Pegozafermin: A GlycoPEGylated FGF21 Analog Designed to address metabolic issues that drive liver and cardiometabolic diseases
Severe Hypertriglyceridemia (SHTG) is a condition characterized by elevated levels of triglycerides, a type of fat, in the blood. Triglycerides are stored in fat cells and provide energy when needed. Over time, stubbornly high levels of triglycerides can wreak havoc on the body, causing fat to accumulate excessively in vital organs like the liver, pancreas, heart, and muscles.

This insidious buildup, known as lipotoxicity, disrupts the body's normal functioning and can lead to insulin resistance, a precursor to diabetes.

Fibroblast growth factor 21 (FGF21) is a critical metabolic regulator that plays a crucial role in glucose and lipid metabolism. It is a member of the FGF superfamily and is produced primarily by the liver.
As a master metabolic regulator, FGF21 exerts its effects through several mechanisms. It regulates glucose metabolism by increasing insulin sensitivity and improving glucose uptake in peripheral tissues. Additionally, it promotes fatty acid oxidation and reduces lipogenesis, leading to a decrease in circulating triglycerides and an increase in energy expenditure. The multifaceted effects of FGF21 on glucose and lipid metabolism, along with its role in appetite regulation, make it an attractive target for the treatment of metabolic diseases.

89bio's Pegozafermin is an investigational FGF21 analog engineered using glycoPEGylation technology with site-specific mutations designed to have prolonged half-life compared to native FGF21 hormone.

Pegozafermin is Designed to Prolong Biologic Activity Due to Proprietary GlycoPEGylation and therefore has the potential to help improve the underlying metabolic abnormalities that drive liver and cardiometabolic diseases.

Pegozafermin's downstream effects include lipid reduction, inflammation and fibrosis inhibition, insulin resistance improvement, and oxidative stress reduction. It restores liver free fatty acid balance, mitigating fat buildup, inflammation, and injury that drive fibrosis, potentially leading to improved liver histology. Additionally, it increases adiponectin production, an adipose tissue hormone with insulin-sensitizing, anti-inflammatory, and anti-fibrotic properties.

Through clinical trials, pegozafermin has proven effective in enhancing liver function and reducing liver fat content in individuals with nonalcoholic steatohepatitis (NASH). Moreover, it offers broader metabolic advantages, such as lowering triglyceride levels in patients with severe hypertriglyceridemia (SHTG).

By targeting these crucial factors, pegozafermin has the potential to mitigate the complications and mortality risks associated with cardiometabolic disorders.

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