pegozafermin (BIO89-100) / 89Bio - LARVOL DELTA

PEGOZAFERMIN DEMONSTRATED ROBUST HISTOLOGICAL IMPROVEMENT AND BENEFIT IN HEPATIC AND METABOLIC BIOMARKERS: RESULTS FROM A 48-WEEK MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2B TRIAL (ENLIVEN) (UEGW 2025) - "At 24 weeks, treatment with PGZ in MASH patients with F2/F3 fibrosis led to significant fibrosis regression and MASH resolution, which was corroborated by improvement across a variety of non-invasive tests including liver fat, inflammation, fibrosis, and metabolic markers. Benefits on NITs were sustained over the full 48-weeks of the study, with favorable safety and tolerability. PGZ is the first therapy to achieve fibrosis regression and MASH resolution with a Q2W dosing regimen."

Biomarker • Clinical • P2b data • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • FGF21

FGF19/FGF21 Analogues in NASH: Systematic Review (ACG 2025) - "We found eight trials of FGF21 analogues (Efruxifermin, Pegozafermin and Pegbelfermin) and two of the FGF19 analogue Aldafermin. Efruxifermin produced significant benefits: in the 24-week HARMONY trial (n=128, F2–F3 fibrosis), 39% of efruxifermin treated patients had ≥1 stage fibrosis improvement (no NASH worsening) vs 20% on placebo. In the 16-week BALANCED trial (F1–F3), efruxifermin decreased hepatic fat fraction on average by 13.26% vs 0.3% with placebo."

Review • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • FGF19 • FGF21

CLINICAL UTILITY OF A 50% RELATIVE DECLINE IN MRI-PDFF IN PREDICTING FIBROSIS IMPROVEMENT IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS (AASLD 2025) - " This is a secondary analysis of a large, multi-center, randomized, placebo-controlled trial study that included 163 participants (64% female) with biopsy-confirmed MASH with stage 2 or 3 fibrosis who were treated for 24 weeks with either pegozafermin or placebo and underwent contemporaneous laboratory testing, MRI-PDFF, and liver biopsy at two time points (Loomba et al... MRI-PDFF super-response predicts fibrosis regression without worsening MASH, and a greater likelihood of MASH resolution without worsening fibrosis than MRI-PDFF response. These data have important implications for clinical trial design in MASH and assessing dose response and dose selection for Phase 3."

Clinical • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Type 2 Diabetes Mellitus

ZONE-SPECIFIC FIBROSIS REDUCTIONS INDUCED BY PEGOZAFERMIN OVER 24 WEEKS ARE SIMILAR IN NON-CIRRHOTIC (F2/F3) AND CIRRHOTIC (F4) MASH (AASLD 2025) - "Background: In the ENLIVEN trial, pegozafermin (PGZ), a glycoPEGylated FGF21 analog administered at 30mg every week (QW) or 44mg every 2 weeks (Q2W) for 24 weeks significantly improved fibrosis without worsening of MASH in F2-F3 patients. PGZ led to consistent patterns of qFibrosis portal zone, peri-portal (zone 1), and peri-sinusoidal (zone 2) regression in non-cirrhotic (F2-F3) and cirrhotic (F4) patients with MASH at 24 weeks. This is the first report of qFibrosis regression in these clinically meaningful zones induced by a therapeutic intervention in MASH cirrhosis. PGZ is currently being studied in Phase 3 studies in non-cirrhotic and cirrhotic MASH."

Fibrosis • Hepatology • Immunology • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

EFFECT OF MODERATE AND SEVERE HEPATIC IMPAIRMENT ON PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PEGOZAFERMIN AFTER SUBCUTANEOUS ADMINISTRATION (AASLD 2025) - "Pegozafermin was safe and well tolerated across subjects with HI. Moderate and severe HI, including the presence of MASH, had no clinically meaningful effect on PK profile or parameters of pegozafermin. Based on these findings, no dose adjustment is warranted in patients with HI."

