89Bio (ETNB) Citi's Biopharma Back to School Conference summary

Market landscape and regulatory developments

• MASH market is expanding with two approved drugs, increasing diagnosis and treatment rates.

• Metabolic drugs like resmetirom and semaglutide are seen as first-generation, with next-gen antifibrotics expected to address fibrosis more effectively.

• GLP-1s are widely used but do not directly treat liver fibrosis; significant unmet need remains.

• Clinical trial design accounts for GLP-1 use, with global studies reflecting varying utilization rates.

• High enthusiasm and patient screening in global ENLIGHTEN studies, especially for cirrhosis.

Clinical development and trial execution

• ENLIGHTEN studies for F2F3 fibrosis and F4 cirrhosis are progressing with over 250 global sites.

• Stratification for GLP-1 use ensures adequate power to detect differences in outcomes.

• Discontinuation rates are low after initial titration, with tolerability and compliance prioritized.

• Interim analysis is limited to histology for accelerated approval, with outcomes as the primary endpoint.

• Standard of care and comorbidity management are standardized across geographies to minimize bias.

Product differentiation and commercial strategy

• Key differentiation factors: efficacy, safety/tolerability, and dosing convenience.

• Pegozafermin shows best relative risk reduction in fibrosis among FGF21s and favorable safety profile.

• Lower GI side effects and no bone density issues position it well for long-term use, especially in F4 patients.

• Liquid formulation allows potential co-formulation with GLP-1s, offering lifecycle management opportunities.

• Combination therapy could improve tolerability and dosing flexibility, with pricing dependent on data strength.