89Bio (ETNB) investor relations material

Program updates and clinical progress

• Three ongoing phase 3 studies: SHTG program completed enrollment with data expected early next year, and two NASH programs (pre-cirrhotic and cirrhotic) actively enrolling.

• Pegosafirmin (FGF21 analog) shows promise in addressing triglyceride reduction and comorbidities like fatty liver and glycemic control, differentiating from APOC3s.

• SHTG phase 3 aims to replicate strong phase 2 results in triglyceride reduction, liver fat improvement, and metabolic markers; a second phase 3 will be needed for filing.

• Commercial positioning may target specific patient populations, such as those with fatty liver or diabetes, to differentiate from competitors.

• Pricing research suggests potential for higher pricing than traditional cardiovascular drugs if broader metabolic benefits are demonstrated.

Regulatory and study design insights

• Agreement with FDA and EMA for potential accelerated approval in compensated cirrhotic NASH if fibrosis improvement is shown at two years.

• FDA discussions led to refined definitions of decompensation events, allowing earlier clinical endpoints and more tractable studies.

• Histology cohort in cirrhotic NASH study focuses on well-compensated patients, with conservative powering based on historical placebo responses.

• Consensus read methodology for histology is consistent across phase 2 and 3, with an expanded panel of pathologists for global studies.

• Bone mineral density is being monitored, with no significant concerns observed so far in F3 or F4 populations.

Industry trends and strategic outlook

• FDA's acceptance of a letter of intent to explore FibroScan as a surrogate endpoint in MASH is seen as a positive step for the field, though full validation will take years.

• Pegosafirmin studies are not directly impacted by this change, but data collection includes VCT, allowing future flexibility.

• Enrollment in global phase 3 studies is progressing well, with strong site activation and enthusiasm from investigators.

• Strategic interest in FGF21 and advanced fibrosis remains high, with recent deals highlighting the value seen in this mechanism.

• Flexibility in allowing background therapies like GLP-1s is maintained to ensure patient retention and real-world relevance.