Fibroblast growth factor 21 (FGF21) is a protein that in mammals is encoded by the FGF21 gene. FGF21 is a stress-inducible hormone that has important roles in regulating energy balance and glucose and lipid homeostasis. FGF21 composes of the co-receptors FGF receptor 1 and β-Klotho, and is the primary endogenous agonist of the FGF21 receptor. Furthermore, FGF21 regulates simple sugar intake and preferences for sweet foods via signaling through FGF21 receptors in the paraventricular nucleus of the hypothalamus. FGF21 is beneficial in rodents or non-human primates with a range of obesity-related metabolic complications. More importantly, FGF21 shows considerable pharmacological benefits, including a reduction in fat mass and alleviation in hyperglycemia, insulin resistance, dyslipidemia, cardiovascular disorders, and non-alcoholic steatohepatitis (NASH). However, native FGF21 is unsuitable for widespread use owing to its poor pharmacokinetic properties. Therefore, it is necessary to develop some analogs of FGF21 for the study of metabolic diseases.

Pegozafermin is a site-specific glycoPEGylated analogue of FGF21.

This compound demonstrates significant benefit in triglyceride (TG) reduction as well as improvements in liver fat and glycemic control. In addition, Pegozafermin (BIO89-100) significantly improves the levels of TG, non-HDL cholesterol, and LDL-C and increases adiponectin. Especially, Pegozafermin has the potential for the study of NASH and severe hypertriglyceridemia (SHTG). For example, subcutaneously injected with Pegozafermin (0-1 mg/kg) every week in spontaneously diabetic cynomolgus monkeys. The results show that it reduces body weight, food intake, glucose, insulin, HbA1c, and serum lipids. Moreover, Pegozafermin also increases adiponectin levels and improves oral glucose test results.

To sum up, Pegozafermin is a site-specific FGF21 analog and has the potential for the study of NASH.


[1] Juan Pablo Frias, et al. Journal of the Endocrine Society. 03 May 2021.

[2] Moti Rosenstock, et al. Conference: EASL Vienna 2019.