89Bio (ETNB) RBC Capital Markets Global Healthcare Conference 2025 summary

Mechanistic rationale and clinical data

• FGF21 targets both metabolic dysregulation and liver fibrosis, offering a dual mechanism for MASH treatment.

• Pegozafermin, an FGF21 analog, showed robust improvements in liver histology and metabolic markers in a 220-patient phase IIB study.

• Comparative analysis of 29 trials highlighted pegozafermin's standout efficacy in fibrosis reduction and MASH resolution.

• FGF21's direct action on liver receptors differentiates it from GLP-1s, which lack hepatic receptors.

• Positive metabolic effects observed include reductions in liver fat, ALT, and lipid levels.

Developments in FGF21 and cirrhosis (F4) population

• Recent data from AASLD on efruxifermin validate FGF21's potential to reverse cirrhosis in F4 patients.

• Over 45% of patients in a small dataset saw cirrhosis reversal with FGF21 analogs, with three-quarters improving from F4 to F3.

• Long-term treatment (24 months) is necessary to observe significant benefits in cirrhotic patients.

• The ongoing phase III study includes a 24-month treatment and biopsy to assess fibrosis reversal.

• Regulatory agencies have agreed that fibrosis reversal could support accelerated approval in the US and conditional approval in Europe.

Regulatory and study design updates

• Written confirmation from the FDA allows for accelerated approval if fibrosis reversal is demonstrated.

• The phase III F4 study will read out in 2028 and includes global enrollment at 225-250 sites.

• The study is powered for both histology and outcomes, with outcomes focused on decompensation events.

• Study design includes earlier decompensation event definitions to accelerate outcome measurement.

• High investigator enthusiasm and rapid site activation reflect strong interest and patient need.