efimosfermin alfa (GSK6519754) / Novartis, Boston Pharma, GSK - LARVOL DELTA

GSK presents data from its advancing liver pipeline at AASLD 2025 (GSK Press Release) - "21 abstracts highlight advances in the treatment of liver conditions, building from GSK’s expertise in inflammation and fibrosis; Phase II B-Sure study sub-analysis shows durability of functional cure in chronic hepatitis B (CHB) patients treated with bepirovirsen and pegylated interferon (Peg-IFN); Late breaking results for once-monthly efimosfermin in metabolic dysfunction-associated steatohepatitis (MASH), supporting the start of phase III clinical trials"

Clinical data • Hepatitis B • Metabolic Dysfunction-Associated Steatohepatitis

BOS-580-201: A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension (clinicaltrials.gov) - P2 | N=231 | Completed | Sponsor: Boston Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

ZENITH-1: A Pivotal Clinical Study to Investigate Efimosfermin Alfa in Participants With Biopsy-confirmed F2- or F3-stage MASH (clinicaltrials.gov) - P3 | N=1200 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P3 trial • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

ZENITH-1: A Pivotal Clinical Study to Investigate Efimosfermin Alfa in Participants With Biopsy-confirmed F2- or F3-stage MASH (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: GlaxoSmithKline | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

ZENITH-2: A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH (clinicaltrials.gov) - P3 | N=1250 | Not yet recruiting | Sponsor: GlaxoSmithKline

New P3 trial • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Progress on 14 key opportunities expected to launch 2025-2031 each with PYS potential above £2 billion (GSK Press Release) - "Phase III development programme for depemokimab COPD started with launch of ENDURA studies; Pivotal/Phase III trial starts planned in H2 25 for: potential cancer treatments GSK'227 B7H3 ADC for ES-SCLC and GSK'981 IDRx-42 for 2L GIST; efimosfermin for treatment of MASH"

New P3 trial • Trial status • Chronic Obstructive Pulmonary Disease • Gastrointestinal Stromal Tumor • Metabolic Dysfunction-Associated Steatohepatitis • Small Cell Lung Cancer

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

GSK completes acquisition of efimosfermin, a potential best-in-class specialty medicine to treat and prevent progression of steatotic liver disease (SLD) (GSK Press Release) - "GSK plc...announced the completion of its previously announced acquisition of efimosfermin alfa from Boston Pharmaceuticals. Efimosfermin is a phase III-ready, potential best-in-class investigational specialty medicine aimed at treating and preventing the progression of SLD. Efimosfermin is a novel, once-monthly...FGF21 analog therapeutic in clinical development for the treatment of metabolic dysfunction-associated steatohepatitis (MASH), including cirrhosis, and future development in alcohol-related liver disease (ALD), both forms of SLD....GSK has acquired BP Asset IX, Inc., a subsidiary of Boston Pharmaceuticals, to access efimosfermin. The total cash consideration for this acquisition amounts to up to $2 billion, comprising an upfront payment of $1.2 billion and up to $800 million in success-based milestone payments. GSK will also be responsible for success-based milestone payments as well as tiered royalties for efimosfermin owed to Novartis Pharma AG."

M&A • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Efimosfermin alfa (BOS-580), a long-acting FGF21 analogue, in participants with phenotypic metabolic dysfunction-associated steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2a trial. (PubMed, Lancet Gastroenterol Hepatol) - P2 | "In participants with phenotypic MASH, efimosfermin had a favourable safety profile and showed improvements in indicators of hepatic steatosis. These results help to inform future studies of efimosfermin in this important disease state."

