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) - No abstract available

Biomarker • Clinical • P2b data • Metabolic Dysfunction-Associated Steatotic Liver Disease

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

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. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review. (PubMed, Pharmaceuticals (Basel)) - "Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen and plozasiran appear to be safer alternatives for volanesorsen regarding the risk of drug-induced thrombocytopenia in patients with FCS or severe HTG. After the failure of vupanorsen, a new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated the potential to decrease TG levels in patients with moderate HTG. Meanwhile, the fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate for the treatment of severe HTG. This comprehensive review outlines pharmacological targets in TG-rich lipoprotein metabolism, discusses international guidelines, and summarizes the latest evidence from clinical trials to provide insight into the current and emerging treatment options for primary HTG."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • ANGPTL3 • FGF21

Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis. (PubMed, Hepatology) - "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."

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

ENLIVEN: Study Evaluating the Safety, Efficacy and Tolerability of BIO89-100 in Subjects With Biopsy-confirmed Nonalcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2 | N=222 | Completed | Sponsor: 89bio, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

89bio Provides Business Update and Outlook for 2025 (GlobeNewswire) - "Completed enrollment in ENTRUST, the Phase 3 trial evaluating the efficacy, safety and tolerability of pegozafermin in patients with SHTG. 89bio expects to report topline 26-week data from this trial in the second half of 2025."

P3 data: top line • Severe Hypertriglyceridemia

Efruxifermin Harmony 96 Weeks/Pegozafermin 48 Week (MASH-TAG 2025) - No abstract available

89bio, Inc. Announces Proposed Underwritten Public Offering of Common Stock and Pre-Funded Warrants (GlobeNewswire) - "89bio, Inc...today announced that it has commenced an underwritten public offering of $100 million of shares of its common stock or, in lieu of common stock to certain investors that so choose, pre-funded warrants to purchase shares of its common stock. In addition, 89bio is expected to grant the underwriters of the offering an option for a period of 30 days to purchase up to an additional $15 million of shares of its common stock at the public offering price, less the underwriting discounts and commissions....89bio intends to use the net proceeds from this proposed offering to fund ongoing clinical activities and development of pegozafermin, manufacturing related costs and other general corporate purposes, including working capital and operating expenses."

Financing • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

89bio Presents New Analyses Evaluating Pegozafermin and Potential Benefit of Non-Invasive Tests from the ENLIVEN Phase 2b Trial in MASH Patients at AASLD The Liver Meeting 2024 (GlobeNewswire) - "89bio, Inc...announced new analyses of data from the Phase 2b ENLIVEN trial evaluating pegozafermin in metabolic dysfunction-associated steatohepatitis (MASH) patients with advanced fibrosis. The findings were presented in four poster sessions at The American Association for the Study of Liver Diseases (AASLD) The Liver Meeting being held in San Diego, California."

P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Safety and Efficacy of Pegozafermin for Treatment of MASH and Hypertriglyceridemia: A Meta-Analysis (ACG 2024) - "247 patients in 3 RCTs were included in the study. The results showed that Pegozafermin increased adiponectin levels and decreased ALT levels, serum triglyceride levels. Moreover, it also showed that the Pegozafermin group had decreased liver volume (Combined effect: -208.96 ml, p < 0.0001) and decreased liver fat content (-8.36%) as compared to the placebo as shown in figure 1."

Retrospective data • Dyslipidemia • Fibrosis • Gastroenterology • Hepatology • Hypertriglyceridemia • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis