efocipegtrutide (HM15211) / Hanmi - LARVOL DELTA

Study to Evaluate Efficacy, Safety and Tolerability of HM15211(Efocipegtrutide) in Subjects (clinicaltrials.gov) - P2 | N=215 | Active, not recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Nov 2026 ➔ Jul 2026

Enrollment closed • Trial completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Multifunctional incretin peptides in therapies for type 2 diabetes, obesity and associated co-morbidities. (PubMed, Peptides) - "Recent studies with peptide-based incretin herapies have focussed mainly on the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide and the dual agonist tirzepatide that engages receptors for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP)...New incretin-based peptide therapies in development include a long-acting glucagon receptor agonist (LY3324954), dual GLP-1/glucagon receptor agonists (survodutide, pemvidutide, mazdutide, G49), triple GLP-1/GIP/glucagon receptor agonists (retatrutide, efocipegtrutide), a combination of semaglutide with the amylin analogue cagrilintide (CagriSema), a unimolecular GLP-1/amylin receptor dual agonist (amycretin), and a GIP receptor antibody with GLP-1 receptor agonism (MariTide). The creation of multi-targeting incretin-based synthetic peptides provides opportunities for improved management of type 2 diabetes and obesity as well as new therapeutic approaches to an expanding list of associated co-morbidities. The..."

Journal • Cardiovascular • Diabetes • Genetic Disorders • Hepatology • Inflammation • Metabolic Disorders • Nephrology • Obesity • Obstructive Sleep Apnea • Orthopedics • Renal Disease • Respiratory Diseases • Sleep Apnea • Sleep Disorder • Type 2 Diabetes Mellitus

Study to Evaluate Efficacy, Safety and Tolerability of HM15211(Efocipegtrutide) in Subjects (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: May 2025 ➔ May 2026

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

Study to Evaluate Efficacy, Safety and Tolerability of HM15211(efocipegtrutide) in Subjects (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Nov 2026 ➔ Nov 2025 | Trial primary completion date: May 2026 ➔ May 2025

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

Study to Evaluate Efficacy, Safety and Tolerability of HM15211 in Subjects (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Nov 2025 ➔ Nov 2026 | Trial primary completion date: May 2025 ➔ May 2026

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

Hanmi showcases efocipegtrutide's potential for liver fibrosis at AASLD conference (Korea Biomedical Review) - "Hanmi Pharmaceutical said Tuesday that it presented results from a study confirming the potential of efocipegtrutide (LAPS Triple agonist), a new drug for metabolic-associated steatohepatitis (MASH), to improve liver fibrosis directly and differentiate treatment efficacy through its glucagon activity....As a result, repeated administration of efosipegtrutide reproducibly confirmed the improvement of inflammation and fibrosis in liver tissue and demonstrated differentiated therapeutic efficacy, especially through glucagon activity, which was not confirmed in other candidates."

Preclinical • Metabolic Disorders • Obesity

Efocipegtrutide: Data from P2b trial (NCT04505436) for MASH in 2025 (Hanmi) - Q3 2024 Results: Completion of P2b trial for MASH in H2 2025

P2b data • Trial completion date • Metabolic Dysfunction-Associated Steatohepatitis

GLUCAGON ENGAGEMENT IS ESSENTIAL FOR THE DIRECT ANTI-INFLAMMATION AND ANTI-FIBROSIS EFFECT OF EFOCIPEGTRUTIDE IN TAA-INDUCED MOUSE MODEL OF LIVER INJURY AND FIBROSIS (AASLD 2024) - "In TAA mice, efocipegtrutide (GCG/GIP/GLP-1 triple) and efpegerglucagon (GCG mono) showed similar anti-inflammatory and anti-fibrosis benefits while tirzepatide (GIP/GLP-1 dual) had relatively little effect. These result demonstrate that GCG engagement could play a crucial role in managing hepatic inflammation and fibrosis. P2b study in biopsy confirmed MASH patients is currently ongoing to assess the clinical relevance of these findings."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • GCG • TIMP1

A First-in-human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HM15211 (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: Hanmi Pharmaceutical Company Limited | Unknown status ➔ Completed

Trial completion • Genetic Disorders • Obesity

Hanmi Pharm's efocipegtrutide phase 2 trial for MASH gets green light from IDMC (Korea Biomedical Review) - "Hanmi Pharm said Wednesday that the Independent Data Monitoring Committee (IDMC) has recommended that the phase 2 clinical trial of efocipegtrutide (LAPSTriple agonist), a candidate for treating metabolic dysfunction-associated steatohepatitis (MASH), 'continue without modification'...The IDMC was held in April to discuss the continuation of the trial based on interim data from the ongoing global Phase 2 trial of efocipegtrutide in Korea and the United States. The meeting discussed safety data from the 144 patients who received the drug."

