gremubamab (MEDI3902) / AstraZeneca - LARVOL DELTA

Genetic characterisation of pseudomonas aeruginosa isolates from bronchiectasis patients in a randomized, double-blind placebo-controlled trial of a bispecific monoclonal antibody targeting Psl and PcrV (GREAT-2) (BTS WM 2025) - "The GREAT-2 trial of gremubamab, a bispecific monoclonal antibody targeting PA Psl and PcrV, demonstrated reduced bacterial load at the end-of-treatment (EoT) (500 mg), and significantly prolonged time-to-first exacerbation (1500 mg) in patients chronically infected with PA...Download figure Open in new tab Download powerpoint Abstract T6 Figure 1 Conclusion PA isolates showed stability through the 6-month treatment period in the GREAT-2 trial. There were no changes or adaptations in the PcrV and Psl targets, suggesting no resistance development."

Clinical • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Molecular detection and quantification of pseudomonas aeruginosa in bronchiectasis: data from the GREAT-2 randomized controlled trial (BTS WM 2025) - "Conclusions Gremubamab reduced bacterial load and improved clinical outcomes in patients with bronchiectasis at both doses. RNA-qPCR identified a greater reduction in bacterial load at the 1500 mg dose which corresponded with clinical benefit suggesting the potential utility of molecular methods as an outcome measure in clinical trials."

Clinical • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Results from the GREAT-2 phase II randomised placebo-controlled trial of the bispecific monoclonal antibody gremubamab targeting Pseudomonas aeruginosa in people with bronchiectasis (WBC 2025) - "Gremubamab treatment reduced P. aeruginosa airway bacterial load, confirmed by multiple measurements, and improved patient-reported quality-of-life in people with bronchiectasis. Ongoing exploratory analysis of the airway microbiome and proteome will further unravel specific beneficial mechanisms of action."

Clinical • P2 data • Bronchiectasis • Cough • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Results from the GREAT-2 phase II randomised placebo-controlled trial of the bispecific monoclonal antibody gremubamab targeting Pseudomonas aeruginosa in people with bronchiectasis (WBC 2025) - "Gremubamab treatment reduced P. aeruginosa airway bacterial load, confirmed by multiple measurements, and improved patient-reported quality-of-life in people with bronchiectasis. Ongoing exploratory analysis of the airway microbiome and proteome will further unravel specific beneficial mechanisms of action."

Clinical • Late-breaking abstract • P2 data • Bronchiectasis • Cough • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Population pharmacokinetics of Gremubamab to inform evaluation in patients with NCFBE (WBC 2024) - "The popPK model successfully captured the clinical data of gremubamab. Using the model, we predicted that depending on the changes in gremubamab PK in patients with NCFBE, either 500 or 1500 mg monthly would achieve a trough concentration 28 days after administration above the target concentration of 1.7 ug/mL at steady state. The GREAT-2 study is intended to show Proof of Concept and determine the exposure required to reduce sputum bacterial density in PsA-colonized bronchiectasis patients."

Clinical • PK/PD data • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pneumonia • Pulmonary Disease

Anti-Psl/PcrV bispecific monoclonal antibody improves bacterial clearance, reduces lung pathology caused by Pseudomonas aeruginosa isolates from cystic fibrosis children who failed eradication therapy (NACFC 2025) - "Background: Inhaled tobramycin (TOB) is routinely used to eradicate new-onset Pseudomonas aeruginosa (PA) infections in people with cystic fibrosis (pwCF) to prevent progression to chronic infection. Gremubamab potentiates neutrophil OPK of PA isolates 565P and 505P in vitro. A single prophylactic dose of gremubamab significantly improved bacterial clearance of 565P and 505P in vivo. Prophylactic treatment with the bispecific mAb in combination with TOB also suggests that combination therapy may further promote bacterial clearance compared to a single modality therapy and reduced against lung pathology."

Clinical • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Respiratory Diseases

A bispecific monoclonal antibody targeting Pseudomonas aeruginosa in bronchiectasis: results from the GREAT-2 trial (ERS 2025) - "Gremubamab treatment significantly reduced P. aeruginosa load, symptoms and exacerbations in bronchiectasis."

Bronchiectasis • Cough • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Developing bispecific monoclonal antibody (mAb) therapies, gremubamab and AZD0292, targeted against Pseudomonas aeruginosa sponsored by AstraZeneca (IDWeek 2025) - No abstract available

Infectious Disease

Exploring Human Use of Monoclonal Antibodies Against Critical Bacteria: A Scoping Review of Clinical Trials. (PubMed, Infect Dis Ther) - "Inconsistent efficacy may stem from complex host-pathogen interactions, biofilm formation, and variations in patient immune status. Future trials should investigate early mAb administration, stratified patient selection, and standardized antibiotic coadministration, poorly addressed thus far. Optimized dosing and mAb combination regimens are promising yet unexplored paths, while high production costs and regulatory issues remain a significant barrier."