Clinical • PK/PD data • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Roche enters into a definitive merger agreement to acquire 89bio, and its phase 3 FGF21 analog for the therapy of moderate to severe MASH (Roche Press Release) - "89bio’s pegozafermin is a FGF21 analog currently in late-stage development for MASH in moderate and severe fibrotic patients (F2 and F3 stages) as well as cirrhotic patients (F4 stage). The transaction is expected to close in the fourth quarter of 2025...Under the terms of the merger agreement, Roche will promptly commence a tender offer to acquire all of the outstanding shares of 89bio common stock at a price of US$14.50 per share in cash at closing, plus a non-tradeable CVR to receive certain milestone payments of up to an aggregate of US$6.00 per share in cash, representing a total equity value of approximately US$2.4 billion at closing..."

M&A • Metabolic Dysfunction-Associated Steatohepatitis

ENTRUST: To Evaluate the Efficacy and Safety of Pegozafermin in Subjects With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=360 | Active, not recruiting | Sponsor: 89bio, Inc. | Trial completion date: Sep 2026 ➔ Apr 2026

Trial completion date • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia • APOB

89bio Reports Second Quarter 2025 Financial Results and Corporate Updates (GlobeNewswire) - "R&D expenses were $103.9 million for the three months ended June 30, 2025, compared to $44.9 million for the three months ended June 30, 2024. The increase in R&D expenses was driven by the Phase 3 ENLIGHTEN trials in MASH and a non-recurring payment of $42.4 million related to the cost of construction of the commercial-scale production facility for pegozafermin. Construction of this facility remains on schedule to support the Biologics License Application (BLA) filing for pegozafermin. The Company’s remaining obligation for the facility is limited to a final milestone payment of $13.5 million to be paid in 2026 upon completion of the construction of the facility."

Commercial • Metabolic Dysfunction-Associated Steatohepatitis

Recent Highlights and Anticipated Milestones (GlobeNewswire) - "(i) Metabolic Dysfunction-Associated Steatohepatitis (MASH): The Phase 3 ENLIGHTEN-Fibrosis trial in non-cirrhotic (F2-F3) MASH and Phase 3 ENLIGHTEN-Cirrhosis trial in compensated cirrhotic (F4) MASH continue to enroll patients, with topline data from the histology cohorts of these trials expected in the first half of 2027 and in 2028, respectively....(ii) Severe Hypertriglyceridemia (SHTG): ENTRUST is a randomized, double-blind, placebo-controlled global study evaluating the efficacy, safety, and tolerability of pegozafermin in SHTG patients randomized to pegozafermin (30 mg, 20 mg) or placebo in a 3:3:2 ratio given once weekly (QW) for 52 weeks....Topline data from the Phase 3 ENTRUST trial in SHTG are expected in the first quarter of 2026."

P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis • Severe Hypertriglyceridemia

FGF21 Analogues and MASLD: A Summary of Preclinical and Clinical Data. (PubMed, Curr Pharm Des) - "Among various others, efruxifermin, pegozafermin, pegbelfermin, and BOS-580 are FGF-21 analogues that have resulted in significant improvements in liver fat, fibrosis, and measures of liver function in the context of phase 2 clinical trials. This review summarizes the preclinical and clinical data from FGF21 analogues for MASLD and MASH."

Clinical data • Journal • Preclinical • Fibrosis • Genetic Disorders • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • FGF21

Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. (PubMed, J Clin Invest) - "Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FASN • FGF21 • PNPLA3

Head-to-head comparison of MASH resolution index versus FAST for non-invasive prediction of resolution of MASH on biopsy. (PubMed, Hepatology) - "The MASH Resolution Index is better than the FAST score in the non-invasive prediction of MASH resolution. These data may have implications for clinical practice and trials."