DSMB • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

[VIRTUAL] ANTI-FIBROTIC EFFECT OF A NOVEL LONG-ACTING GLUCAGON/GIP/GLP-1 TRIPLE AGONIST (HM15211) IN BDL-INDUCED MOUSE MODEL OF LIVER FIBROSIS (AASLD 2020) - "2 days post surgery, the mice were administered either with HM15211 or obeticholic acid (OCA) for 2 weeks (total model induction up to 2 weeks). Considering liver fibrosis without fatty liver in BDL mice, these results suggest the direct anti-fibrotic effect of HM15211. Hence, reduced expression of hepatic TGF-β and α-SMA suggest that the inhibition of hepatic stellate cell activation is essential for fibrosis improvement by HM15211. Further studies are needed to assess the clinical relevance of these findings."

Preclinical • Anesthesia • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • TIMP1

[VIRTUAL] THERAPEUTIC EFFECT OF A NOVEL LONG-ACTING GLUCAGON/GIP/GLP-1 TRIPLE AGONIST (HM15211) IN CDHFD-INDUCED MOUSE MODEL OF NASH AND FIBROSIS MICE (AASLD 2020) - "Based on these results, HM15211 might be a novel therapeutic option for NASH and fibrosis. Hence, better efficacy than acylated GLP-1/GIP further highlight weight loss uncoupled, direct therapeutic effect of HM15211. These results warrant on-going clinical studies for human efficacy translation."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • TIMP1

Hanmi Pharmaceutical and Lilly compete to develop the first triple agent in the field of metabolic diseases [Google translation] (Health Korea News) - "As metabolic disease treatments are emerging as the next generation, the pharmaceutical and bio industries are working hard to develop related treatments. Hanmi Pharmaceutical and Eli Lilly and Company are developing the first triple-action innovative new drug that acts on three major biomarkers of metabolic diseases...Since the indicator of improvement in liver fibrosis is a key criterion for assessing the possibility of commercialization of MASH (metabolic disorder-related steatohepatitis) treatment, Hanmi Pharmaceutical's development of 'efocipegtrutide' is expected to accelerate."

Clinical • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

ANTI-INFLAMMATORY AND ANTI-FIBROTIC EFFECTS BY SIMULTANEOUS ACTIVATION OF GLUCAGON, GIP, AND GLP-1 OF EFOCIPEGTRUTIDE (HM15211) IN THIOACETAMIDE-INDUCED MOUSE MODEL OF LIVER INJURY AND FIBROSIS (AASLD 2023) - "Efocipegtrutide effectively improved liver inflammation and fibrosis in TAA mice. Notably, greater improvement effect over semaglutide and tirzepatide highlights the potential benefit of simultaneous use of GCG, GIP, and GLP-1. Thus, efocipegtrutide could be a novel therapeutic option for fibrosis due to NASH."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis • GCG • TIMP1

Anti-inflammatory and anti-fibrotic effects by simultaneous activation of glucagon, GIP, and GLP-1 of efocipegtrutide (HM15211) in thioacetamide-induced mouse model of liver injury and fibrosis (EASL-ILC 2023) - "Efocipegtrutide effectively improved liver inflammation and fibrosis in TAA mice. Notably, greater improvement effect over semaglutide and tirzepatide highlights the potential benefit of simultaneous use of GCG, GIP, and GLP-1. Thus, efocipegtrutide could be a novel therapeutic option for fibrosis due to NASH."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis • GCG • TIMP1

Improvement of liver fibrosis by a novel long acting Glucagon/GLP-1/GIP triple agonist, efocipegtrutide (HM15211) in carbon tetrachloride-induced mouse model of liver injury and fibrosis (EASL-ILC 2023) - "Efocipegtrutide effectively improved liver fibrosis in CCl4-induced fibrosis mice. These results are consistent with previous study results in various NASH/fibrosis animal models, in which further reinforcing the robust anti-fibrotic effect of efocipegtrutide via simultaneous action of GCG, GIP, and GLP-1. Human study is ongoing to assess the clinical relevance of these findings."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Non-alcoholic Steatohepatitis • GCG • TIMP1 • TNFA

Anti-fibrotic Potential of a Novel Long-acting Glucagon/GIP/GLP-1 Triple Agonist (HM15211) in Preclinical Models of Idiopathic Pulmonary Fibrosis (ATS 2023) - "Here, we evaluated the preclinical efficacy of HM15211 in bleomycin induced mouse model of IPF...As a commercial comparator, pirfenidone and/or nintedanib were included... HM15211 could possess therapeutic potential for IPF with improved treatment effects over current standard of care. On-going mechanistic studies will elucidate the underlying mode of actions, and human study should be followed up to assess the clinical relevance of these findings."

