89Bio (ETNB) BofA Securities 2025 Healthcare Conference summary

Mechanism and differentiation of FGF21 analogs

• FGF21 analogs, such as pegozafermin, target both metabolic dysregulation and liver fibrosis, offering rapid fat reduction and anti-fibrotic effects in the liver, with additional systemic metabolic benefits including improved glycemic control and lipid profiles.

• Compared to other modalities like GLP-1s, FGF21 acts directly on the liver and systemically, providing faster and broader benefits, especially in fibrosis improvement.

• Pegozafermin is engineered for extended half-life, allowing weekly or biweekly dosing, and demonstrates strong efficacy and tolerability, with a favorable safety profile on bone health and lower GI adverse events than competitors.

• The product's liquid formulation in a pre-filled syringe enables potential co-formulation with GLP-1s, enhancing convenience for patients likely to be on both therapies.

• Market research highlights that prescribers prioritize fibrosis benefit and tolerability, while patients value dosing convenience and manageable side effects.

Market dynamics and recent industry developments

• Recent large-scale deals, such as GSK's $800 million upfront acquisition of efimosfermin rights, validate both big pharma's renewed interest in the MASH/NASH space and the FGF21 mechanism.

• FGF21 is seen as critical for addressing the high unmet need in the F4 cirrhotic market, where GLP-1s have shown limited efficacy.

• The market split within the FGF21 class will be driven by benefit-risk profile, patient convenience, and payer coverage, with tolerability being as important as efficacy, especially in frail cirrhotic patients.

• Prescriber adoption is expected to expand from hepatologists and gastroenterologists to endocrinologists, with potential for primary care involvement as diagnostic tools become more widespread.

Clinical development and regulatory strategy

• Phase III programs for pegozafermin are designed with longer treatment durations (24 months) to maximize fibrosis reversal, with regulatory alignment for accelerated approval if F4 to F3 reversal is demonstrated.

• Ongoing studies will continue to collect long-term outcomes data to support broader approval and demonstrate prevention of disease progression.

• Combination studies with GLP-1s are anticipated to show synergistic benefits, but safety and tolerability will be key, especially regarding GI side effects.