Head-to-Head • Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

89bio Reports First Quarter 2025 Financial Results and Corporate Updates (GlobeNewswire) - "Recent Highlights and Anticipated Milestones: (i) Metabolic dysfunction-associated steatohepatitis (MASH): The Phase 3 ENLIGHTEN-Fibrosis trial in non-cirrhotic (F2-F3) MASH and Phase 3 ENLIGHTEN-Cirrhosis trial in compensated cirrhotic (F4) MASH continue to enroll patients, with topline data from the histology cohorts of these trials expected in the first half of 2027 and in 2028, respectively....; (ii) Severe Hypertriglyceridemia (SHTG): ENTRUST is a randomized, double-blind, placebo-controlled global Phase 3 trial evaluating the efficacy, safety and tolerability of pegozafermin in SHTG patients randomized to pegozafermin (30 mg, 20 mg) or placebo in a 3:3:2 ratio given once weekly (QW) for 52 weeks. Topline data from the Phase 3 ENTRUST trial are expected in the first quarter of 2026."

Enrollment status • P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis • Severe Hypertriglyceridemia

EVALUATING THE ROLE OF FIBROBLAST GROWTH FACTOR 21 ANALOGUES (FGF21) IN NASH USING HISTOLOGIC AND CLINICAL BIOMARKERS: A META-ANALYSIS (DDW 2025) - "When we conducted a subgroup analysis based on the FGF21 analogues, pegozafermin showed the highest rates, compared to efruxifermin and pegbelfermin. Conclusions FGF21 analogs showed a significant improvement in the clinical and histological biomarkers in NASH. This analysis supports their potential as a treatment option for patients with NASH."

Biomarker • Retrospective data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

Change in cT1 following interventions in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis (EASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, - 68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Efficacy of pharmacotherapy in improvement of liver fibrosis and steatohepatitis in patients with metabolic dysfunction associated steatotic liver disease (MASLD): a network meta-analysis (EASL 2025) - "Pegozafermin, Lanafibrinor, Obeticholic acid, Resmetirom, Vitamin E and Pioglitazone were significantly better than placebo in achieving  1 stage fibrosis improvement...Efruxifermin, Pegozafermin, Tirzepatide, Semaglutide, Aldafermin, Pioglitazone, Resmetirom and Lanafibrinor were significantly better than placebo in achieving MASH resolution... This study provides an updated relative rank-order of various therapies in terms of their efficacy in fibrosis improvement and MASH resolution. In future, therapies that improve liver fibrosis in patients with MASLD may be combined with therapies which achieve MASH resolution for better treatment response."

Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Comparative efficacy and safety of pharmacologic therapies for metabolic dysfunction-associated steatotic liver disease over 24 weeks in reducing liver steatosis and fibrosis: A network meta-analysis. (PubMed, Diabetes Obes Metab) - "This comprehensive network meta-analysis demonstrates the varying efficacy of pharmacologic interventions for MASLD, with resmetirom and pegozafermin emerging as particularly promising treatments for steatosis and fibrosis, respectively. While most treatments exhibited favourable safety profiles, careful monitoring is warranted, particularly with efruxifermin due to its slightly elevated adverse event profile. These findings provide valuable evidence to guide clinical decision-making in MASLD management, though longer-term studies are needed to confirm the durability of these therapeutic effects and further establish safety profiles."

Journal • Retrospective data • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

TRIGLYCERIDE REDUCTION WITH PEGOZAFERMIN IS HIGHLY CORRELATED ACROSS METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS AND SEVERE HYPERTRIGLYERIDEMIA - Kevin Maki (ACC 2025) - "The clinical data confirm pegozafermin's efficacy in related patient populations (SHTG and MASH) and demonstrate robust reductions in triglycerides. As a result, data from the MASH studies may provide supportive evidence of efficacy for treating SHTG."

Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Severe Hypertriglyceridemia • FGF21

Change in cT1 following interventions in MASLD: A systematic review and meta-analysis (APASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, -68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice. Table and Figure:Figure 1.Figure."

