials, once-weekly pemvidutide has shown compelling weight loss, robust reductions in triglycerides, LDL cholesterol, liver fat content and blood pressure with a clean safety profile to date. The U.S. FDA has granted Fast Track designation to pemvidutide for the treatment of MASH. Pemvidutide has recently completed the MOMENTUM Phase 2 obesity trial and is being studied in the IMPACT Phase 2b MASH trial.

There are over 1 billion people worldwide with obesity and it carries with it an economic burden of $705 billion in the United States alone. It is linked to conditions such as hypertension, cardiovascular complications, diabetes, dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). Given the prevalence of obesity comorbidities, there is a tremendous need for treatment optionality to address the obesity and directly impact the comorbidities.

It is estimated that ~80 million people in the United States have MASLD. The excess liver fat that characterizes MASLD can cause chronic inflammation often leading to fibrosis and eventually liver cirrhosis and increased risk for cardiovascular disease. There are currently no approved treatments for MASH.

Our Phase 2b IMPACT MASH trial is being conducted in approximately 190 subjects with and without diabetes.  The key endpoints will be MASH resolution and fibrosis improvement after 24 weeks of treatment, with subjects followed for an additional 24 weeks for assessment of safety and additional biomarker responses.

Results from a 24-week Phase 1b randomized, placebo-controlled study of pemvidutide in subjects with MASLD showed:

• Class-leading relative reductions in liver fat
• ~55% of subjects had their liver fat content reduced to the normal range in just 12 weeks at the 1.8 mg dose
• Significant reductions of alanine aminotransferase (ALT) and corrected T1 (cT1), two independent measures of liver inflammation
• Meaningful weight loss in addition to the liver effects

IMPACT Phase 2b MASH trial top line data expected in Q1 2025.

Pemvidutide’s clinically-demonstrated combined capability to significantly reduce body weight, liver fat content and serum lipids is an unmatched profile relative to other obesity and MASH drugs and therapeutic candidates. Given this profile, pemvidutide, if approved, has the potential to be an important treatment option for patients with obesity, especially individuals with MASLD/MASH or dyslipidemia or other related comorbidities.