Journal • Review • Infectious Disease • Pneumonia • Respiratory Diseases

A Bispecific Monoclonal Antibody Targeting Psl and PcrV for Chronic Pseudomonas Aeruginosa Infection in Patients With Bronchiectasis: Results From a Randomized, Double-Blind Placebo-Controlled Trial (GREAT-2) (ATS 2025) - "Gremubamab treatment significantly reduced P. aeruginosa airway bacterial load and improved patient-reported quality of life in patients with bronchiectasis, providing proof-of-concept for specific anti-microbial monoclonal antibody therapy."

Clinical • Late-breaking abstract • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

AstraZeneca showcases innovation in infectious disease protection at ESCMID Global 2025 (AstraZeneca Press Release) - "AstraZeneca will share new data across its Vaccines & Immune Therapies portfolio at the 2025 Congress of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID Global 2025) in Vienna, Austria, from 11-15 April 2025. With 13 abstracts, including two oral presentations and two late-breaking poster presentations, the Company will highlight progress in advancing novel immunisations against bacterial and viral infectious diseases and share real-world evidence showing the burden of respiratory viral infections and the continued need for protection."

Clinical data • Preclinical • Bronchiectasis • Infectious Disease • Influenza • Respiratory Diseases

Anti-Psl/PcrV bispecific monoclonal antibody potentiates in vitro and in vivo bacterial clearance of Pseudomonas aeruginosa from children with cystic fibrosis who failed tobramycin eradication therapy (NACFC 2024) - "Background: New-onset Pseudomonas aeruginosa infections in people with cystic fibrosis (PwCF) are routinely treated with antibiotics such as inhaled tobramycin (Tob)...In this study, we examined a new bispecific monoclonal antibody (mAb) (gremubamab) that targets Psl and the type III secretion system protein PcrV as a novel therapy to enhance neutrophil-mediated OPK in vitro and improve P. aeruginosa clearance in vivo... The bispecific anti-Psl/PcrV mAb potentiates in vitro neutrophil OPK of persistent isolates 505P and 565P. A single prophylactic dose of the mAb significantly improved bacterial clearance of 565P and 505P in vivo. Preliminary studies of the bispecific mAb in combination with Tob suggest that combination therapy may promote bacterial clearance more than single-modality therapy."

Preclinical • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Respiratory Diseases

A Bispecific Monoclonal Antibody Targeting Psl and PcrV Enhances Neutrophil-Mediated Killing of Pseudomonas aeruginosa in Patients with Bronchiectasis. (PubMed, Am J Respir Crit Care Med) - "Gremubamab enhanced bronchiectasis patient neutrophil phagocytosis and killing of P.aeruginosa and reduced virulence."

Journal • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

AAV-vectored expression of monospecific or bispecific monoclonal antibodies protects mice from lethal Pseudomonas aeruginosa pneumonia. (PubMed, Gene Ther) - "Serum concentrations of MEDI3902 were ~10× lower than that of αPcrV, but mice treated with this vector showed a greater reduction in bacterial dissemination to the liver, lung, spleen, and blood compared to other AAV-mAbs. These results support further investigation into the use of AAV vectored immunoprophylaxis to prevent and treat P. aeruginosa infections and other bacterial pathogens of public health concern for which current treatment strategies are limited."

Journal • Preclinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases

AAV-Mediated Monoclonal Antibody Expression for the Prevention and Treatment of Pseudomonas aeruginosa Infections (ASGCT 2023) - P2 | "Bispecific hIgG antibody (MEDI3902) which combines single-chain variable fragments of both anti-Psl and anti-PcrV mAbs has been found to provide protection in prevention and treatment of P. aeruginosa infections in vivo and was evaluated in a Phase II clinical trial (NCT02696902)...All vectors provided significant protection, although notably the bispecific vector provided significantly greater protection against bacterial dissemination to the liver, lung, spleen, and blood compared to the monospecific vectors. Together, these results support further investigation of utilizing AAV-mediated mAb expression for the prevention and treatment of P. aeruginosa infections and other bacterial pathogens of public health concern, in which current treatment strategies are limited."

Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. (PubMed, Crit Care) - P2 | "The bivalent, bispecific monoclonal antibody MEDI3902 (gremubamab) did not reduce PA nosocomial pneumonia incidence in PA-colonised mechanically ventilated subjects. Trial registration Registered on Clinicaltrials.gov ( NCT02696902 ) on 11th February 2016 and on EudraCT ( 2015-001706-34 ) on 7th March 2016."