Retrospective data • Review • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Comparative efficacy of pharmacologic therapies for MAFLD in improving fibrosis: Systematic review and network meta-analysis (APASL 2025) - "For the primary outcome, Obeticholic acid (OCA) was superior to placebo in the 1.5-year analysis. In the F1-3 analysis, Pegozafermin, OCA, and Resmetirom all outperformed placebo... Several new drugs currently in clinical trials have shown potential therapeutic effects for fibrosis improvement in MAFLD patients, especially those targeting Fibroblast growth factor 21(FGF21). More definitive efficacy will depend on the results of Phase III clinical trials. This study may assist clinicians in therapy selection and support future clinical trial designs."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF21

Comparison of Pharmacological Therapies for Metabolic Dysfunction-Associated Steatohepatitis: Systematic Review and Network Meta-analysis (APASL 2025) - "For the co-primary endpoint of fibrosis improvement without MASH resolution, pegozafermin, cilofexor + firsocostat, survodutide, obeticholic acid, tirzepatide, and resmetirom were significantly better than placebo in improving ≥ 1 fibrosis stage without worsening MASH. Pegozafermin (SUCRA: 90.18), cilofexor plus firsocostat (SUCRA: 82.82), and cilofexor plus selonsertib (SUCRA: 79.62) were ranked the most effective interventions. For the co-primary endpoint of MASH resolution without worsening fibrosis, pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, and lanifibranor were significantly better than placebo... This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Comparative Efficacy and Safety of Drugs for non-cirrhotic NAFLD: A Systematic Review and Network Meta-Analysis (APASL 2025) - "FGF-21 analogs (especially pegozafermin) and THR-β agonist (resmetirom), both resolving steatohepatitis and reducing fibrosis, were recommended for non-cirrhotic NAFLD. Obeticholic acid demonstrated efficacy but its tolerability should be fully considered. FGF-19 analogs seemed more suitable for reducing ballooning and steatosis, while Vitamin E plus pioglitazone performed well in resolving lobular inflammation."

Retrospective data • Review • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF19 • FGF21

A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis) (clinicaltrials.gov) - P3 | N=1050 | Recruiting | Sponsor: 89bio, Inc. | Trial primary completion date: Dec 2026 ➔ Feb 2029

Trial primary completion date • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

89bio Reports Fourth Quarter and Full Year 2024 Financial Results and Corporate Updates (GlobeNewswire) - "As we look toward 2025 and beyond, we look forward to executing on our clinical trials and completing all scale-up and regulatory activities to position us for a successful Biologics License Application (BLA) filing, pending positive results in the Phase 3 trials....The primary endpoint remains percentage change from baseline in fasting triglycerides (TG) at Week 26 compared to placebo, but it will now be analyzed after study unblinding at Week 52 to minimize any potential bias that may be introduced due to the unblinding of data prior to completion of the trial....As a result, 89bio now expects to report topline data from ENTRUST in the first quarter of 2026....Completed follow-on equity offerings in 4Q 2024 and 1Q 2025 for gross proceeds of $143.7 million and $287.5 million, respectively....Research and Development (R&D) Expenses. R&D expenses were $111.3 million and $345.0 million for the three months and year ended December 31, 2024, respectively, compared to..."

Commercial • FDA filing • P3 data: top line • Metabolic Disorders • Severe Hypertriglyceridemia

89bio Reports Fourth Quarter and Full Year 2024 Financial Results and Corporate Updates (GlobeNewswire) - "The Company initiated the Phase 3 ENLIGHTEN-Fibrosis trial in non-cirrhotic (F2-F3) MASH and Phase 3 ENLIGHTEN-Cirrhosis trial in compensated cirrhotic (F4) MASH in the first half of 2024. 89bio expects topline data from the histology cohorts of ENLIGHTEN-Fibrosis and ENLIGHTEN-Cirrhosis in the first half of 2027 and 2028, respectively. The data from the histology cohorts of both trials are intended to support accelerated approval in the United States and conditional approval in Europe in their respective indications."

P3 data: top line • Metabolic Dysfunction-Associated Steatohepatitis