Journal • P2a data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

GSK to acquire efimosfermin, a phase III-ready potential best-in-class specialty medicine to treat and prevent progression of steatotic liver disease (SLD) (Businesswire) - "GSK plc...and Boston Pharmaceuticals...announced that they have entered into an agreement under which GSK will acquire Boston Pharmaceuticals’ lead asset, efimosfermin alfa....Under the agreement, GSK will pay $1.2 billion upfront, with potential for additional success-based milestone payments totalling $800 million....The acquisition of efimosfermin is highly aligned to GSK’s R&D focus on science related to the immune system and is further evidence of the company’s intent to build on its deep understanding of fibrosis and auto-inflammation to develop precision interventions that stop and reverse disease progression....Efimosfermin will significantly expand our hepatology pipeline and provide us the opportunity to develop a new potential best-in-class medicine with first launch expected in 2029."

Commercial • Launch • Metabolic Dysfunction-Associated Steatohepatitis

ONCE MONTHLY EFIMOSFERMIN ALFA IMPROVES FAST AND FIB-4 COMPOSITE BIOMARKER SCORES FOR MASH STAGE F2/F3 FIBROSIS IN A 24-WEEK PHASE 2 TRIAL (DDW 2025) - P2 | "Once monthly efimosfermin treatment resulted in significant reductions in FAST and FIB-4 composite biomarker scores. FIB-4 scores were rapidly reduced at week 4 and remained low throughout the trial. In the phase 2 trial, efimosfermin improved composite biomarkers in subjects with MASH stage F2/F3 fibrosis, which may translate to reduced liver-related events in longer term trials."

Biomarker • P2 data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Obesity • FGF21

4200: SOA - Update on MASLD Therapies Pipeline (DDW 2025) - "Description: This State-of-the-Art session provides a timely update on the evolving MASLD therapies pipeline, featuring insights into emerging pharmacologic agents and real-world data on current treatments. Topics include the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes, eligibility criteria for resmetirom therapy, and phase 2 results for efimosfermin alfa in MASH with fibrosis.Learning Objectives:• Describe the impact of SGLT-2 and GLP-1 receptor agonists on cirrhosis outcomes• Identify the eligibility criteria for resmetirom therapy• Discuss phase 2 results for efimosfermin alfa in MASH with fibrosis"

Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

ONCE-MONTHLY EFIMOSFERMIN ALFA (BOS-580) IN METABOLIC DYSFUNCTION-ASSOCIATED STEATOHEPATITIS WITH F2/F3 FIBROSIS: RESULTS FROM A 24 WEEK, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2 TRIAL (DDW 2025) - P2 | No abstract available

Clinical • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) MASH (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: Boston Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present the Effect of Efimosfermin Alfa on Collagen Biomarkers in Patients with F2 and F3 MASH at EASL Congress 2025 (Businesswire) - P2 | N=231 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...announced it will present results from an analysis of its Phase 2 study in participants with stage F2 and F3 fibrosis due to MASH. The findings will be presented at the European Association for the Study of the Liver (EASL) Congress 2025, May 7-10, in Amsterdam...'In the analysis, efimosfermin demonstrated improvements in biomarkers related to collagen and a reduction in liver scarring among patients with moderate to advanced liver fibrosis (stages F2-F3) caused by metabolic dysfunction-associated steatotic liver disease.'....Substantial and rapid improvements in cardiometabolic benefits, such as liver fat reduction and improved glycemic control, were also observed in MASH patients with obesity and diabetes. Efimosfermin was generally well tolerated in the Phase 2 study..."

P2 data • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present State-of-the-Art Lecture and Poster for Once-monthly Efimosfermin Alfa at Digestive Disease Week 2025 (Businesswire) - "Boston Pharmaceuticals...announced it will present immunogenicity and biomarker analyses from its Phase 2 study, in participants with stage F2 and F3 fibrosis due to MASH. The results will be presented in a state-of-the-art lecture and poster at Digestive Disease Week (DDW) in San Diego, May 3-6, 2025....Efimosfermin clinical program to advance to Phase 3 pivotal study in fourth quarter of 2025."