Clinical • Journal • P2 data • PK/PD data • Critical care • Infectious Disease • Pneumonia • Respiratory Diseases

Monoclonal antibodies targeting Psl and PcrV potentiate bacterial clearance of Pseudomonas aeruginosa from cystic fibrosis children who failed eradication therapy (NACFC 2022) - "Background:Antibiotics such as inhaled tobramycin (TOB) are routinelyused to treat new-onsetPseudomonas aeruginosainfections in people with cystic fibrosis (CF) to prevent progression to chronic infection, but up to40% fail eradication therapy. Targeting Psl and PcrV with mAb potentiates neutrophil-mediated OPK of persistentP. aeruginosaisolates. Preliminary results suggest that MEDI3902 treatment may also enhance in vivo bacterialclearance of persistent isolates, raising the possibility that such therapiesmay improve the outcome ofP ."

Clinical • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Anti-virulence Bispecific Monoclonal Antibody Mediated Protection Against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model. (PubMed, Antimicrob Agents Chemother) - "Cytokines and chemokines associated with ARDS were significantly downregulated in lungs from rabbits pretreated with MEDI3902 compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing severity of P. aeruginosa ventilator-associated pneumonia."

Journal • Preclinical • Acute Respiratory Distress Syndrome • Hematological Disorders • Infectious Disease • Leukopenia • Metabolic Disorders • Neutropenia • Pneumonia • Pulmonary Disease • Respiratory Diseases

Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice. (PubMed, Vaccines (Basel)) - "MEDI3902 is a multifunctional antibody that targets the P. aeruginosa persistence factor Psl exopolysaccharide, and the type 3 secretion protein PcrV...They reduce infection in mice treated concurrently at inoculation and reduced the signs of cornea pathology in mice with established infection. Taken together, these data indicate treatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the treatment of P. aeruginosa keratitis and suggest that the design of further antibodies to be an additional tool in the treatment of bacterial keratitis."

Journal • Infectious Disease • Keratitis • Ocular Inflammation • Ophthalmology • Pneumonia • Respiratory Diseases

[VIRTUAL] Efficacy, Pharmacokinetics (PK), and Safety Profile of MEDI3902, an Anti-Pseudomonas aeruginosa Bispecific Human Monoclonal Antibody in Mechanically Ventilated Intensive Care Unit Patients; Results of the Phase 2 EVADE Study Conducted by the Public-Private COMBACTE-MAGNET Consortium in the Innovative Medicines Initiative (IMI) Program. (IDWeek 2020) - P2 | "A single IV dose of MEDI3902 provided PK exposure above the target level but did not achieve primary efficacy endpoint of reduction in PA pneumonia. Efficacy trends were observed in subjects with lower levels of baseline inflammatory biomarkers. MEDI3902 may have a path forward in certain patient populations such as ICU patients with lower baseline inflammation."

Clinical • P2 data • PK/PD data • Infectious Disease

Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa blood stream infection and acute pneumonia rabbit models. (PubMed, Antimicrob Agents Chemother) - "MEDI3902 prophylaxis or treatment was protective in both acute models and exhibited enhanced activity when combined with a subtherapeutic dose of meropenem. These findings further support MEDI3902 for prevention or treatment of serious P. aeruginosa infections."

Clinical • Journal • Preclinical • Infectious Disease • Pneumonia • Respiratory Diseases

EVADE: Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (clinicaltrials.gov) - P2; N=188; Completed; Sponsor: MedImmune LLC; Active, not recruiting ➔ Completed

Clinical • Trial completion

EVADE: Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (clinicaltrials.gov) - P2; N=190; Active, not recruiting; Sponsor: MedImmune LLC; Recruiting ➔ Active, not recruiting

Enrollment closed

Pseudomonas aeruginosa PcrV and Psl, the molecular targets of bispecific antibody MEDI3902, are conserved among diverse global clinical isolates. (PubMed, J Infect Dis) - "MEDI3902 maintained potent in vivo activity against various strains, including strains expressing only a single target. Psl and PcrV are highly prevalent in global clinical isolates, suggesting MEDI3902 can mediate broad coverage against P. aeruginosa."

Clinical • Journal

A Phase 1 Study of MEDI3902, an Investigational Anti-Pseudomonas aeruginosa PcrV and Psl Bispecific Human Monoclonal Antibody, in Healthy Adults. (PubMed, Clin Microbiol Infect) - P1; "Phase 1 study results of MEDI3902 in healthy subjects support further evaluation of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia."

Clinical • Journal • P1 data