Preclinical • Fibrosis • Hepatology • Idiopathic Pulmonary Fibrosis • Immunology • Liver Cirrhosis • Pulmonary Disease • Respiratory Diseases

Hanmi Pharmaceutical’s NASH treatment confirms its effectiveness in idiopathic pulmonary fibrosis [Google translation] (Yonhap News Agency) - "Hanmi Pharmaceutical...which is being developed as a NASH (Non-alcoholic Steatohepatitis) treatment, was also effective in idiopathic pulmonary fibrosis (IPF).Hanmi Pharmaceutical announced that it presented the results of a study on the possibility of IPF treatment of Labstriple Agonist at the American Thoracic Society International Conference 'ATS 2023' held in Washington, DC, the United States....The company revealed that blood oxygen saturation and fibrosis indicators were improved following repeated dosing of Labstriple Agonist, and mortality due to disease progression was lowered in animal models. The company explained that this effect is superior to pirfenidone and nintedanib, which are approved for IPF treatment in Korea."

Preclinical • Idiopathic Pulmonary Fibrosis • Interstitial Lung Disease • Non-alcoholic Steatohepatitis

A phase 2, adaptive randomized, double-blind, placebo-controlled, multicenter, 52-week study of HM15211 in patients with biopsy-confirmed non-alcoholic steatohepatitis - Study design and rationale of HM-TRIA-201 study. (PubMed, Contemp Clin Trials) - "An interim analysis is planned after 15 patients/group complete 26 weeks of treatment, after which one HM15211 dose group will be discontinued based on safety and efficacy risk-to-benefit analysis; patients of the dropped dosing arm will be re-randomized into 2 remaining HM15211 groups. The adaptive design study of HM15211 minimizes the number of patients to be exposed to a liver biopsy while optimizing the sample size of patients exposed to safe and effective doses of HM15211 to inform ideal dose for further clinical development in NASH."

Biopsy • Clinical • Journal • P2 data • Addiction (Opioid and Alcohol) • Fibrosis • Genetic Disorders • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity

EFFECTS OF HM15211, A NOVEL LONG-ACTING GLUCAGON/GIP/GLP-1 TRIPLE AGONIST, ON ANTI-INFLAMMATION AND ANTI-FIBROSIS IN TAA-INDUCED MOUSE MODEL OF LIVER INJURY AND FIBROSIS (AASLD 2022) - "HM15211 effectively improved liver inflammation and fibrosis in TAA mice, and related MoAs were elaborated by in vitro studies. Together with previous results, generalized anti-inflammatory and -fibrotic effects of HM15211 were corroborated. Thus, HM15211 could be a novel therapeutic option for fibrosis due to NASH."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Failure • Non-alcoholic Steatohepatitis • IL1B • IL6 • TGFB1 • TNFA

Anti-fibrotic potential of a novel long-acting Glucagon/GIP/GLP-1 triple agonist (HM15211) in preclinical models of idiopathic pulmonary fibrosis (EASD 2022) - "HM15211 could possess therapeutic potential for IPF with improved treatment effects over current standard of care. On-going mechanistic studies will elucidate the underlying mode of actions, and human study should be followed up (required) to assess the clinical relevance of these findings."

Preclinical • Metabolic Disorders

Anti-inflammatory and anti-fibrotic effects of a novel long-acting Glucagon/GIP/GLP-1 triple agonist, HM15211, in TAA induced mouse model of liver injury and fibrosis (EASD 2022) - "HM15211 effectively improved liver inflammation and fibrosis in TAA mice, and related mechanism was elaborated by in vitro studies. Thus, HM15211 could be a novel therapeutic option for fibrosis caused by NASH. Human study is ongoing to assess the clinical relevance of these promising results."

Preclinical • Non-alcoholic Steatohepatitis • IL1B • IL6 • TGFB1 • TNFA

Hanmi Pharmaceutical Announces 3 Innovative New Drug Research Results at the European Diabetes Association (EBN) - PN/A | N=N/A| "Hanmi Pharm also announced the study results showing that HM15211 dramatically improved lung function and survival rate in the idiopathic pulmonary fibrosis (IPF) model. Through this, HM15211 is expected to expand the treatment area for pulmonary fibrosis, which has a large unmet medical need."

Clinical • Idiopathic Pulmonary Fibrosis

Study to Evaluate Efficacy, Safety and Tolerability of HM15211 in Subjects (clinicaltrials.gov) - P2 | N=217 | Recruiting | Sponsor: Hanmi Pharmaceutical Company Limited | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Sep 2022 ➔ May 2025

Trial completion date • Trial primary completion date • Hepatology • Non-alcoholic Steatohepatitis

Direct anti-inflammatory and anti-fibrotic effects of a novel long-acting Glucagon/GIP/GLP-1 triple agonist, HM15211, in thioacetamide-induced mouse model of liver injury and fibrosis (EASL-ILC 2022) - "HM15211 markedly improved liver inflammation and fibrosis in TAA mice, and related MoAs were elaborated by in vitro studies. Together with previous results, generalized anti-inflammatory and -fibrotic effects of HM15211 were corroborated. Thus, HM15211 could be a novel therapeutic option for fibrosis due to NASH."

Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Liver Failure • Non-alcoholic Steatohepatitis • IL1B • IL6 • TGFB1 • TNFA