New P3 trial • P2 data • Metabolic Dysfunction-Associated Steatohepatitis

Efimosfermin alfa once monthly treatment improves collagen biomarker profiles and rapidly induces histological fibrosis regression in subjects with MASH stage F2-F3 fibrosis in a 24-week phase 2 trial (EASL 2025) - P2 | "Efimosfermin treatment rapidly induces fibrosis regression in subjects with MASH stage F2/F3 fibrosis as evidenced by significant improvements in ECM remodeling during a 24-week Phase 2 trial. Efimosfermin showed improvements in collagen biomarkers regardless of baseline MASH stage F2 or F3 fibrosis. Consistent with histology data, decreases in the Pro-C3/CTX-III ratio show a shift in the overall balance between fibrogenesis and fibrolysis towards fibrosis clearance in the efimosfermin treated subjects with MASH stage F2/F3 fibrosis."

Biomarker • Clinical • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • FGF21

A Study of Efimosfermin Alfa in Participants With Biopsy-confirmed Cirrhosis (Compensated) MASH (clinicaltrials.gov) - P2 | N=42 | Not yet recruiting | Sponsor: Boston Pharmaceuticals

New P2 trial • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Once-Monthly Efimosfermin Alfa (BOS-580) in Metabolic Dysfunction-Associated Steatohepatitis With F2/F3 Fibrosis: Results From a 24-Week, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Clinical • Journal • P2 data • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

BOS-580-201: A Study of BOS-580 in Obese Subjects At Risk For, or with Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) with an Extension (clinicaltrials.gov) - P2 | N=231 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | Trial completion date: Jul 2026 ➔ Nov 2025 | Trial primary completion date: Jul 2026 ➔ Nov 2025

Biopsy • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

BOS-580-201: A Study of BOS-580 in Obese Subjects At Risk For, or with Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) with an Extension (clinicaltrials.gov) - P2 | N=231 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | Recruiting ➔ Active, not recruiting

Biopsy • Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Boston Pharmaceuticals to Announce Positive Phase 2 Data on Efimosfermin Alfa (BOS-580) in F2/F3 MASH During Late-Breaking Oral Presentation at AASLD 2024, The Liver Meeting (Businesswire) - P2 | N=245 | NCT04880031 | Sponsor: Boston Pharmaceuticals | "Boston Pharmaceuticals...today announced positive results from a Phase 2 study evaluating the safety and efficacy of once-monthly efimosfermin alfa....Treatment with efimosfermin led to significant improvements in fibrosis ≥1 stage without worsening of MASH, and MASH resolution without worsening of fibrosis over 24 weeks. In the study, efimosfermin demonstrated a favorable tolerability profile. These topline results will be presented on Nov. 19 in a late-breaking oral presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting,® Nov. 15-19, 2024, in San Diego....In addition, study participants treated with efimosfermin showed rapid and significant improvement in fibrosis biomarkers and significant reductions in non-invasive markers of liver injury and liver fat over the study period."

P2 data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Boston Pharmaceuticals to Present Phase 2 Biopsy Results for Long-Acting, Once-Monthly FGF21 Analogue Efimosfermin Alfa (BOS-580) in F2 and F3 MASH in Late-Breaking Oral Presentation at AASLD, The Liver Meeting 2024 (Businesswire) - "Boston Pharmaceuticals...today announced it will present key results including histologic responses from a Phase 2 study evaluating the safety and efficacy of the investigational agent, efimosfermin alfa (formerly known as BOS-580), in participants with stage F2 and F3 fibrosis due to metabolic dysfunction-associated steatohepatitis (MASH) as a late-breaking oral presentation at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting (Nov. 15-19, 2024 in San Diego)."

P2 data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension (clinicaltrials.gov) - P2 | N=245 | Recruiting | Sponsor: Boston Pharmaceuticals | Active, not recruiting ➔ Recruiting | Trial completion date: Dec 2024 ➔ Jul 2026 | Trial primary completion date: Dec 2024 ➔ Jul 2026

Biopsy • Enrollment open • Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH) With an Extension (clinicaltrials.gov) - P2 | N=205 | Active, not recruiting | Sponsor: Boston Pharmaceuticals | N=82 ➔ 205

Biopsy • Enrollment change • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Obesity